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Protective Effect of a Novel Thromboxane Antagonist, BAY‐U3405, on Canine Myocardial Damage After Coronary Artery Occlusion and Reperfusion
Author(s) -
Fiedler Volker B.,
Perzborn Elisabeth,
Seuter Friedel
Publication year - 1991
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1991.tb03601.x
Subject(s) - medicine , ventricular fibrillation , cardiology , coronary occlusion , occlusion , anesthesia , ischemia , artery
The effects of a novel thromboxane antagonist, (3R)‐3‐(4‐fluorophenylsulfonamido)‐1,2,3,4‐tetrahydro‐9‐carbazolepropanoic acid (BAY‐U3405), on myocardial damage due to ischemia and reperfusion (added to accelerate the initiated injury) were studied in anesthetized dogs. The left anterior descending (LAD) coronary artery was occluded for 6 hours and reperfused for 30 minutes. BAY‐U3405, 1 mg/kg, was injected intravenously 15 minutes after LAD occlusion, followed by continuous infusion of 10 mg/kg/hour starting at 30 minutes after occlusion. The drug had no hemodynamic effects. During the experiments 6 of 14 animals died of ventricular fibrillation (VF) in the placebo‐vehicle controls (3 during occlusion and 3 during reperfusion); in the drug‐treated group 5 of 13 dogs died of VF (all during occlusion none during reperfusion). This difference in total mortality and cause was not statistically significant. Reperfusion arrhythmias were largely suppressed by BAY‐U3405: 201 ± 43 versus 689 ± 98 irregular beats during 30 minutes (p < 0.001) in the experimental and control groups, respectively. Coronary collateral flow, obtained from a load‐line analysis by measurement of retrograde coronary flow, and collateral index were similar in both groups. Therefore, BAY‐U3405 did not alter collateral blood supply to the ischemic myocardium. Infarct size, determined with tetrazolium staining, was reduced by 65% (p < 0.01) after its administration. These results suggest that thromboxane antagonism by BAY‐U3405 may delay infarct expansion and reduce the frequency of ventricular arrhythmias during reperfusion of previously ischemic myocardium.