Objective-To assess the importance of genetic background for collateral artery development. Methods and Results-C57BL/6, BALB/c and 129S2/Sv mice were studied after femoral artery ligation by laser Doppler imaging, visible light oximetry, time-of-flight-magnetic resonance imaging, and treadmill testing; C57BL/6 and BALB/c also underwent electron paramagnetic resonance (EPR) oximetry, x-ray angiography, and histology. C57BL/6 had the least initial distal ischemia and most complete recovery. BALB/c had the most severe initial ischemia and poorest recovery. BALB/c had some vasodilatory reserve in their ligated limbs not seen in the other strains at 3 weeks. By in vivo TOF-magnetic resonance angiography, C57BL/6 had larger preexistent and developed collaterals. By x-ray angiography, C57BL/6 had a higher collateral-dependent filling score and number of visible collaterals immediately after femoral ligation and a higher number of visible collaterals at 1 week but not at 4 weeks. EPR oximetry and histology revealed hypoxia and tissue damage in regions of collateral growth of BALB/c but not C57BL/6 mice. In C57BL/6 BrdUrd uptake in the thigh was limited to larger vessels and isolated perivascular cells. Proliferative activity in collateral arterioles was similar in both strains. Conclusions-Genetic differences in preexistent collateral vasculature can profoundly affect outcome and milieu for compensatory collateral artery growth after femoral artery occlusion. Key Words: angiogenesis Ⅲ collateral circulation Ⅲ hypoxia Ⅲ mouse strains Ⅲ vascular biology P re-existent interarterial anastomoses have been identified in the coronary, cerebral, and peripheral circulation of various species. 1 The number and size of these anastomoses varies between species and tissues, resulting in different degrees of protection after arterial occlusion. 1 Pre-existing collateral arterial connections have been found in human hearts without evidence for coronary artery disease. 1-3 Remodeling of preexistent arterioles into mature collateral arteries has been observed in dog hearts, 4 hindlimbs of rabbits, 5-7 rats, 8 and mice, 9 and this process has been suggested to be the dominant mechanism responsible for the restoration of blood flow after arterial occlusion. 10 -12 Previously, we identified differences in perfusion recovery by laser Doppler imaging (LDI) after femoral artery occlusion in inbred strains of mice and attributed these to marginal differences in growth rates of collateral arterioles. 9 However, this study was limited by the fact that LDI and visible light oxygen spectrometry were the only comparative methods of in vivo assessment and histology was confined to isolated gracilis muscle collaterals with minimal surrounding tissue. Diameters of preexistent collaterals on the gracilis muscle were not significantly different between strains.In this study we examined collateral artery development and related parameters after femoral artery ligation in C57BL/6, 129S2 and BALB/c mice using the most comprehensive approach ever attempt...
Background —Angiogenesis is a promising treatment strategy for patients who are not candidates for standard revascularization, because it promotes the growth of new blood vessels in ischemic myocardium. Methods and Results —We conducted a randomized, double-blind, placebo-controlled study of basic fibroblast growth factor (bFGF; 10 or 100 μg versus placebo) delivered via sustained-release heparin-alginate microcapsules implanted in ischemic and viable but ungraftable myocardial territories in patients undergoing CABG. Twenty-four patients were randomized to 10 μg of bFGF (n=8), 100 μg of bFGF (n=8), or placebo (n=8), in addition to undergoing CABG. There were 2 operative deaths and 3 Q-wave myocardial infarctions. There were no treatment-related adverse events, and there was no rise in serum bFGF levels. Clinical follow-up was available for all patients (16.0±6.8 months). Three control patients had recurrent angina, 2 of whom required repeat revascularization. One patient in the 10-μg bFGF group had angina, whereas all patients in the 100-μg bFGF group remained angina-free. Stress nuclear perfusion imaging at baseline and 3 months after CABG showed a trend toward worsening of the defect size in the placebo group (20.7±3.7% to 23.8±5.7%, P =0.06), no significant change in the 10-μg bFGF group, and significant improvement in the 100-μg bFGF group (19.2±5.0% to 9.1±5.9%, P =0.01). Magnetic resonance assessment of the target ischemic zone in a subset of patients showed a trend toward a reduction in the target ischemic area in the 100-μg bFGF group (10.7±3.9% to 3.7±6.3%, P =0.06). Conclusions —This study of bFGF in patients undergoing CABG demonstrates the safety and feasibility of this mode of therapy in patients with viable myocardium that cannot be adequately revascularized.
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