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)
Broderick
T L
TL
Department of Physiology, Midwestern University, Downers Grove, IL 60515, USA.
Christos
S C
SC
Wolf
B A
BA
DiDomenico
D
D
Shug
A L
AL
Paulson
D J
DJ
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002331:Carnitine / Q000172:deficiency* / Q000378:metabolism; D004952:Esters / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D008055:Lipids / Q000097:blood; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D010421:Pentanoic Acids; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D004952:Esters; D005227:Fatty Acids; D008055:Lipids; D010168:Palmitates; D010421:Pentanoic Acids; C005566:pivalic acid; D000255:Adenosine Triphosphate; D005947:Glucose; D002331:Carnitine