Pulmonary NO synthase inhibition and inspired CO2: effects on V ′/Q ′ and pulmonary blood flow distribution

Abstract

Inhaled carbon dioxide decreases ventilation/perfusion ratio (V '/Q ') heterogeneity in dogs. The aim of this study was to test whether inhaled CO 2 improves the V '/Q ' by inhibition of nitric oxide production and whether inhibition of endogenous NO production in the lung alters gas exchange and V '/Q ' matching.Eleven healthy dogs were anaesthetized and mechanically ventilated. The multiple inert gas elimination technique (MIGET) was used to measure V '/Q ' heterogeneity and regional pulmonary blood flow heterogeneity was assessed in five dogs using fluorescent microspheres. In a separate set of five dogs, exhaled NO levels were measured via chemiluminescence. All dogs were studied before and after 4.8% inspired CO 2 , and then given the NO synthase inhibitor N v -nitro-L-arginine methyl ester (L-NAME, 10 mg . kg -1 ) via nebulization, after which they were studied again with room air and inhaled CO 2 .CO 2 and L-NAME improved arterial and alveolar oxygen tension, but the improvements with L-NAME did not reach statistical significance. Improved V '/Q ' matching, as assessed by the MIGET, occurred under all experimental conditions. Exhaled NO levels were reduced by 40% with CO 2 and 70% with L-NAME. The standard deviation of regional pulmonary blood flow assessed via microspheres decreased only with inhaled CO 2 . Fractal analysis of pulmonary blood flow distributions revealed that regional blood flow was highly correlated with flow to neighbouring pieces of lung in all four conditions with no changes in the fractal dimension.Inspired carbon dioxide improves ventilation perfusion ratio matching and is associated with a more homogeneous distribution of pulmonary blood flow. Although inspired carbon dioxide causes a reduction in exhaled nitric oxide, the differences in pulmonary perfusion distributions found between carbon dioxide and N v -nitro-Larginine methyl ester suggest that the carbon dioxide effect is not mediated by a reduction in nitric oxide production. The improved ventilation perfusion ratio matching with inhibition of nitric oxide synthase suggests the intriguing possibility requiring further study that endogenous production of nitric oxide in the lung does not subserve ventilation perfusion ratio regulation. Eur Respir J 2000; 16: 288±295. Addition of low concentrations (2±5%) of carbon dioxide to inspired gas improves gas exchange and arterial oxygenation in normal lungs [1,2]. Using the multiple inert gas elimination technique (MIGET), it was demonstrated that inspired CO 2 reduces ventilation/perfusion ratio (V '/Q ') heterogeneity even with constant ventilation [3]. Although CO 2 has many effects on the lungs that may promote V '/Q ' matching [4,5], it remains unknown how and at what site(s) CO 2 decreases V '/Q ' heterogeneity.Changes in CO 2 concentration or the accompanying pH may affect airways, parenchyma or vessels directly or indirectly through modulation of effector substances such as prostaglandins [6] or calcium [7]. Of considerable interest, also, is nitric oxide, which is ...

Effects of S-Nitrosation and Cross-Linking of Hemoglobin on Hypoxic Pulmonary Vasoconstriction in Isolated Rat Lungs

“…This is in contrast to other species, including rabbits, pigs, dogs, and humans, whereby similar manipulations result in a fall in eNO. 8,[31][32][33][34][35][36][37][38] Our findings are similar to those of other investigators, who have documented eNO concentrations of Ϸ1 to 5 ppb from intact rats and isolated rat lungs, in addition to insensitivity to NOS inhibition and excess NOS substrate (L-arginine). 39 -44 The lack of change in eNO is in contrast to the observed vascular effects seen with addition of free Hb to the perfusate ( Figure 2), NOS inhibition, and addition of GSNO to the perfusate.…”

Acute Hypercapnia Improves Indices of Tissue Oxygenation More than Dobutamine in Septic Shock

“…It is possible that, in their study, the shorter observation period, the high severity of lung injury induced, and the lack of fluid resuscitation may have limited the beneficial effects of hypercapnia from occurring or being observed. Indeed, hypercapnic acidosis has been demonstrated to enhance hypoxic pulmonary vasoconstriction (17) and to decrease regional pulmonary blood flow heterogeneity (36). Although hypercapnia in our experiments did not influence lung compliance or airway pressure globally, we cannot rule out the possibility that CO 2 could have more local bronchodilating effects (37, 38) on dependent areas with altered ventilation/ perfusion matching and regional bronchoconstriction.…”

The Significance of Transcutaneous Continuous Overnight CO2Monitoring in Determining Initial Mechanical Ventilator Application for Patients with Neuromuscular Disease

“…Likewise, a delay in treatment of pulmonary insufficiency may increase the burden of cardiovascular work, which can increase cardiovascular complications 12,13. In early-stage respiratory failure, mechanical ventilator support can resolve the fatigue of respiratory muscles.…”