Brown M D, Hudlicka O
Department of Physiology, University of Birmingham, United Kingdom.
Cardiovasc Res. 1991 Nov;25(11):909-15. doi: 10.1093/cvr/25.11.909.
Growth of capillaries in the adult heart can occur after long term vasodilator treatment. This study investigated the effects of increased stroke volume and/or force of contraction in addition to coronary blood flow on myocardial capillary growth.
Coronary blood flow, cardiac function, and capillary supply were evaluated after chronic treatment with the inotrope dobutamine, at a dose shown to increase contraction force (dP/dt) acutely by 20% (p less than 0.05) and coronary blood flow by 60% (NS).
New Zealand Red rabbits received dobutamine (20 micrograms.kg-1.min-1 by intravenous infusion) for 2 weeks prior to measurements, under pentobarbitone anaesthesia, of coronary blood flow by radiolabelled microspheres, left ventricular dP/dtmax and maximum noradrenaline induced cardiac work, computed from cardiac output (thermodilution) and blood pressure. Capillary density.mm-2 was estimated in frozen 12 microns sections of left ventricular myocardium stained for alkaline phosphatase.
Capillary density was 29% greater after 2 weeks dobutamine infusion than in saline infused controls, which exceeds increases observed after longer infusions of vasodilators alone. Cardiac function was improved; maximum stroke work was significantly higher, stroke volume capacity larger, and dP/dt increased more during noradrenaline challenge. Coronary blood flow was unchanged in dobutamine treated hearts, hence efficiency of utilisation of coronary flow in terms of work was enhanced. Heart to body weight ratio was also greater after dobutamine, at 0.238(SEM 0.008) v 0.206(0.120), p less than 0.05.
Greater capillary growth can be elicited in the heart by increased stretch and/or force of contraction of myocytes in addition to moderate changes in blood flow than by increased blood flow alone. Chronic dobutamine treatment induced adaptive enhancement of maximal cardiac work capacity.
长期血管扩张剂治疗后，成年心脏中的毛细血管可发生生长。本研究调查了除冠状动脉血流量外，增加的每搏输出量和/或收缩力对心肌毛细血管生长的影响。
在用正性肌力药物多巴酚丁胺进行慢性治疗后，评估冠状动脉血流量、心脏功能和毛细血管供应情况。多巴酚丁胺剂量已表明能使收缩力（dP/dt）急性增加20%（p<0.05），冠状动脉血流量增加60%（无统计学意义）。
新西兰白兔在测量前2周接受多巴酚丁胺（静脉输注20微克·千克-1·分钟-1），在戊巴比妥麻醉下，通过放射性微球测量冠状动脉血流量，通过心输出量（热稀释法）和血压计算左心室dP/dtmax以及最大去甲肾上腺素诱导的心脏作功。在左心室心肌冷冻的12微米切片中，对碱性磷酸酶进行染色，估计每平方毫米的毛细血管密度。
多巴酚丁胺输注2周后，毛细血管密度比输注生理盐水的对照组高29%，这超过了单独长期输注血管扩张剂后观察到的增加幅度。心脏功能得到改善；最大每搏作功显著更高，每搏输出量更大，在去甲肾上腺素激发期间dP/dt增加更多。多巴酚丁胺治疗的心脏冠状动脉血流量未改变，因此从作功方面来看，冠状动脉血流的利用效率提高。多巴酚丁胺治疗后心脏与体重之比也更大，分别为0.238（标准误0.008）和0.206（0.120），p<0.05。
与单独增加血流量相比，除血流量适度变化外，通过增加心肌细胞的牵张和/或收缩力，可在心脏中引发更大程度的毛细血管生长。慢性多巴酚丁胺治疗可诱导最大心脏作功能力的适应性增强。
