Nitric oxide system in needle-induced transmyocardial revascularization

Nitric oxide (NO) promotes endothelial proliferation and migration, essential for angiogenesis. The purpose of this study was to determine the cellular expression of inducible and endothelial nitric oxide synthases (iNOS and eNOS) in an ischemic cardiomyopathy animal model of needle-induced transmyocardial revascularization (TMR).

Myocardial infarction was created in rats by ligating the left coronary artery, and animals were divided into two groups: no-TMR group (served as control) and TMR group (underwent concomitant TMR by the creation of six transmural channels with a 25-gauge needle in the ischemic area). Rats were sacrificed at intervals of 1, 2, 4, and 8 weeks. Immunohistochemistry using specific antisera was performed for iNOS, eNOS, and endothelial cell marker factor VIII. Vascular density and positive staining area with either iNOS or eNOS were assessed in the infarcted myocardium.

Vascular density in the infarcted myocardium was significantly increased in the TMR group (p < 0.001). The positive staining area for iNOS and the intensity of iNOS immunoreactivity in cardiomyocytes, vascular endothelium, and macrophages were significantly greater in the TMR group (p < 0.05). However, these differences were seen only in the first 2 weeks after TMR. There was no significant difference in the expression of eNOS between groups.

A mechanical injury using needle puncture in an ischemic myocardium increased vascular density and is associated with increased expression of myocardial iNOS. Increased production of NO derived from iNOS may contribute to the angiogenic response of TMR.