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Notes: Abstract  Background: Controversy exists whether transmyocardial laser revascularization (TMR) is associated with angiogenesis or neuromodulation and whether these are time-dependent phenomena. Accordingly, we performed a time-course analysis of the expression of angiogenic and neuronal factors following experimental percutaneous TMR. Methods and Results: Five weeks after placing ameroid constrictors on the circumflex coronary artery, 16 pigs underwent left ventricular mapping guided TMR using Ho:YAG laser (2 J × 1 pulse) at 30 sites directed at the ischemic zones and 11 animals were ischemic controls. Histology and immunostaining were obtained at 1 and 2 weeks (4 TMR and 3 controls at each time point) and at 4 weeks (8 TMR and 5 controls) for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), nerve growth factor (βNGF), substance P (SP), and monocyte chemoattractant protein-1 (MCP-1). Immunoreactivity was scored using a digital image analysis system. Factor VIII staining was used for blood vessel counting. Enhanced regional expression of VEGF, bFGF and MCP-1 in the TMR group was noted at 1 and 2 weeks with a threefold increase at 4 weeks following TMR compared to controls. βNGF expression in the TMR group was enhanced at 1 and 2 weeks with subsequent decline at 4 weeks to the controls level. SP expression was not significantly different between groups at all time points. There was a twofold increase in the number of blood vessels in the TMR group at 4 weeks, which was not apparent earlier. Conclusions: These immunohistological findings suggest that cytokines expression compatible with angiogenesis and neuromodulation occurs early after TMR. Up-regulation of angiogenic and inflammatory cytokines may be more sustained than neuromodulation.

Notes: Background: Intracoronary radiation (IR) can prevent neointima formation (NF) by reducing smooth muscle cell (SMC) proliferation after balloon angioplasty, but is complicated by subacute and late thrombosis. Rupture or abnormalities of the internal elastic lamina (IEL) structure and subsequent exposure of blood to the injured arterial wall can induce thrombosis and inflammation. The purpose of this study was to evaluate the effect of IR on the media and IEL after balloon overstretch injury in porcine coronary arteries. Methods: Seventeen juvenile swine (25 coronary arteries) were injured by overstretch balloon and subsequently given IR at doses of 0 or 18 Gy 90Y prescribed to 1.2 mm from vessel wall inner surface. Two weeks following treatment, tissue sections were perfusion fixed and stained by hematoxylin-eosin or by Verhoeff-von Giesson. Smooth muscle cell α-actin was detected immunocytochemically and quantified by digital image analysis using arbitrary density units. Histomorphometry was carried out to assess intimal area (IA) and IA corrected for medial fracture length (IA/FL). The roughness index (RI) of the IEL was calculated from the surface profile length and the straight-line length. Results: NF was markedly smaller after IR as compared to control treatment. Mural thrombi were increased significantly in irradiated versus control arteries (11/14 [78%] vs 1/11 [9%]; P 〈 0.001). A significant decrease in SMC density was observed in the irradiated group (128 ± 13 vs 74 ± 10; P 〈 0.001) despite a lack of difference in medial area. The surface of the IEL was more irregular in irradiated arteries, particularly at the medial breaks (RI =20.1 ± 3.1 vs 8.7 ± 1.2; P 〈 0.001). When mural thrombi were present, thrombus area correlated with RI (α= 0.76; P 〈 0.01). Furthermore, in the irradiated group RI correlated positively with SMC density (α=0.64; P 〈 0.01). Conclusion: Medial structure and RI may be useful parameters by which to assess arterial healing following IR. These findings may influence the design of future IR studies aimed at reducing thrombosis and enhancing arterial healing.

Notes: Objective: The purpose of this study was to assess the effect of 186/188rhenium (186/188Re) on the neointimal proliferation and on the vasomotion of irradiated porcine coronary arteries following balloon injury. Background: Intracoronary radiation (IR) at doses of 10–25 Gy reduces intimal hyperplasia in animal models and lowers restenosis in clinical trials. The response of coronary arteries to acetylcholine (ACh) has been used to examine endothelial function, but this has not been reported in porcine coronary arteries subjected to overstretch balloon injury (BI) and subsequent IR. Methods: Vasomotor response was studied at baseline and at 2 weeks in 20 swine. Baseline vasomotor study without BI was carried out in six animals (12 arteries; Group I, no injury, no radiation). Subsequently the left anterior descending (LAD) and the left circumflex (LCX) arteries of 11 animals were subjected to BI. Eight of these animals (15 arteries) were subjected to IR with 186/188Re in the LAD and LCX arteries in doses of 15 Gy followed by vasomotor studies at 2 weeks (Group II, BI, radiation). Three animals, (six arteries) of the BI group were not subjected to IR and their vasomotor functions assessed two weeks later (Group HI, BI, no radiation). Endothelium dependent vasomotion was assessed by Doppler flow wire and by quantitative coronary angiography (QCA) following selective infusion of serial doses of ACh proximal to the injured and irradiated segments. Nitroglycerin (200 μg) was injected intracoronary to detect endothelium independent vasodilatation. Histomorphometry and QCA analysis was performed to confirm the effect of IR on intimal area (IA), and IA corrected for fracture length (IA/FL). Results: Responses to ACh infusion and coronary flow reserve were similar at baseline before injury and at 2 weeks following injury with and without radiation. The irradiated vessels demonstrated normal vasodilatation responses to nitroglycerin. The irradiated vessels showed a marked reduction in IA and IA/FL. Conclusion: The vasoreactivity of irradiated coronary arteries is preserved at doses that inhibit neointima formation in the porcine model.