Evaluation of the Hereditary Syrian Hamster Cardiomyopathy by 31P Nuclear Magnetic Resonance Spectroscopy: Improvement After Acute Verapamil Therapy

• Published in: Circulation research 1986-12, Vol.59 (6), p.597-604
• Main Authors: Markiewicz, Walter, Wu, Shao S, Parmley, William W, Higgins, Charles B, Sievers, Richard, James, Thomas L, Wikman-Coffelt, Joan, Jasmin, Gaetan
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; Cardiomyopathies - drug therapy; Cardiomyopathies - metabolism; Cricetinae; Glucose - metabolism; Hemodynamics - drug effects; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Mesocricetus; Phosphorus - metabolism; Pyruvates - metabolism; Pyruvic Acid; Verapamil - therapeutic use
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.59.6.597

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/1 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. Verapamil administered for as short a period as 24 hours restored left ventricular pressure, oxygen consumption, and coronary flow to normal values whereas the mole fraction of phosphocreatine and the phosphocreatine/inorganic phosphate ratio rose markedly though remaining lower than in healthy animals. Comparison of data using glucose vs. pyruvate as a substrate indicates that glycolysis is impaired in the heart of cardiomyopathic hamsters. Energy production can be improved by short-circuiting limiting steps in the glycolytic pathway.