Nitric oxide system in needle-induced transmyocardial revascularization

Background. Nitric oxide (NO) promotes endothelial proliferation and migrat ion, essential for angiogenesis. The purpose of this study was to determine the cellular expression of inducible and endothelial nitric oxide synthase s (iNOS and eNOS) in an ischemic cardiomyopathy animal model of needle-indu ced transmyocardial revascularization (TMR). Methods. Myocardial infarction was created in rats by ligating the left cor onary artery, and animals were divided into two groups: no-TMR group (serve d as control) and TMR group (underwent concomitant TMR by the creation of s ix transmural channels with a 25-gauge needle in the ischemic area). Rats w ere sacrificed at intervals of 1, 2, 4, and 8 weeks. Immunohistochemistry u sing specific antisera was performed for iNOS, eNOS, and endothelial cell m arker factor VIII. Vascular density and positive staining area with either iNOS or eNOS were assessed in the infarcted myocardium. Results. Vascular density in the infarcted myocardium was significantly inc reased in the TMR group (p < 0.001). The positive staining area for iNOS an d the intensity of iNOS immunoreactivity in cardiomyocytes, vascular endoth elium, and macrophages were significantly greater in the TMR group (p < 0.0 5). However, these differences were seen only in the first 2 weeks after TM R. There was no significant difference in the expression of eNOS between gr oups. Conclusions. A mechanical injury using needle puncture in an ischemic myoca rdium increased vascular density and is associated with increased expressio n of myocardial iNOS. Increased production of NO derived from iNOS may cont ribute to the angiogenic response of TMR. (C) 2001 by The Society of Thorac ic Surgeons.