DEPLETION OF ENERGY RESERVE VIA THE CREATINE-KINASE REACTION DURING THE EVOLUTION OF HEART-FAILURE IN CARDIOMYOPATHIC HAMSTERS

To study the contribution of myocardial energy reserve to the deterior ation of cardiac function during the development of heart failure, we defined energy reserve via the creatine kinase (CK) reaction and the i sovolumic contractile performance in hearts of cardiomyopathic hamster s at the ages of 1.5, 4, 17, 30 and 43 weeks and in age-matched normal hamsters. Energy reserve via the CK reaction was estimated by the pro duct of total CI( activity and the content of total creatine in the he art. Isovolumic contractile performance was measured as rate pressure product (RPP, 10(3) mmHg/min) in isolated hearts. Contractile reserve was assessed as the increase of RPP elicited by high calcium stimulati on. Compared to the controls, decreases in total CK activity and conte nt of total creatine were observed in hearts of 17-, 30- and 43-week-o ld cardiomyopathic hamsters. These changes were not observed in the sk eletal muscle. Although the decrease of baseline RPP first occurred at the age of 30 weeks (11.5 +/- 0.9 v 20.5 +/- 0.8, P < 0.05), the cont ractile reserve was already reduced at the age of 17 weeks (9.9 +/- 1. 3 v 23.6 +/- 1.9, P < 0.05). A linear relationship was found between t he energy reserve via creatine kinase reaction and the contractile res erve of the heart (r(2) = 0.85). Furthermore, concomitant decreases in the CK reaction velocity and the contractile reserve were observed in cardiomyopathic hearts, suggesting that depletion of energy reserve m ay contribute to the development of heart failure. (C) 1996 Academic P ress Limited