Peptide leukotriene receptor antagonism in myocardial ischaemia and reperfusion.
OBJECTIVE
The aim was to investigate the role of peptide leukotrienes in the pathophysiology of myocardial injury during reperfusion of previously ischaemic myocardium.


METHODS
Adult male cats (2.9-5.4 kg) were subjected to left anterior descending coronary artery occlusion for 3 h followed by 3 h of reperfusion. The peptide leukotriene receptor antagonist, LY-171883, was given intravenously only during the reperfusion period (3 mg.kg-1 bolus; 3 mg.kg-1 x h-1 infusion). Ischaemic injury was assessed by nitroblue tetrazolium staining and tissue creatine kinase activity; neutrophil infiltration was determined by myeloperoxidase activity of myocardial homogenates.


RESULTS
There was no significant difference at any time point in the experimental protocol between mean arterial blood pressure or pressure-rate index in cats given LY-171883 (3 mg.kg-1) and cats given vehicle. The area at risk of infarction (AAR) was 24(SEM 2)% for vehicle treated cats and 22(2)% for the drug treated cats. The necrotic area was 48(5)% of the AAR for the vehicle group but only 29(5)% of the AAR for the group given LY-171883 (p < 0.02). Left ventricular maximum +dP/dt tended to be higher with drug treatment compared to vehicle at the end of the reperfusion period. Tissue from the area at risk was assayed for creatine kinase activity and neutrophil specific myeloperoxidase activity as an index of the accumulation of neutrophils in this region. Creatine kinase activity was significantly higher (p < 0.05) in the AAR for drug nu vehicle treated cats following reperfusion, confirming the histochemical analysis. Myeloperoxidase activity increased approximately 12-fold in the AAR of cats receiving vehicle. LY-171883 did not reduce the myeloperoxidase activity significantly in the area at risk.


CONCLUSIONS
LY-171883 has a protective effect in ischaemia-reperfusion injury to the myocardium. These findings suggest a role for peptide leukotrienes both in the extension of ischaemic damage and in post-ischaemic ventricular dysfunction during reperfusion.
Hock
C E
CE
Department of Medicine, University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford 08084.
Beck
L D
LD
Papa
L A
LA
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D018077:Receptors, Leukotriene; D013777:Tetrazoles / Q000494:pharmacology*
D000098:Acetophenones; D015289:Leukotrienes; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013777:Tetrazoles; C044660:LY 171883