Favorable and unfavorable effects of permissive hypercapnia on pulmonary microcirculation - Permissive hypercapnia: Natural or not?

To examine the beneficial effects of permissive hypercapnic ventilation (PHC), we studied alterations in pulmonary microvascular reactivity to hypoxia, hydrogen ions or CO₂ in injured lungs harvested from animals after prolonged exposure to a hyperoxic environment. In addition, the influence of hypercapnic acidosis induced by PHC on cellular and subcellular functions was examined by analyzing changes in intracellular Ca ions and expression of various adhesion molecules in human pulmonary artery endothelial cells (HPAEC). The following conclusions were obtained in lungs injured by exposure to hyperoxia: 1) constriction of precapillary arterioles in response to hypoxic stimulation is attenuated, probably due to upregulation of COX-1, eNOS, and iNOS within the acini, 2) hydrogen ion-elicited arteriolar constriction is significantly increased, although it appears not to be mediated by either COX- or NOS-related vasoactive substances, 3) in association with intraacinar augmentation in COX, CO₂ evoked microvascular dilation is blunted, 4) PHC significantly increases concentration of free Ca ions in HPAECs, 5) depending on the degree of acidosis and on the CO₂ concentration, expression of VCAM-1 and ICAM-1 on HPAEC surface is upregulated. These findings suggest that PHC has some disadvantages in addition to the advantages that have been documented.