Role of thromboxane A2 in the control of myocardial O2 supply/consumption balance and severity of ischemia during pacing-induced ischemia.
The role of thromboxane A2 (TXA2) in the control of O2 supply/consumption variables during pacing-induced ischemia was examined using the TXA2 receptor antagonist SQ 29,548. Anesthetized, open-chest dogs were subjected to left anterior descending coronary artery (LAD) stenosis that produced significant epicardial S-T segment elevation (12 mV) only when superimposed on atrial pacing. Regional myocardial blood flow was determined using radioactive microspheres, and O2 consumption was determined by measuring O2 saturation of venous blood draining the ischemic region. The dogs were treated with saline or 0.2 mg/kg + 0.2 mg/kg/hr SQ 29,548, and the effect on ischemia was determined during 5-minute pacing-induced ischemic episodes at 10, 40, and 70 minutes postdrug or saline treatment. SQ 29,548 significantly reduced S-T elevation at 40 and 70 minutes postdrug compared with saline values and at all times measured compared with its paired predrug pace+stenosis values. SQ 29,548 reduced S-T elevation approximately 45% compared with its paired predrug values at 70 minutes. SQ 29,548 resulted in a significantly higher subendocardial-to-subepicardial flow ratio (0.70 +/- 0.10, p less than 0.05) compared with saline-treated animals (0.42 +/- 0.06), with an overall increase of flow to the ischemic region of approximately 40%. This increased flow was matched by a proportional increase in O2 consumption without a change in O2 extraction. The O2 supply/consumption balance was also unchanged by SQ 29,548 implying that despite the increase in blood flow, the ischemic region was still flow-limited.(ABSTRACT TRUNCATED AT 250 WORDS)
Grover
G J
GJ
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, NJ 08543-4000.
Parham
C S
CS
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004562:Electrocardiography; D005231:Fatty Acids, Unsaturated; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D013928:Thromboxane A2; C045749:SQ 29548