Vasodilator Response to Nifedipine in Human Coronary Arteries with Endothelial Dysfunction

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Abstract
The purpose of the current study was to evaluate nifedipine-induced epicardial and microvascular response in human coronary arteries with and without endothelial dysfunction and intimal thickening. The investigation was performed in 70 patients 5 ± 5 months after heart transplantation. Coronary vasomotor function was determined with intracoronary acetylcholine adenosine, and nifedipine, respectively. Intravascular ultrasound was used to detect significant intimal hyperplasia. In a subgroup (n = 38), coronary sinus and aortic endothelin concentrations were determined. Epicardial dilation to nifedipine was significantly enhanced in coronary arteries with endothelial dysfunction (p = 0.04), whereas adenosine-induced epicardial dilation was attenuated in segments with endothelial dysfunction (p = 0.002). In cases of intimal hyperplasia, nifedipine-mediated distal vasodilation was increased compared with normal segments (p = 0.03). Coronary flow index nifedipine was enhanced in patients with microvascular endothelial dysfunction (p = 0.037). A trend was observed between high endothelin plasma levels in the coronary sinus and an increased microvasodilation to nifedipine (p = 0.04). The study shows that epicardial and microvascular dilation to nifedipine is enhanced in the setting of coronary endothelial dysfunction, suggesting supersensitive dilator response. The association between microvascular response to nifedipine and endothelin levels in the coronary sinus needs further clarification.