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A comparative evaluation of the effects of multiple vasodilators on human internal mammary artery
1Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, USA.
Background:
Vasospasm of arterial grafts represents an unpredictable complication of coronary artery surgery and may compromise myocardial revascularization, and treatment is based on empirical therapy with nitroglycerin. Because of the potential for tolerance to nitroglycerin to occur, the authors studied different vasodilators acting through separate pathways on segments of human internal mammary artery.
Methods:
Isolated vascular rings were precontracted with norepinephrine (1 microM), KCl, or the thromboxane A2 analogue (U46619, 10 nm). Nitroglycerin (a nitrovasodilator), milrinone (a type III phosphodiesterase inhibitor), papaverine (a phosphodiesterase inhibitor), prostaglandin E1, and isradipine (a dihydropyridine calcium channel blocker) were added in a cumulative fashion.
Results:
The analysis of the concentration-response curves showed that vasodilators induced 90-100% relaxation of the constricted segments with norepinephrine or the thromboxane A2 analogue, except prostaglandin E1, which produced 73% relaxation at maximal concentrations. The effective concentrations of vasodilator agent that caused 50% relaxation for nitroglycerin and milrinone were within the range of the reported therapeutic concentrations in plasma. Isradipine was also effective at reversing receptor-mediated contraction (maximal relaxation=100% in internal mammary artery contracted with norepinephrine; maximal relaxation=0% in internal mammary artery contracted with the thromboxane A2 analogue).
Conclusions:
Vasodilator drugs acting through multiple pathways are effective at reversing in vitro vasoconstriction.
Insights
Different vasodilators effectively relax constricted human internal mammary artery segments in vitro. This study explored alternative treatments for arterial graft vasospasm, a complication in coronary artery surgery.
Area of Science:
- Vascular pharmacology
- Cardiovascular surgery
Background:
- Arterial graft vasospasm is a complication of coronary artery surgery.
- Current treatment relies on nitroglycerin, but tolerance can occur.
Purpose of the Study:
- To investigate the efficacy of various vasodilators acting via different pathways on human internal mammary artery segments.
- To identify potential alternatives to nitroglycerin for managing graft vasospasm.
Main Methods:
- Isolated human internal mammary artery vascular rings were precontracted.
- Vasoactive agents tested included nitroglycerin, milrinone, papaverine, prostaglandin E1, and isradipine.
- Concentration-response curves were analyzed to determine relaxation efficacy.
Main Results:
- Most vasodilators achieved 90-100% relaxation of precontracted arterial segments.
- Nitroglycerin and milrinone showed efficacy within therapeutic plasma concentration ranges.
- Isradipine effectively reversed receptor-mediated contraction, but not thromboxane A2-induced contraction.
Conclusions:
- Vasodilator drugs with diverse mechanisms of action are effective in reversing in vitro vasoconstriction.
- These findings support exploring multiple pathways for managing arterial graft vasospasm.