The vasodilator effects of clevidipine on human internal mammary artery

Endothelial dysfunction and platelet activation with thromboxane release may contribute to spasm or alterations in internal mammary artery (IMA) graft flow during coronary artery surgery. Clevidipine, an ultrashort-acting dihydropyridine Calcium Channel blocker, is undergoing clinical development, but there are little data regarding its effects on human vasculature. We investigated the effects of clevidipine on human IMA obtained during surgery. After precontracting IMA segments with an analog of thromboxane (U46619, 10(-8) mol/L), acetylcholine and nitroglycerin were added cumulatively to examine endothelial function. Concentration-response curves to clevidipine were cumulatively obtained during submaximal contraction to the U46619 (10(-8) mol/L) in rings with and without endothelium. In the IMA samples with endothelium, acetylcholine did not completely reverse the U46619-mediated contraction, which implies impaired endothelial function (40% +/- 6% maximal response). Both clevidipine and nitroglycerin completely reversed U46619-induced contraction (clevidipine (50% effective concentration [EC50] = 3.88 +/- 0.84 x 10(-6) mol/L, nitroglycerin EC50 = 4.84 +/- 2.76 x 10(-8) mol/L). The responses to clevidipine were similar in preparations with or without intact endothelium. Clevidipine is an endothelium-independent arterial vasodilator that offers a potential therapeutic option in the treatment of perioperative arterial graft vasospasm and/or hypertension.

Implications: Clevidipine is a new ultrashort-acting dihydropyridine calcium antagonist. In human internal mammary arteries precontracted with a thromboxane A2 analog, clevidipine was an effective vasodilator on vessel segments in the presence and in the absence of endothelium.