Effects of hypercapnia with and without acidosis on hypoxic pulmonary vasoconstriction

Abstract

Acute respiratory disorders and permissive hypercapnic strategy may lead to alveolar hypoxia and hypercapnic acidosis. However, the effects of hypercapnia with or without acidosis on hypoxic pulmonary vasoconstriction (HPV) and oxygen diffusion capacity of the lung are controversial. We investigated the effects of hypercapnic acidosis and hypercapnia with normal pH (pH corrected with sodium bicarbonate) on HPV, capillary permeability, gas exchange, and ventilation-perfusion matching in the isolated ventilated-perfused rabbit lung. No alteration in vascular tone was noted during normoxic hypercapnia with or without acidosis compared with normoxic normocapnia. Hypercapnia with normal pH resulted in a transient increase in HPV during the course of consecutive ventilation maneuvers, whereas hypercapnic acidosis increased HPV over time. Hypercapnic acidosis decreased exhaled NO during hypoxia more than hypercapnia with normal pH and normocapnia, whereas intravascular NO release was unchanged. However, inhibition of NO synthesis by nitro-L-arginine (L-NNA) resulted in a loss of the increased HPV caused by hypercapnic acidosis but not that caused by hypercapnia with normal pH. Furthermore, capillary permeability increased during hypoxic hypercapnia with normal pH but not hypoxic hypercapnic acidosis. This effect was NO-dependent because it disappeared during L-NNA administration. Ventilation-perfusion matching and arterial PO2 were improved according to the strength of HPV in hypercapnia compared with normocapnia during Tween nebulization-induced lung injury. In conclusion, the increased HPV during hypercapnic acidosis is beneficial to lung gas exchange by improving ventilation-perfusion matching and preserving the capillary barrier function. These effects seem to be linked to NO-mediated pathways.hypoxia; hypercapnic acidosis; pH; capillary permeability ACUTE RESPIRATORY DISORDERS such as acute obstructive pulmonary diseases and depression of the respiratory control center may induce alveolar hypoxia and hypercapnic acidosis, which can affect systemic regulatory processes and pulmonary function. However, the use of sodium bicarbonate, one of the most essential extracellular buffers for the normalization of pH in different pathological conditions of respiratory acidosis, is controversial. During resuscitation, application of sodium bicarbonate is generally not recommended for just correction of pH due to severe side effects (40). Furthermore, in permissive hypercapnic strategy, beneficial effects of acidosis have been discussed in the literature (5). In animal studies, a decreased development of pulmonary edema and reduced hypoxemia during hypercapnic acidosis suggests valuable effects of acidosis (13,14,(25)(26)(27), whereas from other studies it could not be distinguished whether the effects were related to hypercapnia or acidosis (12,43). In addition, the mechanisms of improvement of oxygenation and reduced lung edema formation are not known. Improvement in ventilation-perfusion matching and/or of gas diffusion acro...

Effects of Dimethylarginine Dimethylaminohydrolase–1 Overexpression on the Response of the Pulmonary Vasculature to Hypoxia

“…Our finding that the inhibition of the NO-cGMP pathway in isolated lungs only tended to increase acute HPV is consistent with a study showing that endothelial NO modulated the second phase of HPV in particular (36), and that sGC-a1 deficiency did not change the response to acute hypoxia in the lungs of anesthetized mice (37). In contrast to our findings in mice, L-NNA was shown to increase acute HPV in isolated rabbit lungs (2,38), and when comparing studies in mice, the gene deletion of eNOS resulted in an augmentation of acute HPV in isolated lungs (5). Differences in the applied setup and experimental protocol with the specific activation of NOS by specific experimental procedures may account for this discrepancy.…”

Oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction

“…carbon monoxide) [42], metabolism (e.g. pH) [43], physical influence (e.g. blood viscosity) [44], sex [40], hypoxia-inducible factor (HIF) [45], endocannabinoid anandamide [46] or arachidonic acid metabolites [47], which might be particularly relevant under physiological and pathological conditions in vivo.…”

Pulmonary Shunt Is Independent of Decrease in Cardiac Output during Unsupported Spontaneous Breathing in the Pig

“…CPAP = continuous positive airway pressure; MV = mechanical ventilation; PaCO 2 = arterial carbon-dioxide tension; PvO 2 = mixedvenous oxygen tension; SB = spontaneous breathing; s maj = major pulmonary shunt; s min = minor pulmonary shunt; VR Occl = partial occlusion of venous return. 3 † (0-5) 9 (7-11) 4 † (3-5) 10 (7-14) 7 ‡ (3-10) 11 (9-13) 2 † (1-4) In isolated lungs, hypercapnic acidosis improves HPV, but only after 3 h, 38 a considerably longer time than our experiments lasted. In intact animals, hypercapnic acidosis either increases pulmonary vascular resistance without affecting the hypoxic response, 39 or attenuates HPV through complex mechanisms.…”