Acute lung injury augments hypoxic ventilatory response in the absence of systemic hypoxemia
Acute lung injury augments hypoxic ventilatory response in the absence of systemic hypoxemia
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DOI：
10.1152/japplphysiol.00100.2006
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发表时间：
2006-12-01
影响因子：
3.3
通讯作者：
Prabhakar, N. R.
中科院分区：
文献类型：
--
作者：
Jacono, F. J.;Peng, Y. -J.;Prabhakar, N. R.
本研究的目的是探讨早期肺损伤对低氧和高碳酸血症通气控制的影响。对成年雄性Sprague-Dawley大鼠气管内灌注博来霉素（BM； 1单位）诱导肺损伤。对照动物接受生理盐水灌注假手术。注射后5天，脑转移治疗的动物出现肺损伤，支气管肺泡灌洗液中中性粒细胞和蛋白质水平升高，肺组织学和计算机断层扫描图像也发生变化。肺部胶原蛋白含量显示，无肺纤维化迹象。两组动物的基础核心体温、动脉PO2和动脉PCO2具有可比性。在未麻醉的动物中，通过全身容积描记术测量对缺氧（12% O-2）和高碳酸血症（7% CO2）的通气反应。脑内注射组的基线呼吸率和低氧通气反应明显高于对照组（P = 0.003），而高碳酸血症通气反应无统计学差异。在麻醉、自主呼吸的动物中，与对照动物相比，暴露于脑卒中的动物对短暂高氧反应（Dejours试验，一种外周化学受体敏感性指标）和神经缺氧通气反应增强。通过膈肌脊髓电图测量。双侧迷走神经切开术后，低氧敏感性持续增强，但双侧颈动脉窦神经横断使其消失。这些数据表明，在没有肺纤维化和动脉低氧血症的早期肺损伤中，颈动脉体的传入感觉输入有助于选择性地增强缺氧通气驱动。
The objective of the present study was to examine the impact of early stages of lung injury on ventilatory control by hypoxia and hypercapnia. Lung injury was induced with intratracheal instillation of bleomycin (BM; I unit) in adult, male Sprague-Dawley rats. Control animals underwent sham surgery with saline instillation. Five days after the injections, lung Injury was present in BM-treated animals as evidenced by increased neutrophils and protein levels in bronchoalveolar lavage fluid, as well as by changes in lung histology and computed tomography images. There was no evidence of pulmonary fibrosis, as indicated by lung collagen content. Basal core body temperature, arterial PO2, and arterial PCO2, were comparable between both groups of animals. Ventilatory responses to hypoxia (12% O-2) and hypercapnia (7% CO2) were measured by whole body plethysinography in unanesthetized animals. Baseline respiratory rate and the hypoxic ventilatory response were significantly higher in BM-injected compared with control animals (P = 0.003), whereas hypercapnic ventilatory response was not statistically different. In anesthetized, spontaneously breathing animals, response to brief hyperoxia (Dejours' test, an index of peripheral chemoreceptor sensitivity) and neural hypoxic ventilatory response were augmented in BM-exposed relative to control animals. as measured by diaphragmatic electromyelograms. The enhanced hypoxic sensitivity persisted following bilateral vagotomy, but was abolished by bilateral carotid sinus nerve transection. These data demonstrate that afferent sensory input from the carotid body contributes to a selective enhancement of hypoxic ventilatory drive in early lung injury in the absence of pulmonary fibrosis and arterial hypoxemia.