Angiogenesis and microvascularization after cryothermia-induced myocardial infarction: a quantitative fluorescence microscopic study in rats.

OBJECTIVE

Microvascularization of infarcted myocardial tissue may be a prerequisite for successful therapeutic interventions, including cardiomyoblast or satellite cell transplantation. Because little is known on microvascular restitution within infarcted tissue, we studied angiogenesis and microvascularization after cryothermia-induced myocardial infarction using intravital fluorescence microscopic techniques.

METHODS

In anesthetized, orally intubated and ventilated Sprague-Dawley rats (n = 20), a sternotomy was performed and a standardized cryolesion was induced to the right ventricle by freezing for 5 min to -160 degrees C. Myocardial angiogenesis and microvascularization were analyzed quantitatively after rethoracotomy on days 7 (n = 6) or 28 (n = 8). Sham-operated animals (n = 6) served as controls.

RESULTS

Seven days after cryothermia, the central tissue area of the injured myocardium (28.4 +/- 9.2 mm2) was characterized by complete lack of capillary perfusion, while the periphery of the cryolesion (27.6 +/- 5.7 mm2) revealed a heterogeneous capillary perfusion pattern with a density of 300.9 +/- 38.9 cm-1. Adjacent myocardial tissue showed intact capillary perfusion (density: 563.0 +/- 44.4 cm-1) comparable with that of sham-operated controls. After 28 d the area with lack of capillary perfusion was found significantly reduced to 7.3 +/- 3.7 mm2 (P < 0.05); however, it was still surrounded by a heterogeneously perfused area of myocardial tissue of 57.7 +/- 19.2 mm2 (density: 271.1 +/- 52.7 cm-1), indicating partial restitution of capillary perfusion. Although at day 7 within the central zone of the cryolesions, capillary perfusion was completely shut down, perfusion of microvessels larger than capillaries, i.e., arterioles and venules, were found maintained, however, with a density markedly lower (1.96 +/- 1.04 mm-1) when compared with that of sham-controls (4.28 +/- 1.52 mm-1). After 28 d the number of these larger-sized microvessels increased significantly with values of density even higher compared with those observed in controls (6.89 +/- 1.71 mm-1; P < 0.05), indicating new vessel formation.

CONCLUSIONS

Our study indicates partial restitution and function of the microvascular network within infarcted myocardial tissue, which may serve as an appropriate prerequisite for successful application of novel therapeutic strategies to improve myocardial function.