Fatty acid oxidation and cardiac function in the sodium pivalate model of secondary carnitine deficiency.

Carnitine-deficiency syndromes are often associated with alterations in lipid metabolism and cardiac function. The present study was designed to determine whether this is also seen in an experimental model of carnitine deficiency. Carnitine deficiency was induced in male Sprague-Dawley rats supplemented with sodium pivalate for 26 to 28 weeks. This treatment resulted in nearly a 60% depletion of myocardial total carnitine content as compared with control hearts. When isolated working hearts from these animals were perfused with 5.5 mmol/L glucose and 1.2 mmol/L palmitate and subjected to incremental increases in left-atrial filling pressures, cardiac function remained dramatically depressed. The effects of carnitine deficiency on glucose and palmitate utilization were also assessed in hearts perfused at increased workload conditions. At this workload, function was depressed in carnitine-deficient hearts, as were rates of 1.2-mmol/L [U-14C]-palmitate oxidation, when compared with control hearts (544 +/- 37 vs 882 +/- 87 nmol/g dry weight.min, P < .05). However, glucose oxidation rates from 5.5 mmol/L [U-14C]-glucose were slightly increased in carnitine-deficient hearts. To determine whether the depressed fatty acid oxidation rates were a result of reduced mechanical function in carnitine-deficient hearts, the workload of hearts was reduced. Under these conditions, mechanical function was similar among control and carnitine-deficient hearts. Palmitate oxidation rates were also similar in these hearts (526 +/- 69 v 404 +/- 47 nmol/g dry weight.min for control and carnitine-deficient hearts, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium pivalate reduces cardiac carnitine content and increases glucose oxidation without affecting cardiac functional capacity.

This study determined how selected functional, metabolic, and contractile properties were impacted by sodium pivalate, a compound which creates a secondary carnitine deficiency. Young male rats received either sodium pivalate (20 mM, PIV) or sodium bicarbonate (20 mM, CONTR) in their drinking water. After 11-12 weeks cardiac function and glucose oxidation rates were measured in isolated, perfused working heart preparations. Hearts were also analyzed for carnitine content, activities of hexokinase (HK), citrate synthase (CS), and B-hydroxyacyl CoA dehydrogenase (HOAD), and myosin isoenzyme distribution. Sodium pivalate treatment significantly reduced cardiac carnitine content and increased glucose oxidation but did not alter cardiac functional capacity. HK activity was increased in the PIV group (p < 0.05), and HOAD activity decreased (p < 0.05). CS activity and myosin isoform distribution (VI > 85%) remained unchanged. These results demonstrate that pivalate treatment of this duration and the accompanying carnitine deficiency shift cardiac substrate utilization without compromising cardiac functional capacity.

Hemodynamic responses to upright exercise of adolescent cardiac transplant recipients.

To characterize the hemodynamic response to exercise after cardiac transplantation, we asked seven adolescent transplant patients (aged 15.1 +/- 0.7 years; mean +/- SE) to perform upright discontinuous exercise to volitional exhaustion on a mechanically braked cycle ergometer. Data were compared with those of seven control subjects matched for age, gender, body mass, percentage of fat, and body surface area. The transplant group had lower peak power output values (92 +/- 13 vs 146 +/- 30 watts; p less than or equal to 0.001) and maximum oxygen consumption values (22 +/- 8 vs 32 +/- 8 ml/kg per minute; p less than or equal to 0.03), despite achieving the same peak venous lactic acid concentration (6.2 +/- 3 vs 5.9 +/- 3 mEq/L; p = not significant). The transplant group had a diminished heart rate in response to exercise--44% lower than the control group had (delta = 49 +/- 6.4 vs 87 +/- 9.1 beats/min; p = 0.005). The cardiac output response to exercise was maintained in the transplant group (delta = 6.5 +/- 1.5 vs 4.6 +/- 0.8 L/min; p = not significant) by an augmented stroke volume response (delta = 31 +/- 10 vs -4 +/- 3.4 ml; p = 0.01), which may relate to a greater decrease in systemic vascular resistance during exercise (delta = -13.7 +/- 2.2 vs -6.3 +/- 1.2 Wood units; p = 0.02). Thus adolescents who have undergone cardiac transplantation have a normal cardiac output response to upright exercise. This is accomplished, despite a blunted heart rate response, by an augmented stroke volume that may relate to the greater decrease in systemic resistance during exercise.