CARDIAC RECEPTOR ACTIVITY IN PREGNANCY

怀孕期间的心脏受体活动

• 批准号: 2431051
• 负责人: MARY Christina HINES
• 金额: $ 10.57万
• 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/2431051
• 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.

正常妊娠时，血浆体积扩大约50%。这是 由于血容量减少，对怀孕的关键调整是 与子痫前期直接相关的仍然是母体的主要原因 死亡，并伴有胎儿发育迟缓。卷通过的机制 怀孕期间的扩张还没有定义，尽管有很好的描述 雄性动物的体积调节机制。血浆中的体积 未怀孕的动物由心脏中的受体控制，众所周知 作为心脏受体，它们对增加的血液做出反应 通过激活传入纤维的神经反射通路来调节体积 迷走神经、脑干的中枢连接和传出流 主要是肾脏，那里的交感神经活动减少 引起体液流失并降低血压。有证据表明 这种反射的敏感度在怀孕时会降低，因此伸展 心脏受体可引起较小的反射效应。这可能是一个 允许血容量大幅扩张的重要改变 不会出现非妊娠动物会出现的反射性液体丢失。 这项研究将检验心脏受体活性的假设 在迷走神经的单个传入纤维中测量，在 与处女大鼠相比，怀孕了。心脏受体在深层 麻醉大鼠(n=20只/组)将被机械激活， 向右心房注射分级体积的生理盐水或充气 在化学上，使用分级剂量的心房内注射 苯双胍。对这些刺激的反应将在放电中进行测量 单个心脏感受器传入纤维的活动，血压，和 肾交感神经活动。这些技术将被用于 特征：1)阈值刺激(生理盐水或气囊体积和 苯双胍剂量)增加心脏感受器放电，以及 刺激/反应关系的敏感性(心脏 感受器传入放电随着刺激的增加而增加 强度)，2)反射减弱的胎龄 敏感度可以测量(即在怀孕早期，当血容量 尚未扩张或在扩张最大时处于妊娠晚期)，以及 3)传入心脏感受器活动的变化对 钝性反射改变传出肾交感神经活动和 血压(总反射增益)。预计结果将是 将对澄清的总体目标做出重大贡献 血液循环神经控制改变的机制 怀孕了。确定具体的启动机制和 在怀孕期间保持扩大的血容量具有重要的临床意义 描述对孕妇护理管理的启示 作为关键临床观察和治疗基础的生理变化 预防和治疗中涉及的治疗方式 子痫前期和胎儿宫内发育迟缓。