Effects of drugs on the ischemic changes in cardiac function, myocardial energy metabolism and ion permeability-A study by nuclear magnetic resonance spectroscopy (NMR)9

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Role played by endogenous catecholamines (CA) in the production of pH fall during early ischemia.Effects of isoproterenol, <beta>-blockers (propranolol, pindolol and celiprolol), 6-OH dopamine and reserpine on the fall of myocardial intracellular pH during early ischemia were studied with ^<31>P-NMR in the isolated perfused rat heart preparations. Only propranolol produced a dose-related inhibition of the pH fall. However, the inhibition was closely related to the suppression of the myocardial energy consumption produced by this compound. Thus, the idea of involvement of the endogenous CA in the pH fall during early ischemia was not substantiated.2) Changes in energy metabolism during a prolonged period of ischemia.^<31>P-NMR studies revealed the appearance of a new inorganic phosphate (Pi) peak around 90 min after induction of ischemia downfield to the original intracellular Pi peak which had undergone an upfield shift due to acidification of the intracellular space. This peak increas … More ed in size as ischemia progressed in association with a decrease in the original Pi peak. These findings indicate the increase in the numbers of cells so severely damaged that the concentration gradient of the proton between the intra- and extracellular fluid compartments almost disappeared. Thus, the peak can be used as a measure of the degree of development of the irreversible ischemic damage.3) Changes in intracellular Na^+ during ischemia. In the presence of a shift reagent the intracellular Na peak was detected soon after induction of ischemia dissociated form the extracellular one, and became greater in two stages as ischemia progressed. The first stage corresponded to the fall of intracellular pH and was ascribed to acceleration of Na-H exchange due to the fall of pH The second stage occurred simultaneous with an almost complete depletion of ATP and a marked rise of the intracellular Pi and the ventricular diastolic pressure and was taken to denote the onset of the irreversible ischemic damage. Less