Mechanisms of coronary spasm of isolated human epicardial coronary segments excised 3 to 5 hours after sudden death.
Isolated segments of epicardial coronary artery with and without severe atherosclerotic lesions excised from human hearts 3 to 5 hours after sudden coronary death demonstrated spontaneous contractile activity that was dependent on the external calcium level and was inhibited by calcium antagonists and activation of beta-adrenoceptors (isoproterenol and high concentrations of norepinephrine). Isoproterenol, with a median effective dose (ED50) of 6.3 X 10(-7) M, relaxed coronary segments that had been precontracted with 30 mM potassium. Stimulation of the alpha-adrenoceptors activated spontaneous contractions and increased tension. Norepinephrine ED50 (in the presence of 10(-6) M propranolol) was 2.3 X 10(-7) M, and tension at a maximal concentration of 10(-4) M was 385.4 +/- 51.4 mg. The ED50 for acetylcholine and histamine, the potent activators of coronary segment tone and phasic contractility, was 3.98 X 10(-7) and 8.9 X 10(-7) M, respectively; the maximal increase in tension was 1,079.5 +/- 175 (at 10(-4) M) and 1,131.3 +/- 302 mg (at 10(-5) M), respectively. Acetylcholine and histamine increased whereas high concentrations of norepinephrine failed to inhibit rhythmic activity and tension of coronary artery segments with severe atherosclerotic lesions. Membrane electrogenic mechanisms and ways of activating the contractile elements of human coronary artery smooth muscle are discussed.
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Vedernikov
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000787:Angina Pectoris / Q000503:physiopathology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003327:Coronary Disease / Q000503:physiopathology; D003329:Coronary Vasospasm / Q000209:etiology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D003645:Death, Sudden; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013997:Time Factors
D002121:Calcium Channel Blockers; D010643:Phenoxybenzamine; D006632:Histamine; D011433:Propranolol; D007545:Isoproterenol; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine