Protective actions of a thromboxane receptor antagonist, SQ 29548 on the ischemic myocardium: morphologic and hemodynamic effects.
The effects of thromboxane A2 (TXA2)/prostaglandin endoperoxide receptor blockade on myocardial infarct size and cardiac dynamics were determined in a canine model of 24 h acute myocardial infarction. Anesthetized open-chest dogs were subjected to left anterior descending (LAD) coronary artery occlusion. Twenty minutes post-occlusion the dogs were given i.v. saline (0.9% NaCl solution) (n = 12) or the TXA2 receptor antagonist SQ 29548 (0.2 mg/kg i.v. loading dose +0.2 mg/kg/h i.v. for 4 h) (n = 10). SQ 29548 treatment resulted in a significant (P < 0.01) reduction in infarct size. Heart rate (HR) and systolic blood pressure (SAP) were not markedly affected by the drug. The sharp rise in the left ventricular end diastolic pressure (LVEDP) in the saline-treated animals was significantly lowered by SQ 29548 treatment and the correction of this variable was maintained till 24 h post-occlusion. The lowered maximal rate of rise of left ventricular pressure (LVdP/dt max) in the saline-treated animals was corrected albeit non-significantly by the drug treatment. Thus, SQ 29548 treatment resulted in a significant salvage of myocardial tissue and marked alterations in left ventricular dynamics. The study suggests a deleterious role for thromboxane A2 in ischemia; indicating that TXA2 blockade may have potential as a mode of therapy for ischemic heart disease.
Singh
J
J
Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Seth
S D
SD
Manchanda
S C
SC
Seth
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004285:Dogs; D005231:Fatty Acids, Unsaturated; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006834:Hydrazines / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013928:Thromboxane A2 / Q000378:metabolism / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; C045749:SQ 29548