Transgenic and transmural revascularization: regional myocardial tissue pressure during chronic ischemia*1

Abstract

Channel patency and a cavito-myocardial pressure gradient are prerequisites for one potential mechanism of transmyocardial laser revascularization (TMLR), namely indirect (non-coronary) myocardial perfusion. We assessed the effect of TMLR combined with vascular endothelial growth factor (VEGF) on the myocardial tissue pressure (MTP) in chronic ischemia questioning firstly, whether transmural pressure allows perfusion of laser channels, and secondly, whether additional application of VEGF improves channel patency. One week after creation of an operative left anterior descending artery stenosis (2nd operation), pigs were designated to untreated ischemia (n=7), TMLR (n=8) or TMLR+VEGF-cDNA (2 mg intramyocardially, n=6). MTP and left ventricular pressure (LVP) were recorded simultaneously in the endo-, mid-, and epimyocardium before and after stenosis (1st operation), before and after therapy (2nd operation), and 12 weeks later (3rd operation). Myocardial samples were subjected to immunohistochemistry. Endo- and epimyocardial MTP exceeded LVP in all groups throughout the study, whereas midmyocardial MTP was constantly below LVP (P<0.05). Immediately after combined TMLR+VEGF, the endo-MTP decreased from 246.5+/-44.2 to 176.7+/-20.7 mmHg (P=0.043), remaining higher than LVP. After 12 weeks, it increased to 225.6+/-31.8 mmHg (P=0.04), but did not reach baseline values (P=0.04). Histological examination revealed occluded channels with surrounding vascular proliferation in both treatment groups. Additional VEGF-cDNA application in the vicinity of TMLR channels does not improve long-term patency. Direct blood flow from the cavity into the myocardium is impossible due to the high endomyocardial pressure. This limitation might be overcome by implantation of endomyocardial stents.