Protective effect of the specific thromboxane receptor antagonist, BM-13505, in reperfusion injury following acute myocardial ischemia in cats.
The ability of BM-13505, 4-[2-(4-chlorobenzenesulfonylamino) ethyl]-benzene acetic acid), a specific thromboxane/endoperoxide receptor antagonist, to protect the myocardium against ischemia and reperfusion injury, was assessed in an anesthetized cat model. Cats were rendered ischemic by left anterior descending (LAD) coronary artery ligation for 1 1/2 hours followed by reperfusion for 4 1/2 hours. BM-13505 or its vehicle (i.e., Na2CO3) was administered intravenously 30 minutes before reperfusion at a rate of 1 mg/kg followed by 1 mg/kg/hr. BM-13505 significantly (p less than 0.001) reduced the area of ischemic tissue as a percent of total left ventricular mass and total area at risk, without altering basic hemodynamics (i.e., arterial blood pressure, heart rate, or their product) and thereby not influencing myocardial oxygen demand. The mechanism of the protective effect of the thromboxane receptor antagonist appears to be cytoprotective but may involve the prevention of neutrophil-induced cellular damage.
Bhat
A M
AM
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Sacks
H
H
Osborne
J A
JA
Lefer
A M
AM
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D003327:Coronary Disease / Q000201:enzymology / Q000503:physiopathology*; D003402:Creatine Kinase / Q000097:blood; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010648:Phenylacetates / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D010648:Phenylacetates; D013449:Sulfonamides; D013931:Thromboxanes; D003402:Creatine Kinase; C051762:daltroban