A rat cryothermia-induced myocardial infarction model was used to study microvascularization and ventricular function after local alginate-encapsulated angiogenic growth factor treatment in rat model by Huwer et al. (21). After exposing the hearts of Sprague-Dawley rats through a left lateral thoracotomy, cryothermia was induced to the LV wall using a 5-mm cryoprobe cooled to -120°C, and 0.2 mL of calcium-algineate beads were injected into the cryoinjured tissue. The beads contained 0.4 ^g bFGF, 0.1 ^g vascular endothelial growth factor (VEGF), or 4.2 ^g epidermal growth factor (EGF). Four weeks later the chest was reopened and the formation of microvessels within the myocardial lesion, hemody-namics, and LV function were evaluated. The results of the study indicated that although the functional capillary density did not improve, there was a significant increase in the number of microvessels larger than capillaries. The increased number of microvessels within the infarcted tissue only marginally improved the LV function. The same group earlier investigated angiogenesis and microvascularization after cryothermia-induced myocardial infarction using intravital fluorescence microscopic techniques in rat model (22). A standardized cryolesion was induced to the right ventricle by freezing for 5 min to -160°C. Myocardial angiogenesis and microvascularization were analyzed quantitatively on d 7 or 28. Seven days after cryothermia, the central area of the injured myocardium indicated a complete lack of capillary perfusion, while the periphery of the lesion revealed a heterogeneous capillary perfusion pattern with a density of 301 ± 39 cm1. Adjacent myocardial tissue showed intact capillary perfusion (density: 563 ± 44 cm1) comparable with that of sham-operated controls. After 28 d, the area lacking capillary perfusion was found to be significantly reduced, still surrounded by a hetero-geneously perfused area of myocardial tissue, indicating partial restitution of capillary perfusion. Although at d 7 capillary perfusion was completely shut down within the central zone of the cryolesions, perfusion of microvessels larger than capillaries was maintained, but with a markedly lower density when compared with that of sham controls. After 28 d, the number of these larger-sized microvessels increased significantly with values of density even higher compared with those observed in controls, indicating new vessel formation. The results of this work indicated 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.
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