22 Part I / Introduction
Fig. 5. Cellular functions of ATP in cardiomyocytes. Reprinted with permission (110).
states depends on the relative proportions of the determinants of myocardial oxygen
consumption.
The determinants of MVO
2
in terms of the whole organ are as follows: (1) useful
external work (62,63), (2) development of wall tension (64,65), (3) noncontractile basal
cellular metabolism (64), (4) depolarization and activation (66), (5) heart-rate-related
energy expenditure (67), and (6) contractility or inotropy-related energy expenditure
(58,64,68). Under different conditions, the three major determinants of myocardial oxy-
gen consumption are systolic wall tension, contractility, and heart rate (62,63,66,68–72),
although what proportion of these are wasted as heat and which are converted into use-
ful external work is difficult to ascertain. During normal physiological contractions,
probably the highest cost in terms of energy consumption is in the development of left
ventricular wall tension (64,65). Wall tension development unaccompanied by forward
stroke volume (e.g., during a nonejecting extrasystolic beat) is a wasteful consumption
of energy. Similarly, a dilated ventricle requires more energy to develop a much higher
wall tension to generate the same intraventricular pressures according to the Law of
LaPlace [wall stress = (pressure × radius)/(2 × wall thickness)] (73). MVO
2
is also influ-
enced by the supply of substrates to the heart. The use of free fatty acids increases
MVO
2
, and catecholamines sensitize the heart to the oxygen-wasting effect of free fatty
acids (63). Alteration of myocardial metabolism from mainly free fatty acid to carbohy-
drate oxidation reduces the extent of myocardial ischemic injury (74).
Energetics and Metabolism of Hypoperfused Myocardium
As a result of circulatory shock and hypoperfusion of the myocardium, aerobic cel-
lular metabolism cannot be maintained. The regeneration of high-energy phosphate
compounds, CP and ATP, is impaired and intracellular high-energy reserves therefore
decline. When oxygen delivery to the cardiomyocytes is inadequate, oxidative metabo-
lism ceases, cellular citrate and ATP levels fall, and the cell switches to glycolytic
anaerobic metabolism to produce a limited amount of ATP. The rate of glucose uptake
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