Chapter 2 / Physiological and Biochemical Concepts 9
In addition to a decline in systolic function, there is also a substantial decrease in left
ventricular compliance, increasing the filling pressure at a given end-diastolic volume
(1–4). The increased left ventricular end-diastolic pressure causes pulmonary conges-
tion, leading to hypoxemia and ischemia, which further reduces coronary perfusion
pressure. Myocyte swelling occurs (5) as a consequence of an intracellular accumula-
tion of sodium and calcium resulting from anaerobic glycolysis, further decreasing left
ventricular compliance (6). The further reduction in compliance and the myocyte
swelling lead to an increase in ventricular wall stress, elevating myocardial oxygen
requirements. As the myocardium becomes less compliant, the pumping capacity of the
heart becomes less efficient, increasing the imbalance between myocardial oxygen
requirements and supply.
Soon after the onset of cardiogenic shock, compensatory mechanisms are activated.
In mammals, a primary objective of the regulatory system of the circulation is to main-
tain arterial pressure (7–10) to preserve perfusion to the vital organs such as the brain
and the heart. This is accomplished by activation of neurohumoral systems, not dissim-
ilar from the responses observed during hemorrhagic shock and exercise. In particular,
there are withdrawal of the parasympathetic system and activation of the sympathetic,
renin–angiotensin–aldosterone and vasopressin systems, culminating in arterial and
venous vasoconstriction, salt and fluid retention, positive chronotropy, and inotropy.
Although beneficial in hemorrhagic shock and severe exercise, these compensatory
mechanisms may be detrimental in cardiogenic shock. For instance, venoconstriction
and salt and fluid retention would increase the preload and arterial vasoconstriction
would increase the afterload, thereby overloading the already failing ventricles.
Increased heart rate and myocardial contractility would increase the demands in the
face of limited supply of oxygenated blood to at-risk myocardial regions (ischemic ter-
ritories and the subendocardium). The skill of immediate management is therefore to
curb the excesses of the compensatory mechanisms without negating some of their
potential beneficial effects.
As the shock state persists, hypoperfusion of both the myocardium and peripheral
tissues will induce anaerobic metabolism in these tissues and may result in lactic aci-
dosis. An earlier study has shown that the serum lactate level is an important prognostic
factor in cardiogenic shock (11). Uncorrected, the accumulation of lactic acid may
cause mitochondrial swelling and degeneration, inducing glycogen depletion, which, in
turn, impair myocardial function and inhibit glycolysis, leading to irreversible
ischemic damage (12). Unfavorable effects on other organ functions follow. The shock
state in patients with an acute myocardial infarction leads to a vicious cycle that causes
a downward spiral of worsening ischemia: As cardiac output falls, arterial pressure
falls and coronary perfusion is lowered, thus exacerbating the low output state. This
eventually leads to further ischemia and extension of necrosis in the left ventricle. Sev-
eral compensatory mechanisms occur during this chain of events that, if left untreated,
lead to cardiac pump failure and, ultimately, death.
Compensatory Sympathetic Nervous System Activation
When myocardial function is depressed, several compensatory mechanisms occur.
However, the compensatory mechanisms may become maladaptive and actually
worsen myocardial ischemia. Initially, as cardiac pump function declines, there is a
redistribution of blood flow, in order to ensure adequate perfusion of the heart and
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