Evaluation of the hereditary Syrian hamster cardiomyopathy by 31P nuclear magnetic resonance spectroscopy: improvement after acute verapamil therapy.

Abstract

The relation between metabolic and functional derangement in various cardiomyopathies has not been well characterized. This information was specifically sought in a spontaneous cardiomyopathic model. Metabolic and hemodynamic parameters were obtained in glucose-perfused beating hearts of 180-200-day-old cardiomyopathic Syrian hamsters and age-matched healthy animals. This period in the cardiomyopathic hamster lifetime is intermediary between the necrotic phase and the appearance of heart failure. We used 31P nuclear magnetic resonance spectroscopy to analyze energy metabolites and intracellular pH. Cardiomyopathic hamsters had significantly higher mole fraction values for inorganic phosphate, lower phosphocreatine mole fraction as well as lower phosphocreatine/inorganic phosphate and adenosine triphosphate/inorganic phosphate ratios. Analysis of pH indicated the presence of regions of increased acidity within the heart of myopathic hamsters. Cardiomyopathic hamsters also had significantly lower left ventricular pressure, coronary flow, and myocardial oxygen consumption. Separate groups of normal and myopathic hamsters were given verapamil for 24 hours (one injection of 4 mg/kg s.c. followed by 1.2 g/l in drinking water). Verapamil-treated myopathic hamsters had evidence of markedly improved mitochondrial function when compared with untreated animals. Left ventricular pressure and coronary flow rose to normal levels. Replacing glucose by pyruvate in the perfusate of myopathic hamsters results in a marked increase in left ventricular pressure, coronary flow, and oxygen consumption with a moderate rise in phosphocreatine. Thus, 180-200-day-old cardiomyopathic hamster heart is characterized by evidence of decreased mitochondrial function, by areas of increased acidity within the heart, and by reduced left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

“…A recent study by Sanbe et al (29) examined high-energy phosphate stores in residual intact myocardium of rat hearts with infarct sizes similar to our work using a columnfreezing method. In agreement with our results, these authors found significant reductions of CP and creatine [1][2][3][4][5][6][7][8][9][10][11][12] wk after MI. In contrast, however, they also found significant reductions of ATP and of Pi.…”

“…These results show that myocytes in the noninfarcted region do not maintain normal levels of creatine. Reduced creatine and CP levels are characteristic of many models of chronic cardiac injury (6)(7)(8)(39)(40)(41).…”

“…One attractive mechanism that may directly contribute to contractile failure after MI is a reduction of energy reserve (for review see reference 5). Altered energy metabolism has been observed for many experimental models of cardiac hypertrophy and failure, such as hyperthyroidism (6), aortic stenosis (7), dilated cardiomyopathy in the Syrian hamster (8), uninephrectomy plus steroid treatment (9), or the spontaneously hypertensive rat (10). The purpose of the present work was, therefore, to define performance, oxygen consumption, and parameters of energy reserve, i.e., tissue contents of ATP and creatine phosphate (CP), creatine kinase (CK) activity and isoenzyme distribution, and phosphoryl transfer rates via CK (using 3P-magnetization transfer), in normal rat heart and in residual intact myocardium after MI.…”

Ketone bodies maintain normal cardiac function and myocardial high energy phosphates during insulin-induced hypoglycemia in vivo

“…The 20 % increase in MVO2 during hypoglycemia was due to an increase in pressure-work. A sufficient myocardial energy supply under this condition can be assumed because of a) an unchanged myocardial contractile function, b) constant high energy phosphate levels, and c) a constant mitochondrial activity, as estimated by the PCr/Pi ratio (20).…”

31P and 1H magnetic resonance spectroscopy of acute alcohol cardiac depression in rats

“…31P MR spectra of the beating heart were obtained on a vertical 5.6-T 76-mm-bore spectrometer as described earlier (14). 31P MR spectra were obtained without proton decoupling at 97.3 MHz.…”