Energy-linked functional alterations in experimental cardiomyopathies

¹ Institute of Experimental Cardiology, USSR Cardiology Research Center, Moscow 121552; Moldavian Institute of Prophylactic and Clinical Medicine, Kishinev, USSR; and Laboratory of Cardiac Cellular Physiology, University Paris-Sud, Orsay, France

Changes in high-energy phosphate content and cardiac contractile function of isolated rat hearts as well as changes in Ca²⁺ sensitivity and mitochondrial respiration of myocardial skinned fibers were assessed in hereditary cardiomyopathies and in cardiomyopathies induced by chronic treatment with adriamycin or norepinephrine, by autoimmunization, by diabetes, or by creatine deficiency. The sum of ATP and phosphocreatine contents as well as cardiac output at standard load conditions was substantially lower in almost all groups. The common features of cardiac pump failure were mild bradycardia, elevated left ventricular (LV) diastolic pressure, and stiffness that limited cardiac contractile adaptation to volume or resistance loads. The LV diastolic stiffness at maximal functional load was inversely correlated with high-energy phosphate content. Increased myofibrillar sensitivity to Ca²⁺ and defective function of mitochondrial creatine kinase were found in skinned myocardial fibers. These results suggested that both increased myofibrillar Ca²⁺ sensitivity and energy deficiency within myofibrils may contribute to increased myocardial stiffness. Increased stiffness limits LV filling but facilitates pressure development, which partly compensates for decreased contractility of cardiomyopathic hearts.