Effects of propionyl-L-carnitine on isolated mitochondrial function in the reperfused diabetic rat heart.
The effects of propionyl-L-carnitine (PLC) on isolated mitochondrial respiration in the ischemic reperfused diabetic heart were studied. Oral PLC treatment of STZ-diabetic rats was initiated for a period of 6 weeks. After treatment, isolated working hearts from diabetic rats were perfused under aerobic conditions then subjected to 25 min of no-flow ischemia followed by 15 min of aerobic reperfusion. At the end of reperfusion, heart mitochondria was isolated using differential centrifugation and respiration measured in the presence of pyruvate, glutamate, and palmitoylcarnitine. Our results indicate that diabetes was characterized by a pronounced decrease in heart function under aerobic conditions as well as during reperfusion following ischemia. Treatment with PLC resulted in a significant improvement in heart function under these conditions. The depressions in state 3 mitochondrial respiration with both pyruvate and glutamate seen in reperfused hearts from diabetic rats were prevented by PLC. State 3 respiration in the presence of palmitoylcarnitine was also improved in the ischemic reperfused diabetic rat heart. Our results show that PLC improves recovery of mechanical function following ischemia in the diabetic rat heart. The beneficial effects of PLC are associated with enhanced mitochondrial oxidation of fuels.
Felix
C
C
Department of Pharmacology, Faculty of Medicine, Dalhousie University, B3H 4H7, Halifax, NS, Canada.
Gillis
M
M
Driedzic
W R
WR
Paulson
D J
DJ
Broderick
T L
TL
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D003971:Diastole / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D015425:Myocardial Reperfusion; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013599:Systole / Q000187:drug effects
D001786:Blood Glucose; D002316:Cardiotonic Agents; C003223:propionylcarnitine; D002331:Carnitine