DECREASED ENERGY RESERVE IN AN ANIMAL-MODEL OF DILATED CARDIOMYOPATHY- RELATIONSHIP TO CONTRACTILE PERFORMANCE

An animal model was used to test the hypothesis that in heart failure the decrease in the ability to resynthesize ATP through the creatine k inase (CK) reaction (which we call energy reserve) contributes to the inability of the heart to maintain its normal function and contractile reserve. One week-old turkey poults were fed furazolidone for 14 days to induce dilated cardiomyopathy. Isolated Langendorff-perfused heart s from these myopathic animals showed a 73% decrease in baseline isovo lumic contractile performance. Neither increasing [Ca2+](o) nor electr ical pacing rate increased isovolumic contractile performance, Measure d by P-31 nuclear magnetic resonance magnetization transfer and chemic al assay, ATP concentration was decreased by 23%, phosphocreatine conc entration by 42%, CK enzyme activity by 34%, and the pseudo first-orde r rate constant for the CK reaction by 50%. Measured CK reaction veloc ity decreased by 71%. The reduced ability to increase cardiac performa nce in response to increasing [Ca2+](o) in hearts with lower CK reacti on velocity was reproduced in part by feeding a separate group of turk ey poults beta-guanidinopropionic acid to specifically reduce CK react ion velocity by decreasing guanidino substrate concentration. These he arts had normal baseline performance but blunted contractile re serve. These observations provide further support for the hypothesis that a decrease in energy reserve via the CK system contributes to reduced ca rdiac function in the failing heart.