Promoting Angiogenesis Protects Severely Hypertrophied Hearts From Ischemic Injury

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Abstract

Background

Myocardial hypertrophy is associated with progressive contractile dysfunction, increased vulnerability to ischemia-reperfusion injury, and is, therefore, a risk factor in cardiac surgery. During the progression of hypertrophy, a mismatch develops between the number of capillaries and cardiomyocytes per unit area, suggesting an increase in diffusion distance and the potential for limited supply of oxygen and nutrients. We hypothesized that promoting angiogenesis in hypertrophied hearts increases microvascular density, thereby improves tissue perfusion and substrate availability, maintains myocardial function, and improves postischemic recovery.

Methods

Left ventricular hypertrophy was created in 10-day-old rabbits by aortic banding and progression was monitored by echocardiography. At 4 weeks (compensated hypertrophy), 2 μg of vascular endothelial growth factor (VEGF) or placebo was administered intrapericardially. After 2 weeks, microvascular density, coronary flow (CF), and glucose uptake (GU) were measured. Tolerance to ischemia was determined by cardiac function measurements before and after ischemia-reperfusion using an isolated heart preparation.

Results

Microvascular density increased significantly following VEGF treatment (1.43 ± 0.08/nuclei/field vs 1.04 ± 0.06/nuclei/field untreated hypertrophy). Concomitantly, there was an increase in CF (7 ± 0.5 vs 5 ± 0.4 mL/min/g) and GU (1.24 ± 0.2 vs 0.69 ± 0.2 μmoles/g/30 minutes; p ≤ 0.05). In vivo contractile function (−0.08 ± 0.48 vs −1.39 ± 0.35 untreated hypertrophy; p ≤ 0.05) and postischemic myocardial recovery (% recovery: 93 ± 2.0 vs 73 ± 6.8 untreated hypertrophy; p ≤ 0.05) were significantly improved in VEGF-treated hearts compared to untreated hypertrophied hearts.

Conclusions

Treatment of hypertrophied hearts with VEGF resulted in an increase of microvascular density, improved tissue perfusion, and glucose delivery. Promoting angiogenesis proved useful in preserving myocardial function in late hypertrophy and improving postischemic recovery of contractile function.

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