The Cardiovascular System • Right AV valve –tricuspid valve.

Introduction • Left AV valve –aka mitral valve; bicuspid valve.

HEART –serves as a pump for the blood.
BLOOD VESSELS –transport blood throughout the body.
Under normal conditions, this system is a continuous, closed circuit, meaning
that the blood is found only in the heart and blood vessels.
Right side of the heart –pumps blood to the lungs through the pulmonary
circulation so that gas exchange, uptake of oxygen and elimination of CO2
can take place.
Left side of the heart –pumps blood to the rest of the tissues of the body
through the systemic circulation.
Arterial system: arteries and arterioles
–carry blood away from the heart and toward the tissues.
Capillaries –where the exchange of substances between the blood and
tissues takes place.
Venous system: veins and venules
–carry blood back to the heart.
• Semilunar valves –separate the ventricles from their associated arteries;
tricuspid.
• Pulmonary valve –is found between the right ventricle and the
pulmonary artery.
• Aortic valve –is found between the left ventricle and the aorta.
• First Heart Sound –occurs when the ventricles contract and the AV valves
close.
• Second Heart Sound –occurs when the ventricles relax and the semilunar
valves close.
The wall of the heart has three layers:
• Epicardium –thin membrane on the external surface of the heart.
• Endocardium –consists of a thin delicate layer of cells lining the chambers
of the heart and the valve leaflet; continuous with the endothelium, which
lines the blood vessels.
• Myocardium –the muscular layer; thickest layer of the heart.
• Length-tension relationship –when the resting sarcomere length is altered,
the amount of tension developed by the myocardium upon stimulation is
altered as well.

Functional anatomy of the Heart

• Pericardium –a double-walled fibrous sac that encloses and anchors the
heart in place.
• Pericardial fluid

CHAMBERS OF THE HEART

• Atria (sing. atrium) –are chambers that receive blood returning to the heart
through the veins.
• Ventricles –delivery chambers of the heart.
• Valves –ensure the one-way or forward flow of the blood.
• Atrioventricular (AV) valves
Electrical Activity of the Heart
Cardiac muscle is myogenic or self-excitatory; the muscle spontaneously
depolarizes to threshold and generates action potentials without external
stimulation.
• Sinoatrial node -region of the heart with the fastest rate of inherent
depolarization which initiates the heart beat and determines the heart rhythm;
“pacemaker.”
-located in the wall of the right atrium near the entrance of the
superior vena cava.
-spontaneously depolarize to threshold and generate 70 to 75 heart
beats per minute.
-resting membrane potential/pacemaker potential: approx. -
55mV

Heart rate is modulated by input from the autonomic nervous system. The
sympathetic and parasympathetic systems innervate the SA node.
• Sympathetic stimulation causes an increase in heart rate or an
increased number of beats/min.
• Norepinephrine –stimulates β1-adrenergic receptors;
increases the rate of pacemaker depolarization by increasing the
permeability to Na and Ca++ ions.
• If the heart beat is generated more rapidly, then the result
is more beats per minute
• Parasympathetic stimulation –causes a decrease in heart rate
• Acetylcholine –stimulates muscarinic receptors, increases
the permeability to K+.
• It takes longer for the SA node to reach threshold and
generate an action potenital.
• If the heart beat is generated more slowly, then fewer beats
per minute are elicited.
Electrocardiogram (ECG)
• Represents the sum of all electrical activity throughout the heart at
any given moment.
• The ECG provides information concerning:
• Relative size of heart chambers
• Various disturbances of rhythm and electrical conduction
• Extent and location of ischemic damage to the myocardium
• Effects of altered electrolyte concentrations
• Influence of certain drugs (e.g., digitalis and antiarrhythmic
drugs)
Pharmacy application: Antiarrhythmic Drugs
• Arrhythmia –any abnormality of the initiation or propagation of the impulse;
most common clinical problem encountered by a cardiologist.
• Verapamil –class IV antiarrhythmic drug, Ca++ channel blocker; is an
effective agent for atrial or supraventricular tachycardia.
-effects: decrease in heart rate and in conduction velocity of the
electrical impulse through the AV node.
-the resulting increase in duration of the AV nodal delay, (which is
illustrated by a lengthening of the PR segment in the ECG), reduces the
number of impulses permitted to penetrate to the ventricles to cause
contraction.
• Procainamide –class IA antiarrhythmic drug; effective for ventricular
tachycardia.
-MOA: blocks the fast Na+ channels responsible for phase 0 in the
fast response tissue of the ventricles; most pronounced in the Purkinje fibers.
-effects: decrease in excitability of myocardial cells and in conduction
velocity; decrease in the rate of phase 0 upstroke and a prolonged
repolarization are observed.
-duration of the action potential and the associated refractory period
is prolonged and the heart rate is reduced.
-illustrated by an increase in the duration of the QRS complex.
Cardiac Cycle
-period of time from beginning of one heart beat to beginning of the next.
-two phases:
• Systole –chambers contract and eject the blood.
• Diastole –chambers relax allowing blood to fill them.
• Atria –diastole is the predominant phase.
• Ventricles –systole is much longer lasting.
• Ventricular filling –occurs during ventricular diastole.
 • The initial phase of filling is rapid because blood had accumulated
in the atrium prior to the opening of the AV valve; once this valve opens, the
accumulated blood rushes in.
• The second phase of filling is slower as blood continues to flow
from the veins intro the atrium and then into the ventricle. This phase of filling
is referred to as diastasis.
• End-diastolic volume (EDV) –approx. 120-130mL at rest.
• Aortic (semilunar) valve is closed.
• Ventricular contraction –occurs during ventricular systole.
• When the ventricular myocardium begins to contract, pressure
increases rapidly.
• AV valve is closed; until ventricular pressure exceeds aortic
pressure, the aortic valve also remains closed.
• Isovolumetric contraction –both valves leading into and out of the
chamber are closed.
• Ejection –aka ventricular emptying; occurs when the build-up of ventricular
pressure overtakes the aortic pressure and the aortic valve.
• End-systolic volume (ESV) –approx. 50-60mL at rest.
• Stroke volume (SV) –volume of blood pumped out of each ventricle per
beat; 70mL in a healthy adult heart at rest.
After systole, the ventricles abruptly relax.
• Isovolumetric relaxation –ventricular pressure is below aortic pressure
and above atrial pressure.
The heart contracts to pump the blood into the arteries and then it relaxes so
it can once again fill with blood. However, capillary blood flow is not
interrupted by this cycle because blood flow to the tissues is continuous.
• Rapid addition of the stroke volume causes arterial distention, or
stretch, resulting in “storage” of a portion of this blood in these vessels.
• During diastole, when the heart relaxes, the arteries recoil and
regain their original shape. This recoil squeezes down on the store blood and
pushes it forward toward the tissues.
• Blood flow is continuous during ventricular systole and diastole.
Cardiac Output
-volume of blood pumped into the aorta per minute.
Cardiac output (CO) = heart rate (HR) x stroke volume (SV)
An average adult at rest may have a heart rate of 70 beats per minute and a
stroke volume of 70mL per beat. In this case, the cardiac output would be:
CO = 70 beats/min x 70mL/beat = 4900mL/min or 5 L/min
This is approximately equal to the total blood volume in the body.
• Level of activity
• Cardiac reserve –is the difference between the cardiac output at
rest and the maximum volume of blood that the heart is capable of pumping
per minute.
• Endurance training increases cardiac reserve so that performance
is maximized and muscle fatigue is delayed.
• Patients with heart conditions such as congestive heart failure or
mitral valve stenosis cannot increase their cardiac output.
• Size of the body
• Cardiac index –normalizes cardiac output for body size and is
calculated by the CO per square meter of body surface.
• An average person weighing 70kg has a body surface area of
approx. 1.7 square meters.
• Therefore: CI: 5 L/m ÷ 1.7 m2 = 3 L/min/m2
• Age
• Rises to a peak of more than 4 L/min/m2 at age 10 and then
steadily declines to about 2.4 L/min/m2 at the age of 80.
Control of Heart Rate
• Heart rate –normal: 70 beats per minute.
-children: higher.
-emotional excitement/exercise: greater than 100 bpm
-sleep: decrease by 10-20 beats
-athletes: 50bpm –training induced bradycardia; reduces the
workload of the heart.
• Chronotropism –refers to changes in heart rate.
 • Positive chronotropic effect –increases heart rate
• Negative chronotropic effect –decreases heart rate
Factors: 1. Autonomic nervous system –exerts primary control on HR.
-heart rate results from the balance or sum of their inputs.
-SA node and AV node are innervated by both subdivisions.
-the specialized ventricular conduction pathway and ventricular muscle are
innervated by the sympathetic system only.
• Sympathetic stimulation –increases HR; norepinephrine binds
to β1 receptors and causes the following effects:
• Increased rate of discharge of the SA node
• Increased rate of conduction through the AV node
• Increased rate of conduction through the bundle of His and
the Purkinje fibers.
-involves enhanced depolarization of these cells due to decreased
K+ permeability and increased Na+ and Ca++ permeability.
• Parasympathetic stimulation –decreases heart rate;
acetylcholine released from the vagus nerve binds to muscarinic
receptors and causes the following effects:
• Decreased rate of discharge of the SA node
• Decreased rate of conduction through the AV node.
-increased permeability to potassium. -predominates at rest.
2. Release of catecholamines (Epinephrine and norepinephrine) from the
adrenal medulla –same effect as sympathetic stimulation.
3. Body temperature –alters the rate of discharge of the SA node; an
increase of 1⁰F in body temp. results in an increase of 10 bpm.
Control of Stroke Volume
Two important concepts:
(1) The heart can only pump what it gets
(2) A healthy heart pumps all of the blood returned to it
Factors:
• Length of diastole –maximal HR during exercise is 195 bpm.
• Venous return –the volume of blood returned to the right atrium per minute;
CO = VR.
• Preload –ventricular blood volume prior to contraction; equal to
EDV.
• Frank-Starling law of the heart –when ventricular filling is increased,
the walls of the chambers stretch and contract more forcefully (like a
rubberband).
Pharmacy Application: Diuretics and Cardiac Output
• Diuretics –reduce the volume of body fluids.
-MOA: involves an increase in the excretion of Na+ and Cl- ions and,
consequently, an increase in urine production.
-reduces plasma volume; less blood is available for ventricular filling; less
preload.
-beneficial for patients with hypertension or heart failure; relieves congestion
and edema.
• Contractility of the myocardium -increased by the sympathetic nervous
system and catecholamines; positive inotropic effect.
• Ejection fraction –the ratio of the volume of blood ejected from the
left ventricle per beat (stroke volume) to the volume of blood left in the left
ventricle at the end of diastole (end-diastolic volume):
EF = SV ÷ EDV
-resting conditions: 55-60%; exercise: 80%
• Afterload –the pressure in the artery leading from the ventricle. -sustained
or chronic increase will increase cardiac workload:
-hypertrophy of left ventricle
-disruption of balance between O2 supply and O2 demand in the
heart, decreasing stroke volume and CO and heart failure.
• Heart rate –calcium influx occurs more frequently and time for calcium
removal is reduced.
Pharmacy Application: Cardiac glycosides and Cardiac output
• Heart failure –cardiac output is insufficient to meet the metabolic demands
of his body.
• Cardiac glycosides: Digoxin –positive inotropic effect.
-MOA: binds to and inhibits Na+-K+ ATPase, leading to an increase in
intracellular conc. of calcium.
-increased myocardial contractility, SV and CO.