The effects of lipoxygenase inhibitor and peptidoleukotriene antagonist on myocardial injury in a canine coronary occlusion-reperfusion model.
We studied effects of lipoxygenase inhibitor (AA-861) and peptidoleukotriene antagonist (ONO-1078) on infarct size, polymorphonuclear leukocyte (PMNs) infiltration, gross myocardial hemorrhage and ventricular arrhythmias in canine coronary occlusion (2 hr)-reperfusion (5 hr) model. Infarct size (IS) and risk area (RA) were determined by dual staining technique. Thirty minutes before coronary occlusion dogs were randomly assigned to one of the following three groups: lipoxygenase inhibitor group (n = 11) receiving AA-861 3 mg/kg i.v., peptidoleukotriene antagonist group (n = 11) receiving continuous intravenous infusion of ONO-1078 1 micrograms/kg/min and vehicle control group (n = 15). Both AA-861 and ONO-1078 reduced infarct size [AA-861: 21.8 +/- 1.3% of RA (mean +/- SEM), ONO-1078: 22.5 +/- 4.4% vs


METHODS
54.0 +/- 6.4%, p less than 0.01 and p less than 0.01, respectively] and area of gross myocardial hemorrhage (AA-861: 5.1 +/- 2.4% of IS, ONO-1078: 5.2 +/- 2.5% vs


METHODS
22.3 +/- 3.9%, p less than 0.01 and p less than 0.01, respectively). Both drugs also decreased frequency of ventricular premature contractions both during occlusion and during reperfusion, and that of ventricular tachycardia during reperfusion. AA-861 inhibited PMNs recruitment into infarcted area. However, ONO-1078 had no significant influence on degree of PMNs infiltration. These results suggest that lipoxygenase products, especially peptidoleukotrienes (LTC4, D4 and E4) may play important roles in the pathogenesis of myocardial ischemic and reperfusion injuries.
Toki
Y
Y
2nd Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Hieda
N
N
Torii
T
T
Hashimoto
H
H
Ito
T
T
Ogawa
K
K
Satake
T
T
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D016227:Benzoquinones; D002465:Cell Movement / Q000187:drug effects; D002867:Chromones / Q000627:therapeutic use*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D006470:Hemorrhage / Q000517:prevention & control; D016859:Lipoxygenase Inhibitors; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects; D011809:Quinones / Q000627:therapeutic use*; D013189:SRS-A / Q000037:antagonists & inhibitors*
D016227:Benzoquinones; D002867:Chromones; D016859:Lipoxygenase Inhibitors; D011809:Quinones; D013189:SRS-A; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; C047681:pranlukast