AJP - Heart and Circulatory Physiology, Vol 253, Issue 5 1261-H1270, Copyright © 1987 by American Physiological Society
Factors influencing myocardial response to metabolic acidosis in isolated rat hearts
T. A. Watters, M. F. Wendland, W. W. Parmley, T. L. James, E. H. Botvinick, S. T. Wu, R. Sievers and J. Wikman-Coffelt
Department of Medicine (Cardiology), University of California, San Francisco 94143.
We assessed the effects of metabolic acidosis in Langendorff rat hearts to
identify factors influencing myocardial response to metabolic acidosis.
Intracellular pH (pHi), beta-ATP, phosphocreatine, and inorganic phosphate
(Pi) content were measured by 31P nuclear magnetic resonance spectroscopy
along with simultaneous measurements of coronary flow and developed
pressure during 30 min of perfusion at pH = 6.8, followed by 15 min of
reequilibration at pH = 7.4. Under high work-load conditions, pHi,
high-energy phosphates, coronary flow, and developed pressure were severely
reduced during metabolic acidosis. Each of these hearts exhibited a
progressive decline in developed pressure and stopped beating during
reequilibration. Lowering work load prevented severe biochemical or
mechanical deterioration, allowing complete recovery during
reequilibration. In the presence of high work load, factors found to
improve myocardial tolerance to metabolic acidosis included maintaining
base-line or higher levels of coronary flow with vasodilators or
substitution of pyruvate for glucose as the energy-producing substrate.
Raising perfusate osmolality did not prevent severe decreases in coronary
flow and developed pressure during acidosis, but did allow a dramatic
recovery during reequilibration. Recovery of biochemical and mechanical
performance after 30 min of metabolic acidosis was directly related to 1)
ln[ATP]/[ADP]f[Pi] greater than or equal to 4.1, where [ADP]f is the
concentration of free ADP; 2) pHi greater than 6.40; and 3) ATP level
greater than or equal to 75% of control.
