Influence of drugs on diseased states of the heart. A 31P NMR and [Ca]i study

Abstract

Phosphorus 31 magnetic resonance spectroscopy (MRS) can be used to monitor the direct effect of drugs on energy metabolites of the heart. Using the isolated perfused heart of the cardiomyopathic hamster (late heart failure), drugs that exacerbate the diastolic level of calcium [Ca]i (e.g., dobutamine and digoxin) augment intracellular phosphomonoester sugars, while drugs which increase cyclic adenosine mono-phosphate [cAMP]i (e.g. isoprel, dibutyryl cAMP, and amrinone) lower phosphomonoester sugars. The phosphomonoester sugars are inversely related to developed pressure and oxygen consumption. Accumulation of sugar phosphates indicates inhibition of glycolysis and limited delivery of pyruvate to the mitochondria, thereby decreasing oxygen consumption. The phosphorylation potential obtained from standardized 31P MRS values showed a direct relationship to the rate pressure product in hamsters with heart failure; however, the two parameters were inversely related in control hamsters.