ABSTRACT
Placement of an ameroid constrictor in large-conduit pig coronary arteries causes progressive stenosis and distal myocardial ischemia. Blood perfusion in the ischemic region is partly dependent on vasomotor responses to neural and humoral factors distal to the occlusion site. To ascertain the degree of impairment of vascular function in pigs, the authors induced myocardial ischemia by placing an ameroid constrictor in the left circumflex coronary artery and examined vascular reactivity and histopathology distal to the constriction site. The sensitivity of the distal left circumflex coronary and nonoccluded control left anterior descending arteries to PGF(2alpha) was similar. After nitric oxide blockade using Nw-nitro-l-arginine methylester (l-NAME), the sensitivity and maximal contraction to PGF(2alpha) were significantly increased in both the left circumflex coronary (EC50: 5.86 +/- 0.74 vs. 3.28 +/- 0.84 microM; C(max): 4.63 +/- 0.28 vs. 6.25 +/- 0.30 g, P < 0.01) and left anterior descending (EC50: 6.57 +/- 0.73 vs. 2.78 +/- 0.16 microM; C(max): 5.09 +/- 0.37 vs. 6.95 +/- 0.39 g, P < 0.01) arteries. Substance P-induced relaxation (100 pM) was blocked to a larger degree in the distal left circumflex coronary artery when compared with the left anterior descending artery (76.9 +/- 4.2% vs. 56.4 +/- 3.1%, P < 0.05). Endothelium-independent relaxation to sodium nitroprusside was similar in the left circumflex coronary and left anterior descending arteries before and after nitric oxide blockade. Histopathologic examination showed no major differences between distal left circumflex coronary artery segments and left anterior descending artery controls. However, scanning electron microscopy showed endothelial hypertrophy and activation in specimens from the left circumflex coronary arteries. In summary, as a result of the major hemodynamic changes induced by a chronic constriction and eventual occlusion of a large coronary artery, distal segments underwent adaptive compensatory changes. Such compensation may be related to an increased nitric oxide production by the hypertrophic endothelium in response to alterations in coronary hemodynamics.
Subject(s)
Coronary Disease/physiopathology , Coronary Vessels/physiology , Vasomotor System/physiology , Animals , Coronary Disease/diagnostic imaging , Coronary Disease/pathology , Coronary Vessels/drug effects , Coronary Vessels/pathology , NG-Nitroarginine Methyl Ester/pharmacology , Radiography , Substance P/pharmacology , Swine , Vasoconstriction/drug effects , Vasoconstriction/physiology , Vasomotor System/diagnostic imaging , Vasomotor System/drug effects , Vasomotor System/pathologyABSTRACT
Vascular brachytherapy has shown to be effective for in-stent restenosis, but efficacy in de novo lesions remains uncertain. We evaluated feasibility and outcome of intracoronary beta-radiation therapy in de novo coronary lesions using a (186)Re liquid-filled balloon system. Thirty-three patients received 20 Gy (186)Re beta-radiation immediately after balloon angioplasty. The 6-month restenosis rate was 41% (12/29) and restenosis was located within the target lesion in eight patients and at the edges of the injured and irradiated segment, outside the target lesion, in four patients. At 6 months, four patients (12%), all stented during the initial procedure, had experienced a late (> 30 days) total occlusion. Intracoronary beta-radiation therapy of de novo coronary lesions using (186)Re is technically feasible. No reduction in restenosis was observed. The high incidence of late total occlusions may have been prevented by avoiding new stent implantation and prolonging double antiplatelet therapy.
