Effects of β-Blockers on the Fall of pH in the Early Phase of Ischemia in the Isolated Perfused Rat Heart

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Abstract
To elucidate the role played by catecholamines in the early phase of ischemic derangement of the myocardial energy metabolism, effects of .beta.-blockers (propranolol, pindolol, and celiprolol) and isoproterenol, and of pretreatment with reserpine and 6-hydroxydopamine (6-OHDA), were studied using the isolated perfused rat heart. .beta.-Blockers an disoproterenol were infused for 12 min prior to induction of global ischemia. The myocardial energy consumption rate was assessed by calculating the product of left ventricular pressure and heart rate (LVP .times. HR). The myocardial cell creatine phosphate (CP), ATP and pH were determined with 31P nuclear magnetic resonance (31P-NMR). Global ischemia induced by cross-clamping of the aortic inflow line for 15 min resulted in falls in CP, ATP, and pH. Propranolol (6 .times. 10-8 and 1.8 .times. 10-7 mol/min) and pindolol (6 .times. 10-7 mol/min) produced a decrease in LVP .times. HR and suppressed the pH fall during ischemia. Celiprolol was without significant effects on these two parameters. Isoproterenol (6 .times. 10-12 mol/min) produced an increase in LVP .times. HR and tended to accelerate the pH fall. Catecholamine depletion with reserpine or 6-OHDA produced no beneficial effects on the pH fall. It was concluded that the beneficial effects of .beta.-blockers on the pH fall during early ischemia were not due to the specific .beta.-blocking action but to the nonspecific cardiodepressant effects of these compounds.

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