Friehs Ingeborg, Moran Adrian M, Stamm Christof, Choi Yeong-Hoon, Cowan Douglas B, McGowan Francis X, del Nido Pedro J
Cardiac Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA.
Ann Thorac Surg. 2004 Jun;77(6):2004-10; discussion 2011. doi: 10.1016/j.athoracsur.2003.11.003.
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.
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 microg 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.
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 micromoles/g/30 minutes; p <or= 0.05). In vivo contractile function (-0.08 +/- 0.48 vs -1.39 +/- 0.35 untreated hypertrophy; p <or= 0.05) and postischemic myocardial recovery (% recovery: 93 +/- 2.0 vs 73 +/- 6.8 untreated hypertrophy; p <or= 0.05) were significantly improved in VEGF-treated hearts compared to untreated hypertrophied hearts.
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.
心肌肥大与进行性收缩功能障碍、对缺血再灌注损伤的易感性增加相关，因此是心脏手术中的一个危险因素。在肥大进展过程中，单位面积内毛细血管与心肌细胞数量之间出现不匹配，提示扩散距离增加以及氧气和营养物质供应可能受限。我们假设促进肥厚心脏中的血管生成可增加微血管密度，从而改善组织灌注和底物可用性，维持心肌功能，并改善缺血后恢复。
通过主动脉缩窄在10日龄兔中诱导左心室肥大，并通过超声心动图监测其进展。在4周时（代偿性肥大），心包内注射2微克血管内皮生长因子（VEGF）或安慰剂。2周后，测量微血管密度、冠状动脉血流（CF）和葡萄糖摄取（GU）。使用离体心脏标本通过缺血再灌注前后的心脏功能测量来确定对缺血的耐受性。
VEGF治疗后微血管密度显著增加（1.43±0.08/核/视野 vs 未治疗肥大组的1.04±0.06/核/视野）。同时，CF增加（7±0.5 vs 5±0.4 mL/min/g），GU增加（1.24±0.2 vs 0.69±0.2微摩尔/g/30分钟；p≤0.05）。与未治疗的肥大心脏相比，VEGF治疗的心脏在体内收缩功能（-0.08±0.48 vs 未治疗肥大组的-1.39±0.35；p≤0.05）和缺血后心肌恢复（恢复百分比：93±2.0 vs 未治疗肥大组的73±6.8；p≤0.05）方面有显著改善。
用VEGF治疗肥大心脏可增加微血管密度，改善组织灌注和葡萄糖输送。促进血管生成被证明有助于在晚期肥大中保留心肌功能并改善缺血后收缩功能的恢复。
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