Hypoxic pulmonary vasoconstriction and gas exchange in acute canine pulmonary embolism

Abstract

Hypoxic pulmonary vasoconstriction (HPV) is inhibited in several models of acute lung injury. Whether HPV is preserved in pulmonary embolism is unknown. We investigated the effects of a reduction in the fraction of inspired O2 (FIO2) on pulmonary hemodynamics and gas exchange in anesthetized dogs before and after autologous blood clot pulmonary embolism. In a first group of 14 dogs, stimulus-response curves for HPV were constructed as pulmonary arterial pressure (Ppa) vs. FIO2 varied between 1.0 and 0.06 at a cardiac output (Q) kept constant at 3.5 l.min-1.m-2. Gas exchange was evaluated by using the multiple inert-gas elimination technique at FIO2 of 1.0, 0.4, and 0.1. Embolism decreased the relative magnitude of HPV, expressed as the gradient between Ppa and pulmonary arterial occluded pressure in hypoxia divided by (Ppa-pulmonary arterial occluded pressure) at FIO2 of 1.0, from 1.8 to 1.2 (P < 0.05). Retention minus excretion gradients for sulfur hexafluoride and ethane were increased by decreased FIO2 (P < 0.005 and P < 0.05, respectively) before but not after embolism. Hypoxia-induced deterioration in gas exchange before embolism was related to the amount of baseline very low ventilation-perfusion (VA/Q) ratios. Similar results were obtained in a second group of seven dogs with Q decreased to maintain Ppa at the same average value as before embolism. However, gas exchange was not affected by inspiratory hypoxia before as well as after embolism in this group, which presented with a lesser amount of baseline very low VA/Q. In both groups of dogs, increase in the FIO2 from 0.4 to 1.0 did not affect gas exchange. We conclude that 1) pulmonary embolism is associated with a partial inhibition of HPV, 2) HPV does not contribute to preserve gas exchange in pulmonary embolism, and 3) a strong HPV may deteriorate gas exchange in severe hypoxia in the presence of minor very low VA/Q inequality.