Effects of cardiotrophin-1 on hemodynamics and cardiomyocyte apoptosis in rats with acute myocardial infarction.
The effects of cardiotrophin-1 on hemodynamics, cardiac function, cardiomyocyte apoptosis, and expression of P53, Fas, Bax and Bcl-2 proteins in myocardium were determined in a rat model of acute myocardial infarction. Twenty-four male Sprague-Dawley rats weighing approximately 310 g were subjected to left coronary artery ligation. Seven days before surgery, the rats were randomized to receive cardiotrophin-1 (treated group) or phosphate-buffered saline (control group). Recombinant rat cardiotrophin-1 (2 microg in 1 ml phosphate-buffered saline) or phosphate-buffered saline (1 ml) was administered daily via the tail vein for 7 days (n = 12 for each group). Hemodynamic parameters, apoptotic index, P53, Fas, Bax and Bcl-2 expression in myocardium were measured at 24 hours after coronary ligation. As compared with control animals, rats treated with cardiotrophin-1 had significantly higher mean arterial pressure, left ventricular systolic pressure and the maximum rate of left ventricular pressure rise or fall, and significantly lower left ventricular end-diastolic pressure. Cardiotrophin-1 pretreatment did not affect the heart rate, heart weight, body weight or the ratio of heart weight to body weight. The number of apoptotic cardiomyocytes in cardiotrophin-1 treated group was less than that in control group [(15.8+/-5.2) % vs (34.6+/-7.7) %, P<0.01]. Cardiotrophin-1 pretreatment significantly inhibited P53, Fas and Bax, and increased Bcl-2 expression in myocardium.
Ruixing
Yin
Y
Department of Cardiology, Institute of Cardiovascular Diseases, Guangxi Medical University, Nanning, Guangxi, China.
Dezhai
Yang
Y
Jiaquan
Li
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000378:metabolism
C494828:Bax protein, rat; D002316:Cardiotonic Agents; D016207:Cytokines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C092073:cardiotrophin 1