Diastolic dysfunction and altered energetics in the alphaMHC403/+ mouse model of familial hypertrophic cardiomyopathy.

摘要: An arginine to glutamine missense mutation at position 403 of the beta-cardiac myosin heavy chain causes familial hypertrophic cardiomyopathy. Here we study mice which have this same (alphaMHC403/+) using an isolated, isovolumic heart preparation where cardiac performance is measured simultaneously with energetics 31P nuclear magnetic resonance spectroscopy. We observed three major alterations in physiology and bioenergetics alphaMHC403/+ mouse hearts. First, while there was no evidence systolic dysfunction, diastolic function impaired during inotropic stimulation. Diastolic dysfunction manifest as both a decreased rate left ventricular relaxation increase end-diastolic pressure. Second, under baseline conditions hearts had lower phosphocreatine increased inorganic phosphate contents resulting decrease calculated value for free energy released from ATP hydrolysis. Third, that were studied unpaced responded perfusate calcium by decreasing approximately twice much wild types. conclude demonstrate work load-dependent resembling human form Changes high-energy content suggest energy-requiring process may contribute dysfunction.