B. L. Eisenstein

Hypocapnia worsens arterial blood oxygenation and increases VA/Q heterogeneity in canine pulmonary edema

BackgroundHyperventilation frequently is employed to reduce carbon dioxide partial pressure in patients in the operating room and intensive care unit. However the effect of hypocapnia on oxygenation is complex and may result in worsening in patients with preexisting intrapulmonary shunt. To better define the interplay between hypocapnia and oxygenation, the effects of hypocapnia and hypercapnia on the matching of ventilation (VA) and perfusion (Q) were studied in dogs with oleic acid-induced pulmonary edema, using the multiple inert gas elimination technique. MethodsEight pentobarbital-anesthetized, closed-chested dogs were administered 0.06 ml/kg of oleic acid at least 150 min prior to study. Ventilation was set with an F1o2; of 0.90, a tidal volume of 20 ml/kg, and a respiratory rate of 35 breaths/ min. The arterial carbon dioxide tension (PaCo2) was varied in a randomized order to three levels (26, 38, and 50 mmHg) by altering the amount of CO2 in the inspired gas mixture. Gas exchange was assessed by true shunt, dead space, the log standard deviation of the perfusion (log SDQ) and the ventilation (log SDv) distributions, and the tracer inert gas arterial-alveolar difference ([a-A]D) area. ResultsCardiac output (4.1 ± 0.4 I./min), mean pulmonary artery pressure (25 ± 1 mmHg), inert gas shunt (22 ± 3%), and dead space (38 ± 4%) during normocapnia were not different from that during hypocapnia and hypercapnia. Hypocapnia increased (P <.05) the alveolar-arterial oxygen tension difference (P[A-a]o2) and decreased (P <.05) the arterial blood oxygen tension (Pao2 181 ± 33 mmHg vs. 221 ± 35 mmHg with normocapnia). P[A-a]o2 and Pao2 were unaffected by hypercapnia. During hypocapnia, VA/Q inequality increased, demonstrated by an increase (P <.05) in log SDQ (1.60 ± 0.15 vs. 1.35 ± 0.19 with normocapnia) and in the [a-A]D area (0.63 ± 0.09 vs. 0.50 ± 0.09 with normocapnia) indexes of VA/Q heterogeneity. During hypercapnia, the [a-A]D area (0.63 ± 0.11) and log SDv (1.13 ± 0.10 compared to 0.97 ± 0.12 with normocapnia) also were increased (P <.05). With hypocapnia, there was a small but insignificant increase in blood flow to shunt and low VA/Q areas (29 ± 4% compared to 26 ± 4% with normocapnia). In the presence of a high F1o2 this small increase in shunt and low VA/Q may result in a significant decrease in Pao2. ConclusionsBoth hypocapnia and hypercapnia were associated with an increased VA/Q inequality. However, PaOi decreased and P[A-a]o2 increased with only hypocapnia. These results suggest that hyperventilation to reduce PaCo2 may be detrimental to arterial Po2 in some patients with lung disease.

Increased pulmonary perfusion worsens ventilation-perfusion matching.

BackgroundSevere exercise and administration of vaso-pressors may adversely affect pulmonary gas exchange in humans. The role of increases in pulmonary perfusion in worsening ventilation-perfusion (&OV0312;A/&OV0422;) relationships is unclear, however, because concomitant changes in ventilation and alveolar gas composition occur. The purpose of this study was to determine whether increasing of lobar blood flow increased &OV0312;A/&OV0422; heterogeneity in the absence of changes in respiratory parameters. MethodsSix pentobarbital-anesthetized dogs underwent bilateral thoracotomies, left upper lobectomy, and placement of an electromagnetic flow probe on the left lower lobe (LLL) pulmonary artery, and catheters were inserted into the LLL pulmonary artery distal to the flow probe and confluent trunk of the LLL pulmonary vein. A bronchial divider was inserted to allow separate ventilation of the right lung and LLL. Blood flow to the LLL (&OV0422;LLL) was increased in random order to two and three times baseline blood flow by opening an arteriovenous fistula and partially occluding the right pulmonary artery. Minute ventilation and alveolar Pco2 of the lobe were unchanged due to use of constant tidal volume and respiratory rate and inspiration of variable amounts of carbon dioxide. &OV0312;a/&OV0422; distributions of the LLL were obtained using the multiple inert gas elimination technique. The tracer inert gas arterialalveolar difference ([a-A]D) area was used to assess &OV0312;a/&OV0422; mismatch. ResultsIncreasing &OV0422;LLL increased mean pulmonary artery pressure in the LLL (LLL Ppa). The PO2 of the LLL pulmonary venous blood remained unchanged, as the mixed venous oxygen tension (Pvo2,) was markedly increased. &OV0312;a/&OV0422; inequality was increased, indicated by a 40% increase in the [a-A]D area when &OV0422;lll was increased to two times greater than baseline &OV0422;LLL and a 58% increase in the [a-A]D area with three times greater than baseline &OV0422;LLL. The [a-A]D area was highly correlated with the lobar blood flow (r = 0.97) and LLL Ppa (r = 0.97). ConclusionsMarked increases in lobar blood flow and Ppa worsened pulmonary gas exchange. The degree of impairment was correlated with the degree of increase in lobar perfusion. However, increased lobar perfusion did not affect LLL pulmonary venous blood oxygenation because the decrease in Po2, due to increased &OV0312;a/&OV0422; mismatch, was opposed by an increase in PO2, due to increased PvO2.

Alveolar hypoxia, inhibition of hypoxic pulmonary vasoconstriction, and permeability edema

We previously reported that regional alveolar hypoxia reduces oleic acid-induced permeability edema formation [Cheney et al. (1987). J. Appl. Physiol. 62: 1690-1697]. In order to define the role of hypoxic pulmonary vasoconstriction (HPV) on this effect, we studied the effects of regional alveolar hypoxia on permeability edema formation with this response inhibited. Dogs weighing 25 +/- 1 kg in which the HPV response had been inhibited by the administration of minoxidil (1 mg/kg i.v.) were anesthetized, mechanically ventilated and had a bronchial divider placed so the left lower lobe (LLL) could be ventilated with an FIO2 = 0.05 or FIO2 = 1, while the right lung was continuously ventilated with an FIO2 = 1.0. In 10 study animals the LLL was ventilated with an FIO2 = 0.05 for 4 h after induction of bilateral permeability pulmonary edema with 0.05 ml/kg of intravenous oleic acid. In six control animals the LLL was ventilated with an FIO2 = 1 for 4 h after the same injury. Postmortem gravimetric analysis indicates that alveolar hypoxia of the LLL with the HPV response inhibited had no effect on pulmonary edema formation. We conclude that inhibition of HPV abolishes the protective effect of regional alveolar hypoxia on oleic acid-induced permeability edema formation.