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 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 beta-guanidino-propionic 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.
Liao
R
R
Cardiovascular Disease and Muscle Research Laboratories, Harvard Medical School, Boston, Mass, USA.
Nascimben
L
L
Friedrich
J
J
Gwathmey
J K
JK
Ingwall
J S
JS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D003401:Creatine / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005664:Furazolidone; D006146:Guanidines / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology; D011422:Propionates / Q000494:pharmacology; D012016:Reference Values; D013997:Time Factors; D014422:Turkeys
D006146:Guanidines; D011422:Propionates; D005664:Furazolidone; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D003401:Creatine; C005775:guanidinopropionic acid