© 1996 American Heart Association, Inc.
Articles |
Decreased Energy Reserve in an Animal Model of Dilated Cardiomyopathy
Relationship to Contractile Performance
From the Cardiovascular Disease and Muscle Research Laboratories and the Department of Cellular and Molecular Physiology, Harvard Medical School (R.L., J.K.G.), the Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory, Beth Israel Hospital (R.L., J.K.G.), and the NMR Laboratory for Physiological Chemistry, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (L.N., J.F., J.S.I.), Boston, Mass.
Correspondence to Joanne S. Ingwall, PhD, NMR Laboratory for Physiological Chemistry, Department of Medicine, Brigham and Women's Hospital, Room BLI 247, 221 Longwood Ave, Boston, MA 02115. E-mail luigin@bustoff.bwh.harvard.edu.
Abstract An animal model was used to test the hypothesis that in heart failure the decrease in the ability to resynthesize ATP through the creatine kinase (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 hearts from these myopathic animals showed a 73% decrease in baseline isovolumic contractile performance. Neither increasing [Ca2+]o nor electrical pacing rate increased isovolumic contractile performance. Measured by 31P nuclear magnetic resonance magnetization transfer and chemical assay, ATP concentration was decreased by 23%, phosphocreatine concentration by 42%, CK enzyme activity by 34%, and the pseudo first-order rate constant for the CK reaction by 50%. Measured CK reaction velocity decreased by 71%. The reduced ability to increase cardiac performance in response to increasing [Ca2+]o in hearts with lower CK reaction velocity was reproduced in part by feeding a separate group of turkey poults ß-guanidinopropionic acid to specifically reduce CK reaction velocity by decreasing guanidino substrate concentration. These hearts had normal baseline performance but blunted contractile reserve. These observations provide further support for the hypothesis that a decrease in energy reserve via the CK system contributes to reduced cardiac function in the failing heart.
Key Words: cardiomyopathy • cardiac performance • creatine kinase • phosphocreatine • 31P nuclear magnetic resonance magnetization transfer
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