The combined use of transmyocardial laser revascularization (TMLR) and fibroblastic growth factor (FGF-2) enhances perfusion and regional contractility in chronically ischemic porcine hearts.

Abstract

The purpose of this study was to determine the combined effect of transmyocardial laser revascularization (TMLR) and recombinant human basic fibroblastic growth factor (rhFGF-2) treatment in chronically ischemic hearts. To employ this porcine ischemic model, an operative severe stenosis of the left anterior descending artery (LAD) was created (first operation). One week later, the animals were studied at baseline (second operation) by analyzing perfusion (microsphere technique) and regional contractility (ultrasonic crystals). Afterwards, pigs were randomized into one of the four groups: ischemic control group (n = 7), TMLR-group (n = 7), FGF-2-group receiving 500 microg rhFGF-2 (n = 6), and FGF-2 + TMLR-group receiving TMLR with 500 microg rhFGF-2 (n = 6). Twelve weeks later, the animals were re-examined (third operation) and the hearts underwent additionally histochemical and immunohistologic analysis. Three months after therapy, regional myocardial blood flow (RMBF) in the LAD territory was significantly higher at rest in the FGF-2 group and FGF-2 + TMLR group compared to baseline, control and TMLR group (FGF-2 group: 1.17 +/- 0.10 versus baseline 0.28 +/- 0.10, P = 0.028; versus control 0.49 +/- 0.12, P = 0.01; and versus TMLR 0.34 +/- 0.20, P = 0.0081; FGF-2 + TMLR group: 0.88 +/- 0.29 versus baseline 0.41 +/- 0.14, P = 0.028; versus control 0.49 +/- 0.12, P = 0.019 and versus TMLR group 0.34 +/- 0.20 ml/g per min, P = 0.0032). Furthermore, the FGF-2 + TMLR-group demonstrated higher RMBF values in the LAD territory under stress conditions compared to baseline (1.79 +/- 0.69 versus 0.41 +/- 0.14; P = 0.028) and control (1.79 +/- 0.69 versus 0.78 +/- 0.55 ml/g per min; P = 0.038) at the end of the study. In contrast to these groups, RMBF in the control and TMLR group was unchanged. After 3 months, the FGF-2- and FGF-2 + TMLR-groups' regional contractility in the LAD territory revealed an improvement at rest (FGF-2: 84.00 +/- 26.22 versus baseline: 53.76 +/- 13.49, P = 0.003; FGF-2 + TMLR: 104.46 +/- 28.62 versus control: 61.27 +/- 5.13; P = 0.005 and versus TMLR: 59.74 +/- 41.23%; P = 0.041), whereas control and TMLR animals did not show any difference. TMLR as well as FGF-2 + TMLR treatment resulted in an increased number of capillaries and of arterioles in the channel area compared to untreated ischemia (P < 0.005). In contrast to the TMLR- and control group, CO(2)-laser revascularization combined with the application of intramyocardial growth factor, FGF-2, significantly ameliorates perfusion at rest and stress in this model of chronic regional ischemia, whereas sole FGF-2 application showed an improvement at rest only. This was mirrored by an enhancement of regional contractility in the FGF-2 + TMLR- and FGF-2-group at rest.