To determine the effect of isoproterenol on cardiac energetics and function in an animal preparation of cardiomyopathy, we studied Langendorff perfused hearts from Syrian cardiomyopathic hamsters. High-energy phosphate metabolites (phosphocreatine [PCr], ATP, inorganic phosphate [Pi] and intracellular pH (pH(i)) were measured by 31P nuclear magnetic resonance spectroscopy and correlated with left ventricular developed pressure, coronary flow, and O2 consumption before and during a 10-6M infusion of isoproterenol. Total intracellular calcium was also determined by atomic absorption spectroscopy with the use of potassium ethylenediamine tetra-acetate cobaltate as a marker for extracellular space. In cardiomyopathic hamsters, isoproterenol infusion increased mean developed pressure by 300% (p < .005 compared with control; n = 5), O2 consumption eightfold (p .0005), and PCr by 40% (p < .05). PCr/Pi ratio, which is analogous to phosphorylation potential, improved 100% (p = .05). In normal hamsters, isoproterenol infusion resulted in an 83% increase in developed pressure (p < .001) and a 25% increase in O2 consumption (NS). However, mean PCr and PCr/Pi decreased by 30% and 50%, respectively (p < .05 for both), during isoproterenol infusion. pH(i) decreased in normal animals (p < .01), but tended to improve in diseased animals (NS) during isoproterenol infusion. Freeze-clamp measurements of phosphate metabolites correlated well with the nuclear magnetic resonance data. Intracellular calcium increased from 0.0102 ± 0.002 to 0.144 ± 0.030 μmol/ml heart water in normal hamsters during isoproterenol infusion. Cardiomyopathic hamsters had a markedly elevated baseline calcium content of 60.82 ± 5.85 μmol/ml heart water due to the presence of dystrophic calcification. Isoproterenol did not significantly alter this calcium content. We conclude that in cardiomyopathic hamsters, isoproterenol markedly increases contractile function and energy demand without an associated deterioration in the high-energy phosphate profile. In contrast, normal hamsters are unable to synthesize sufficient ATP to replenish the amount used in meeting the increased workload during isoproterenol infusion.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)