INTEGRATIVE ASPECTS OF CARDIOVASCULAR FUNCTION

描述(改编自申请人的摘要)：总体目标 本申请中提出的项目是为了加深我们对 产生血流动力学调节的机制伴随着动力学 锻炼身体。这些研究将调查如何以及何时机械(或 液压)因素和反射控制机制促成了这些 调整。需要了解身体过程如何在健康中发挥作用 去了解疾病。压倒一切的方法论方法是 因此，循环系统的组成部分可以在一个 时尚与流通的其他要素相结合进行调控。 目标一：骨骼肌有节律性的收缩和松弛驱动血液 流经活跃的肌肉，称为骨骼肌泵。虽然 肌泵对右心房的心输出量有很大影响 运动中的血压和动脉血压相对较小 了解肌肉泵的机械性能。这一空白将是 通过研究孤立的肌肉泵来填充。后肢肌肉 麻醉的动物将在短暂的时间内给自己灌胃。 由电引起的宫缩。这将通过分流来实现 静脉血液从活跃的肌肉直接回流到 供应肌肉的动脉。从本质上讲，活跃的肌肉会灌流 通过驱使血液绕过一条将 来自循环其余部分的肌肉；这类似于孤立的 心肺制剂极大地增加了我们对 室内泵的机械性能。目标二：《行动纲领》的影响 心脏充盈压对心脏机械活动的影响 将会被评估。伴随着锻炼而来的心率上升必须 导致平均时间内储存的血量减少 心腔，由于舒张期末期时间减少 音量。心脏体积的下降必然会导致心脏体积的互换增加 心外血容量和血压。心脏提升的能力 当心率上升时，它自己的充盈压力将通过使 心脏泵入相同的心输出量，在低心率下，然后再以 心率过高。禁食时心脏充盈压应较高 由于心腔血容量的转移而引起的心脏起搏 到中央静脉。目的三：静脉系统在造血中的作用 可用于心脏的检查将通过确定对心脏的影响 主动改变心输出量分布的充盈压 在顺从和不顺从的循环之间。方法是 控制和操控心输出量和后肢血流量(a 非顺应性循环)通过计算机控制的心室起搏和 血管封堵器袖带。目的四：肌肉化学反射的影响， 通过使收缩肌肉缺血或动脉压力感受器反射来刺激 将研究刺激-反应曲线，以确定肌肉是否 化学反射在运动中将压力反射“重置”到一个更高的操作点。 目的V：肌肉化学反射提高心脏充盈的能力 将对压力进行评估。

DESCRIPTION (Adapted from the applicant's abstract): The overall goal of the projects proposed in this application is to further our understanding of the mechanisms producing the hemodynamic adjustments that accompany dynamic exercise. The studies will investigate how, and when, mechanical (or hydraulic) factors and reflex control mechanisms contribute to these adjustments. Knowledge of how bodily processes function in health is needed to understand disease. The overriding methodological approach is one whereby the components of the circulatory system can be studied in an integrative fashion with the other elements of the circulation regulated. AIM I: Rhythmic contraction and relaxation of skeletal muscle drives blood flow through the active muscles, termed the skeletal muscle pump. Although the muscle pump exerts a profound influence on cardiac output, right atrial pressure, and arterial blood pressure in exercise, relatively little is known about the mechanical properties of the muscle pump. This void will be filled by studying the isolated muscle pump. Hindlimb muscles of anesthetized animals will be made to perfuse themselves during brief periods of electrically induced contractions. This will be accomplished by shunting venous blood draining from the active muscles directly back into the arteries supplying the muscles. In essence, the active muscles will perfuse themselves by driving blood around a "short-circuit" that isolates the muscles from the remainder of the circulation; this is analogous to isolated heart-lung preparations that have greatly increased our understanding of the mechanical properties of the ventricular pumps. AIM II: The effects of changes in the mechanical activity of the heart on cardiac filling pressure will be assessed. The rise in heart rate that accompanies exercise must lead to a decrease in the time-averaged volume of blood "stored" in the heart chambers, owing to the reduction in time spent at end-diastolic volume. A fall in heart volume must cause a reciprocal increase in extra-cardiac blood volume and pressure. The ability of the heart to raise its own filling pressure when heart rate rises will be tested by making the heart pump the same cardiac output at a low heart rate and then again at a high heart rate. Cardiac filling pressure should be higher during fast pacing of the heart owing to transfer of blood volume from cardiac chambers to central veins. AIM III: The role of the venous system in making blood available to the heart will be examined by determining the effect on cardiac filling pressure of actively changing the distribution of cardiac output between compliant and non-compliant circulations. The approach is to control and manipulate cardiac output and hindlimb blood flow (a non-compliant circulation) by computer controlled ventricular pacing and vascular occluder cuffs. AIM IV: The influence of the muscle chemoreflex, stimulated by making contracting muscles ischemic, or arterial baroreflex stimulus-response curves will be investigated to see if the muscle chemoreflex "resets" the baroreflex to a higher operating point in exercise. AIM V: The ability of the muscle chemoreflex to raise cardiac filling pressure will be assessed.