Can growth of capillaries in the heart and skeletal muscle be explained by the presence of an angiogenic factor?

Capillary growth was induced in rabbit hearts by long-term bradycardial pacing, and in skeletal muscles by long-term electrical stimulation. In order to find out what factors may be responsible for it, samples of all tissues were analysed for angiogenic activity (AA). To estimate the possible role of mechanical factors, blood flow was measured at rest and during maximal dilatation. Rabbit hearts were paced at half the normal frequency for 24 h/day for 1-2 months by electrodes implanted in the right atrium. Gastrocnemius-plantaris muscles were stimulated at 10 Hz via implanted electrodes, 8 h/day for 14 days. Unpaced hearts and non-stimulated muscles served as controls. Capillary density (estimated in frozen cross-sections stained for alkaline phosphatase) was higher in paced than in control hearts (2235 +/- 86, s.e.m. cap/mm2, 1815 +/- 83, P less than 0.005); capillary/fibre ratio was 2.84 +/- 0.21 in stimulated and 1.243 +/- 0.06 in control gastrocnemius (P less than 0.001). The presence of AA was assayed on chicken chorioallantoic membrane (CAM). All paced and 50% of control hearts showed positive CAM results. Control gastrocnemii gave positive results in 25%, plantaris in 30%: stimulated muscles showed 30% and 37.5% positive responses. Coronary blood flow at rest was significantly lower in chronically paced than control hearts (2.172 g/ml/min, 3.025 +/- 0.187, P less than 0.05) and not significantly different during maximal dilatation (9.217 +/- 1.722 and 11.166 +/- 1.158 respectively). Blood flow per heart beat was significantly higher during acute bradycardia as well as in bradycardially paced hearts at rest. Blood flow in stimulated muscles was significantly higher than in controls both at rest (26.2 +/- 3.36 ml/100 g/min as compared to 8.5 +/- 2.15, P less than 0.001) and during muscle contractions (56.1 +/- 4.5 and 20.7 +/- 2.6). It can thus be concluded that growth of capillaries in skeletal muscles may be due to mechanical factors connected with the increased blood flow while in the heart AA may act in concert with blood flow changes.