ONE-MONTH HISTOLOGIC RESPONSE OF TRANSMYOCARDIAL LASER CHANNELS WITH MOLECULAR INTERVENTION

Background. Transmyocardial revascularization reduces the symptoms and morbidity of patients with endstage ischemic heart disease. The mecha nism is postulated to be the formation of transmural left ventricular channels through which oxygenated blood directly perfuses the myocardi um. New techniques for molecular enhancement of angiogenesis and endot helial cell motility may represent strategies to augment this clinical benefit. Methods. Triads of transmyocardial revascularization channel s were placed in eight separate nonischemic sites on the hearts of 7 p igs weighing 68 to 78 kg, which were allowed to recover and were then sacrificed at 28 days. In addition, one triad pair was injected with v ascular endothelial growth factor, and two triad pairs received an ade novirus vector with or without the gene encoding for human profilin, w hich increases endothelial cell motility and adhesion. The remaining t riad pair stood untreated (laser only). The histologic changes were gr aded (0 through 3) by an independent pathologist without knowledge of the treatment modality. Profilin production and vascular endothelial g rowth factor activation using a tyrosine kinase assay were monitored. Results. Transmyocardial revascularization alone resulted in a signifi cant injury response (p < 0.01), including increased vascularity witho ut patent channels. Vascular endothelial growth factor increased surro unding inflammation (p < 0.01) without improving vascularity or patenc y. Profilin content in tissues was increased but nonspecifically becau se inflammation resulting from adenovirus also induces higher profilin concentrations. Conclusions. The clinical benefit of transmyocardial revascularization may result simply from a nonspecific histologic resp onse to injury. Molecular interventions appear to stimulate more infla mmation but no additional angiogenesis. Further improvement in the cli nical benefit of transmyocardial revascularization awaits the successf ul stimulation of a true angiogenic response.