Impaired arteriolar vasodilation induced by thrombosis of a coronary arterial stenosis.
This study tested the hypothesis that aggregation of platelets and release of thromboxane A2 at the site of a coronary arterial stenosis may contribute to myocardial ischemia by impairing flow regulation of the distal coronary bed. Measurements of hemodynamics, flow (microspheres), lactate metabolism, and prostaglandin (PG) metabolites (thromboxane B2 and 6-keto-PGF1 alpha) were made in closed-chest anesthetized pigs instrumented with a stenosis (65% diam reduction) in the left anterior descending (LAD) coronary artery. Data were acquired prior to stenosis insertion (control) and 5 and 15 min after insertion, during which time thrombotic occlusion of the device was occurring. Heart rate was controlled by atrial pacing. Distal LAD zone endocardial flow (ml X min-1 X g-1) declined versus control (1.15 +/- 0.20, mean +/- SD) at 5 min (0.89 +/- 0.40, P less than 0.05) and 15 min (0.41 +/- 0.36, P less than 0.01) of occlusion. Distal endocardial resistance (mmHg X ml-1 X min X g), however, did not change versus control (72 +/- 12) at 5 (66 +/- 12) or 15 min (61 +/- 38). Distal epicardial resistance (mmHg X ml-1 X min X g) declined versus control (90 +/- 17) at 5 (66 +/- 35, P less than 0.05) and 15 min (43 +/- 26, P less than 0.01) postinsertion. Finally, lactate extraction (%) at control (42 +/- 19) changed to production 15 min postinsertion (-36 +/- 93, P less than 0.05) and arterial-anterior interventricular vein thromboxane B2 difference (pg/0.1 ml) changed from 13.1 +/- 17.8 pre to -15.8 +/- 30.0 at 5 min post (P less than 0.05). Thus platelet aggregation and release at a spontaneously thrombosing stenosis contribute to ischemia not only by reduction of stenosis diameter but also by impairment of flow regulation in endocardial layers distal to it.
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000503:physiopathology*; D001241:Aspirin / Q000494:pharmacology; D003326:Coronary Circulation; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012039:Regional Blood Flow; D013552:Swine; D013927:Thrombosis / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000096:biosynthesis; D014655:Vascular Resistance; D014664:Vasodilation
D007093:Imidazoles; D007773:Lactates; D011450:Prostaglandin Endoperoxides, Synthetic; C039242:dazmegrel; D019344:Lactic Acid; D013928:Thromboxane A2; D001241:Aspirin