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The purpose of these studies was to characterize the rates of fatty acid oxidation in reperfused myocardium and test the influence of excess fatty acids (FA) on mechanical function in the extracorporeally perfused, working swine heart model. Seventeen animals were prepared. Eight were untreated (LOW FA group; serum FA averaged 0.55 +/- 0.07 mumol/ml) and nine received a constant infusion of 10% Intralipid with heparin to raise serum FA to about 1.4 +/- 0.21 mumol/ml (HIGH FA group). Coronary flow in both groups was held at aerobic levels for an equilibrium period of 40 minutes, acutely reduced regionally in the anterior descending circulation by 60% for 45 minutes, and acutely restored to aerobic levels for 60-minute reflow. Appreciable mechanical depression (-47 delta% from aerobic values; p less than 0.01) during reperfusion was noted in both groups. This was associated with modest reductions in myocardial oxygen consumption (p less than 0.05) and losses of total tissue carnitine stores (p at least less than 0.02). Reperfused myocardium showed a strong preference for and aerobic use of FA during reflow such that 14CO2 production from labeled palmitate exceeded preischemic levels (+89 delta% in LOW FA hearts; +111 delta% in HIGH FA hearts). This suggested relative preservation of restoration of certain elements in mitochondrial function during reflow. The findings argue for uncoupling between substrate metabolism and energy production, accelerated but useless energy drainage, or some impairment between energy transfer and function of contractile proteins as possible explanations for the persistent depression of mechanical function (stunning) during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

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A model for high output heart failure (HCO) was developed in male, Sprague-Dawley rats using an abdominal aortocaval shunt equal to 50% of total cardiac output (CO) with 2 mo of postsurgical recovery. The model was evaluated by analysis of hemodynamics, peripheral blood flows (BF) (radioactive microspheres), and plasma catecholamine levels as well as mass and fluid content of organs. In HCO, CO and left ventricular end-diastolic pressure were increased with significant left and right ventricular hypertrophy. Mean blood pressure (BP) was unchanged, but pulse BP was increased in HCO. BF to skeletal muscle, cutaneous, and some splanchnic regions was reduced to HCO, whereas BF to the cerebral, coronary, and renal beds was protected. Plasma epinephrine and norepinephrine levels were significantly elevated in HCO suggesting enhanced sympathetic as well as adrenal catecholamine release. Tissue analysis indicated altered circulatory status secondary to HCO in liver, kidney, spleen, and lung. The results indicate that this model will be a relevant tool for studies of the circulatory effects of heart failure.

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An experimental animal model of hibernating myocardium is presented. Sixteen animals were initially prepared of which seven were selected for final review. Hearts were instrumented in two separate surgical procedures such that maximum phasic flow velocity in the left anterior descending (LAD) coronary artery was reduced by 50% and followed over 1 wk. Regional shortening declined at 1 wk to 62% of aerobic values (P less than 0.048) and did not improve over 2 h reperfusion. Metabolic determinations, obtained after 1 wk of coronary stenosis and immediately sampled before and after release of the LAD flow constrictor, showed no evidence of acidosis, hypercarbia, or an inability to extract oxygen at the tissue level. Thereafter, during the 2-h reperfusion period, hearts were able to respond to dobutamine (10 micrograms/kg infusion over 1 min) challenge with an appropriate shift in an end-systolic length estimate of contractility. Mitochondrial respiration at the conclusion of the studies in the reperfused bed demonstrated near normal recovery compared with aerobic values. None of the seven hearts showed gross evidence of infarction and only one heart was noted to have a few microfocal changes of healing infarction. Thus a new model of coronary stenosis is presented, which affected substantial reductions in mechanical function consistent with the concepts of hibernating myocardium. These mechanical events were not associated with marked metabolic abnormalities, reflecting advanced ischemia or mitochondrial dysfunction and could be transiently improved with inotropic stimuli. This model may prove beneficial as a tool in understanding mechanistic events underlying the hibernating heart.

Fatty acids in excess impair mechanical function and electrical stability in ischemic hearts. The purpose of the present studies was to test whether oxfenicine, an agent capable of reducing fatty acid metabolism, can prevent these consequences and in so doing improve hemodynamic performance. Two groups of working swine hearts (n = 15), extracorporeally perfused with whole blood, were compared over 90 min of controlled coronary perfusion. An emulsion of triacylglycerols (Intralipid) with heparin were administered systemically to augment serum fatty acids threefold (0.30 to 0.92 mumol/ml). Labeled [U14C]palmitate was administered selectively into the left anterior descending coronary circulation to follow fatty acid oxidation. Coronary flow in this bed was decreased by 50% over the final 30 min of perfusion. Saline (n = 7) or oxfenicine (17-33 mg/kg, n = 8) was administered to placebo or treated animals at 30 min perfusion. 14CO2 production from labeled palmitate was decreased by 55% (P less than 0.025) at normal flows in oxfenicine-treated hearts and was reduced further during ischemia. Tissue levels of acyl carnitine were significantly reduced and acetyl CoA levels significantly increased in oxfenicine-treated hearts both in aerobic and ischemic myocardium. These changes were associated with an improvement in mechanical function. Left ventricular systolic and developed pressures and maximum left ventricular dP/dt were increased by 36 delta %, P less than 0.01; 46 delta %, P less than 0.025; and 41 delta %, P less than 0.025, respectively, at end ischemia as compared with placebo hearts.(ABSTRACT TRUNCATED AT 250 WORDS)