CARDIAC RECEPTOR ACTIVITY IN PREGNANCY

怀孕期间的心脏受体活动

• 批准号: 2668864
• 负责人: MARY Christina HINES
• 金额: $ 11.15万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2668864
• 关键词: afferent nerve; atrium; autonomic reflex; blood volume; chemical stimulation; denervation; embryo /fetus surgery; female; gestational age; heart electrical activity; heart rate; hemodynamics; intracardiac pressure; laboratory rat; mechanical stress; neuroregulation; pregnancy circulation; receptor sensitivity; sensory thresholds; stretch receptors; stretch reflex; sympathetic nervous system; vagus nerve; vascular resistance

Plasma volume expands by approximately 50% in normal pregnancy. This is a critical adjustment of pregnancy since a reduced blood volume is directly correlated with preeclampsia still a major cause of maternal death, and with fetal growth retardation. The mechanism by which volume expands during pregnancy is not yet defined, in spite of well described volume regulatory mechanisms in male animals. Plasma volume in the nonpregnant animal is controlled by receptors in the heart, known collectively as cardiac receptors, which respond to increased blood volume by activating a neural reflex pathway with afferent fibers in the vagus nerve, central connections in the brainstem, and efferent outflow primarily to the kidney, where sympathetic nerve activity is reduced evoking fluid loss and lowering blood pressure. Evidence suggests that the sensitivity of this reflex is reduced in pregnancy such that stretch of cardiac receptors elicits smaller reflex effects. This may be an important alteration which allows the large expansion of blood volume without reflex fluid loss which would occur in the nonpregnant animal. This study will test the hypothesis that cardiac receptor activity measured in single afferent fibers of the vagus nerve, is reduced in pregnant compared to virgin rats. Cardiac receptors in deeply anesthetized rats (n=20/group) will be activated mechanically, by injecting graded volumes of saline into the right atrium or by inflation of an atrial balloon, and chemically, using graded doses of intra-atrial phenylbiguanide. Responses to these stimuli will be measured in discharge activity of single cardiac receptor afferent fibers blood pressure, and renal sympathetic nerve activity. These techniques will be used to characterize: 1) the threshold stimulus (volume of saline or balloon and dose of phenylbiguanide) for an increase in cardiac receptor firing, and the sensitivity of the stimulus/response relationship (how cardiac receptor afferent discharge increases for an increase in stimulus intensity), 2) the gestational age at which the reduction in reflex sensitivity can be measured (i.e. early in pregnancy when blood volume is not yet expanded or in late gestation when expansion is maximal), and 3) the effect of changes in afferent cardiac receptor activity on the blunted reflex changes in efferent renal sympathetic nerve activity and blood pressure (total reflex gain). It is anticipated that the results will contribute significantly to the overall goal of elucidating mechanisms for alterations in neural control of the circulation during pregnancy. The identification of specific mechanisms which initiate and maintain an expanded blood volume during pregnancy has important clinical implications for nursing management of the pregnant woman by describing the physiologic changes which underlie critical clinical observations and therapeutic modalities involved in prevention and treatment of preeclampsia and intrauterine growth retardation.

血浆体积在正常妊娠中增加约50%。这是 这是怀孕的关键调整，因为血容量减少， 直接相关的先兆子痫仍然是一个主要的原因产妇 死亡，并伴有胎儿生长迟缓。音量调节的机制 在怀孕期间扩张尚未定义，尽管描述良好， 雄性动物的体积调节机制。血浆容量 非妊娠动物是由心脏中的受体控制的， 共同作为心脏受体，对增加的血液 通过激活具有传入纤维的神经反射通路， 迷走神经、脑干中的中枢连接和传出流出 主要是肾脏，那里的交感神经活动减少 引起体液流失和降低血压。证据表明 这种反射敏感性在怀孕期间降低 心脏感受器的反射效应较小。这可能是一个 一个重要的改变，它允许血液容量的大幅扩张 而没有在非妊娠动物中会发生的反射性液体损失。 这项研究将检验心脏受体活性 在迷走神经的单个传入纤维中测量， 怀孕的老鼠相比。心脏受体位于深处 麻醉的大鼠（n=20/组）将被机械激活， 向右心房注射不同体积的生理盐水或通过充气 心房球囊，和化学，使用分级剂量的心房内 苯基双胍。对这些刺激的反应将在放电中测量 单个心脏感受器传入纤维血压的活动，以及 肾交感神经活动这些技术将用于 表征：1）阈值刺激（生理盐水或球囊的体积，以及 苯基双胍剂量）用于增加心脏受体放电，和 刺激/反应关系的敏感性（心脏如何 感受器传入放电随刺激的增加而增加 强度），2）反射减少的胎龄 可以测量灵敏度（即，在怀孕早期， 尚未扩增或处于妊娠晚期，此时扩增最大），以及 3)传入心脏受体活动的变化对心脏的影响 传出肾交感神经活动的反射变化变钝， 血压（总反射增益）。预计结果 将大大有助于阐明 神经控制循环的改变机制， 怀孕确定启动和 在怀孕期间保持扩张的血容量具有重要的临床意义。 对孕妇护理管理的影响， 作为关键临床观察结果基础的生理变化， 预防和治疗的治疗方式 先兆子痫和宫内发育迟缓。