Protective effects of a thromboxane synthetase inhibitor, a thromboxane antagonist, a lipoxygenase inhibitor and a leukotriene C4, D4 antagonist on myocardial injury caused by acute myocardial infarction in the canine heart.
We studied the effects of a thromboxane A2 synthetase inhibitor (RS-5186), a thromboxane A2 antagonist (ONO-3708), a 5-lipoxygenase inhibitor (AA-861) and a peptidoleukotriene antagonist (ONO-1078) on infarct size, polymorphonuclear leukocyte infiltration, gross myocardial hemorrhage and arrhythmias in the canine coronary occlusion (2 hour)-reperfusion model (5 hour). The infarct size and risk area were determined by a double staining technique. Thirty minutes prior to occluding the coronary arteries, dogs were randomly assigned to one of the following five groups: the thromboxane A2 synthetase inhibitor group (n = 11) receiving RS-5186 10 mg/kg i.v., the thromboxane A2 antagonist group (n = 12) receiving continuous intravenous infusion of ONO-3708 1 microgram/kg/min, the lipoxygenase inhibitor group (n = 11) receiving AA-861 3 mg/kg i.v., the peptidoleukotriene antagonist group (n = 11) receiving continuous intravenous infusion of ONO-1078 1 microgram/kg/min and the vehicle control group (n = 15). Except for ONO-3708, all the other drugs reduced the infarct size (RS-5186: 26.3 +/- 2.4% of risk area (mean +/- SEM), AA-861: 21.8 +/- 1.3%, ONO-1078: 22.5 +/- 4.4% vs control: 54.0 +/- 6.4%, p less than 0.01 respectively) as well as reducing the area of gross myocardial hemorrhage (RS-5186: 3.9 +/- 2.6% of infarct size, AA-861: 5.1 +/- 2.4%, ONO-1078: 5.2 +/- 2.5% vs control: 22.3 +/- 3.9%, p less than 0.01 respectively). RS-5186 and AA-861 reduced the intensity of polymorphonuclear leukocyte infiltration into the infarcted area, however, neither ONO-3708 nor ONO-1078 had any significant influence.(ABSTRACT TRUNCATED AT 250 WORDS)
Ito
T
T
2nd Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Toki
Y
Y
Hieda
N
N
Okumura
K
K
Hashimoto
H
H
Ogawa
K
K
Satake
T
T
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control; D016227:Benzoquinones; D009202:Cardiomyopathies / Q000209:etiology / Q000517:prevention & control; D002867:Chromones / Q000627:therapeutic use*; D003327:Coronary Disease / Q000209:etiology / Q000517:prevention & control*; D004285:Dogs; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control; D016859:Lipoxygenase Inhibitors; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D011809:Quinones / Q000627:therapeutic use*; D013189:SRS-A / Q000037:antagonists & inhibitors*; D013876:Thiophenes / Q000627:therapeutic use*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D016227:Benzoquinones; D002867:Chromones; D016859:Lipoxygenase Inhibitors; D011809:Quinones; D013189:SRS-A; D013876:Thiophenes; C055806:RS 5186; D013928:Thromboxane A2; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; C049855:ONO 3708; D013930:Thromboxane-A Synthase; C047681:pranlukast