Cardiovascular A&P

The Basics
● 3 major elements in the circulation
○ A pump (heart)
○ Channels or tubes (blood vessels)
○ A fluid medium (blood)
● The heart generates pressure to drive blood through the vessels
● Blood flow must meet metabolic demands during exercise

Major Functions
● Delivery of oxygen and other nutrients
● Removal of carbon dioxide and other metabolic waste
● Transport or hormones
● Thermoregulation
● Maintenance of acid-base balance and overall body fluid balance
● Immune function

Two Pumps in One

● Anatomically RIGHT heart — Pulmonary Circulation
○ Pumps deoxygenated blood from body to lungs
○ Flow: superior/inferior vena cava ⇒ RIGHT atrium ⇒ tricuspid valve ⇒
RIGHT ventricle ⇒ pulmonary valve ⇒ pulmonary arteries ⇒ lungs
● Anatomically LEFT heart — Systemic Circulation
○ Pumps oxygenated blood from lungs to body
○ Lungs ⇒ pulmonary veins ⇒ LEFT atrium ⇒ mitral valve ⇒ LEFT ventricle
⇒ aortic valve ⇒ aorta

Myocardium
● The Cardiac Muscle
○ LV is the most powerful and largest chamber
■ Mostly due to its need to drive blood through the systemic circulatory
system
○ Thickness of all the chamber walls vary based on “stress” place on chamber wall
○ This thickness is known as hypertrophy
■ Mostly commonly seen in LV
 ■ Can have both exercise and clinical etiologies
● Myocardial Cells
○ One fiber type
○ Similar to Type 1 skeletal muscle
○ High capillary density
○ High number of mitochondria
○ Striated
● Should contract as a single unit
● Cardiac muscle fibers connected by intercalated discs
○ Desmosomes (cell to cell adhesion) which anchor the individual cells together
○ Gap junctions
■ Rapidly conduct action potentials
■ Allow all fibers within each chamber of the heart contract together as
one unit
■ This is functional syncytium

Myocardium v Skeletal Muscle

● Skeletal muscle cells
○ Large, long, unbranched, multinucleated
○ Intermittent, voluntary contractions
○ Ca2+ released from the SR
● Myocardial cells
○ Small, short, branched, singular/multinucleated
○ Continuous, involuntary rhythmic contractions
○ Calcium-induced calcium release

Cardiac Conduction System — Structure

● Spontaneous rhythmicity
○ Pacemaker cells generate and spread
electrical signal
○ Sinoatrial (SA) node
○ Atrioventricular (AV) node
○ AV bundle and branches
○ Purkinje fibers

Intrinsic Control of Heart Activity

● SA node: initiates contraction signal
○ Pacemaker cells in upper posterior RA wall HIGHLY excitable
○ Signal spread from SA node via RA/LA to AV node
 ○ Stimulates RA, LA contraction
● AV node: delays, relays signal to ventricles
○ In RA wall near center of the heart
○ Delay allows RA, LA to contract before RV, LV
○ Relays signal to AV bundle after delay
● AV Bundle: relays signal to RV, LV
○ Travels along interventricular septum
○ Divides into right and left bundle branches
○ Sends signal toward apex of heart
● Purkinje fibers: send signal into RV, LV
○ Terminal branches of right and left bundle branches
○ Spread throughout entire ventricle wall
○ Stimulate RV, LV contractions
● Intrinsic HR = 100 beats/min
○ Any increases or decreases from 100 are an act of the parasympathetic and
sympathetic nervous system

Electrocardiogram (ECG)
● Provides a graphical record of the electrical activity of the heart and can be used to aid
clinical diagnosis
● 3 basics
○ P wave: atrial depolarization
○ QRS complex: ventricular depolarization
○ T wave: ventricular repolarization

Cardiac Function
● Cardiac cycle
○ Diastole
○ Systole
● Stroke volume (SV)
● Ejection Fraction (EF)
● Cardiac Output (Q)

Cardiac Cycle
● The mechanical and electrical events that occur during one heartbeat (systole to systole)
○ Systole is the contraction phase
■ Chamber ejects blood
○ Diastole is the relation phase
■ Chambers fill with blood
 ■ About 2x as long

Ventricular Systole Phase

● QRS Complex to T Wave
● ⅓ of the cardiac cycle
● Contraction begins
○ Ventricular pressure rises
○ Atrioventricular valves close (mitral and tricuspid)
○ Aortic and Pulmonary valves open
○ Blood ejects
○ At end, blood in ventricle = end-systolic volume (ESV)

Ventricular Diastole Phase

● T wave through P wave
● ⅔ of the cardiac cycle
● Relaxation beings
○ Ventricular pressure drops
○ Aortic and pulmonary valves close
○ Atrioventricular valves open
○ Fill 70% passively, 30% by atrial contraction (P waves)
 ○ At end, blood in ventricle = end diastolic volume (EDV)

Stroke Volume and Ejection Fraction

● Stroke Volume (SV): volume of blood pumped in a single heartbeat
○ During systole, most (not all) blood ejected
○ EDV - ESV = SV
○ 100mL - 40mL = 60mL
● Ejection fraction (EF): percentage of EDV pumped
○ EF = SV/EDV
○ 60mL/100mL = 0.6 or 60%
○ Clinical index of heart contractile function
○ When blood is pumped, chambers do not completely empty
○ EF averages ~60% at rest in healthy person

Cardiac Output (Q)

● Total volume of blood pumped per minute
● Q = HR x SV
● Resting Q is about ~5L/min
 ○ Average total blood volume ~5L
○ Total blood volume circulates once every minute
● Resting HR ~70bpm, standing SV ~70mL/beat
● 70bpm x 70mL/beat = 4900mL/min
● Use L/min (4.9L/min)

The Vascular System

● Arteries, arterioles, capillaries, venules, veins
● Blood pressure
○ Drives blood flow
○ Systolic BP
■ Highest pressure in artery (during systole)
■ Pressure DURING heartbeat
■ Top number of BP reading
○ Diastolic BP
■ Lowest pressure in artery (during diastole)
■ Pressure BETWEEN heartbeats
■ Bottom number of BP readings
○ Mean Arterial Pressure (MAP)
■ Average pressure over entire cardiac cycle
■ MAP = ⅔ DBP + ⅓ SBP
● Hemodynamics
○ Blood flows from region within vessel of high pressure to a region within the
vessel with lower pressure
■ High to low
○ Pressure gradient across the entire cardiovascular system = 100mmHg
 ○ Blood vessels and blood itself provide resistance to blood flow

Acute CV Responses to Exercise

Response to acute exercise
● Each component of the CV system must meet the demands put on them by increased
demands for blood flow to their exercising muscle
● This is accomplished by changes in
○ Heart rate
○ Stroke volume
○ Cardiac output
○ Blood pressure
○ Blood flow
○ Blood itself

HR
● Resting HR
○ Normal ranges
■ Untrained RHR: 60-80 bpm
■ Trained RHR: as low as 30-40 bpm
■ Can be affected by
● Temperature
● Altitude
 ● Sympathetic/parasympathetic stimulation
● Intrinsic HR is about 100 bpm
○ Great for walking around but bad for just sitting there
● Extrinsic control of heart — parasympathetic
○ Reaches heart via vagus nerve (cranial nerve X)
■ Vagal stimulation = parasympathetic stimulation
○ Carries impulses to SA and AV nodes
■ Slight hyperpolarization of conduction cells
■ Decrease HR and force contraction
○ Decrease HR below intrinsic HR
■ Maximal vagal stimulation is 20-30 bpm
● Extrinsic control of heart —- sympathetic
○ Opposite effects of parasympathetic
○ Sympathetic nerves carry impulses to SA and AC nodes
■ Increase HR and force contraction
○ Increase HR above intrinsic HR
■ Determined HR during physical and emotional stress
■ Maximal sympathetic stimulation is ~250 bpm
● HR vs Relative workload
○ Direct linear relationship between variables
■ Heart rate and VO2
■ Vo2 is maximal oxygen consumption
● Intrinsic vs extrinsic control of the heart
○ Intrinsic
■ The heart has a natural internal pace making ability
■ This is about 100 bpm
○ Extrinsic
■ Parasympathetic nervous system
● Decreased HR and force of contraction
○ Acetylcholine (ach)
■ Sympathetic
● Increases
● Epi and norepi
○ Released from the adrenal medulla
○ Increases HR
● During acute exercise
○ Chronotropic capacity
■ Capacity alter (increase) contraction frequency
 ○ HR increases in direct proportion to the increased exercise intensity
● Phases of HR during Acute exercise
○ Anticipatory response of HR
■ HR slightly above RHR just prior to the start of exercise
● Decreases vagus tone
● Increase norepi and epi
○ Max HR
■ Highest HR achieved in “all-out” effort to volitional fatigue
● Highly reproducible
● Declined slightly with age
○ Steady state of HR
■ Optimal HR for meeting metabolic demands at a given submaximal
intensity
● If intensity increases, so does steady-state HR
● Adjustments to new instrinsity can take 2-3 mins

Stroke Volume
● The major determinant of cardiorespiratory endurance capacity (aka “aerobic capacity”
aka VO2max)
● Increases with increases in work rate (exercise intensity)
● Usually plateaus at ~40-60% of VO2max
● 4 factors that determine SV
○ Ventricular filling capacity
○ The volume of venous blood returned to the heart (preload)
○ Ventricular contractility (inotropy)
○ Aortic or pulmonary artery pressure (afterload)
● Why does it increase during exercise
○ Frank-Starling mechanism
■ The ability of the heart to change its force of contraction and therefore
stroke volume in response to venous return
■ Increased preload (greater volume of blood enters the ventricles)
■ Causes ventricles to stretch
■ Ventricle contracts with more force
○ Increase inotropy (force of contraction)
■ Increased ventricular contractility is due to increased sympathetic
stimulation and circulating catecholamines
■ Independent of frank-starling mechanism
○ Decreased total peripheral resistance
 ■ Reduced afterload due to increased vasodilation of blood vessels going to
active muscles

Cardiac Output (Q)

● Q = HR x SV
● Resting value is ~5L/min
● What happens to Q during exercise?
○ Increases with increased intensity and increases up to ~20-40 L/min
○ It can vary based on body size and endurance training

CV Drift
● Gradual decrease in SV and increase in HR (at the same workload)
● Applies during prolonged aerobic exercise (at one workload) and/or environmental
factors (heat)
● Influencing factors
○ Hypovolemia
■ Low blood volume
■ Gradual hydration with exercise can reduce plasma volume 5-10% or
more
● Water component of plasma moves from the blood to the
interstitial space
● Plasma volume is lost through sweat, especially in hotter
environments
○ Hypothermia
■ Increases in core body temp
■ Causes increase in HR
● Direct effect on temp on SA node
● Associated with increased body temp and dehydration
● SV drifts down
○ Skin blood flow increases
○ Plasma volume decreases (sweating)
○ Venous return (preload) decreases
● HR drifts up to compensate (homeostasis of Q)

BP
● MAP (Mean arterial pressure)
○ MAP = Q x total peripheral resistance
○ Systolic BP increases to proportional to exercise intensity
 ○ DBP decreases slightly (due to vasodilation) or slightly increases at maximal
effort
● Increased MAP facilitates the increase in blood
○ Think about pressure gradient
● Also aids substrate delivery to working muscles
○ Hydrostatic pressure
● Why does SBP increase during AE
○ Increase Q
○ Greater arterial pressure helps “push” blood through the vascular system
● Why doesn't DBP increase during AE
○ Sympathetic nervous system engagement
■ Overall vasodilation systemically
○ Localized vasodilation
■ Vessels at the muscle are vasodilation too
○ Decreased resistance = decreased pressure

Chronic Adaptations with CVS Exercise

Terms
● Aerobic training
○ Cardiorespiratory endurance training
○ Utilizes and optimizes aerobic (oxidative) metabolism
○ Running, swimming
● Anaerobic training
○ Short term, high intensity exercise
○ Increases tolerance for acid-base balance
○ Improves ATP-PC and glycolytic energy systems
○ Weightlifting and sprinting
● Adaptation
○ The body’s physiological response to training
■ Acute adaptations
● The body’s physiological response to a singular bout of training
■ Chronic adaptations
● The body’s physiological response to a series of training bouts
● Submaximal
○ An aerobic effort below max effort
 ○ Cardiorespiratory endurance
■ Ability to sustain prolonged, dynamic exercise
■ Achieved through multisystem adaptations
● Cardiovascular, respiratory, muscle, metabolic
● Endurance training
○ Increased maximal endurance capacity or increased VO2
○ Increased submaximal endurance capacity
■ Lower HR at same submaximal exercise intensity
■ More related to competitive endurance performance

CVS: Major Chronic Adaptations

● Heart size (increase)
○ O2 transport system and fick equation
■ Increased VO2max = increased max SV x max HR x increased max (a-v-)O2
difference
■ VO2max = (Q)(AVO2 difference)
○ Heart size
■ With training, heart muscle mass and LV volume increase
■ Increased target HR ⇒ cardiac hypertrophy ⇒ increased SV
■ Increased plasma volume (from an increase in albumin and increase in
kidney hormones ADH and aldosterone causing water and Na retention)
● increased LV volume ⇒ increased EDV ⇒ increased DV
■ Volume loading effect
● SV (increase)
○ Increases after endurance training program
■ Resting, submax, and maximal
■ Plasma volume increases with training increase ⇒ increased EDV ⇒
increased preload
■ Resting and submax HR decreases with training ⇒ increased filling
time ⇒ increased EDV
■ Increased LV muscle mass with training ⇒ increased force of
contraction
■ Attenuated increased TPR with training ⇒ increased afterload
○ SV adaptations to training decrease with age
● HR (decreased)
○ Resting HR
■ Decreased markedly (~1 beat/min per week of training)
 ■ Increased parasympathetic, decreased sympathetic activity in heart
○ Submaximal HR
■ Decreased HR for some given absolute intensity
■ More noticeable at higher submaximal intensities
○ Maximal HR
■ No significant change with training
■ Decrease with age
○ HR and SV interact to optimize cardiac output
○ HR recovery
■ Faster recovery with training
■ Indirect index of cardiorespiratory fitness
● Q (stay same)
○ Training created little to no change at rest, submaximal exercise
○ Maximal Q increases considerably (due to increased SV)
○ HR and SV interact to optimize cardiac output
● Blood flow (more to muscles)
○ Increased blood flow to active muscle
■ Increased capillarization (angiogenesis)
● Increased capillary to fiber ratio
■ Greater recruitment of existing capillaries
■ More efficient blood flow redistribution from inactive regions
○ Increased blood volume
■ Prevents any decrease in venous return as a result of more blood in
capillaries
● BP (decreases)
○ Decrease in BP at given submax intensity
○ Increased systolic BP, decreased diastolic BP at max intensity
● Blood volume (increase)
○ Total volume increases rapidly
○ Increased plasma volume via increased plasma proteins, increased water, and
Na+ retention (all in first 2 weeks)
○ Increased RBC volume (though hematocrit may decrease)
○ Decreased plasma viscosity

The Respiratory System

A&P Review
● Upper respiratory system
○ Above trachea
● Lower respiratory system
● Cardiopulmonary A&P connected

The Upper Respiratory System

● Purpose
○ Filter, warm, and humidify in order to protect the delicate lower half of the
system
● Constitution
○ nose/mouth
■ entry/exit for air in/out of the system
○ Nasal cavity
■ Deposit location for air after passing through a sophisticated filtering
system and warmed here
○ Paranasal sinuses
■ Provides humidification and warmth to the incoming air
○ Pharynx
■ The intersection of the digestive and respiratory system that acts to move
air, food, and water to the proper areas

The Lower Respiratory System

● Purpose
○ Pull in the air from the URS to absorb O2 and release CO2
● Constitution
○ The larynx
■ Cartilaginous structure designed to protect the glottis which is the
narrowing opening to the trachea
○ Trachea
■ Windpipe is a tough flexible tube about 1” in diameter
■ Surrounded by cartilage to protect from damage but is “c-shaped”
protecting it from items that protrude during swallowing
○ Bronchi
■ Divided into left and right that supply each sided lung
■ The bronchi find their termination at the hilus
○ Bronchioles
 ■ Terminal subdivision of the intrapulmonary bronchi
■ large ly smooth muscle which allows for muscular dilation/contraction
which adjusts airflow at this level
○ Alveoli
■ The terminal ending of the bronchi of the bronchi where the exchange of
O2 and CO2 occur

Respiratory System Overview

● Purpose
○ Carry O2 to and remove CO2 from all body tissues
● Carried out by 4 processes
○ Pulmonary ventilation (external respiration)
■ Movement of air into and out of the lungs
○ Pulmonary diffusion (external respiration)
■ The exchange of O2 and CO2 between the lungs and the blood
○ Transport of gases via blood
■ Movement of O2 and CO2 by the blood
○ Capillary diffusion (internal respiration)
■ The exchange of O2 and CO2 between the capillary blood and the
metabolically active tissue
○ It becomes internal once it reaches pulmonary vein

Pulmonary Ventilation
● Anatomy of lung, pleural sacs, diaphragm, and rib cage determines airflow into and out
of lungs
● Lungs suspended by pleural sacs
○ Parietal pleura lines thoracic wall
○ Visceral (pulmonary) pleura attached to lungs
○ Lungs take size and shape of rib cage
● Biphasic process
○ Inspiration
○ Expiration
Resting State
● Atmospheric pressure= 760 mmHg
● Itrapulmonic pressure= 760 mmHg
● Intrapleural pressure= 756 mmHg
Inspiration
● Active process
● Atmospheric pressure= 760 mmHg
● Itrapulmonic pressure= 758 mmHg
● Intrapleural pressure= 754 mmHg
● Involved muscles
○ Diaphragm flattens
○ External intercostals move rib cage and sternum up and out
● Expands thoracic cavity in 3 dimensions
● Expands volume inside thoracic cavity and lungs
● Boyle’s law
○ At constant temperature, pressure and volume inversely proportionally
● If lung volume increases than intrapulmonary pressure must decrease and vice versa
● Air passively rushes in due to pressure difference
● Forced breathing uses additional muscles
○ Scalenes, sternocleidomastoid, pectorals
○ Raise ribs even faster

Expiration
● Atmospheric pressure= 760 mmHg
● Itrapulmonic pressure= 763 mmHg
● Intrapleural pressure= 756 mmHg
● Usually passive process
○ Inspiratory muscles relax
○ If lung volume decreases intrapulmonary pressure increases
○ Air is forced out of lungs
● Active process (forced breathing)
○ Internal intercostals pull ribs down
○ Latissimus dorsi, quadratus lumborum
○ Abdominal muscles force diaphragm back up

Ventilation and the Respiratory Pump

● Changes in intra-abdominal, intrathoracic pressure promote venous return to heart
○ Increase pressure → venous compression/squeezing
○ Decrease pressure → venous filling
● Milking acton from changing pressure assists in atrial filling (respiratory pump)
Lung Volumes
● Tidal volume (TV)
○ Normal breath
● Vital capacity (VC)
○ Forced Vital Capacity (FVC)
● Residual volume (RV)
○ Leftover air after FVC
○ It's impossible for all air to leave lungs
○ Functional residual capacity is what's left over after normal breath
● Total lung capacity (TLC)
○ All the air
○ VC+RV
● Diagnostic tool for respiratory disease
● Measured using spirometry

Regulation of Pulmonary Ventilation

● Body must maintain homeostatic balance between blood PO2, PCO2, pH
● Requires coordination between respiratory and cardiovascular systems
● Coordination occurs via involuntary regulation of pulmonary ventilation

Mechanisms of Pulmonary Regulation

● Respiratory centers
○ Located in brain stem (medulla oblongata, pons)
○ Establish rate, depth of breathing via signals to respiratory muscles
○ Cortex overrides signals if necessary
● Chemoreceptors
○ Central
■ Stimulated by increased CO2 in cerebrospinal fluid
■ Increased rate and depth of breathing
■ Removes excess CO2 from body
○ Peripheral
■ In aortic bodies, carotid bodies
■ Sensitive to blood PO2, PCO2, H+
● Partial pressure
● Mechanoreceptors (stretch)
○ In pleurae, chondioles, alveoli
○ Excessive stretch leads to reduced depth of breathing
 ○ Hering-breuer reflex

Pulmonary Diffusion
● Gas exchange between alveoli and capillaries
○ Inspired air arrives at alveoli
○ Blood path
■ Right ventricle to pulmonary arteries to pulmonary capillaritis
○ Capillaries surround alveoli and gas exchange occurs via diffusion across
respiratory membranes
■ Alveolar-capillary membrane
● 2 major functions
○ Replenishes blood oxygen supply that has been depleted from oxidative energy
production
○ Removes carbon dioxide from returning venous blood

Pulmonary Diffusion During Exercise

● At rest, O2 diffusion capacity limited due to incomplete lung perfusion (and inflation)
○ Only bottom of lung perfused with blood
○ Top ⅔ lung surface area → poor gas exchange
● During exercise, O2 diffusion capacity increase due to more even lung perfusion and
inflation
○ Systemic blood pressure increases opens top ⅔ perfusion
○ Gas exchange over full lung surface area
● Maximal exercise = increase in O2 diffusion capacity partially from increased surface
area
○ Decrease in venous o2 → PO2 bigger gradient
○ Diffusion capacity increases by 3 times the resting rate
● So during Exercise
○ Increases surface area and…
○ Increase partial pressure gradient

Respiratory Membrane
● Also called alveolar-capillary membrane
○ Alveolar wall
○ Capillary wall
○ Respective basement membranes
● Surface across which gases are exchanged
○ Large surface area: 300 million alveoli
 ○ Very thin: 0.5 to 4 micrometers
○ Maximizes gas exchange

Blood Flow to the Lungs at Rest: Pulmonary Hemodynamics

● Blood path: right ventricle → pulmonary arteries → pulmonary capillaries (diffusion
takes place here) → pulmonary veins → left atrium
● At rest, lungs receive 5 L/min of blood flow
● Low pressure and resistance circulation compared to the systemic circulation
○ Pulmonary artery MAP = 15 mmHg
■ Aortic MAP= 95-100 mmHg
○ Left atrial pressure = 5 mmHg

What Affects Diffusion? (Fick’s Law)

● Rate of diffusion proportional to
○ Surface area
■ Large surface = more diffusion
○ Partial pressure gradient
■ PO2 gradient: 65 mmHg
■ PCO2 gradient: 6 mmHg (diffuses easier than oxygen)
○ Barrier thickness
■ Thickness is relatively constant (in healthy people)
○ Diffusion constant
■ Dependent on physical/chemical properties (different for each gas)

Partial Pressures of Gases

● Room air is made up of (79.04%) N2, (20.93%) O2, and (0.03%) CO2

Oxygen Exchange in the Alveoli

● Fick’s law: rate of diffusion proportional to surface area and partial pressure gas
gradient
○ PO2 gradient: 65 mmHg permits diffusion
 ○ PCO2 gradient: 6 mmHg
● CO2 diffuses across cell membranes more easily than O2 because of lower diffusion
constant
○ Despite its lower gas gradient
● Alveolar PO2 about 105 mmHg
● Pulmonary artery PO2 about 40 mmHg

Carbon Dioxide Exchange

● Pulmonary artery PCO2 ~46 mmHg
● Alveolar PCO2 ~40 mmHg
● 6 mmHg PCO2 gradient permits diffusion
○ CO2 diffusion constant 20x greater than O2
○ Allows diffusion despite lower gradient

Partial Pressure of Gases

● Partial P gradient most important factor for determining gas exchange
○ Nothing happens if in equilibrium
● Each gas exerts pressure in proportion to its concentration
● Individual pressure from each gas
● P(air)= PN2 +PO2+PCO2

Oxygen Transport in the Blood

● 20 mL O2 / 100mL blood
● >98% bound to hemoglobin (Hb) in red blood cells
○ O2 + Hb : oxyhemoglobin
○ Hb alone: deoxyhemoglobin
● <2% dissolved in plasma

Hemoglobin Saturation
● Depends on
○ Partial pressure of O2
○ Affinity between O2 and hemoglobin
● High PO2 (in lungs)
○ Loading portion of O2-Hb dissociation curve
○ Small change in Hb saturation per mmHg change in PO2
○ Hemoglobin remains highly saturated
● Low PO2 (in body tissues)
○ Unloading portion of O2-Hb dissociation curve
○ Large change in Hb saturation per mmHg change in PO2
 ○ Unloads oxygen to tissues demanding it

Factors Affecting Hemoglobin Saturation

● Blood pH (Bohr Effect)
○ More acidic leads to O2-Hb curve shift to right
○ More O2 unloaded at acidic exercising muscle
● Blood temperature
○ Warmer leads to O2-Hb curve shifts to right
○ Promotes tissue O2 unloading during exercise

Blood O2 Carrying Capacity During Exercise

● Hb 98 to 99% saturated at rest
○ 0.75 second transit time
 ● Slightly lower saturation with exercise
○ Shorter transit time
● However the unique S shaped curve helps out
○ High Hb-O2 affinity at the top (lung)
● Anemia → decreased hb content → decreased O2 capacity

Carbon Dioxide Transport

● Released as waste from cells
● Carried in blood 3 ways
○ As bicarbonate ions
○ Dissolved in plasma
○ Bound to hemoglobin (carbaminohemoglobin)
○ CO2 + H2O — H2CO3 — HCO3- + H+
■ H+ binds to Hb, triggers Bohr Effect

Bicarbonate Ion and Dissolved CO2

● Transports 60-70% of CO2 in blood to lungs
● CO2 + water yields carbonic acid (H2CO3) which yields bicarbonate ion (HCO3- + H+)
○ Occurs in red blood cells
○ Catalyzed by carbonic anhydrase
○ H+ binds to Hb (buffer), triggers Bohr effect
○ Bicarbonate ion diffuses from red blood cells into plasma
● 7-10% of CO2 dissolves in plasma

Carbaminohemoglobin
● 20-33% of CO2 transported bound to Hb
● Doesn't compete with O2-Hb binding
○ O2 binding to heme portion of Hb
○ CO2 binds to protein (-globin) portion of Hb
● Hb saturation state and PCO2 affect O2-Hb binding
○ Deoxyhemoglobin binds to CO2 easier vs oxyhemoglobin
○ Increased PCO2 yields easier O2-Hb binding
○ Decreased PCO2 yields easier O2-Hb dissociation

Respiratory Regulation of Acid-Base Balance

● Acidosis
○ H+ concentration above normal
● Alkalosis
○ H+ concentration below normal
 ● Metabolic processes (especially anaerobic) produce H+ = decreased pH
● Buffer systems help control pH
○ H+ + buffer = H-buffer
● Physical mechanisms to control pH
○ Chemical buffers: bicarbonate, phosphates, proteins, hemoglobin
■ Bicarbonate helps remove H+ as H2O and CO2 in lungs
■ Hemoglobin also carries some CO2 to the lungs

Arteriovenous Oxygen (A-VO2) Difference

● A-V O2 difference
○ Difference between arterial and venous O2
○ Reflects tissue O2 extraction
○ As extraction increases,
■ Venous O2 decreases
■ (A-V-) O2 differences increases
● Arterial O2 content
○ 20 mL O2 / 100 mL blood
● Mixed venous O2 content varies
○ Rest
■ 15-16 mL O2 / 100m mL blood
○ Heavy exercise
■ 4-5 mL O2 / 100 mL blood

Oxygen Transport in Muscle

● O2 transported in muscle by myoglobin
○ Similar structure to hemoglobin
○ Higher affinity for O2
● O2-myoglobin dissociation curve shaped
differently
○ At PO2 0-20 mmHg, slope very steep
○ Loading portion at PO2 = 20 mmHg
○ Releasing portion at PO2 = 1-2 mmHg

Arterial-venous Oxygen Difference

● (a-v) O2 difference
○ Difference between arterial and venous
O2
○ Reflects tissue O2 extractions
○ As extraction increases, venous O2 decreases, (a-v)O2 difference increases
 ● Arterial O2 content: 20 mL O2/100 mL blood
● Mixed venous O2 content varies
○ Rest: 15 to 16 mL O2/100 mL blood
○ Heavy exercise: 4 to 5 mL O2/100 mL blood

Factors Influencing O2 Delivery and Uptake

● O2 content of blood
○ Represented by PO2, Hb percent saturation
○ Creates arterial PO2 gradient for tissue exchange
● Blood flow
○ Increased blood flow = increased opportunity to deliver O2 to tissue
○ Exercise increases blood flow to muscle
● Local conditions (pH, temp)
○ Shift O2-Hb dissociation curve
○ Decrease pH, increase temperature promote unloading in tissue

Fick Principle
● VO2 = Q x (a-v)O2 difference
● VO2 = (HR x SV) v (a-v)O2 difference

Respiratory Limitations to Aerobic Capacity (VO2 Max)

● Ventilation (central adaptations) usually not limiting factor
○ Respiratory muscles account for 10% of VO2, 15% of Q during heavy exercise
○ Very fatigue resistant
● Airway resistance and gas diffusion usually not limiting factor

Ventilation During Exercise

● Immediate increase in ventilation
○ Begins before muscle contractions
○ Anticipatory effect: central command
● Gradual increase in ventilation over time (2nd phase)
○ Driven by
■ Chemical changes in arterial blood by chemoreceptors that sense
increases in CO2 and H+ ions
■ Right atrial stretch receptors
● Ventilations increase proportional to the metabolic demand of the tissues
○ At low intensity exercise
■ Mainly volume increases
○ At high intensity exercise
 ■ Rate follows volume
● Ventilation recovery after exercise is delayed
○ Recovery can take several minutes
○ Regulated by blood pH, CO2, temp
■ How many and quickly one rid themselves of metabolic by-products the
faster the recovery

Ventilation & Energy Metabolism

● We know that ventilation matches rate of energy metabolism during state activity
● However, there can be mismatches at higher exercise intensity
○ Ventilatory threshold (VT) occurs at 55-70% VO2max
■ Point during higher intensity exercise when ventilation increases
disproportionately to oxygen consumption

Oxygen Diffusion Capacity

● At level of muscle
● The volume of O2 diffused per minute per 1 mmHg of pressure gradient
● At rest
○ O2 diffusion capacity
■ 21 mL O2 / min / 1 mmHg of gradient
● At maximal exercise
○ Venous O2 decreases which leads to larger PO2 gradient
○ Diffusion capacity increases by 3 times resting rate

Oxygen Exchange in the Alveoli

● At rest, O2 diffusion capacity limited due to incomplete lung perfusion
○ Only bottom ⅓ of lung perfused with blood
○ Top ⅔ lung surface area are poor areas of exchange
● During exercise, O2 diffusion capacity increases due to more even lung perfusion
 ○ Systemic blood pressure increases opens top ⅔ perfusion
○ Gas exchange over full lung surface area

Principles of Aerobic Exercise Training

Physical Activity Guidelines
● AHA says
○ 30 min/day for 5 x/wk, mild-moderate
■ Like walking
○ 35 min/day for 3 x/wk, vigourous
■ running

Principles of Training
● Individuality
○ Any training program must consider the specific needs and abilities of the
individual for whom it is designed
○ Genetic differences
○ Biological and physiological differences
■ Variations in metabolism and cardiorespiratory and neuroendocrine
regulation are all considerations
● Specificity
○ Adaptations to training are highly specific to the nature of the training activity
and should be carefully matched to an athlete's specific performance needs
○ Training program must stress MOST relevant physiological systems for given goal
○ Training adaptations reflect type of activity, training volume, and intensity
● Reversibility
○ Training programs must include a maintenance plan to ensure that the
adaptations from training are not lost
○ Training yields improvements in CV and metabolic functions
○ Detraining yields the reciprocal
● Progressive overload
○ The training stimulus must be progressively increased as the body adapts to the
current stimulus
○ Must increase demands on body to make further improvements
■ Increase workloads as you train
● Variation
 ○ Aka periodization
○ Systemically changes one or more variables to keep training challenging
■ Intensity, volume, and/or mode
■ Increase volume, decreased intensity and vice versa
○ Macrocycles (big cycles) > mesocycles (medium cycles)
■ In-season training vs off-season training
■ Base building phase vs sport-specific vs recovery
■ All athletes should have periodization of training

Exercise Prescription
● Minimum threshold
○ Point below which no improvements occur
○ Exists for frequency, duration, and intensity
○ Varies with each individual
● Once minimum threshold exceeded, aerobic capacity increases

ExRx for Cardiovascular Fitness (Prescribed Exercise)

● Exercise program designed to improve aerobic capacity for overall health
● FITT principle
○ Frequency
○ Intensity
○ Time
○ Type

Frequency
● How often one performs exercise
○ Optimal:
■ 3-5 days per week
○ Minimum:
■ Depends on the other portions of the FITT principle
■ At least 3 days/wk if vigorous
■ At least 5 days/week if mild-moderate
● General rule of thumb
○ Start gradually
■ Avoid burnout/fatigue
○ Be consistent
■ Develop a habit of exercise
Intensity
● Workload at which exercise is conducted
● Intensity most important factor/ others depend on it
○ Usually moderate to vigorous for benefits
■ 50-69% VO2max for moderate
■ 70-85% VO2max for vigorous
● Determined by
○ VO2 (direct but impractical)
○ Heart Rate (indirect but practical)
○ METs (estimate and clumsy)
○ RPE (estimate and unreliable)
● Graded exercise test (if it is available)
○ Obtained while exercising on a treadmill or cycle
ergometer
○ Linear relationship between VO2max and HR during
graded exercise test
● GXT used to screen for
○ Arrhythmias
○ Coronary artery disease
○ Abnormal blood pressure responses
● To determine maximal HR (or near max HR) for exercise
prescription and/or maximal O2 consumption (VO2max)
● Karvonen Method (allows us to calculate a percentage of HR
Reserve)
○ Heart rate reserve (Use actual HRmax if available from
GXT or age predicted)
■ HRreserve = HRmax - HRrest
○ Target HR (THR) is calculated (this percentage
corresponds to percentage of VO2max)
■ THR75%= [0.75(HRmax - HRrest )]+HRrest
○ Training heart rate ranges can be calculated:
■ 60-70% HRreserve
Metabolic Equivalent (MET)
● Based on the value of resting metabolic rate
○ 3.5ml/kg/min = 1 MET (little work)
○ 35 ml/kg/min = 10 METS (lots of work)
 ● Useful for training guidelines, but it fails to account for environmental conditions, and
doesn't allow for changes in fitness
● Can be used to prescribe exercise in the event that doing a GXT is not possible

Time
● Warm-up, exercise, cool down
● Actual exercise time
○ 20-60 min/session
○ Not including warm up and cool down
○ May be continuous or intermittent (>10. each)
■ This is done if someone does not have enough time for one long session.
Breaking them up into shorter bouts of exercise for at least 10 minutes
can give similar results)
● Optimal
○ 20-30 min per day
○ One long bout of multiple shorter bouts nor <10 min
○ Inverse relationship between duration and intensity
● How low can we go? (Time and Intensity)
○ Dr. Martin Gibala
■ Exercise physiologist at McMaster University in Canada
■ 19 sedentary and overweight men
■ Compared Gibala’s 1 min sprint interval workout to a typical 45-minute
steady state exercise bout at 70% max HR
■ Results
● Peak O2 uptake increased after training by 19% in both groups
● Insulin sensitivity index increased similarly
● Skeletal muscle mitochondrial content increased similarly as
primarily reflected by the maximal activity or citrate synthase
 ○ Gibala’s sprint interval workout
■ 2 min warm-up
■ 3 sets
● 20-sec intervals of all-out, hard as you can exercise
● 2 min rest/recovery
■ 3 min cooldown
■ Performed workout 3x/wk
● Exercise interval intensity
○ %HRmax a good indicator of physiological stress
■ HRmax determined by all out effort at VO2 max test
○ ATP-PCr training
■ ~90-100% HRmax
○ Anaerobic glycolytic training
■ ~85-100% HR max
○ Aerobic-oxidative training
■ ~70-90% HRmax
○ Heart rate monitors are a helpful tool!
● Max Aerobic Energy Expenditure
○ VO2max
■ Point at which O2 consumption doesn't increase with further increase in
intensity
■ Best single measurement for aerobic fitness
■ Not a best predictor of endurance performance
■ Plateaus after 8-12 weeks of training
● Performance continues to improve
● More training allows athlete to compete at higher percentage of
VO2max
● Energy Expenditure During Exercise
○ No activity 100% aerobic or anaerobic
○ Estimates of anaerobic effort involve
■ Excess post-exercise O2 consumption (EPOC)
■ Lactate threshold

Type
● Any form of rhythmic physical activity which uses large muscle groups
● Prescribe what patients enjoys most
● Modes most frequently prescribed
○ walking/hiking/jogging/running
 ○ Cycling
○ Rowing
○ Swimming
○ Spinning
○ Aerobic dance
○ Racket sports
● Continuous Training
○ No rest intervals can can vary from low to high intensity training
● High intensity interval training (HIIT)
○ Repeated bouts of high to moderate intensity exercise interspersed with periods
of rest or reduced intensity exercise
○ Combines aerobic and anaerobic training

Aerobic Training
● LSD = Long, Slow Distance
○ Train at !60-80% HRmax
■ 50-75% VO2max
○ Main objective: distance, not speed
○ Les cardiorespiratory stress
○ Greater joint/muscle stress, overuse injuries
● Fartlek - “speed play”
○ Vary pace from sprint to jog at discretion
○ Continuous training + interval elements
○ Primarily used by distance runners

Interval-Circuit Training
● Combined interval and circuit training
○ Varied intensity
○ Combining traditional strength exercises, plyometrics, and low intensity
cardiovascular exercises
○ Short or no rest periods
○ Intervals target different muscle groups
● Bases for many group fitness classes

Successful Endurance Athletes

● High VO2max
● High lactate threshold (as % VO2max)
● High economy of effort
● High percentage of type I muscle fibers
Purpose of Warm-up
● Prepares the cardiovascular, respiratory, and musculoskeletal systems for the “work”
ahead
● Facilitates the transition from rest to exercise
○ Improves blood circulation
○ Increases the metabolic rate
○ Increases body temperature
○ Reduces risk for musculo-skeletal injury

Purpose of Cool Down

● Gradual recovery from the “exercise” phase
○ Adjust the circulatory response (HR and BP)
○ Improve venous return
■ Reduce risk of post-exercise hypotension and dizziness (vasovagal
response)
○ Reduce risk for cardiovascular complications
■ Sudden cardiac death

Acute Cardiopulmonary Exercise Response

CV Responses to Acute Exercise
● Increases blood flow to working muscle
● Involves heart function, peripheral circulatory adaptations

Beta Blockers
● Beta — Adrenergic Blocking Medications
○ Reduce workload of heart
○ Decreasing neural excitation and contractility
○ Decrease HR about 30-35%

Blood Flow Redistribution

● Sympathetic vasoconstriction
○ Shunts blood away from less-active regions
● Local vasodilation
○ Permits additional blood flow in exercising muscle
○ Triggered by metabolic, endothelial products
○ Local neural modulation of vasoconstriction in working muscle offsets
sympathetic vasoconstriction
■ Local VD > neural VC
● Example
○ As temp rises, skin VD occurs
○ Decreased sympathetic VC, increased sympathetic VD
○ Permits heat loss through skin

Factors Affecting Plasma Volume

● Capillary fluid movement into and out of tissue
○ Hydrostatic pressure (pulls fluid out) vs. oncotic pressure (protein — albumin,
pulls fluid into circulatory system)
○ Osmotic pressure
■ Prevents inward flow of fluid across semipermeable membrane
● Upright exercise ⇒ decreased plasma volume
○ Increased MAP ⇒ increased capillary hydrostatic pressure
○ Metabolite buildup ⇒ increased tissue osmotic pressure
○ Sweating further ⇒ decreased plasma volume

Hemoconcentration
● Decreased plasma volume ⇒ hemoconcentration
○ Fluid % of blood decreases, cell % of blood increases
 ○ Hematocrit increases up to 50% or beyond
● Net effects
○ RBC concentration increases
○ Hemoglobin concentration increases
○ O2-carrying capacity increases
● Benefits of altitude training

Central Regulation of CV Responses

● What stimulates rapid changes in HR, Q, and BP during exercise?
○ Precede metabolite buildup in muscle
○ HR increases within 1s of onset of exercise
● Central command
○ Higher brain centers
○ Coactivates motor and CV centers

Integration of the Exercise Response

● CV response to exercise complex, fast, and finely tuned
● First priority: maintenance of BP
○ BP must remain stable to maintain blood flow
○ Prioritized before exercise, thermoregulatory, etc

Ventilation During Exercise

● Immediate increase in ventilation
○ Begins before muscle contractions
○ Anticipatory response from central command
● Gradual second phase of increase in ventilation
○ Driven by chemical changes in arterial blood
○ Increased CO2, H+ sensed by chemoreceptors
○ Right atrial stretch receptors
■ Increases in stretch and so ventilations meet demands
● Ventilation increases proportional to metabolic needs of muscle
○ At low-exercise intensity, only tidal volume increases
○ At high-exercise intensity, rate also increases
● Ventilation recovery after exercise is delayed
○ Recovery takes several minutes
○ May be regulated by blood pH, PCO2, temp

Breathing Irregularities
● Dyspnea (shortness of breath)
 ○ Common with poor aerobic fitness
○ Caused by inability to adjust to high blood PCO2, H+
○ Also, fatigue in respiratory muscles despite drive to increase ventilation
● Hyperventilation (excessive ventilation)
○ Anticipation or anxiety about exercise
○ Increased PCO2 gradient between blood, alveoli
○ Decreased blood PCO2 ⇒ increased blood pH ⇒ decreased drive to breathe
● Valsalva maneuver: potentially dangerous but accompanies certain types of exercise
○ Close glottis
○ Increased intra-abdominal (bearing down) and intrathoracic (contracting
breathing muscles) pressure
● High pressures collapse great veins ⇒ decreased venous return ⇒ decreased Q ⇒
decreased arterial BP

Ventilation and Energy Metabolism

● Ventilation matches rate of energy metabolism during steady state activity
● Ventilatory equivalent for O2
○ Ratio between volume of air expired and volume of O2 consumed by the tissues
○ VE/VO2 (L air breathed / L O2 consumed per minute)
● Ventilatory threshold
○ Point where L aired breathed > L O2 consumed
○ Around 55-70% of VO2max
○ Around the same time, more lactate appears to remain in the blood
○ Lactic acid is buffered by sodium bicarbonate and ventilation increases due to
increased CO2 stimulating the chemoreceptors

Lactate Threshold
● Excess lactate
● LT: Lactate production > lactate uptake and clearance
● Ventilatory threshold as surrogate/estimate measure for lactate threshold?
○ Excess lactic acid + sodium bicarbonate (buffer) = sodium lactate, H2O, CO2
○ Increased CO2 stimulates chemoreceptors to increase ventilation
● Direct measure of lactate threshold through blood sampling

Limitations to Performance
● Ventilation usually not limiting factor
○ Respiratory muscles account for 10% of VO2, 15% of Q during heavy exercise
○ Very fatigue resistant
● Airway resistance and gas diffusion usually not limiting factors at sea level
 ● Restrictive or obstructive respiratory disorders can be limiting
○ COPD, emphysema, chronic bronchitis, asthma
● Exception 1
○ Elite endurance-trained athletes exercising at high intensities
■ Ventilation may be limiting
■ Insufficient time for blood to saturate with oxygen in the lungs due to
extremely high cardiac output
● Exercise-induced arterial hypoxemia (EIAH)
● Ventilation-perfusion mismatch
● Expectation 2
○ COPD (asthma. Chronic bronchitis, emphysema)
○ Ventilation and diffusion may be limiting

Acid-Base Balance
● Metabolic processes produce H+ ⇒ decrease pH
● H+ + buffer ⇒ H-buffer
● At rest, body slightly alkaline
○ 7.1 - 7.4
○ Higher pH = alkalosis
● During exercise, body slightly acidic
○ 6.6 - 6.9
○ Lower pH = acidosis
● Physiological mechanisms to control pH
○ Chemical buffers (bicarbonate, phosphates, proteins, hemoglobin)
○ Increased ventilation helps H+ bind to bicarbonate
○ Kidneys remove H+ from buffers, excrete H+
● Active recovery facilitates pH recovery
○ Passive recovery
■ 60-120 min
○ Active recovery
■ 30-60 min
● Buffering capacity
○ Bicarbonate 64%
○ Hemoglobin 29%
○ Proteins 6%
○ Phosphates 1%
Aerobic Exercise & CVD
CVD Prevalence
● US
○ Leading cause of serious illness and death in the US
○ Accounts for ⅓ of all US deaths annually
○ ~$300B in annual costs
○ 1 american dies every 37 secs from CVD
○ Represents the cause of 25% of all deaths in the US
● Globally
○ #1 cause of death globally
○ 17.9M people die each year from CVDs
■ An estimate 31% of all deaths worldwide
○ >71% of CVD deaths occur in low and middle income countries
○ 85% of all CVD deaths are due to heart attach and strokes
○ Out of 17M premature deaths (under the age of 70)
■ 82% are in low or middle income countries
■ 37% are caused by CVD

Risk Factors
● Uncontrollable risk factors
○ heredity/family history
○ Race
○ Sex (male>females)
○ Age
● Controllable CVD primary risk factors
○ Tobacco use (smoking)
○ Hypertension
○ Dyslipidemia
○ Poor cardiorespiratory fitness
○ overweight/obesity
○ Insulin resistance/diabetes
● Other risk factors
○ + first degree relative (male<55 yo, female <65 yo)
○ C-reactive protein (CRP)
○ Coronary artery calcium (CAC)
 ○ Ankle-brachial index (ABI)
■ Ankle SBP/brachial SBP <0.9 is abnormal
○ Inflammatory processes and markers may be involved in risk
● As the number of risk factors increase, the risk of CVD increases too
● Prevailing approach is to minimize the onset or the impact of the preventable risk
factors

Determining Individual Risk

● Epidemiology of CHD and hypertension reveals relationships of disease factors not
causal mechanisms
○ Large-scale public studies, often longitudinal
○ Framingham heart study
● Gives researchers with valuable insights into disease risk factors

Hypertension
● High blood pressure
○ Affects 32% of
US adult
population
● Heart must work
harder to eject blood
● Places greater strain on
arteries
● Causes enlarged heart,
scarred/stiff arteries
● Prevalence
○ Poorly
understood
condition
○ 90-95% of cases
idiopathic
○ Remaining 5-
10% secondary
to other issues
■ Kidney
disease
■ Adrenal
tumors
■ Congenital defect of aorta
Hyperlipidemia
● Elevated blood triglycerides
● Elevated blood cholesterol
● Lipoproteins
○ VLDL cholesterol (risk factor)
○ LDL cholesterol (risk factor)
○ HDL cholesterol (beneficial)
● Total cholesterol:HDL ratio
○ Lower is better

Smoking
● Nicotine, carbon monoxide, free radicals and cytokines fundamentally negatively
influence circulation
○ Increase HR, BP, endothelial injury, increase “stickiness” of platelets
● Create and destabilize atherosclerotic plaque
● Most important single risk factor in coronary artery disease, sudden cardiac death,
ischemic stroke, aortic aneurysm formation, peripheral vascular disease

Forms of CVD
● Coronary heart disease (CHD)
○ Aka Coronary Artery Disease (CAD)
○ Most common
● Cerebral artery disease aka stroke
● Heart failure (cardiomyopathy) and congestive heart failure
● Peripheral vascular disease (PVD), valvular, congenital heart defect

CAD
● Accumulation of vascular smooth muscle cells (VSMCs) form a fibrous cap that thickens
● Characteristics
○ Is a general part of aging that is magnified by chronic disease and lifestyle
choices
■ Fatty streaks appear in infancy/childhood
■ Fatty streaks appear in coronary arteries in teenage years
■ Fibrous plaques develop in 20s
■ Hardening and stiffening of arteries due to aging and disease
progressions
● Etiology
○ Primary
 ■ Aging
○ Secondary
■ HTN, DM, HLD
● signs/symptoms
○ None, until it is too late
● Treatment
○ Treatment for chronic disease conditions
○ angioplasty/bypass depending on location

Understanding the Disease Process

● Pathology of CHD affects vessel wall
● Theory
○ Monocytes attach between endothelial cells and become macrophages
○ Ingest oxidized LDL
○ Become larger foam cells, form fatty streaks
○ Endothelial cells slough off
○ Exposure underlying connective tissue
○ Allows platelets to attach
● Endothelial injury or disruption comes from
○ High blood LDL
○ Free radicals from cigarette smoke
○ Hypertension
○ High plasma homocysteine
○ Infectious microorganisms
● Atherosclerosis now considered to be inflammatory disease
● Plaque consists of
○ Smooth muscle, inflammatory cells, lipids
○ Fibrous cap (thick or thin)
○ Thin caps = more unstable = easier rupture
○ Rupture ⇒ thrombus formation
● Rupture and thrombus account for 70% of MIs
● Plaques are dynamic (erode, repair, grow)

CHD
● Progressive narrowing of coronary arteries that leads to MI
● Characteristics
○ CHD doesn't really have characteristics
○ It can lead to myocardial ischemia (chest pain)
● Etiology
 ○ Primary
■ Atherosclerosis
○ Secondary
■ HLD, HTN, smoking, aging
● Signs/symptoms
○ CHD itself has very few, if any, S/S
○ MI is noted with radiating chest pain, pressure, and SOB
● Resolution
○ Acute
■ Angioplasty or bypass
○ Treatment of comorbidity
● Accounts for ~50% of CVD deaths

Peripheral Arterial Disease (PAD)

● Atherosclerosis in peripheral arteries
● Most often in the lower extremity
● Causes cramping sensation of extremities (claudication)
○ Ischemia in peripheral skeletal muscle

Ischemic Stroke
● The sudden death of brain cells caused by a blockage of the blood vessels
● Characteristics
○ It is the most common form
○ They can be caused by 2 types of blockages
■ Cerebral thrombosis (clot)
■ Cerebral embolism (blockage)
● Etiology
○ Very similar to ischemic heart Dz
● S/S
○ Headache, arm weakness, facial droop, slurred speech
● Treatment
○ Management of comorbid conditions
○ Exercise
○ Acutely
■ Intravenous tissue plasminogen activator (tPA)

Hemorrhagic Stroke
● The sudden death of brain cells caused by a “brain bleed”
● Characteristics
 ○ Arises from aneurysms
■ A bulging, weak part of an artery wall (secondary to HTN and/or
atherosclerotic damage)
○ This weak point in a vessel of the brain ruptures
○ Rupture leads to ischemia of brain tissue and causes pressure on brain which
leads to tissue death
● Etiology
○ Atherosclerosis
○ HTN
● S/S
○ The same as ischemic stroke
○ Headache, arm weakness, facial droop, slurred speech
● Treatment
○ Acturely
■ Surgical intervention to reduce or stop bleeding and its affects
○ Chronic disease management

Impact of Stroke (regardless of type)

● Effects of stroke depends on region(s) affects
○ Right-sided stroke impacts
■ Vision and memory centers
■ Quick, inquisitive behavior
○ Left-sided stroke
■ speech/language and memory centers
■ Slow, cautious behavior
● General principles
○ The side of the brain determines the opposite but impacted side of the body
○ Hemiparesis is a common and quite debilitating physical symptom of a stroke
Heart Failure
● The chronic, progressive weakening of the heart
○ Common causes: hypertension, Valvular diseases, MI
○ Ultimately requires heart transplant in most severe cases
● Characteristics
○ The tissue of the heart becomes too weak to maintain Q
○ This can be defined as a Ejection Fraction that is <30%
● Etiology
○ Primary
■ HTN
○ Secondary
■ Atherosclerosis
■ Valvular disease
■ Viral infection
■ MI
● S/S
○ Peripheral and pulmonary edema
● Treatment
○ Treatments of symptoms
 ○ Monitored and progressive exercise
○ Heart transplant
● Diastolic Dysfunction (affects filling)
○ Stiff and thick chambers
○ Smaller EDV leads to same or reduced EF
○ Decreased SV
● Systolic Dysfunction (affects contractility)
○ Stretched and thin chambers; enlarged heart
○ Increased EDV
○ Decreased EF
○ Decreased SV

Other Heart Disease

● Peripheral vascular disease (PVD)
○ A general term for disease process that occur in the extremities and peripheral
aspects of the vascular system
○ Peripheral arterial disease, varicose veins, phlebitis
● Valvular diseases
○ Damage or defect of one of the valves of the heart (mitral, aortic, tricuspid, and
pulmonary)
○ Often caused by viral infections, rheumatic heart disease, or congenital defects
● Congenital heart defect
○ Poorly or underdevelopment (in utero) of the tissue or vessels of the heart
○ Often affects aorta, valves, septum, or combination of each

Physical Inactivity & CVD

● London transport workers study 1953
○ Drivers were more likely to do have coronary occlusion (MI) and early mortality
(within 3 days of MI) than conductors
○ Physical inactivity doubles the risk of CAD
● Harvard Alumni Study 2000
○ Inactive group had higher risk associated with cvd for any of the risk factors
except diabetes

Cardiorespiratory Fitness (VO2max)

● What happens to VO2max as we age?
○ Aerobic capacity peaks between 20-30 years of age
○ Decreases ~1% per year in sedentary people
○ Accelerated rate of decline beyond age ~60
 ● How does exercise training affect this?
○ Active people tend to have higher relative VO2max across the age spectrum
● Summary of Epidemiological Evidence
● Physical inactivity doubles the risk of CAD
● Low-intensity physical activity is sufficient to reduce the risk of this disease
process
○ There is greater benefit in risk reduction for people who are physically fit
as opposed to just physically active
● Health benefits do not require high-intensity exercise, but more vigorous
exercise provides greater benefits

Reducing CVD Risk Through Aerobic Exercise

● Physical adaptations to exercise that may reduce risk
○ Increased contractility of myocardium
○ Increased diameter and capacity of coronary vessels
○ Increased endothelial function and vasodilation
○ Reduced vascular inflammation
■ Inflammation contributes to atherosclerosis and arterial stiffening
● Exercise and fitness are independently associated with CAD risk, but also affect other
risk factors
● Exercise reduces risk factors
○ Lowers BP by 6-7 mmHg
○ Lowers triglycerides
○ Increases HDL-cholesterol (5-15%)
○ Helps with healthy weight management
○ Helps with T2DM management
○ Stress reduction
○ Anxiety reduction

Exercise Training/Rehabilitation of Patients with Heart Disease

● Aerobic exercise helps prevent future complications
○ Increases blood flow to heart (and skeletal muscle)
■ Promotes angiogenesis and collateral artery formation around areas of
muscle death or decreased blood flow
○ Increases (or maintains) O2 supply to heart
○ Increases LV function
● Reduce risk factors to prevent progression or development of additional CVD
● Exercise rehabilitation improves outcomes
○ Reduces all-cause mortality and risk of death from subsequent MI
Cardiorespiratory Responses to Training

Chronic Aerobic Exercise Training

● regular , vigorous aerobic exercise training
○ At least 3 days/week
○ At least 30 min/session
○ At least 70% VO2max

Maximal Oxygen Consumption

● VO2max
○ Highest rate of oxygen consumption attainable during maximal exercise
○ How much can we increase VO2max after 6 months of aerobic exercise training?
■ 15% on average; variable among individuals
● VO2 does not change at any absolute workload (oxygen requirement at workload levels
stays the same for pretraining and post training)
● VO2max and maximal workload increases

Absolue vs. Relative Workloads

● Absolute= fixed workload
○ 100 watts, 6 mph, etc
○ With increases in VO2max, one can achieve a higher absolute maximal workload
● Relative=% of individual maximum
○ Example: 50% VO2max
○ If VO2max increases, this is still 50% of VO2max
○ But...the corresponding absolute workload is higher
○ Basically, the corresponding workload for chosen percentage of VO2max will
increase after training, but the percentage of VO2max itself does not change

Increases in VO2max with Aerobic Training

● Recall the fick equation:
○ VO2= SV * HR (or Q cardiac output) *(a-v)O2 difference
Cardiovascular Adaptation to Training- Central
● Central (what changes in the heart)
○ Heart size
○ Stroke volume
 ○ Heart rate
○ Cardiac output
● Peripheral
○ Blood flow
○ Muscle perfusion
○ Blood volume
● Cardiac Output and Aerobic Training
○ After training, what happens to Q at the same absolute exercise intensity
■ Q typically does not change at rest or at the same absolute submaximal
exercise intensity
■ VO2 doesn't change at at the same absolute submaximal exercise
intensity
○ What happens to maximal Q after training?
■ Maximal cardiac output increases substantially after training
■ Follows the same trend as VO2max
● SV and Aerobic Training
○ After training, what happens to SV during maximal exercise?
■ SV increases
○ During submaximal exercise at the same absolute workload?
■ SV increases
○ At rest?
■ SV increases
● Heart Size and Aerobic Training
○ The left ventricle changes significantly in response to endurance training
○ Internal dimensions of left ventricle increase (end diastolic volume is higher)
○ Thickness of myocardium increases (left ventricular hypertrophy) or an increase
in stroke volume (SV)
● Left ventricular Hypertrophy
○ Pathological
■ An issue with the filling of the heart
■ Left ventricle dimensions get smaller
■ Left ventricle gets larger but the muscle gets weaker or nonfunctional
○ Physiological
■ Left ventricular volume increases
■ Thickening of the muscle around LV for more forceful contraction
● So Why does SV increase
○ Increases in EDV
■ Increase in left ventricular size
 ■ Increase in blood plasma volume
○ Ventricular hypertrophy leads to increased contractility
○ Increased ventricular filling (preload) leads to greater contractility (frank-starling
mechanism)
○ Reduced systemic vascular resistance (afterload)
● Heart rate and Aerobic Training
○ Maximal HR (HRmax) does not change (may even decrease slightly)
■ Similar response to sympathetic stimulation
■ If your heart rate is too fast the period of ventricular filling is reduced and
your SV might be compromised
○ Resting HR decreases with aerobic exercise training
■ Increased heart size and stroke volume
■ Increased parasympathetic (vagal tone)
○ Submaximal HR (at same absolute workload) is lower
■ Again, increased heart size and SV
■ Also vagal tone at lower intensities
● The Karvonen method and Aerobic Training
○ Why does prescribing exercise using the Karvonen method (target Hr range)
automatically incorporate the principle of progressive overload?
■ Do not have to adjust HR ranges as people train to accomplish the
principle of progressive overload
Cardiovascular Adaptation to Training- Peripheral
● Blood Flow and Aerobic Training
○ Maximal blood flow to exercising muscle is increased with endurance training
due to:
■ Increased blood volume (more blood to carry more oxygen)
■ Increased Q (heart is pumping out more blood)
■ More effective blood flow redistribution from inactive regions (decrease
blood flow to inactive regions)
● Digestive organs vs active skeletal muscle
○ Muscle perfusion is created with endurance training to:
■ increase capillarization of trained muscle
■ Greater recruitment of existing capillaries in trained muscles
● Greater surface area for capillary diffusion
● More O2 can be delivered to the muscle
● Blood Volume and Aerobic Training
○ BV increases rapidly with endurance training
○ Plasma volume increases due to:
 ■ Increased plasma proteins (albumin)
■ Increased antidiuretic hormone and aldosterone
○ Red blood cell volume increases
■ Hemoglobin increase leads to O2 carrying capacity increase
● Respiratory Adaptations to Training
○ Pulmonary changes
■ Pulmonary ventilation
● Unchanged at rest
● Max pulmonary ventilation increases due to
○ Increased tidal volume (ability to breathe in more air)
○ Increased breathing rate during max exercise
■ Pulmonary diffusion
● Refers to gas exchange at alveoli
● Does not increase at rest or submax
● At max, more blood flow to lungs after training leads to increased
diffusion
● MAXIMAL Q INCREASES = MORE FLOW TO SYSTEMIC AND
PULMONARY CIRCULATION
○ Arterial-venous oxygen difference changes
■ Maximal (a-v)O2 difference
● Increases with exercise training
● Increased (a-v)O2 difference indicates greater uptake of O2 by the
muscle
● Arterial O2 concentration remains similar
● Lower venous O2 concentration
■ Total amount of oxygen diffusion increases
● Due to increased (a-v)O2 difference and higher blood flow
■ Increases due to:
● Increased perfusion of muscle (capillary density so more blood
reaches higher surface area)
● Increased myoglobin (which carries oxygen to muscle tissue)
● Increased mitochondria in muscle
○ Metabolic Adaptations in Muscle Mitochondria
■ Increase in the number and size of muscle mitochondria = increase in
mitochondrial volume
■ Oxidative enzyme activity increase
■ Increased capacity of oxidative metabolism
○ Kreb’s Cycle
 ■ Both citrate synthase and succinate dehydrogenase increase with more
aerobic training
■ Increase in metabolic adaptations when someone is highly aerobic
trained
○ Cumulative Effects of Peripheral Adaptations on VO2max

Chronic Adaptations to Training

Terms
● Hypertrophy
○ Increases in the cross-sectional size of the muscle
● Submaximal
○ An aerobic effort below max effort

Training
● Principles of training include
○ Overload
○ Specificity
○ Reversibility
● These principles can be applied to all exercises and strength development

Overload
● Organ system/tissue must be stressed beyond comfort in order to adapt
● Without proper stress, sub-optimal adaptation occurs or no adaptation
● 3 variables can greatly affect overload
○ Intensity
○ Duration
○ Frequency
● Adaptation happens over time not instantly

Reversibility
● What happens when you stop exercising
● Gains by exercising or training through overload will be lost quickly when training
creases
● Aka detraining
Specificity
● Effect that exercise training is specific to muscles, energy systems, contraction velocity,
type of muscular contraction involved in the activity
● How specific to main goal
● Adaptations are specific to training activity
● Aerobic type exercises result primarily in capillary density and mitochondrial number
○ Anaerobic resistance training resulting in increases in contractile proteins may
reduce this number

Aerobic Training Adaptation

● Studies show that repeated endurance training increases fat oxidation at rest and during
submax exercise
● Improved ability to utilize intramuscular TGs for fuel
● 4 factors contribute to increased lipolysis
○ Increased blood flow to working muscle
○ Increased fat mobilizing/metabolizing enzymes
○ Enhanced mitochondrial capacity
○ Decreased catecholamine release for same intensity exercise
● Endurance training
○ Increased maximal endurance capacity = increased VO2max
○ Increased submax endurance capacity
■ Lower HR at same submax exercise intensity
■ More related to competitive endurance performance

Important CV Adaptation
● Heart size (increase)
● SV (increase)
● HR (decreased)
● Q (stay same)
● Blood flow (more to muscles)
● BP (decreases)
● Blood volume (increase)

Aerobic CV Adaptations
● O2 transport system and fick equation
○ Increased VO2max = increased max SV x max HR x increased max (a-v-)O2
difference
● Long term endurance training generally will increase heart’s mass and volume
 ● Cardiac hypertrophy is generally focused on the LV
● The intraventricular lumen will expand, accepting more blood
● Muscular wall thickens (in a good way) with increased muscle mass
● The heart can receive good stress and bad stress
○ The good stress (exercise) is a temporary
■ Rest periods allow for recuperation
■ “Athlete's heart” is not a dysfunctional organ
● Normal systolic/diastolic function
● Superior functional capacity for SV and Q

Cardiac Output Increases

● Maximum HR decreases slightly with training
● The increased Q comes directly from improved SV
● This adaptation is what separates the men from the boys and women from girls
● The key in achieving a high level of aerobic fitness
● Study
○ In one study, average submax Q decreased after 16 weeks of aerobic training
○ Maximal Q increased by 8%
○ Reduced Q means a higher a-VO2 diff
○ Better O2 extraction at submax levels
○ More effective distribution of blood
○ Muscles more effective at generating ATP with less O2

SV increases
● Training causes SV to increase during rest
○ LV volume increases
○ Reduced arterial stiffness
○ Slower HR allows for increased filling time
● Why might it increase?
○ Increased plasma volume
○ Increase in RBC count

Plasma Volume Increases

● Measurable changes in as little as 24 hrs
● 12-20% increase in absence of increased RBC mass
● Can occur as quickly as 3-6 aerobic training sessions
 ● Plasma volume increase enhances circulatory reserve, increases EDV, SV, O2 transport,
temperature regulating ability
● Plasma volume returns to normal following 1 week of detraining

Frank-Starling Law of the Heart

● EDV is thought of as the “preload” on the heart
● Discovered an interesting phenomenon
○ As EDV increases, ventricular contraction increases
○ Cardiac muscle fibers stretch as EDV increases
○ This stretching allows for greater contractility of the heart muscle
○ What it means and why it's beneficial
■ Increased blood flow per beat
■ More oxygenated blood to tissues

Fiber Type Changes

● Aerobic training results in shift toward slow twitch fibers
● Shift represents the increase in mechanical efficiency
○ Type I fibers use less ATP
● Magnitude of change depends on training
○ Intensity
○ Duration
● Capillary supply to muscles also increases
● Very strong correlation between capillary density and VO2max
● Increased capillarization allows for increased/faster gas exchange/substrate delivery
● Metabolic wastes also dispersed quicker

Metabolic Rate During Submax Exercise

● Metabolism increases in direct proportion to the increase in exercise intensity
● During exercise at a constant power output (work rate) VO2 increases from its resting
value to a steady-state value within 1-2 minutes
● There is a linear increase in the VO2 with increases in power output (work rate)

4 factors that affect aerobic training responses

● Initial level of fitness
● Training intensity
● Training frequency
● Training duration
Positive Training Adaptations Don’t Require Pain
● 65-70% of max HR is usually a moderate exercise intensity with no discomfort
● Represents the “controversial exercise” intensity
● Sufficient intensity to stimulate training effect, yet no discomfort
○ At or around level of overbearing lactate accumulation

Training Sensitive Zone

● Generally, higher training intensity, the higher greater improvements for VO2 max
● However, a “ceiling” may exist
○ Generally thought to be around 85% VO2max, or 90% max HR
○ Excessive training intensity/abrupt increases may cause injury
● APMHR usage
○ Based on average populations
● Generally a variation of +/- 10 BPM from individual to individual
● This does not affect effective training for healthy individuals

Aerobic Metabolic Adaptations

● Long term improvement
○ Highest possible VO2max achieved after 12-18 months
○ Performance continues to increase after VO2max plateaus because lactate
threshold continues to increase with training
● Individual responses dictated by
○ Training status and pre training VO2max heredity
● Training status and pre training VO2max
○ Relative improvement depends on fitness
○ The more sedentary the individual, the greater the increase
○ The more fit the individual, the smaller the % increase
● Heredity
○ Finite VO2max range determined by genetics, training alters VO2max within the
range
○ Accounts for 25-50% of variance in VO2max
● Adaptations in muscle
○ Increase in Type IIa, IIx cross-sectional area
○ Decrease in Type I cross-sectional area
■ Lesser extent
○ Decrease % of type I fibers
■ Increased % of type II
○ Anaerobic power and capacity increase with training
Aerobic Training
● Short duration
○ Less than 5 minutes
● Focuses on strength and power
○ Moving more weight over less time
● Utilizes anaerobic metabolism
○ ATP-PC and glycolytic pathways
● Predominantly using Type IIa and Type IIx muscle fibers
○ Less mitochondrially dense
● Sprinting, olympic weightlifting, resistance training