Cardio-Respiratory Interaction: Contribution in Syncope

呼吸和心血管调节系统具有相同的动态平衡目标，然而，其中一个系统动态地不适当的调整可能会在另一个系统中引发不良后果。我们的一般假设是动态的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经有几年的轶事报道。来自最近研究的证据支持这些观察结果。我们假设了以下一连串的事件：动脉二氧化碳分压(PCO2)的一过性紊乱，由血流的波动引起，触发了呼吸机的调整。这些摆动在直立时幅度增大。对于那些对二氧化碳具有夸大化学敏感性的人来说，换气调整会导致换气可变性增加。由此导致的高呼吸和低碳酸血症，通过脑血流的改变、化学反射介导的交感神经收缩或胸腔内机制的改变，触发血流动力学不稳定、崩溃和晕厥。我们将验证对化学刺激变化的夸大敏感性是否会在晕厥前引起换气改变，量化换气改变的两个后果--化学驱动和胸腔内力学--独立和共同在晕厥发生中的作用。我们将在人类中使用抬头倾斜，以1)验证出现晕厥症状的受试者对二氧化碳扰动的动态呼吸反应是否比没有出现晕厥症状的受试者夸大，2)在呼吸没有变化的情况下，量化动脉二氧化碳分压(PCO2)下降对脑血管收缩和晕厥的影响，以及3)量化PCO2缓冲变化对呼吸改变、呼吸过度、脑血管收缩和晕厥的影响。我们的研究将提供回答这些重要问题的结果：晕厥前经常观察到的呼吸变异性增加的原因是什么？在通气量保持不变的情况下，二氧化碳分压降低对晕厥有什么影响？在二氧化碳分压保持不变的情况下，改变通气量对晕厥有何影响？总而言之，这些结果将创造知识，进一步了解晕厥的机制，这种虚弱的、有时甚至是危险的情况影响着超过10%到15%的年轻人和成年人。

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.