ABSTRACT
PURPOSE: Endovascular irradiation inhibits neointimal hyperplasia in ballooned and stented arteries but impacts both diseased and adjacent normal tissue. Little is known about the effects of irradiation on downstream vasculature. In this study, we investigated vascular function and structure of pig coronary arteries distal to sites of endoluminal irradiation. MATERIALS AND METHODS: Vasomotor responses of distal arteries to contraction of KCl and PGF2alpha and endothelium-dependent (substance P and A23187) and -independent (sodium nitroprusside) relaxation were studied in naïve, sham-treated, irradiated, stented, and stented plus irradiated vessels. Light and scanning electron microscopy were used to assess vascular morphology. RESULTS: Relaxations to substance P and A23187 at 1 month post treatment were significantly decreased in the irradiated group, whereas contractile response to PGF2alpha was significantly increased. Hemorrhage, mural thrombus, and inflammation were present at the upstream-irradiated site; inflammatory cells were also present adherent to the endothelium in the distal segments. CONCLUSIONS: Distal vasomotor function reflects an influence from the nature of a proximal intervention. The effect of irradiation on downstream conduit arteries to increase the threshold of contractility and suppress endothelium-dependent relaxation may be related to the presence of inflammatory cells at both the upstream-instrumented site as well as the distal location.
Subject(s)
Coronary Vessels/pathology , Coronary Vessels/radiation effects , Endothelium, Vascular/radiation effects , Stents , Analysis of Variance , Animals , Cardiac Catheterization/methods , Coronary Vessels/ultrastructure , Disease Models, Animal , Endothelium, Vascular/pathology , Female , Immunohistochemistry , Male , Microscopy, Electron, Scanning , Organ Culture Techniques , Probability , Sensitivity and Specificity , Swine , Vasoconstriction/radiation effects , Vasodilation/radiation effectsABSTRACT
PURPOSE: To assess the effects of endovascular irradiation on vascular structure and function in pig coronary arteries in the absence of vascular injury. METHODS AND MATERIALS: Vasomotor responses to contractions of KCl and prostaglandin F2alpha (PGF2alpha), relaxations to endothelium-dependent (substance P, A23187) and -independent (sodium nitroprusside, SNP) agents; endothelial morphology and superoxide anion (02*-) production were investigated in control (naive), sham and irradiated (20 Gy, 32P) arteries 1 month after irradiation. RESULTS: Contractions to KCl and PGF2alpha in the presence of L-NAME were significantly decreased, relaxations to substance P and A23187 were abolished and SNP-induced relaxation was potentiated in irradiated arteries compared to naive and sham-treated vessels. Scanning electron microscopy (SEM) revealed enlarged endothelial cells (ECs) exhibiting surface microvilli. O2*- production was significantly increased in irradiated vessels (437.0 +/- 37.3 vs. 126.0 +/- 11.6 RLU/s/mg tissue, P < .01). CONCLUSIONS: One month after brachytherapy, normal pig coronary arteries showed abnormal vascular reactivity, altered endothelial morphology and increased production of O2*-. Lack of relaxation to substance P and A23187 reflects ionizing radiation-mediated damage to ECs, whereas potentiation of relaxation to SNP suggests additional deleterious effects on medial smooth muscle cells (SMCs). Increased O2*- production might have contributed to endothelial dysfunction by scavenging nitric oxide (NO).
