CIRCULATORY AND METABOLIC ADAPTATIONS IN ISCHEMIC LIMBS

该项目将探索并记录 四肢肌肉供血有限。这个项目的总体目标是 项目的目的是测试是否存在并记录 动态和适应性相互关系的特点 其中(1)肢体总血流量和特定部位的血流量 骨骼肌(腓肠肌)，(2)小腿的能力 肌肉来执行工作，以及(3)这项工作的代谢物 在对正常人进行分级的稳态运动强度期间 老鼠。我们将把重点放在大鼠缺血的下肢作为一个 结扎后每隔一段时间建立动物模型并进行研究 股浅动脉和分级运动的反应 训练。我们将评估高能磷酸盐代谢 状态、细胞内pH和肌肉机械性能 在急性和慢性缺血期，无论是静息和 作为对刺激的反应。将对机械工作进行评估 通过测量神经刺激时的肌力。这个 这种收缩活动的代谢成本将从 高能磷酸盐对大鼠肌肉组织含量的影响 用核磁共振31P测定化合物 光谱学。关键代谢酶及其异构体的含量 将测量肌球蛋白和其他蛋白质。我们将通过以下方式记录 血管造影术显示侧支循环的时间进程和范围 开发，并通过直接采血评估其功能能力 流量测量。我们将检验正态分布的假设 缺血肢体的血液动力学和生化指标均为 适应性，以及对股动脉的适应性反应 结扎和狭窄与正常人相似。 运动训练。我们的工作假设是，在一个 扰乱能源供应平衡的流量减少 和需求，不仅有血管系统的适应，而且 此外，机械、肌球蛋白和其他蛋白质同工酶和 肢体肌肉系统的代谢特点。这个 假设的适应预计是那些减少 单位工作的代谢成本，即适应更多的 有氧和缓慢抽动的肌肉。我们的长期目标是 对患有以下疾病的患者计算出相同的参数 外周血管疾病。

This project will probe for and document the adaptive response of limb muscle to a limited blood supply. The overall goal of this project is to test for the existence and document the characteristics of the dynamic and adaptive interrelationships among (1) total limb blood flow and blood flow to a specific skeletal muscle (gastrocnemiusplantaris), (2) the capacity of calf muscle to perform work, and (3) the metabolic co of this work during graded intensities of steady-state exercise of the normal rat. We will focus on the ischemic lower limb of the rat as an animal model and study it at intervals after ligation of the superficial femoral artery and in response to graded exercise training. We will assess the high-energy phosphate metabolic state, intracellular pH, and muscle mechanical performance during the phases of acute and chronic ischemia, both at rest and in response to stimulation. The mechanical work will be assessed by measuring the muscle force during nerve stimulation. The metabolic cost of this contractile activity will be assessed from the changes in muscle content of high-energy phosphate compounds measured by nuclear magnetic resonance 31P spectroscopy. Content of key metabolic enzymes and isoforms of myosin and other proteins will be measured. We will document by angiography the time course and extent of collateral circulation development, and assess its functional capacity by direct blood flow measurements. We will test the hypotheses that the normal and ischemic limb is both hemodynamically and biochemically adaptable, and that the adaptive responses to femoral artery ligation and stenosis are similar to those occurring in normal exercise training. Our working hypothesis is that, with a reduction in flow that disturbs the balance between energy supply and demand, there is an adaptation not only of the vasculature but also the mechanical, myosin and other protein isoenzymes and metabolic characteristics of the limb musculature. The postulated adaptations are expected to be those that decrease the metabolic cost per unit work, i.e., adaptation towards a more aerobic and slow-twitch muscle. Our long range objective is to work out these same parameters with respect to patients with peripheral vascular disease.