Myocyte performance during evolution of myocardial infarction in rats: effects of propionyl-L-carnitine.
To determine whether alterations in the mechanical properties and calcium transients of myocytes are important factors in the evolution of the postinfarcted heart, these physiological parameters were measured in the viable muscle cells of the left ventricle 6 h, 2-3 days, 1 wk, and 1 mo after coronary artery occlusion and the documentation of left ventricular failure. In addition, the effects of propionyl-L-carnitine (PLC) on shortening properties and calcium dynamics of single myocytes were established to demonstrate whether the potential increase in ATP generation by this intervention improved myocyte cell function. Myocardial infarction was associated with a progressive increase in length of the spared myocytes, whereas the changes in myocyte diameter were apparent only at the 1-mo interval. Mechanically, myocyte shortening was decreased 43% at 6 h, 34% at 2-3 days, 26% at 1 wk, and 41% at 1 mo after infarction. Similar abnormalities were noted in the velocity of myocyte shortening. Peak systolic calcium was decreased at all intervals after infarction. In contrast, diastolic calcium remained within control values. PLC was capable of ameliorating the mechanical behavior and calcium transients of myocytes, particularly 1 mo after infarction. Thus alterations in muscle cell performance may be important determinants in the development and progression of ischemic cardiomyopathy, and interventions improving myocyte contractility may interfere with the unfavorable outcome of the disease.
Li
P
P
Department of Medicine, New York Medical College, Valhalla 10595, USA.
Park
C
C
Micheletti
R
R
Li
B
B
Cheng
W
W
Sonnenblick
E H
EH
Anversa
P
P
Bianchi
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; C003223:propionylcarnitine; D002331:Carnitine; D002118:Calcium