Plasticity of central chemoreceptors:: Effect of bilateral carotid body resection on central CO2 sensitivity
Plasticity of central chemoreceptors:: Effect of bilateral carotid body resection on central CO2 sensitivity
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DOI：
10.1371/journal.pmed.0040239
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发表时间：
2007-07-01
期刊：
影响因子：
15.8
通讯作者：
Teppema, Luc
中科院分区：
文献类型：
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作者：
Dahan, Albert;Nieuwenhuijs, Diederik;Teppema, Luc
人类的呼吸是由反馈和前馈控制机制调节的，允许代谢需求和肺部氧气摄取之间的严格匹配。最重要的控制机制，代谢通气控制系统，是由两组化学感受器精细调节的，即颈动脉体中的外周化学感受器（位于颈总动脉分叉处）和髓质腹侧的中央CO2化学感受器。动物数据表明，切除颈动脉小体除了会导致外周化学感受器的丧失外，还会导致中央二氧化碳传感器的活性降低。我们评估了三名患颈动脉体肿瘤后行双侧颈动脉体切除术（bbcr）的患者的急性和慢性效果。方法与结果3例患者（2男1女）均为颈动脉体遗传肿瘤。他们在手术前和bbr后2-4年的定期间隔进行研究。我们获得了对缺氧和CO2的吸气分钟通气（V-i）反应。采用通风控制系统的双室模型，将V-i-CO2反应分为外围（快速）反应和中心（慢）反应。手术后，周围化学感受器的通气CO2敏感性和缺氧反应与术前值的零或低于10%没有差异。中枢化学感受器的通气CO2敏感性在手术后下降了约75%，在手术后3至6个月达到峰值。随后，在2 y内缓慢恢复到接近术前值的值。在此缓慢恢复期间，V-i-CO2响应缓慢向右移动约8mm hg。结论：颈动脉小体丢失后中央V-i-CO2敏感性的降低表明，颈动脉小体对中枢化学感受器的输出施加了强直驱动或强直促进作用，而中枢化学感受器在切除后丢失。观察到的中央CO2敏感性的回归是通风控制系统中中央可塑性的明确证据。我们的数据虽然样本量有限，但表明通风控制系统的响应机制不是静态的，而是依赖于传入输入，并表现出很大程度的恢复或可塑性。此外，bbr术后缺氧呼吸反应的永久缺失可能加重睡眠呼吸障碍的病理后果。
Background Human breathing is regulated by feedback and feed-forward control mechanisms, allowing a strict matching between metabolic needs and the uptake of oxygen in the lungs. The most important control mechanism, the metabolic ventilatory control system, is fine-tuned by two sets of chemoreceptors, the peripheral chemoreceptors in the carotid bodies (located in the bifurcation of the common carotid arteries) and the central CO2 chemoreceptors in the ventral medulla. Animal data indicate that resection of the carotid bodies results, apart from the loss of the peripheral chemoreceptors, in reduced activity of the central CO2 sensors. We assessed the acute and chronic effect of carotid body resection in three humans who underwent bilateral carotid body resection (bCBR) after developing carotid body tumors.Methods and Findings The three patients (two men, one woman) were suffering from a hereditary form of carotid body tumors. They were studied prior to surgery and at regular intervals for 2-4 y following bCBR. We obtained inspired minute ventilation (V-i) responses to hypoxia and CO2. The V-i-CO2 responses were separated into a peripheral (fast) response and a central (slow) response with a two-compartment model of the ventilatory control system. Following surgery the ventilatory CO2 sensitivity of the peripheral chemoreceptors and the hypoxic responses were not different from zero or below 10% of preoperative values. The ventilatory CO2 sensitivity of the central chemoreceptors decreased by about 75% after surgery, with peak reduction occurring between 3 and 6 mo postoperatively. This was followed by a slow return to values close to preoperative values within 2 y. During this slow return, the V-i-CO2 response shifted slowly to the right by about 8 mm Hg.Conclusions The reduction in central V-i-CO2 sensitivity after the loss of the carotid bodies suggests that the carotid bodies exert a tonic drive or tonic facilitation on the output of the central chemoreceptors that is lost upon their resection. The observed return of the central CO2 sensitivity is clear evidence for central plasticity within the ventilatory control system. Our data, although of limited sample size, indicate that the response mechanisms of the ventilatory control system are not static but depend on afferent input and exhibit a large degree of restoration or plasticity. In addition, the permanent absence of the breathing response to hypoxia after bCBR may aggravate the pathological consequences of sleep-disordered breathing.