Role of acidosis in early contractile dysfunction during ischemia: evidence from pHo measurements

Abstract

To investigate the contribution of acidosis to contractile dysfunction during early myocardial ischemia, miniature intramyocardial pH electrodes (0.2 mm tip diam) were used to correlate changes in extracellular pH (pHo) with tension in the isolated arterially perfused rabbit interventricular septum. A number of findings argue against acidosis as the major cause of contractile failure during early ischemia. During hypoxia without glucose present, the rate and pattern of tension decline was very similar to total ischemia, suggesting that a common mechanism is involved. Throughout the initial period in which tension declined by 50%, however, pHo increased in the six of eight preparations during hypoxia without glucose. During hypoxia with glucose present, tension fell less rapidly than during hypoxia without glucose despite a significantly greater fall in pHo in the former case. The maximal rate of relaxation (-dT/dt) was markedly more sensitive to ischemia, hypoxia, or exposure to inhibitors of aerobic metabolism (2,4-dinitrophenol and Na azide) than the maximal rate of force development (+dT/dt). In contrast, +dT/dt and -dT/dt decreased almost symmetrically during exposure to respiratory acidosis. During ischemia, the change in pHo associated with 50% reduction in tension was 0.11 +/- 0.04 units. During respiratory acidosis, this value was 0.45 +/- 0.02 units. From these observations we concluded that acidosis is unlikely to be a major factor in the early decline of tension during ischemia.

Traditional Resuscitative Practices Fail to Resolve Metabolic Acidosis in Morbidly Obese Patients After Severe Blunt Trauma

“…This is in stark comparison to normal weight patients without persistent metabolic acidosis, of whom less than half developed MOF, and although not significant, represents an increase over morbidly obese patients not remaining in metabolic acidosis at 48 hours. This is not particularly surprising given the consequences of acidosis, including possible cardiorespiratory depression [38, 39], immune dysfunction [40–43], and further alterations of cellular metabolism [44, 45]; however, it does highlight the importance of determining the causes of acidosis, particularly in the high risk morbidly obese patient cohort.…”

Extracellular proton depression of peak and late Na+ current in the canine left ventricle

“…A similar reduction in extracellular pH was observed in rabbit hearts subjected to global ischemia. Using pH-sensitive electrodes, Weiss et al (36) found that external pH was 7.3 under control conditions and decreased 0.75 log units after 10 min of ischemia.…”

Changes in extracellular and intracellular pH in ischemic rabbit papillary muscle.

“…[15][16][17][18] An analysis of the change in pHi in ischemia or hypoxia was made through the distribution of the weak acid dimethyl-2,4-oxizolidinedione'9 20 or by 31P nuclear magnetic resonance21-24 in whole hearts. Ion-selective microelectrodes have been used in subepicardial layers of ischemic guinea pig hearts and in a model of simulated ischemia (superfused guinea pig papillary muscle).25 '26 In simulated ischemia, it was shown that the degree of Yan and Klber pHo and pH; in Myocardial Ischemia 461 intracellular acidification depended significantly on the buffer present in the superfusate; the physiological CO2/HCO3-buffer system provided a better protection against intracellular acidosis than the presence of organic buffers.…”