Impaired cardiac function in rats with healed myocardial infarction: cellular vs. myocardial mechanisms.
The inotropic responsiveness of isolated perfused rat hearts and single left ventricular (LV) myocytes to extracellular Ca2+ ([Ca2+]o) was examined 3 wk after ligation of left main coronary artery. Myocytes isolated from myocardial infarcted (MI) hearts were 10% longer. At [Ca2+]o of 1.1 mM, cell shortening as well as intracellular Ca2+ concentration dynamics were similar between MI and sham LV myocytes. At [Ca2+]o of 4.9 mM, maximal extent of cell shortening was significantly less in MI myocytes (16 +/- 1 vs. 22 +/- 1%), and peak intracellular Ca2+ concentration was also substantially lower. Thus, under conditions of high [Ca2+]o, decreased sarcolemmal Ca2+ influx and Ca2+ release during excitation-contraction may contribute to systolic dysfunction in MI hearts. Perfused working hearts and isovolumic heart preparations with infarcted LV displayed depressed maximal systolic pressure and decreased sensitivity to the inotropic effects of [Ca2+]o. Our data also indicate that, in addition to possible abnormalities in the contractile response of single myocytes, global factors such as loss of functional myocardium, altered chamber geometry, tissue fibrosis, and/or subendocardial ischemia contributed to depressed LV function in post-MI hearts perfused at physiological [Ca2+]o.
Cheung
J Y
JY
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Musch
T I
TI
Misawa
H
H
Semanchick
A
A
Elensky
M
M
Yelamarty
R V
RV
Moore
R L
RL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D006321:Heart / Q000503:physiopathology*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D016276:Ventricular Function
D002118:Calcium