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.