FATTY-ACID OXIDATION AND CARDIAC-FUNCTION IN THE SODIUM PIVALATE MODEL OF SECONDARY CARNITINE DEFICIENCY

Carnitine-deficiency syndromes are often associated with alterations i n lipid metabolism and cardiac function. The present study was designe d to determine whether this is also seen in an experimental model of c arnitine 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 carn itine content as compared with control hearts. When isolated working h earts from these animals were perfused with 5.5 mmol/L glucose and 1.2 mmol/L palmitate and subjected to incremental increases in left-atria l filling pressures, cardiac function remained dramatically depressed. The effects of carnitine deficiency on glucose and palmitate utilizat ion were also assessed in hearts perfused at increased workload condit ions. At this workload, function was depressed in carnitine-deficient hearts, as were rates of 1.2-mmol/L [U-C-14]-palmitate oxidation, when compared with control hearts (544 +/- 37 v 882 +/- 87 nmol/g dry weig ht min, P < .05). However, glucose oxidation rates from 5.5 mmol/L [U- C-14] glucose were slightly increased in carnitine-deficient hearts. T o determine whether the depressed fatty acid oxidation rates were a re sult of reduced mechanical function in carnitine-deficient hearts, the workload of hearts was reduced. Under these conditions, mechanical fu nction was similar among control and carnitine-deficient hearts. Palmi tate oxidation rates were also similar in these hearts (526 +/- 69 v 4 04 +/- 47 nmol/g dry weight min for control and carnitine-deficient he arts, respectively). Our results show that work performed by hearts fr om carnitine-deficient animals is rate-limiting in the oxidation of pa lmitate. Despite this, our findings suggest that the sodium pivalate m odel of carnitine deficiency may prove to be useful for the investigat ion of functional and metabolic aspects of carnitine deficiency. Copyr ight (C) 1995 by W.B. Saunders Company