A COMPARATIVE-EVALUATION OF THE EFFECTS OF MULTIPLE VASODILATORS ON HUMAN INTERNAL MAMMARY ARTERY

Background: Vasospasm of arterial grafts represents an unpredictable c omplication of coronary artery surgery and may compromise myocardial r evascularization, and treatment is based on empirical therapy with nit roglycerin. Because of the potential for tolerance to nitroglycerin to occur, the authors studied different vasodilators acting through sepa rate pathways on segments of human internal mammary artery. Methods: I solated vascular rings mere precontracted with norepinephrine (1 mu M) , KCl, or the thromboxane A(2) analogue (U46619, 10 nM). Nitroglycerin (a nitrovasodilator), milrinone (a type III phosphodiesterase inhibit or), papaverine (a phosphodiesterase inhibitor), prostaglandin E-1, an d isradipine (a dihydropyridine calcium channel blocker) were added in a cumulative fashion. Results: The analysis of the concentration-resp onse curves showed that vasodilators induced 90-100% relaxation of the constricted segments with norepinephrine or the thromboxane A(2) anal ogue, except prostaglandin E-1, which produced 73% relaxation at maxim al concentrations. The effective concentrations of vasodilator agent t hat caused 50% relaxation for nitroglycerin and milrinone were within the range of the reported therapeutic concentrations in plasma. Isradi pine was also effective at reversing receptor-mediated contraction (ma ximal relaxation = 100% in internal mammary artery contracted with nor epinephrine; maximal relaxation = 90% in internal mammary artery contr acted with the thromboxane Al analogue). Conclusions: Vasodilator drug s acting through multiple pathways are effective at reversing in vitro vasoconstriction.