Cardio-Respiratory Interaction: Contribution in Syncope

心肺相互作用：晕厥的贡献

• 批准号: 6537891
• 负责人: Abhijit R. Patwardhan
• 金额: $ 10.74万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6537891
• 关键词: baroreflex; brain circulation; carbon dioxide; cardiovascular function; clinical research; human subject; hyperpnea; hypocapnia; pulmonary respiration; respiratory gas; syncope; vasoconstriction

Respiratory and cardiovascular regulatory systems share goals of homeostasis, however, dynamically inappropriate adjustments in one may precipitate undesirable consequences in other. Our general hypothesis is that dynamic cardio-respiratory interaction contributes importantly in genesis of syncope. Changes in respiratory patterns preceding syncope have been anecdotally reported for several years. Evidence from recent studies support these observations. We hypothesize the following chain of events: transient disturbances in arterial partial pressure of carbon dioxide (PCO2), precipitated by oscillations in perfusion, trigger ventilatory adjustments. These oscillations increase in amplitude during orthostasis. The ventilatory adjustments, in those with exaggerated chemical sensitivity to carbon dioxide, leads to increased ventilatory variability. The resulting periods of hyperpnea and hypocapnia, through changes, either or collectively, in cerebral blood flow, chemoreflex mediated sympathetic withdrawal, or altered intrathoracic mechanics, trigger hemodynamic instability, collapse and syncope. We will, verify whether exaggerated sensitivity to changes in chemical stimuli produces altered ventilation preceding syncope, quantify the role of two consequences of altered ventilation, chemical drive and intrathoracic mechanics, independently and together, in genesis of syncope. We will use head up tilt in humans, to 1) verify whether the dynamic ventilatory response to carbon dioxide perturbations in subjects who develop syncopal symptoms is exaggerated than those that do not, 2) quantify the effects of decrease in arterial partial pressure of carbon dioxide (PCO2), in the absence of changes in respiration, on cerebral vasoconstriction and syncope, and 3) quantify the effects of buffered changes in PCO2, on altered breathing, hyperpnea, cerebral vasoconstriction and syncope. Our study will provide results to answer these important questions; what causes the often observed increased ventilatory variability before syncope?, what are the effects on syncope of decreases in PCO2, while ventilation remains unchanged? what are the effects on syncope of changes in ventilation, while PCO2 remains unchanged? Collectively, these results will create knowledge to further understand the mechanisms of the debilitating and sometimes dangerous condition of syncope that affects upwards of 10 to 15 percent of young and adult population.

呼吸和心血管调节系统共享稳态的目标，然而，在一个动态不适当的调整可能会沉淀在其他不良后果。 我们的一般假设是，动态心肺相互作用在晕厥的发生中起重要作用。晕厥前呼吸模式的改变已有数年的报道。 最近的研究证据支持这些观点。 我们假设以下事件链：动脉二氧化碳分压（PCO2）的短暂扰动，灌注振荡沉淀，触发解释性调整。 这些振荡在直立时振幅增加。 在那些对二氧化碳化学敏感性过高的人中，这种解释性调整导致解释性变异性增加。 通过脑血流的变化、化学反射介导的交感神经退缩或胸内力学的改变，导致的呼吸过度和碳酸过少的时期触发血液动力学不稳定、虚脱和晕厥。 我们将验证对化学刺激变化的过度敏感是否会在晕厥前产生通气改变，量化通气改变的两种后果，化学驱动和胸内力学，独立和共同在晕厥发生中的作用。 我们将在人体中使用头高位倾斜，以1）验证在发生晕厥症状的受试者中对二氧化碳扰动的动态缓解反应是否比未发生晕厥症状的受试者更夸张，2）在呼吸没有变化的情况下，量化动脉二氧化碳分压（PCO2）降低对脑血管收缩和晕厥的影响，和3）量化PCO2的缓冲变化对呼吸改变、呼吸过度、脑血管收缩和晕厥的影响。 我们的研究将提供结果来回答这些重要的问题：是什么原因导致了晕厥前经常观察到的排尿变异性增加？当通气量保持不变时，二氧化碳分压降低对晕厥有什么影响？当PCO2保持不变时，通气量的变化对晕厥的影响是什么？总的来说，这些结果将创造知识，以进一步了解晕厥的衰弱和有时危险的情况，影响10%至15%的年轻人和成年人的机制。