Acute lung injury augments hypoxic ventilatory response in the absence of systemic hypoxemia

1 Department of Medicine, Division of Pulmonary and Critical Care, 2 Department of Physiology and Biophysics, and 3 Department of Radiology, Division of Nuclear Medicine, Case Western Reserve University, Cleveland, Ohio Submitted 25 January 2006 ; accepted in final form 27 July 2006 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; 1 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 P O 2 , and arterial P CO 2 were comparable between both groups of animals. Ventilatory responses to hypoxia (12% O 2 ) and hypercapnia (7% CO 2 ) were measured by whole body plethysmography 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. carotid body; hypoxia; control of breathing Address for reprint requests and other correspondence: F. Jacono, Dept. of Medicine, Division of Pulmonary & Critical Care, Case School of Medicine, BRB Rm. 321, 10900 Euclid Ave., Cleveland, Ohio 44106 (e-mail: frank.jacono{at}case.edu )