Biomaterial Database

The novel thromboxane A2 receptor antagonist KW-3635 reduces infarct size in a canine model of coronary occlusion and reperfusion. 1993

K Higo, and J Sano, and A Karasawa, and K Kubo

Department of Cardiovascular Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.

The effect of KW-3635, a novel thromboxane A2 receptor antagonist, on infarct size was examined in anesthetized dogs subjected to 1.5 hr of occlusion of the left anterior descending coronary artery followed by 4.5 hr of reperfusion. KW-3635 (1 mg/kg, i.v.) was administered 1 hr before reperfusion and continuously infused (1 mg/kg/hr, i.v.) throughout the experiment. KW-3635 significantly (p < 0.001) reduced the infarct size (30.5% in the KW-3635-treated group as compared with 58.7% in the vehicle-treated group). KW-3635 almost completely inhibited platelet aggregation (ex vivo) induced by epinephrine (10 microM) + U-46619 (1 microM). KW-3635 attenuated the loss of creatine phosphokinase activity from the ischemic myocardium. Histopathological examination revealed that KW-3635 prevented neutrophil accumulation into the ischemic myocardium, ameliorated eosinophilic changes and inhibited contraction band formation in the ischemic myocardium. These results indicate that KW-3635 has a cardioprotective activity and suggest that the inhibition of activation or accumulation of neutrophils is involved in the cardioprotection following thromboxane A2 receptor blockade.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009203	Myocardial Infarction	NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).	Cardiovascular Stroke,Heart Attack,Myocardial Infarct,Cardiovascular Strokes,Heart Attacks,Infarct, Myocardial,Infarction, Myocardial,Infarctions, Myocardial,Infarcts, Myocardial,Myocardial Infarctions,Myocardial Infarcts,Stroke, Cardiovascular,Strokes, Cardiovascular
D010974	Platelet Aggregation	The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.	Aggregation, Platelet
D010975	Platelet Aggregation Inhibitors	Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.	Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D003402	Creatine Kinase	A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.	Creatine Phosphokinase,ADP Phosphocreatine Phosphotransferase,ATP Creatine Phosphotransferase,Macro-Creatine Kinase,Creatine Phosphotransferase, ATP,Kinase, Creatine,Macro Creatine Kinase,Phosphocreatine Phosphotransferase, ADP,Phosphokinase, Creatine,Phosphotransferase, ADP Phosphocreatine,Phosphotransferase, ATP Creatine
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D005260	Female		Females
D006321	Heart	The hollow, muscular organ that maintains the circulation of the blood.	Hearts
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001562	Benzimidazoles	Compounds with a BENZENE fused to IMIDAZOLES.