Myocardial carnitine metabolism in congestive heart failure induced by incessant tachycardia.
Persistent tachycardia induces congestive heart failure (CHF), but the mechanism(s) of progressive ventricular dysfunction is (are) unclear. This study was designed to define possible metabolic causes of myocardial dysfunction in rapid ventricular pacing induced CHF. Twelve adult mongrel dogs were paced to 250 beats/min for 19 days. Plasma carnitine, norepinephrine and renin were measured at 0, 1, 2, and 3 weeks. Myocardial high energy phosphates, carnitine, glycogen, glucose, non-collagenous protein and collagen were measured at 19 days. Cardiac output, arterial pressure and pulmonary wedge pressure, measured at baseline and with CHF, showed a decrease in cardiac output and increase in pulmonary wedge pressure. Neurohumoral activation was evident by progressively increasing plasma norepinephrine and renin activity and depletion of myocardial norepinephrine. Plasma free carnitine rose significantly from 12.6 +/- 2.0 control to 28.3 +/- 3.8 nmol/ml at 19 days (p < 0.001), whereas myocardial total carnitine was lower in paced than in control dogs (6.0 +/- 1.9 vs. 14.1 +/- 3.5 nmol/mg non-collagenous protein, p < 0.001). Myocardial ATP ATP and ADP were unchanged, while AMP decreased 22%, and creatine phosphate decreased 30% compared to control animals. Myocardial glucose was normal but glycogen was decreased 54% (p < 0.005). The low myocardial carnitine and elevated plasma carnitine in pacing induced CHF suggests altered carnitine transport or membrane integrity.
Pierpont
M E
ME
Department of Pediatrics, University of Minnesota, School of Medicine, Minneapolis.
Foker
J E
JE
Pierpont
G L
GL
D000818:Animals; D002304:Cardiac Pacing, Artificial; D002331:Carnitine / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D004285:Dogs; D004734:Energy Metabolism; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D012083:Renin / Q000097:blood; D013610:Tachycardia / Q000150:complications*
D002395:Catecholamines; D010710:Phosphates; D012083:Renin; D002331:Carnitine