Chronic Phosphocreatine Depletion by the Creatine Analogue β-Guanidinopropionate Is Associated With Increased Mortality and Loss of ATP in Rats After Myocardial Infarction
Open Access
- 9 October 2001
- journal article
- other
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 104 (15), 1844-1849
- https://doi.org/10.1161/hc3901.095933
Abstract
Background The failing myocardium is characterized by reductions of phosphocreatine (PCr) and free creatine content and by decreases of energy reserve via creatine kinase (CK), ie, CK reaction velocity (Flux CK ). It has remained unclear whether these changes contribute directly to contractile dysfunction. In the present study, myocardial PCr stores in a heart failure model were further depleted by feeding of the PCr analogue β-guanidinopropionate (GP). Functional and metabolic consequences were studied. Methods and Results Rats were subjected to sham operation or left coronary artery ligation (MI). Surviving rats were assigned to 4 groups and fed with 0% (n=7, Sham; n=5, MI) or 1% (n=7 Sham+GP, n=8 MI+GP) GP. Two additional groups were fed GP for 2 or 4 weeks before MI. After 8 weeks, hearts were isolated and perfused, and left ventricular pressure-volume curves were obtained. High-energy phosphate metabolism was determined with 31 P NMR spectroscopy. After GP feeding or MI, left ventricular pressure-volume curves were depressed by 33% and 32%, respectively, but GP feeding in MI hearts did not further impair mechanical function. Both MI and GP feeding reduced PCr content and Flux CK , but here, effects were additive. In MI+GP rats, PCr levels and Flux CK were reduced by 87% and 94%, respectively. Although ATP levels were maintained in the GP and MI groups, ATP content was reduced by 18% in MI+GP hearts. Furthermore, 24-hour mortality in GP-prefed rats was 100%. Conclusions Rats with an 87% predepletion of myocardial PCr content cannot survive an acute MI. Chronically infarcted hearts subjected to additional PCr depletion cannot maintain ATP homeostasis.This publication has 17 references indexed in Scilit:
- Functional and Energetic Consequences of Chronic Myocardial Creatine Depletion by β -Guanidinopropionate in Perfused Hearts and in Intact RatsJournal of Molecular and Cellular Cardiology, 1999
- Preservation of Left Ventricular Mechanical Function and Energy Metabolism in Rats After Myocardial Infarction by the Angiotensin-Converting Enzyme Inhibitor QuinaprilJournal of Cardiovascular Pharmacology, 1996
- Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.JCI Insight, 1995
- The acute effects of the creatine analogue, β-guanidinopropionic acid, on cardiac energy metabolism and functionBiochimica et Biophysica Acta (BBA) - Bioenergetics, 1993
- Aggravation of left ventricular dilatation and reduction of survival by a calcium channel blocker in rats with chronic myocardial infarctionAmerican Heart Journal, 1993
- Altered myocardial high-energy phosphate metabolites in patients with dilated cardiomyopathyAmerican Heart Journal, 1991
- Hormone regulation of cardiac energy metabolism: I. Creatine transport across cell membranes of euthyroid and hyperthyroid rat heartBiochemical Medicine, 1985
- Creatine kinase kinetics, ATP turnover, and cardiac performance in hearts depleted of creatine with the substrate analogue β-guanidinopropionic acidBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1985
- The Creatine Kinase System in Normal and Diseased Human MyocardiumThe New England Journal of Medicine, 1985
- Study of Moderately Rapid Chemical Exchange Reactions by Means of Nuclear Magnetic Double ResonanceThe Journal of Chemical Physics, 1963