Myocardial protective effect of tezosentan, an endothelin receptor antagonist, for ischemia-reperfusion injury in experimental heart failure models.
The myocardial protective effects of endothelin antagonist in ischemic cardiomyopathy (ICMP), doxorubicin-induced cardiomyopathy (DOX) and pressure-overload hypertrophy by transverse aortic constriction (TAC) models have been predicted to be different. The objective of this experiment, therefore, is to evaluate the myocardial protective effect of tezosentan, an endothelin receptor antagonist, in various experimental heart failure models. Sprague-Dawley rats (6-8 weeks old, 200-300 g) were randomized to three experimental groups (n=30 each): ICMP; DOX; and TAC group. Each of these groups was randomly assigned further to the following subgroups (n=10 each): sham-operated ischemia-reperfusion subgroup (SHAM); tezosentan treated ischemia-reperfusion subgroup (Tezo); and tezosentan non-treated ischemia-reperfusion subgroup (N-Tezo). Total circulatory arrest was induced for 1 hr, followed by 2 hr of reperfusion. The left ventricular developed pressure, peak positive and negative first derivatives, and coronary blood flow were significantly different (P<0.05) among the SHAM, Tezo, and N-Tezo subgroups of the ICMP group at 30 min of reperfusion, but there were no statistically significant differences among the subgroups of the DOX and TAC groups. In conclusion, tezosentan, an endothelin receptor antagonist, showed myocardial protection effects only on the ischemic cardiomyopathy rat model, but not in the non-ischemic heart failure rat models.
Department of Thoracic and Cardiovascular Surgery, College of Medicine, Kangwon National University, Chuncheon, Korea.
Se Min
SM
Ryu
Hark Jei
HJ
Kim
Kyu Ran
KR
Cho
Won-Min
WM
Jo
D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D003331:Coronary Vessels / Q000502:physiology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D065128:Endothelin Receptor Antagonists; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006984:Hypertrophy / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D011312:Pressure; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery; D013777:Tetrazoles / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D017466:Receptors, Endothelin; D013777:Tetrazoles; D014665:Vasodilator Agents; C120582:tezosentan; D004317:Doxorubicin