Unmasking of thrombin vasoconstriction in isolated perfused dog hearts after intracoronary infusion of air embolus.
Effects of intracoronary thrombin and acetylcholine administration on coronary vascular reactivity were studied in isolated perfused (Langendorff) dog hearts before and after air embolus treatment. Under constant flow condition with control coronary perfusion pressure of 71.4 +/- 5.4 mm Hg (mean +/- S.E.M. of eight hearts), infusion of thrombin (0.1 U/ml) resulted in an immediate decrease (-32.8 +/- 2.7 mm Hg) in coronary perfusion pressure, reaching a maximum in approximately 20 to 25 sec. Similar vasodilatory response (-30.5 +/- 1.9 mm Hg, M +/- S.E.M. of six hearts) also was observed with administration of 0.1 microM acetylcholine. Introduction of 0.3 ml air embolus into the coronary circulation before thrombin or acetylcholine testings, however, showed a 100 and 63% decrease in their respective coronary vasodilatory responses. More importantly, infusion of thrombin into these previously air embolus-treated hearts actually resulted in a potent vasoconstriction by increasing the coronary perfusion pressure (+48.2 +/- 5.7 mm Hg, mean +/- S.E.M. of six hearts) above the control level. The coronary vasoconstrictory effect of thrombin was reversible upon cessation of thrombin infusion or with concurrent administration of sodium nitroprusside (1 microM). Similarly, synthetic thrombin inhibitor phenylalanyl-prolyl-arginine chloromethyl ketone (0.1 microM) also was capable of both inhibiting and reversing thrombin-induced vasoconstriction. The present finding of a potent thrombin-induced coronary vasoconstriction in intact hearts after air embolus infusion further supports the hypothesis that an activation of thrombin in certain pathological states with injured endothelium may have an important role in the genesis of coronary vasospasm.
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Department of Pharmacology, University of Alabama at Birmingham.
D000109:Acetylcholine / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004618:Embolism, Air / Q000503:physiopathology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D013917:Thrombin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D000590:Amino Acid Chloromethyl Ketones; D009599:Nitroprusside; D013917:Thrombin; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone; D000109:Acetylcholine