Studies with Isolated Human Coronary Arteries: Some General Observations, Potential Mediators of Spasm, Role of Calcium Antagonists

Abstract

We studied the basic mechanisms involved in human coronary artery smooth-muscle contraction in an attempt to gain insight into the pathophysiology and pathopharmacology of coronary spasm. Coronary arteries were obtained from recipient hearts of patients receiving cardiac transplantation at Stanford University. Coronary ring segments were studied in an organ bath using standard Tyrode's solution. Observation included characterizations of spontaneous contractile activity, factors affecting basal tone, type of agonist-induced contractile response, receptor distribution, activity of cardioactive drugs, and species differences. Agents mediating contraction included histamine, acetylcholine, norepinephrine, potassium, and prostaglandins. Because of recent clinical interest in calcium antagonists, diltiazem was studied extensively. Diltiazem demonstrated noncompetitive antagonism to the effects of several agonists and competitive antagonism to calcium. The exact cause and mechanism of coronary spasm is still unknown, but we have identified new areas for future investigation. We studied the basic mechanisms involved in human coronary artery smooth-muscle contraction in an attempt to gain insight into the pathophysiology and pathopharmacology of coronary spasm. Coronary arteries were obtained from recipient hearts of patients receiving cardiac transplantation at Stanford University. Coronary ring segments were studied in an organ bath using standard Tyrode's solution. Observation included characterizations of spontaneous contractile activity, factors affecting basal tone, type of agonist-induced contractile response, receptor distribution, activity of cardioactive drugs, and species differences. Agents mediating contraction included histamine, acetylcholine, norepinephrine, potassium, and prostaglandins. Because of recent clinical interest in calcium antagonists, diltiazem was studied extensively. Diltiazem demonstrated noncompetitive antagonism to the effects of several agonists and competitive antagonism to calcium. The exact cause and mechanism of coronary spasm is still unknown, but we have identified new areas for future investigation.