Cellular mechanisms of alterations in myocardial contractile function in experimental cardiomyopathies.
The high-energy-phosphate content, myocardial ultrastructure, left ventricular (LV) pressure, and pump function of isolated rat hearts were determined in four kinds of chronic myocardial damage induced by either autoimmunization, treatment of rats with adriamycin or noradrenaline in increasing doses, or infection with smallpox virus. Mild fibrosis, swollen mitochondria, and hyper-contracted and overdistended sarcomeres were typical ultrastructural alterations. The ATP and phosphocreatine content as well as cardiac output at standard load conditions were substantially lower in all four experimental groups. Mild bradycardia and increased LV diastolic pressure and stiffness occurred in all except the autoimmunized group. LV diastolic stiffness was inversely correlated with cardiac output and phosphocreatine content and directly correlated with LV systolic pressure. Both increased myofibrillar sensitivity to Ca2+ ions and energy deficiency within myofibrils may have contributed to increased myocardial stiffness. The increased stiffness limits LV filling but facilitates pressure development, and in this way partly compensates for the decreased contractility of cardiomyopathic hearts.
Kapelko
V I
VI
Institute of Experimental Cardiology, Academy of Medical Sciences of the USSR, Moscow.
Veksler
V I
VI
Popovich
M I
MI
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004317:Doxorubicin / Q000633:toxicity; D004734:Energy Metabolism; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology; D008297:Male; D009124:Muscle Proteins / Q000032:analysis; D009200:Myocardial Contraction; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D009210:Myofibrils / Q000648:ultrastructure; D009638:Norepinephrine / Q000633:toxicity; D051381:Rats; D012899:Smallpox / Q000150:complications; D016277:Ventricular Function, Left
D009124:Muscle Proteins; D004317:Doxorubicin; D009638:Norepinephrine