Background. Transmyocardial revascularization reduces the symptoms and morbidity of patients with endstage ischemic heart disease. The mechanism is postulated to be the formation of transmural left ventricular channels through which oxygenated blood directly perfuses the myocardium. New techniques for molecular enhancement of angiogenesis and endothelial cell motility may represent strategies to augment this clinical benefit. Methods. Triads of transmyocardial revascularization channels were placed in eight separate nonischemic sites on the hearts of 7 pigs 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 vascular endothelial growth factor, and two triad pairs received an adenovirus vector with or without the gene encoding for human profilin, which increases endothelial cell motility and adhesion. The remaining triad pair stood untreated (laser only). The histologic changes were graded (0 through 3) by an independent pathologist without knowledge of the treatment modality. Profilin production and vascular endothelial growth factor activation using a tyrosine kinase assay were monitored. Results. Transmyocardial revascularization alone resulted in a significant injury response (p < 0.01), including increased vascularity without patent channels. Vascular endothelial growth factor increased surrounding inflammation (p < 0.01) without improving vascularity or patency. Profilin content in tissues was increased but nonspecifically because inflammation resulting from adenovirus also induces higher profilin concentrations. Conclusions. The clinical benefit of transmyocardial revascularization may result simply from a nonspecific histologic response to injury. Molecular interventions appear to stimulate more inflammation but no additional angiogenesis. Further improvement in the clinical benefit of transmyocardial revascularization awaits the successful stimulation of a true angiogenic response.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine