Transmyocardial laser revascularization dose response: enhanced perfusion in a porcine ischemia model as a function of channel density.

BACKGROUND

Transmyocardial laser revascularization (TMR) appears to provide symptomatic relief to patients with ischemic heart disease, but evidence that TMR enhances perfusion to ischemic myocardium remains limited. Furthermore, it is uncertain whether there exists a TMR dose-response relationship that is a function of channel number. We therefore compared restoration of blood flow as analyzed by rest and stress 99mTc-sestamibi scans and histologic grading of neovascularization after 50-channel, 25-channel, or 10-channel TMR using the excimer laser in an established model of porcine myocardial ischemia.

METHODS

Yorkshire swine underwent a thoracotomy and placement of an ameroid constrictor around the proximal circumflex coronary artery. Three weeks later, the animals underwent resting and adenosine stress 99mTc-sestamibi scans for evaluation of ischemia immediately before repeat thoracotomy and TMR with either 50 channels (n = 4), 25 channels (n = 4), or 10 channels (n = 4) in the circumflex territory. The animals underwent repeat perfusion analyses 4 weeks later, after which the animals were sacrificed and the hearts were perfusion fixed for histologic evaluation of neovascularization.

RESULTS

All animals survived to sacrifice. Semiquantitative analyses of the sestamibi perfusion scans 4 weeks after lasing demonstrated significant improvement (p < 0.04) in stress-induced ischemia in the 50-channel TMR animals, but not in the 25- or 10-channel TMR groups, as compared with scans obtained immediately before lasing. A computerized image analysis of perfusion scans similarly demonstrated an improvement in the area of ischemia of 42% +/- 22% in the scans obtained 4 weeks after lasing compared with scans obtained immediately before lasing in the 50-channel group (p < 0.004), but only a 12% +/- 9% improvement in the 25-channel group and an 8% +/- 4% improvement in the 10-channel group (p > 0.05). Histologic assessment of neovascularization demonstrated significantly greater number of microvessels per low-power field in the 50- versus the 25- and 10-channel groups (p < 0.001).

CONCLUSIONS

In an animal model of myocardial ischemia, TMR appears to enhance myocardial perfusion. A dose-response relationship related to channel number may be of significance when evaluating the efficacy of various treatment strategies.