CONTROL CARDIOVASCULAR AND RENAL EFFECTS OF POTASSIUM

这个项目的目标仍然是：1）发展一种理解 控制细胞外钾和钾平衡的系统，以及2） 分析K在病理生理范围内的变化对 心血管和肾功能。 实现这些目标， 有关的一个很大一部分的医疗保健问题处理的 医学界每天 事实上，三分之一的普通医疗- 患者接受钾补充剂以纠正与 K调节不当。 此外，最常用的处方之一 抗高血压药物，氢氯噻嗪，每天服用大量 在10%的普通人群中， 经常发生低钾血症和钾耗竭。 最后是低钾血症 是全身麻醉、手术应激、心肌缺血 梗塞和创伤状态，而高钾血症是一种 循环性休克的标志 尽管极端K的影响 已知超过病理生理学范围的浓度具有严重的 心血管和肾脏的后果，很少有人知道， 在这个范围内经常遇到的K变化的影响， 临床医学 我们对K的影响的理解上的差距 在临床相关范围内，以及必须 调节K是本申请项目的目标。 研究 心血管效应的分析包括对心脏 在慢性钾耗竭过程中的力学，一个定量研究的影响， 钾耗竭对心律失常的影响，一项研究， 降低钾对冠状动脉血流调节的影响，以及对 假设运动后心源性猝死综合征是 这是由于K的快速下降，这发生在第一分钟后， 停止锻炼。 肾血流动力学与肾素释放 由于长期高钾血症，钾的变化对 钠摄入量和动脉血压之间的关系，我们将 研究钙通道阻滞剂对肾脏血流动力学的长期影响 和肾素释放调节，重点是开发和理解 为什么钙离子进入阻滞剂治疗对高肾素无效 高血压 对调节K的系统的分析旨在 支持控制的数学模型假设的发展 系统，类似于以前开发的支持， 关于长期控制K的补助金在几天和几周的时间内。 在即将到来的项目期间，我们将进行实验和 数学分析的控制系统，朝着一个完整的 了解在以下条件下调节K的系统， 麻醉、手术应激、心肌梗死、剧烈运动，以及 其他严重创伤的情况

The goals of this project continue to be: 1) to develop an understanding of the system which controls extracellular K and K balance, and 2) to analyze the effects of changes in K within the pathophysiological range on cardiovascular and renal function. Achieving these goals is closely relevant to a large fraction of the health care problems dealt with by the medical community each day. In fact, one-third of all general medical in- patients receive K supplementation to correct conditions associated with improper K regulation. Furthermore, one of the most commonly prescribed antihypertensive medications, hydrochlorothiazide, taken daily by a large percentage of the 10% of the general population with hypertension, frequently produces hypokalemia nad K depletion. And finally, hypokalemia is a consistent sequelae to general anesthesia, surgical stress, myocardial infarction, and traumatic states in general, while hyperkalemia is a hallmark of circulatory shock. Although the effects of extreme K concentrations beyond the pathophysiological range are known to have severe cardiovascular and renal consequences, very little is known about the effects of variations in K within this range so frequently encountered in clinical medicine. This gap in our understanding of the effects of K within the clinically relevant range, and of the control system which must regulate K are the targets of the project in this application. The studies of the cardiovascular effects include analyses of changes in cardiac mechanics during chronic K depletion, a quantitative study of the effects of K depletion on cardiac arrhythmia, a study of the effects of rapid decreases in K on coronary blood flow regulation, and a test of the hypothesis that the syndrome of post-exercise sudden cardiac death is caused by the rapid decrease in K which occurs in the first minutes after the cessation of exercise. The renal hemodynamics and renin release resulting from long-term hyperkalemia, the effects of changes in K on the relationship between sodium intake nad arterial blood pressure, and we will study the long-term effects of calcium entry blockers on renal hemodynamic and renin release regulation, with emphasis on developing and understanding why calcium entry blocker therapy is ineffective in high renin hypertension. The analyses of the system which regulates K are designed to support the development of a mathematical model-hypothesis of the control system, analogous to the one developed previously with support of this grant concerning the long-term control of K over periods of days and weeks. During this coming project period we will conduct both experimental and mathematical analyses of the control system, working towards a complete understanding of the system which regulates K during conditions such as anesthesia, surgical stress, myocardial infarction, severe exercise, and other acutely traumatic conditions.