Optimal Concentration of Papaverine for the Inhibition of Internal Thoracic Artery Vasospasm during Coronary Artery Bypass Graft Surgery.

Abstract

Introduction: The internal thoracic artery is commonly used as a graft in coronary artery bypass grafting. In this study, we aimed to investigate whether papaverine prevents vasoconstriction caused by various vasospasm inducers, including 5-hydroxytriptamine or serotonin, in endothelium-denuded internal thoracic artery at concentrations as low as 1.25 mM used for radial arteries.

Methods: Human internal thoracic artery tissue was obtained from patients (n=6) undergoing coronary artery bypass grafting. The organ bath technique was used to determine the inhibitory effects of papaverine on vasoconstriction induced by ergonovine, adenosine diphosphate, 5-hydroxytriptamine, noradrenaline, and angiotensin II in isolated endothelium-denuded internal thoracic artery. Moreover, the inhibitory effect of papaverine on collagen-stimulated human platelet aggregation was examined at the same concentration.

Results: Papaverine inhibited ergonovine-induced vasoconstriction in a concentration-dependent manner. Papaverine at concentrations > 30 μM not only blocked ergonovine-induced vasoconstriction but also induced vasodilation. Papaverine at 30 μM significantly suppressed the vasoconstriction induced by 5-hydroxytriptamine or noradrenaline and completely blocked that induced by adenosine diphosphate or angiotensin II. However, 100 μM papaverine completely blocked the vasoconstriction induced by adenosine diphosphate, 5-hydroxytriptamine, noradrenaline, and angiotensin II. Additionally, papaverine significantly inhibited collagen-stimulated human platelet aggregation in a concentration-dependent manner.

Conclusion: Overall, 100 μM papaverine prevented vasoconstriction by various vasospasm inducers, such as 5-hydroxytriptamine, and significantly suppressed collagen-stimulated platelet aggregation. These results suggest that papaverine at 100 μM, which is 1/10th the concentration used for radial artery, is sufficient to prevent vasospasm in internal thoracic artery during coronary artery bypass grafting.