Role of eicosanoid inhibition of ischemia reperfusion injury: intact and isolated rat heart studies.
The effects of FPL-55712 (leukotriene receptor antagonist) and OKY-046 (thromboxane synthase inhibitor) were studied on ischemic and reperfused myocardium using in vivo and in vitro rat heart paradigms. The in vivo studies included production of regional ischemia by coronary artery ligation for 72 h followed by reperfusion. Macroscopic methods using nitro blue tetrazolium (NBT) staining were employed to measure infarct size. For in vitro studies, isolated rat hearts were perfused by Langendorff's technique. Regional ischemia was produced for 60 min followed by reperfusion. Coronary outflow and creatine phosphokinase (CPK) release in the coronary effluent were measured. Both these parameters showed a correlation with the duration of reperfusion. In isolated heart studies, FPL-55712 reduced CPK release and improved coronary outflow significantly, whereas OKY-046 did not show any beneficial effect. In intact heart studies, FPL-55712 did not reduce the infarct size, whereas OKY-046 decreased the myocardial infarct to a significant extent. The present study demonstrates a definite involvement of leukotrienes and thromboxanes in reperfusion injury. Inability of FPL-55712 to reduce infarct size may be due to the very short half-life of the drug. Lack of efficacy of OKY-046 in isolated studies suggests the involvement of platelet-derived thromboxanes in the reperfusion injury as these are not available in isolated heart preparations.
Shekher
A
A
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Singh
M
M
D000818:Animals; D002867:Chromones / Q000494:pharmacology*; D003402:Creatine Kinase / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D002867:Chromones; D016859:Lipoxygenase Inhibitors; D008689:Methacrylates; C006312:FPL 55712; D003402:Creatine Kinase; D013930:Thromboxane-A Synthase; C034364:ozagrel