CONTROL CARDIOVASCULAR & RENAL EFFECTS OF POTASSIUM

这个项目的目标仍然是：1)建立一种理解 控制细胞外钾和钾平衡的系统，以及2) 分析钾在病理生理范围内的变化对心脏功能的影响 心血管和肾脏功能。实现这些目标是非常紧迫的 与政府处理的大部分医疗保健问题有关 每天的医疗界。事实上，在所有普通医疗中，有三分之一- 患者接受K补充剂以纠正与 K调节不当。此外，最常用的处方之一 降压药，氢氯噻嗪，每天由一个大的 占总人口10%的高血压患者的百分比， 经常导致低钾血症和钾耗竭。最后是低钾血症 是全身麻醉、手术应激、心肌梗死的持续后遗症 梗塞和创伤状态，而高钾血症是一种 是循环系统休克的特征。虽然极端K的影响 已知，超出病理生理范围的浓度有严重的 心血管和肾脏后果，人们对此知之甚少 在这个范围内的K变化的影响如此频繁地出现在 临床医学。我们对K的影响的理解上的这个差距 在临床相关的范围内，并且控制系统必须 调节K是本项目在本申请中的目标。这些研究 对心血管的影响包括对心脏变化的分析 慢性钾耗竭过程中的力学机制及其影响的定量研究 快速钾对心律失常影响的研究 K降低对冠脉血流调节的影响，并测试 运动后心源性猝死综合征的假说 由钾的迅速下降引起的，这发生在之后的第一分钟 停止锻炼。肾血流动力学与肾素释放 由于长期的高钾血症，K的变化对 钠摄入量与动脉血压之间的关系，我们将 钙通道阻滞剂对肾血流动力学远期影响的研究 和肾素释放调节，重点是开发和理解 为什么钙通道阻滞剂治疗对高肾素无效 高血压。对调节K的系统的分析设计为 支持开发一个数学模型--控制假设 系统，类似于之前在此支持下开发的系统 关于K在几天和几周期间的长期控制的赠款。 在即将到来的项目期间，我们将进行试验性和 控制系统的数学分析，努力实现一个完整的 了解在下列情况下调节钾的系统 麻醉、手术压力、心肌梗死、剧烈运动，以及 其他严重创伤性疾病。

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.