Positive end-expiratory pressure ventilation elicits increases in endogenously formed nitric oxide as detected in air exhaled by rabbits

Abstract

Background: Nitric oxide (NO) formed from L-arginine is exhaled by mammals and regulates pulmonary vascular tone. Little is known about how its formation is stimulated. Methods: The concentration of NO in exhaled air was monitored by chemiluminescence in pentobarbital-anesthetized rabbits receiving mechanical ventilation by tracheostomy with graded positive end- expiratory pressure (PEEP). Results: Introduction of PEEP (2.5-15 cmH2O) elicited dose-dependent and reproducible increments in exhaled NO and in arterial oxygen tension (Pa(O2)). The increase in exhaled NO exhibited a biphasic pattern, with an initial peak followed by a partial reversal during the 4-min period at each level of PEEP. Thus, at a PEEP of 10 cmH2O, exhaled NO initially increased from 19 ± 4 to 30 ± 5 parts per billion (ppb) (P < 0.001, n = 9) and then decreased to 27 ± 5 ppb (P < 0.005) at the end of the 4-min observation period. Simultaneously, Pa(O2) increased from 75 ± 12 mmHg in the control situation to 105 ± 11 mmHg (P < 0.05) at a PEEP of 10 cmH2O. After bilateral vagotomy, including bilateral transection of the depressor nerves, the increase in exhaled NO in response to PEEP was significantly reduced (P < 0.01). Thus, after vagotomy, a PEEP of 10 cmH2O elicited an increase in the concentration of exhaled NO from 13 ± 3 to 17 ± 3 ppb (n = 7). Vagotomy did not affect the baseline concentration of NO in exhaled air. The PEEP-induced increments in Pa(O2) were not affected by the NO synthase inhibitor L-N(ω)-arginine-methylester (30 mg · kg-1 intravenously). In open-chest experiments, PEEP (10 cmH2O) induced a reduction in cardiac output from 317 ± 36 to 235 ± 30 ml · min-1 and an increase in exhaled NO from 23 ± 6 to 30 ± 7 ppb (P < 0.05, n = 5). Reduction in cardiac output from 300 ± 67 to 223 ± 52 ml · min-1 by partial obstruction of the pulmonary artery did not significantly increase exhaled NO (from 23 ± 7 to 25 ± 6, difference not significant; n = 3). Conclusions: PEEP elicited increments in exhaled NO, perhaps by a stretch- dependent effect on the respiratory system. This finding may be attributed in part to a vagally influenced mechanism.