17
Hemodynamics of cardiac arrest
Stroke volume and cardiac output
Each ventricle normally ejects approximately 70–75 ml
with each heart beat (the stroke volume) at a rate of
approximately 70 beats per minute, resulting in a cardiac
output of approximately 5 litres per minute.
Stroke volume is determined by:
1. the intrinsic contractile properties of the heart (which
are modified by the effects of ischemia, by circulating
hormones, and by autonomic stimulation);
2. the degree of stretch of the left ventricle during diastole,
i.e., its “preload” (the Frank–Starling phenomenon).
This in turn is dependent on:
(a) total blood volume,
(b) venous tone, which determines the distribution
of blood volume between the venous and central
compartments
(c) left ventricular compliance – determined by intrin-
sic left ventricular myocardial compliance, and in
some circumstances by external constraint from the
right ventricle, pericardium, and mediastinal struc-
tures (see later)
3. The “Afterload” against which the heart contracts. When
the heart contracts against a high afterload, stroke
volume tends to fall.
Arterial physiology and hemodynamics
Small arteries and arterioles
Mean arterial blood pressure (2⁄3 diastolic BP  1⁄3 systolic
BP) is the product of cardiac output and systemic vascular
Cardiac Arrest: The Science and Practice of Resuscitation Medicine. 2nd edn., ed. Norman Paradis, Henry Halperin, Karl Kern, Volker Wenzel, Douglas
Chamberlain. Published by Cambridge University Press. © Cambridge University Press, 2007.
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Michael. P. Frenneaux and Stig Steen
Department of Cardiovascular Medicine, University of Birmingham, UK
Department of Cardiothoracic Surgery, University Hospital of Lund, Sweden
resistance. Systemic vascular resistance is a static resist-
ance, principally determined by the tone of arterioles. This
tone is controlled by humoral and neural factors (particu-
larly sympathetic tone)1 and by paracrine factors (including
nitric oxide, prostaglandins, endothelium-derived hyper-
polarizing factor, and endothelin).2 Systemic vascular
resistance represents the global resistance produced by
small artery and arteriolar tone. At a local level, changes in
resistance vessel tone modulate tissue perfusion.
Large arteries
The large arteries are more than simply passive conduits.
The fixed and dynamic properties of the large arteries pro-
foundly affect blood pressure and left ventricular perform-
ance. In healthy young subjects the large arteries (such as
the aorta, and iliac vessels) are very compliant and exert a
damping effect on pulsatile left ventricular outflow, result-
ing in a relatively lower systolic pressure and a higher dias-
tolic pressure. Aging of the large arteries renders them less
compliant, impairing this damping function and resulting
in relatively higher systolic and lower diastolic blood pres-
sures for any given mean blood pressure. Furthermore, in
the elderly, central aortic pressure is augmented by pres-
sure wave reflection from the periphery. Following left ven-
tricular ejection there is a forward travelling pressure wave
which is then reflected back from branch sites (where there
is impedance mismatch). In healthy young arteries the
pressure wave travels relatively slowly and returns to the
aorta in diastole, where it helps to maintain diastolic pres-
sure and flow, whereas in stiffer elderly arteries it travels
more rapidly, returning to the central aorta in systole, aug-
menting the systolic pressure.3
347
 348 M.P. Frenneaux and S. Steen
In summary, whereas the arterioles modulate static
resistance, the properties of the large arteries determine
dynamic impedance, which is analogous to resistance but
relates to pulsatile rather than to steady flow.
Venous capacitance
The capacitance vessels serve a reservoir function. Over
70% of total blood volume is located in the venous com-
partment. Of this, the vast majority is in the small veins
and venules, with the minority in the medium sized and
large veins. Because of the large volume of blood within
the venous compartment, relatively small changes in
venous tone markedly alter the distribution of blood
volume. An increase in venous tone shifts blood from the
venous compartment to the heart, increasing intracardiac
pressures, whereas a reduction in venous tone has the
opposite effect. In patients with heart failure, for example,
diuretic treatment may reduce total blood volume yet
central blood volume (and jugular venous pressure) may
remain high because of venoconstriction. Unlike the
arteries, the venous system exerts only a modest resist-
ance to blood flow.
Coronary blood flow
Whereas flow in most organs occurs predominantly in
systole, flow in the coronary arteries occurs mainly during
diastole.4 The high pressures generated in the left ventricle
during systole impede flow through the intramural micro-
vessels (i.e., coronary vascular resistance rises markedly
during systole) by generating a backward travelling com-
pression wave, and forward flow in the coronary arteries
during the latter part of isovolumic relaxation is mainly a
“suction” phenomenon due to rapid relaxation of the left
ventricle, with an associated rapid reduction in the pres-
sure within the intramural coronary microvessels.5
Compared with other tissues, the perfusion gradient
across the heart is smaller. Because flow occurs in diastole,
the upstream pressure is aortic diastolic rather than mean
pressure. Furthermore, although the coronary sinus drains
into the right atrium, coronary microvascular pressure is
markedly influenced by left ventricular diastolic pressure,
which is usually substantially higher than right atrial pres-
sure. The perfusion of the heart may be compromised by a
reduction in aortic diastolic pressure, the presence of
stenoses in the epicardial coronary arteries, an increase in
coronary microvascular resistance, or an increase in left
ventricular end diastolic pressure.
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Hemodynamic changes occurring following
cardiac arrest
Most of the experimental studies published have examined
the hemodynamic changes occurring after the onset
of ventricular fibrillation (VF). VF results in totally incoor-
dinate ventricular activity, with effective cessation of ven-
tricular contraction. Interestingly, as first described by
William Harvey,6 atrial contractions may continue for a
considerable period after the onset of cardiac arrest. The
effects of these atrial contractions may be evident in the
aortic pressure tracing (Fig. 17.1).
At the instant of cardiac arrest, a large pressure gradient
exists between the central aorta (mean arterial pressure)
and the right side of the heart. Despite cessation of ven-
tricular contraction, this pressure gradient drives ante-
grade blood flow which will continue until the pressure
gradient has been completely dissipated. Direct visual
inspection and cardiac MRI studies have shown a rapid
increase in right ventricular volume following cardiac
arrest, as blood is translocated from the systemic circula-
tion to the right side of the heart along its pressure gradi-
ent (Fig. 17.2).7,8 There is also a pressure gradient between
pulmonary artery and left atrium, and flow therefore con-
tinues through the pulmonary circulation to dissipate this
gradient. When these pressures equalise, this flow ceases
and the pulmonary vasculature including the extraperi-
cardial component of the pulmonary veins is distended
with blood (Fig. 17.3). The theoretical pressure at which
the pressures converge throughout the circulation was
termed “Statischer Fullungsdruck” by Weber in 1851,9 or
“Static Blood Pressure” by Starr in 1940.10 Guyton pro-
posed that arterial and systemic venous pressure would
almost reach equilibrium (at a pressure he called “Mean
Circulatory Filling Pressure”) 30–50 seconds after the
heart stopped beating.11 This equilibrium pressure is
determined by total blood volume and by total vascular
“capacitance” (of which venous capacitance provides the
largest contribution). Consequently, this concept has
been used by physiologists to assess the effects of inter-
ventions on venous capacitance in animal models. Mean
circulatory filling pressure is estimated during brief
induced ventricular fibrillation. As blood pressure falls
however, baroreflex inactivation may be expected to
increase sympathetic outflow, increasing venous tone
and leading to an equilibrium pressure which overesti-
mates the venous tone that existed prior to cardiac arrest.
Consequently, some groups have calculated a theoretical
equilibrium pressure on the basis of the pressure changes
in the arteries and veins occurring during the first few
seconds after onset of VF.12 Postmortem studies have
 Hemodynamics of cardiac arrest 349

140
Ascending aorta
120
VF
100
Blood pressure (mmHg)

80

60

40

20
Right atrium

–20
–5 0 5 10 15 20 95 100
Time (S)
Fig. 17.1. Example of aortic pressure and RA pressure in the pig model following the onset of VF cardiac
arrest. Phasic changes in both pressures are seen due to continuing atrial contraction. (Figure provided
by S. Steen.)

shown an equilibrium pressure in human corpses (well
after death) of approximately 6 mmHg.10
Studies in animals and in man have shown that the
decay in arterial pressure and the increase in venous pres-
sure does not conform to a single mono-exponential func-
tion.8,13 Schipke and colleagues recently studied patients
with heart failure who had undergone implantation of an
automatic implantable cardioverter defibrillator (AICD).13
Ventricular fibrillation was induced in order to assess the
defibrillation threshold. Haemodynamic changes were
assessed during an average of 13 seconds of VF. In a sub-
group, the duration of VF was over 20 seconds. The aver-
aged data for this subgroup is shown in Fig. 17.4. As
expected, LV and aortic pressure were almost identical, and
both decayed rapidly. Right atrial pressure increased
rapidly. Nevertheless, even at 20 seconds an arteriovenous
pressure gradient of almost 10 mmHg persisted. It is clear
from the data that Guyton’s prediction that an equilibrium
pressure would exist throughout the circulation in 30–50
seconds is not correct. This study showed that the decay in
arterial pressure and the increase in right arterial pressures
both conformed best to exponential curves. Exponential
curves should approach an equilibrium at five times the
time constant of the curve. During the first few seconds
the time constant of the arterial pressure decay was
2.9 seconds – which would have predicted a plateau at
approximately 14.5 seconds, yet this was not seen. The
reason is that the time constraint of the exponential decay
progressively lengthened. Why might this be so? First,
hypotension-induced baroreflex withdrawal would be
expected to increase sympathetic outflow, and indeed
a marked increase in sympathetic circulating cate-
cholamines of adrenal, and to a lesser extent neural, origin
has been reported after cardiac arrest.14–16 This would be
expected to increase arteriolar tone and also to increase
venous tone. Secondly, it may be due to “waterfall” phe-
nomena. As arterial pressure falls, some microvascular
beds may close down, resulting in a net increase in vascu-
lar resistance. In anesthetised dogs a “waterfall” has also
been demonstrated in the inferior vena cava at the level of
the diaphragm.17 However, no significant inferior vena
cava waterfall was demonstrated at the level of the
diaphragm before or during VF in humans.12
Steen and colleagues studied the hemodynamic changes
occurring in anesthetised pigs during much longer periods
of VF.8 A typical example of the changes in arterial and right
atrial pressures occurring after the onset of VF in non-
ventilated pigs is shown in Fig. 17.5. The first 20 seconds of
this recording are very similar to the human data reported
by Schipke et al.13 There is an early progressive reduction of

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 350 M.P. Frenneaux and S. Steen

Fig. 17.2. External appearance of the heart following VF Cardiac Arrest in Pig Model. The right
ventricular volume rapidly increases as blood flows from the aorta to the right heart. (Reproduced with
permission from Resuscitation.8)

aortic pressure, reaching a minimum of 20 mmHg after
about 30 seconds. Aortic pressure then increases slightly to
about 25 mmHg at 2 minutes, thereafter gradually decreas-
ing over the next 5 minutes to approximately 10 mmHg.
Right atrial pressure increases gradually after induction of
VF, reaching a peak of about 18 mmHg after 2 min, decreas-
ing thereafter to approximate aortic pressure by about
7 min. Mean circulatory filling pressure at this point is
approximately 9 mmHg.
These findings cannot be explained purely by a “water-
fall” effect. The increase in arterial pressure between
30 seconds and 2 minutes is probably related to transient
sympathetically mediated vascular constriction. As the
brainstem becomes more ischemic this sympathetic
outflow is presumably reduced again, resulting in a fall in
both arteriolar resistance and venous tone and a decline in
both aortic and right atrial pressures.
Carotid blood flow changes following
VF cardiac arrest
Figure 17.6 shows the changes in carotid blood flow
following VF cardiac arrest in the anesthetised non-
ventilated pig. Carotid blood flow declines exponentially
after the onset of VF, but measurable carotid blood flow
continues for approximately 4 minutes.
Coronary blood flow changes following
VF cardiac arrest
The gradient between aorta and right atrium is often
referred to as the “coronary perfusion pressure,” i.e., the
gradient during coronary blood flow during cardiac arrest.
A “coronary perfusion pressure” of less than 15 mmHg

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 Hemodynamics of cardiac arrest 351

Fig. 17.3. MRI of pig heart following VF cardiac arrest. The extrapericardial component of the pulmonary vein becomes distended.
(S. Steen – unpublished data.)

100

80
Part (mmHg)

60

40

20 Aortic pressure
Right atrial
0 pressure
1 3 5 7 9 11 13 15 17 19
Time (S)
Fig. 17.4. Pressure changes in a subgroup of patients following VF arrest in which ventricular
fibrillation lasted at least 20 s (n
14). There is progressive decrease in arterial pressure and an increase
in right atrial pressure. These changes do not conform to single monoexponential functions. Note that,
at 20 seconds, a significant arterio-venous pressure gradient (9.6 mmHg) persists. (Reproduced with
permission from the American Journal of Physiology11.)

during the release phase of CPR has been shown to be a
good predictor that recovery of spontaneous circula-
tion (ROSC) is unlikely in both humans and in animal
models.18,19 It has been assumed in the past that this
was because, below this “coronary perfusion pressure,”
myocardial perfusion was totally inadequate to support
recovery of myocardial function after restoration of electri-
cal activity.
In fact, the changes in coronary blood flow and of carotid
blood flow following VF cardiac arrest without CPR do not
parallel each other in the anesthetised non-ventilated pig
model. As shown in Fig. 17.7, coronary blood flow rapidly

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 352 M.P. Frenneaux and S. Steen

120
Intrathoracic aortic pressure
Right atrial pressure
Coronary perfusion pressure
100

80

60
Pressure (mmHg)

40

20

–20
0 1 2 3 4 5 6 0 1 2 3
VF cardiac arrest CPR begun
–40
Time (min)

Fig. 17.5. Changes in aortic pressure, right atrial pressure and calculated coronary perfusion pressure in the pig model following VF
cardiac arrest. (Reproduced with permission from Resuscitation.8)

declines to zero by 1 minute. For the next 2 minutes, coro-
nary blood flow is retrograde before declining again to zero.
These observations, suggest that the term “coronary per-
fusion pressure” may be misleading, because “coronary
perfusion pressure” is positive during this period when
coronary flow is retrograde. Although the coronary sinus
drains into the right atrium and therefore the aortic minus
right atrial pressure gradient might be expected to deter-
mine coronary blood flow, the intramural coronary
microvascular pressure is also profoundly influenced by
the left ventricular intracavity pressure. The conventional
“coronary perfusion pressure” therefore provides an over-
estimate of the actual pressure gradient driving coronary
blood flow – explaining the observations above.
Hemodynamics during cardiopulmonary
resuscitation
How does CPR eject blood into the aorta?
Closed chest CPR results in phasic blood flow. There has
been considerable controversy regarding the mechanisms
responsible for this forward blood flow. According to the
“cardiac compression theory,” direct compression of the
left and right ventricles between the sternum and vertebral
column creates a pressure gradient between the ventricle
and the aorta (or pulmonary artery in the case of the right
ventricle). This pressure gradient closes the mitral (and tri-
cuspid) valve and ejects blood forward out of the ventricle.
According to this paradigm, the ventricle then refills during
the decompression phase. The theory was proposed by
Kouwenhoven and colleagues.20 This view was essentially
unchallenged until the 1970s. In 1976, Criley and colleagues
described the phenomenon of “cough cardiopulmonary
resuscitation” and ascribed the forward flow generated by
coughing to the increased intrathoracic pressure generated
during coughing.21 In the 1980s, studies in dogs22 and in
man23 led to the proposal of the “thoracic pump” theory for
antegrade flow during CPR. According to the thoracic pump
theory, external chest decompression increases intrathor-
acic pressure, forcing blood to flow from the thoracic to the
systemic circulation. Retrograde flow from the right side of
the heart to the systemic veins is prevented by the venous
valves. According to this paradigm, the heart acts merely
as a passive conduit without having a pump function.

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 Hemodynamics of cardiac arrest 353

0.25

Left carotid artery flow

0.20

0.15
Flow (l/min)

0.10

0.05

VF cardiac arrest DC cardioversion

0 1 2 3 4 5 6 0 1 2 3

–0.05
Time (min)
Fig. 17.6. Changes in carotid artery flow in the pig model following VF cardiac arrest. (Modified from Steen et al. Resuscitation 2003;
58: 249–258. Reproduced with permission from Resuscitation.8)

60
55
50
45
Flow (mL/min)

40
35
30
LAD Left carotid artery
25
20
15
10
VF
5
0
–5
–10
–1 0 1 2 3 4 5 6 7 8 9 10
Time (min)
Fig. 17.7. Changes in left anterior descending coronary artery and left carotid artery flow following VF cardiac arrest do not parallel each
other. (With permission from Professor S. Steen, University of Lund.)

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 354 M.P. Frenneaux and S. Steen
This theory requires the AV valves to be open during the
compression phase of CPR. Two transthoracic echocardio-
graphic studies reported in the early 1980s during CPR in
man supported the thoracic pump theory.24,25 Guerci and
colleagues also concluded, on the basis of observations of
the aortic pressure-flow relation during CPR in dogs, that
aortic flow was due to fluctuations in intrathoracic pres-
sure.26 Other studies performed in dogs and in pigs,
however, supported the cardiac pump hypothesis.27–29
The availability of transesophageal echocardiography has
provided the opportunity to study the mechanisms involved
during CPR in man in much greater detail. Transesophageal
echocardiography can be performed without interrupting
cardiac massage and the quality and stability of the imaging
is generally superior to transthoracic echocardiography.
Several studies concluded that the mechanism of antegrade
flow during CPR was consistent with the cardiac pump
theory.30,31 This conclusion was based on the observations
that the mitral valve closed during the compression phase
and opened during the decompression phase, and that the
size of both left and right ventricular cavities fell during the
compression phase. In contrast, another study performed in
17 patients undergoing CPR suggests that the physiological
mechanisms responsible for antegrade flow may differ from
patient to patient.32 In this study both pulmonary venous
and trans-mitral flow were assessed. In 5 of the 17 patients
the mitral valve closed during the compression phase of
CPR, with associated mitral regurgitation and forward aortic
Blood flow during chest compression
PV PV
LA LA
MV MV
LV LV
AO AO
LV pump chest pump
Fig. 17.8. Schematic representation of the three mechanisms by which CPR ejects blood into the aorta.
LA – left atrium, LV – left ventricle, PV – pulmonary vein, Ao – aorta, MV – mitral valve. (Reproduced
with permission from Circulation.32)
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flow, consistent with the cardiac pump theory. In the
remaining 12 patients the mitral valve remained open
during both the compression and decompression phases of
CPR, and peak forward mitral flow also occurred during the
compression phase in this group. In 8 of these 12 patients,
forward mitral flow during the compression phase was
accompanied by forward pulmonary vein flow, consistent
with the classic “thoracic pump” mechanism. In the remain-
ing 4 patients, forward mitral flow during the compression
phase was accompanied by backwards pulmonary vein flow,
which the authors suggested implied a “left atrial pump”
mechanism, in which the left atrium rather than the left ven-
tricle was the major target of chest compression. Downtime
was much shorter in the 5 patients in whom the cardiac
pump mechanism was thought to be operating than in the
remaining 12 patients.
These three mechanisms are summarized schematically
in Fig. 17.8. Whatever the mechanism, it is clear that ante-
grade flow occurs in both the thoracic aorta and the pul-
monary artery during the compression phase of CPR and
retrograde flow occurs in these vessels during the release or
decompression phases.
Changes in aortic and pulmonary artery pressures
during CPR
Steen and colleagues reported the hemodynamic effects of
CPR using the LUCAS (Lund University Cardiac Arrest
PV
LA
MV
LV
AO
LA pump
 Hemodynamics of cardiac arrest 355

System) device in anesthetised pigs.33 The LUCAS device
provides automatic mechanical chest compression; active
“physiological” decompression.33 CPR was instituted for
3–5 minutes after 6.5 minutes of VF (when the “coronary
perfusion pressure” has reached zero). The hemodynamic
effects in a typical animal are shown on the right of
Fig. 17.5. Here, the compression phase is akin to “systole”
and the decompression phase is akin to “diastole.” During
the entire 31⁄2 minutes of CPR the compression pressure in
the right atrium (top pressure trace) exceeded the pressure
in the intrathoracic aorta (the second highest pressure
trace). This reveals a negative “coronary perfusion pres-
sure” during the compression phase. There was also a
negative “coronary perfusion pressure” during the decom-
pression phase for 1 minute after instituting CPR, but the
“coronary perfusion pressure” during decompression then
became positive, reaching a peak of 18 mmHg at 11⁄2
minutes before declining slightly. Intrathoracic aortic pres-
sure reached approximately 40 mmHg during CPR.
Observations in man during CPR have shown peak systolic
arterial pressures of between 60 and 80 mmHg.34–36
A study in pigs has shown that during closed chest
CPR, compression phase pulmonary artery pressure was
approximately 80–90 mmHg, mean pulmonary artery
pressure was approximately 40 mmHg, and mean left atrial
pressure approximately 3–4 mmHg lower than this.37
Cardiac output during CPR
Studies in dogs and in pigs have suggested that during
optimal CPR, cardiac output is between 25% and 40% of
pre-arrest values.27,37–39
Carotid and cerebral blood flow during CPR
In the pig model, Steen and colleagues showed that
appreciable common carotid blood flow is apparent
within seconds of initiating compression/decompression
CPR using the LUCAS device. Values of approximately
300 ml/ min were obtained when CPR was sustained, but
even brief interruptions of CPR dramatically reduced
carotid blood flow Fig. 17.9.33 Cerebral blood flow is
determined by the gradient between carotid artery and
intracranial pressure. Assuming an ischemic threshold
level of cerebral tissue oxygen content of 8 mmHg, a
recent report suggested that, during standard CPR in

Fig. 17.9. The blood flow in the left internal carotid artery during 3.5 minutes of mechanical compressions followed
by defibrillation attempts with (II) and (III) interrupting the chest compressions. Mean value  S.E.M., n
5 in each
group. (Reproduced with permission from Resuscitation.8)

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 356 M.P. Frenneaux and S. Steen
man, cerebral tissue oxygen content may be lower than
this value much of the time. However, optimally per-
formed CPR that maintained coronary perfusion pressure
at least 25 mmHg was associated with cerebral tissue
oxygen content greater than 8 mmHg.40 A study in dogs
demonstrated that if CPR is started immediately and
“coronary perfusion pressures” are maintained above
25 mmHg, cerebral blood flow (measured by using
microspheres) and cerebral ATP were both maintained at
approximately 60% of pre-cardiac arrest values. In con-
trast, when CPR was delayed for 6 minutes after cardiac
arrest, a coronary perfusion pressure of 35 mmHg was
required to produce similar cerebral blood flow and cere-
bral ATP content. Furthermore, when CPR was delayed
for 12 minutes, even this level of coronary perfusion pres-
sure failed to restore cerebral blood flow.41 Lindner and
colleagues demonstrated that active compression–
decompression CPR produced greater cerebral perfusion
pressures and greater cerebral oxygen delivery than did
standard CPR in a pig model.42
Coronary blood flow during CPR
Studies in animal models have shown that coronary flow is
retrograde during the compression phase of CPR and ante-
grade during the release or decompression phase.37,43,44 The
retrograde flow during the compression phase continued
even when the “coronary perfusion pressure” was raised
throughout the CPR cycle by more effective CPR.44 This pre-
sumably is related to the importance of left ventricular
intra-cavity pressure in determining coronary blood flow. In
the pig model, assessing CPR by using a mechanical device,
even at 2.5-inch thumper strokes, coronary blood flow was
less than 50% of pre-arrest values, and with thumper strokes
of 1.5 inches, coronary flow was approximately 15% of base-
line pre-arrest values.43 Changes in coronary blood flow
during CPR in dogs were related to changes in “coronary
perfusion pressure.”45 Wolfe and colleagues observed that in
dogs coronary blood flow fell at very high compression rates
because of a reduction in “diastolic perfusion time” (i.e., the
time spent in the relaxation phase during which antegrade
coronary flow occurs). Optimal coronary flow occurred at a
compression rate of 120/min.46
Effects of interruption of CPR on hemodynamics
Interrupting CPR for rescue breathing adversely affects
hemodynamics. Berg and colleagues compared the effects
of CPR at 100 compressions per minute with a brief rest
period every minute for the rescuer to take 2 deep breaths
vs. a protocol involving cycles of 15 compressions at
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100 per minute each interrupted by 2 rescue breaths. The
integrated coronary perfusion pressure over each cycle
was substantially reduced in the rescue breathing group
because of a reduction in aortic pressure during the
rescue breathing phase, and because the number of chest
compressions was also lower in this group.47 Furthermore,
Steen and colleagues showed in the pig model that
periods of 30 seconds of CPR between defibrillation
attempts were insufficient to generate an adequate “coro-
nary perfusion pressure” (i.e., at least 15 mmHg) and, on
the basis of these observations, the authors recom-
mended at least 90 seconds of CPR between each defibril-
lation attempt.8
Coronary perfusion pressure and recovery of
spontaneous circulation (ROSC)
In 1940, Wiggers noted that 3 to 5 minutes after the onset of
VF (appreciably earlier than the “irretrievable failure of the
central nervous system”), the heart enters an “atonic
phase” in which “anoxia causes depression of contractile
force and slows conduction.”48
The impact of “coronary perfusion pressure” on the like-
lihood of ROSC has been described in animals and in
man.18,19,49,50 The probability of ROSC is low when coronary
perfusion gradient is  15–20 mmHg. Fig. 17.10 shows
human data relating likelihood of ROSC to coronary perfu-
sion pressure during CPR.19
There are two potential reasons why this might be so.
1. At lower coronary perfusion pressures, profound
myocardial ischemia may prevent ROSC. Ralston and col-
leagues have shown in a dog model that a mean myocardial
blood flow less than 0.13 ml/min per g tissue was associated
with no survival, whereas a flow of  0.16 ml/min per g tissue
was associated with survival.51 Although this is likely to be a
contributory factor, cardiac contractile function recovers
after even relatively long periods of total ischemia. In the iso-
lated perfused dog heart, postischemic contractile function
was markedly depressed after 25 and 30 minutes of nor-
mothermic global ischemia, but the reduction in left ven-
tricular contractile function after 15 to 20 minutes of global
ischemia was only mild.52 This threshold of 20 minutes is
consistent with observations in other species.53–55 In the
swine model, even at 20 minutes of VF (without CPR), 89% of
animals had myocardial ATP levels  20% of control and
adenylate charge ratio  0.60 – values known to be associ-
ated with reversibility of myocyte injury.56
2. “Coronary perfusion pressure” is defined as the pres-
sure difference between aorta and right atrium during the
decompression phase. During VF aortic pressure is almost
identical to LV pressure and right atrial pressure is almost

100
80
% of patients with ROSC
60
40
20
0% 0%
(n = 9) (n = 16)
0
0 5
Fig. 17.10. Percentage of patients with return of spontaneous circulation (ROSC) as a function of the
maximal coronary perfusion pressure.
identical to RV pressure. Accordingly, coronary perfusion
pressure provides a measure of the pressure gradient across
the interventricular septum during cardiac arrest. This is a
measure of the true “preload” acting on the left ventricle. As
discussed below, this may be an important determinant of
ROSC, because it determines the degree of myocyte stretch
and therefore, according to the Frank–Starling mechanism,
the force of myocyte contraction when it is activated by
electrical depolarization.
The concept of left ventricular preload and the
Effect of Constraint from the Pericardium and
Right Ventricle
Frank57 first described the importance of the degree of
cardiac muscle stretch during diastole (preload) in deter-
mining its subsequent force of contraction. The mech-
anism of this observation is related predominantly to the
nature of the actin-myosin interaction in the sarcomere.
The force generated by a single sarcomere is proportional
to the number of actin-myosin bonds and the available
energy from ATP hydrolysis. Generation of optimal force
is achieved when the sarcomere length is approximately
2.2 to 2.3 microns, which corresponds to the maximum
number of actin–myosin interactions. At sarcomere
lengths less than approximately 1.5 microns, there are
no actin–myosin interactions and force generation is
more or less eliminated. In addition to the actin–myosin
interaction, the giant filamentous protein Titin which
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Hemodynamics of cardiac arrest 357
100%
(n = 2)
80% 80%
(n = 5) (n = 5)
57%
50%
(n = 14)
(n = 2)
36%
(n = 14)
0%
(n = 19)
10 15 20 25 30 35 40 45
Maximal coronary perfusion pressure, (mmHg)
spans the sarcomere, acts like a molecular “spring,” storing
potential energy when it is stretched and it may also play a
role in development of stretch-dependent passive
tension.58 As a result of the length dependency of the
actin–myosin interaction and of titin tension develop-
ment, below a certain “slack length,” myocytes do not gen-
erate tension. Patterson and Starling observed that the
output of the left ventricle was related to changes in the
venous pressure.59 In clinical practice it has been
assumed that changes in left atrial pressure (or LV end
diastole pressure or pulmonary capillary wedge pressure)
parallel those of LV diastole stretch (“preload”) and that
changes in pressure can be used as a surrogate for changes
in stretch. Indeed, the literature commonly refers to the
Frank-Starling relationship, as if Frank and Starling had
described the same phenomenon. Within the physiologi-
cal range, the use of change in LVEDP to predict changes in
preload is generally valid, but in certain pathophysiologi-
cal states it is not. The effective distending pressure acting
on the left ventricle at end diastole is the left ventricular
end diastolic pressure minus external pressures acting on
the left ventricle from the pericardium, and from the right
ventricle via the interventricular septum. In health, both
RV end diastolic pressure and pericardial pressure are
close to zero; therefore, changes in LVEDP generally paral-
lel those of LV end diastolic volume. As the pericardium is
stretched, however, there is an exponential increase in
pericardial pressure (Fig. 17.11).60 In most situations,
RVEDP and pericardial pressure are almost identical,
because the RV is thin walled and therefore maintains only
 358 M.P. Frenneaux and S. Steen

25

20

Pressure (mmHg)
15

10

0
150 200 250 300 350 400 450
Volume (mL)

RV LV

RV LV

RV vol/pressure overload
Fig. 17.11. The pericardium has a J-shaped stress–strain relation. When it is stretched (e.g., by right ventricular volume overload)
pericardial pressure and RV end-diastolic pressure become elevated. The filling of the LV is then impeded by external constraint
from the pericardium and RV, despite a high LVEDP. The interventricular septum is shifted to the left. From Frenneaux,
M. Cardiopulmonary resuscitation: some physiological considerations. Resuscitation 2003; 58: 259–265. Reproduced with
permission from Resuscitation.

a small pressure gradient across it.61 In experimental situ-
ations in which the pericardium is stretched by acute
enlargement of the right ventricle (e.g., experimental pul-
monary embolism), the pericardial and right ventricular
end diastolic pressures may be substantially more than
zero. In this situation the filling of the left ventricle is
impeded by the external constraint from the pericardium
(pericardial constraint) and from the right ventricle (dias-
tolic ventricular interaction). The measured intracavity
LVEDP overestimates the true LV preload. The interven-
tricular septum, normally convex to the right at end dias-
tole, becomes flattened, and the position of the septum at
end diastole has been shown to be very closely related to
the trans-septal pressure gradient, i.e., it reflects the
degree of ventricular interaction.62
Pericardial constraint and diastolic ventricular interac-
tion have been well described in animal experimental
models of acute right ventricular pressure and volume
overload.63 Important diastolic ventricular interaction is
also seen in many patients with chronic heart failure.64,65
Reducing central blood volume in these patients (using a
lower body “suction” device) resulted in a fall in RV volume,
and of right atrial and pulmonary capillary wedge pres-
sures, but despite this, left ventricular diastolic volume
increased (Fig. 17.12). The explanation was confirmed in a
canine rapid pacing heart failure model. While central
blood volume unloading reduced LV end diastolic pressure,
it reduced pericardial pressure and RV end diastolic pres-
sure even more; therefore, the effective distending pres-
sure increased, resulting in an increase in LV diastolic
volume and stroke volume.66 These observations are shown
in Fig. 17.13.

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Rest
Rest
A
(a)
RV
RV LV
LV
(b)
B
RV
RV LV
LV
Fig. 17.12. Schematic representation of changes in ventricular volumes that occur during acute volume unloading such as that
produced by application of lower body suction. (a) – Normal individuals, (b) – direct diastolic ventricular interaction in heart failure
patients with pericardial constraint, RV – right ventricle, LV – left ventricle. (Reproduced with permission from The Lancet.64)
Steen’s observations in the pig model suggest that
important pericardially mediated ventricular interaction
may occur following cardiac arrest.8 As noted previously,
Steen and colleagues observed that as blood flowed along
its pressure gradient from the aorta to the right side of the
heart, the right ventricle became markedly distended.
Furthermore, there was a progressive increase in right
atrial pressure (and, by implication right ventricular pres-
sure) during the first 2 minutes or so after cardiac arrest,
before this slowly declined again. Pericardial pressure also
rose progressively during the first 2 minutes after cardiac
arrest before gradually declining. As expected, right atrial
pressure and pericardial pressure changes paralleled each
other almost exactly, with pericardial pressure marginally
lower than right atrial pressure. These changes are shown
in Fig. 17.14. These observations, performed in open chest
pigs, clearly show that the pericardium was stretched suf-
ficiently to raise pericardial pressure substantially. In the
closed chest situation, this effect would be expected to be
greater. Right ventricular volume fell slightly when right
atrial and pericardial pressures started to decline. As dis-
cussed earlier, this decline in right atrial and pericardial
pressures and right ventricular volume after about 3–4
minutes presumably reflects the withdrawal of sympa-
thetic tone, as the brainstem vasomotor centers become
profoundly ischemic.
As noted previously, there is also a temporary increase in
aortic pressure between approximately 1 and 3 minutes
after the onset of VF (Fig. 17.5), presumably due to the
combined effects of increased sympathetic outflow and
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Hemodynamics of cardiac arrest 359
Lower-body suction
Lower-body suction
RV
RV LV
LV
RV
RV LV
LV
“waterfall” phenomena, then aortic pressure starts to
decline again, presumably because of a reduction in sym-
pathetic outflow.
If we make the reasonable assumptions that intrathor-
acic aortic pressure approximates the left ventricular
pressure and that right atrial pressure approximates the
right ventricular pressure during cardiac arrest, then we
can calculate the serial changes in left ventricular trans-
mural pressure gradient (LV minus pericardial pressure)
and trans-septal pressure gradient (left ventricular minus
right ventricular pressure gradient). Changes in septal
position and left ventricular volume would be expected to
parallel changes in these gradients, which are in effect the
distending pressures acting on the left ventricle. We have
applied these calculations to a typical recording of aortic,
RA, and pericardial pressures reported by Steen and col-
leagues.8 A rapid initial fall in trans-septal and transmural
gradients is followed by a slight increase, until approxi-
mately 4 minutes (corresponding to the period during
which aortic pressures increase), followed by a subsequent
decline to about zero. Berg and colleagues recently
reported the changes in left and right ventricular volume
after VF arrest in the pig.7 Typical short axis MRI appear-
ances are shown in Fig. 17.15. During the first 30 seconds
after cardiac arrest there is a dramatic increase in right ven-
tricular volume, with a shift of the interventricular septum
to the left and a marked reduction in left ventricular
volume. Between approximately 1 and 5 minutes, left
ventricular volume increases modestly (but not back to
baseline), although the interventricular septum remains
 360 M.P. Frenneaux and S. Steen

40
Volume load Volume removal
Pressure (mmHg)

LVEDP – left ventricular end diastolic pressure

20 RVEDP (º) LVEDP PerP – Pericardial pressure
PerP (•)
TSG (º) TLVEDP – Transmural LV pressure gradient
TLVEDP (•)
0
20 800

SW (mmHg ◊ ml)
SV
SV – Stroke volume
SV (ml)

10 400 SW – Stroke work

SW

0 0
50

SLVFW
SLVFW – Septum to LV free wall dimension
45
SRVFW – Septum to RV free wall dimension
SRVFW

40
0 20 40 60 80 100
Time (S)
Fig. 17.13. Example of a study in the canine rapid pacing heart failure model. Volume unloading reduced pericardial pressure more than
it reduced LV diastolic pressure, therefore true filling pressure increased and stroke volume increased. (Reproduced with permission from
the American Journal of Physiology.66)

120

100

AP
Pressure (mmHg)

20
RAP
VF

Intrapericardial pressure

⫺2 0 2 4 6 8 10
Time (min)
Fig. 17.14. Changes in aortic pressure (AP), right atrial pressure (RAP) and pericardial pressure
following VF cardiac arrest in the pig Model. (Reproduced with permission from Resuscitation.8)

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 Hemodynamics of cardiac arrest 361

TIME ZERO 30 SECONDS ONE MINUTE

5 MINUTES 10 MINUTES 15 MINUTES

20 MINUTES 25 MINUTES 30 MINUTES

Fig. 17.15. Short-axis views of RV and LV through same mid-ventricular slice in 1 animal during 30 minutes of untreated VF. Time 0 refers
to time VF was induced, and next 8 views were at respectively labeled duration of untreated VF. (Reproduced with permission from
Circulation.7)

dramatically flattened. Subsequently, left ventricular
volume starts to decline again. These changes imply the
rapid development of very marked ventricular interaction
with some amelioration of this interaction between 1 and 5
minutes, and are entirely to be anticipated on the basis of
the changes in the pressure gradient calculated form the
data of Steen et al. In Fig. 17.16, the right and left ventricu-
lar volume changes reported by Berg and colleagues are
plotted above the calculated changes in transmural gradi-
ent in the data reported by Steen and colleagues. As
expected, the left ventricular volume changes closely
mirror the changes in the transmural and trans-septal
pressure gradients. Because, during cardiac arrest, aortic
pressure is approximately LV pressure and since RA pres-
sure is approximately RV pressure, AO-RA pressure is a
close approximation to the pressure gradient between LV
and RV (the “trans-septal” gradient).
This may have important implications for our under-
standing of the mechanism of ROSC. When ventricular
interaction is marked, the degree of myocyte stretch may
be so small that return of electrical activity generates only
a minimal force of contraction, especially if the myocytes
are also profoundly ischemic.
Effects of ventilation on hemodynamics during
cardiac arrest
It is common practice to ventilate patients during cardiac
arrest, on the assumption that this will improve oxygen
delivery to the tissues, particularly the brain. Recent
observations have called into question the validity of this
assumption. Jellinek et al. reported the hemodynamic
effects of positive airways pressure in patients undergoing

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 362 M.P. Frenneaux and S. Steen

70
RV volume
60

50
LV volume

40

30

20

Aortic pressure
10 RA pressure

0 ‘Coronary perfusion
pressure’
0

0
0

0
00
50

00
50
00

50

00
50

00

50

00

50
00

50
00

50

00
50

00
50

0
.0

.5
.0

.5

.0
0.
0.

1.
1.
2.

2.

3.
3.

4.

4.

5.

5.
6.

6.
7.

7.

8.
8.

9.
9.
–2

–1
–1

–0

10
Fig. 17.16. The MRI calculated LV and RV volumes reported in the swine model by Berg et al.63 are plotted against the changes in aortic,
RA and coronary perfusion pressures reported by Steen et al.8 There are no MRI data points between 1 and 5 minutes, but the changes in
LV volume are predictable on the basis of changes in “coronary perfusion pressure.”

AICD threshold testing. Before VF occurred, positive
airway pressure increased right atrial pressure and
reduced aortic pressure and left ventricular stroke volume.
During VF arrest, positive airway pressure modestly
reduced the coronary perfusion pressure. There was no
evidence of collapse of the inferior vena cava, but in some
patients there was a marked reduction in the diameter of
the superior vena cava.12 In the dog, positive airway pres-
sure has been shown to cause collapse of the inferior vena
cava resulting in a “waterfall effect.”17
In addition to the direct effect of positive airways pres-
sure on coronary perfusion pressure, ventilation is asso-
ciated with substantial interruptions in compressions,
and, as discussed above, this may cause substantial and
prolonged reductions in coronary perfusion pressure.
Woollard and colleagues reported on a randomized trial
comparing compression-only vs. standard telephone CPR
instructions in simulated cardiac arrest. Two and a half
times more compressions were delivered during a stand-
ard ambulance response time in compression-only CPR in
the compression-only group.67 Furthermore, in pigs, CPR
with rescue breathing was shown by Berg and colleagues to
be associated with substantially lower “integrated
coronary perfusion pressure” and left ventricular blood
flow than compression-only CPR.7
An alternative approach to ventilation is the use of
the so-called “inspiratory impedance threshold Device”
(ITV). During the inflow phase, this provides a respiratory
resistance which increases the negative intrathoracic
pressure, analogous to the Müller maneuver. The hemo-
dynamic effects of adding the device to the respiratory
circuit in pigs was assessed during VF cardiac arrest.
There was a non-significant increase in the coronary per-
fusion pressure (from 12.5.  1.5 to 14.8  1.3 mmHg
averaged during 28 minutes of CPR) associated with sig-
nificant increases in left ventricular and cerebral blood
flows.68 Pilot studies in humans suggest that use of the ITV
during CPR is associated with improved short term sur-
vival.69,70
The combination of positive end expiratory pressure
ventilation (PEEP) with the inspiratory threshold device
was reported to have particularly beneficial hemody-
namic effects during active compression-decompression
CPR in the pig. The addition of PEEP did not alter diastolic
coronary perfusion pressure, but may nevertheless
increase myocardial perfusion because the gradient of
the diastolic aorta to left ventricular pressure was aug-
mented, probably because PEEP reduces alveolar col-
lapse, leading to an increase in indirect myocardial
compression.71

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 Hemodynamics of cardiac arrest 363

Hemodynamic effects of spontaneous gasping
during cardiac arrest
Gasping was first described by Legallois in 1812, in a variety
of animal species including man.72 It is very common in the
human newborn and is also frequently observed after
cardiac arrest. In this setting it appears to be triggered by
ischemia of the brainstem and persists until the respiratory
center in the caudal medulla is completely disabled. In the
pig model it is typically observed between the first and
second minute after the onset of cardiac arrest if no CPR
is given. It begins weakly, increasing to a maximum, and
then disappears typically by about 5 minutes, but some-
times longer. If effective cardiac compressions are given to
gasping pigs they continue to gasp as long as the chest com-
pressions create a minimum blood flow to the brainstem.
Gasping produces gas exchange, and a sharp increase in
arterial oxygen saturation, and a fall in arterial carbon
dioxide tension typically follows the gasp.73,74 As shown in
Fig. 17.17, during the expiratory phase of a gasp there is

Fig. 17.17. The effects of a gasp on aortic pressure, central venous pressure, tracheal and pleural pressures and carotid flow in the swine
VF model are shown. Note the effects of persistent atrial contractions following VF arrest. During the expiratory phase of the gasp there is
an increase in carotid flow. (S. Steen, unpublished observations.)

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 364 M.P. Frenneaux and S. Steen
an increase in aortic pressure and in carotid blood flow.
The breath occurs against a partially closed airway and
generates a negative intrapleural pressure of approxi-
mately 40 mmHg. This negative intrapleural pressure
markedly reduces right atrial and pericardial pressures and
increases the pressure gradient between aorta and RA. Xie
and colleagues showed in the pig that during the inspira-
tory phase of the gasp, left ventricular area substantially
increased and then returned to its “pre-gasp” value during
the expiratory phase. This generated a stroke volume of
approximately 60% of that seen in the spontaneously
beating heart. The expiratory phase of the gasp was also
associated with a substantial increase in end-tidal carbon
dioxide.75
The appearance of gasping in a patient with cardiac
arrest should not therefore be considered as a sign of recov-
ery that discourages continued resuscitative measures, but
implies that the brainstem is ischemic but still viable. The
frequency of gasping has been reported to be predictive of
the success of resuscitation.76,77
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