Are Age-Related Differences in Response to Myocardial Ischemia and Cardioplegia pH Dependent?

Abstract

Phosphorus-31 nuclear magnetic resonance and left ventricular pressure development (dP/dt) were used to test the hypothesis that age-related differences in myocardial functional recovery after ischemia and cold crystalloid cardioplegia (CCC) are the result of an inverse relationship between recovery and the decrease in intracellular pH (pH_i) during ischemia. Neonatal (3-8 days) and adult rabbit hearts were Langendorff perfused using two protocols: (1) control – 30min perfusion, 30 min global ischemia, 2 h reperfusion; (2) CCC – the same except ischemia was initiated after a 4-min infusion of cold hyperkalemic solution. Analysis of variance and the Tukey test showed the following significant differences between the protocols (p < 0.05). CCC decreased inorganic phosphate (Pi) during ischemia in both age groups, but more in adult hearts, and decreased Pi during reperfusion in adult hearts. CCC increased pH_i during ischemia and ATP during ischemia and reperfusion in both age groups but more in adult hearts. CCC increased dP/dt during reperfusion only in adult hearts. The results are consistent with the hypothesis.

Effects of cold cardioplegia on pH, Na, and Ca in newborn rabbit hearts

“…Our results (Fig. 1) reconfirm that CCC diminishes the fall in pH i otherwise observed during ischemia (6,50). Again, one predicts from the general hypothesis that, after cardioplegia, diminished proton accumulation will decrease stimulation of Na-dependent pH regulation and thereby diminish Na uptake (16,49) and Na i accumulation during ischemia (7,10).…”

“…pH i was determined from the chemical shift of Pi (6). High-energy phosphates are reported as percentage of control peak intensity (10).…”

“…Controversy remains concerning whether the bulk of Ca entry occurs during ischemia or reperfusion, but there is near consensus that much of the Ca entry is a consequence of Na loading (13, 41). It has also been repeatedly demonstrated that cold, crystalloid cardioplegia (CCC) decreases the ischemiainduced fall in pH i (6).Because newborn and adult hearts respond differently to hypoxia, ischemia, and cardioplegia (6,9,11, 19,37) and the need for basic science studies aimed at understanding and improving cardioplegia for newborns has not diminished (1, 24), we tested the hypothesis that in newborn rabbit hearts, CCC will limit increases in cytosolic [H], Na i , and [Ca] i during ischemia-reperfusion and thereby diminish injury. The observed effects of CCC on [H], Na i , and injury were not surprising and wholly consistent with the hypothesis.…”

“…Because newborn and adult hearts respond differently to hypoxia, ischemia, and cardioplegia (6,9,11,19,37) and the need for basic science studies aimed at understanding and improving cardioplegia for newborns has not diminished (1,24), we tested the hypothesis that in newborn rabbit hearts, CCC will limit increases in cytosolic [H], Na i , and [Ca] i during ischemia-reperfusion and thereby diminish injury. The observed effects of CCC on [H], Na i , and injury were not surprising and wholly consistent with the hypothesis.…”

“…Animals used in this study were treated according to the American Physiological Society's "Guiding Principles in the Care and Use of Animals" with a protocal approved by the University of California, Davis. The methods used were modified from those previously reported (6,10). New Zealand White rabbits (4 -7 days old) were anesthetized (pentobarbital sodium 35-65 mg/kg ip) and heparinized (1,000 United States Pharmacopeia units/kg iv).…”