Hypercapnic acidosis transiently weakens hypoxic pulmonary vasoconstriction without affecting endogenous pulmonary nitric oxide production.

PURPOSE: Hypercapnic acidosis often occurs in critically ill patients and during protective mechanical ventilation; however, the effect of hypercapnic acidosis on endogenous nitric oxide (NO) production and hypoxic pulmonary vasoconstriction (HPV) presents conflicting results. The aim of this study is to test the hypothesis that hypercapnic acidosis augments HPV without changing endogenous NO production in both hyperoxic and hypoxic lung regions in pigs. METHODS: Sixteen healthy anesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Eight pigs received 10% carbon dioxide (CO(2)) inhalation to both lung regions (hypercapnia group), and eight pigs formed the control group. NO concentration in exhaled air (ENO), nitric oxide synthase (NOS) activity, cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured. RESULTS: There were no differences between the groups for ENO, Ca(2+)-independent or Ca(2+)-dependent NOS activity, or cGMP in hypoxic or hyperoxic lung regions. Relative perfusion to LLL (Q (LLL)/Q (T)) was reduced similarly in both groups when LLL hypoxia was induced. During the first 90 min of hypercapnia, Q (LLL)/Q (T) increased from 6% (1%) [mean (standard deviation, SD)] to 9% (2%) (p < 0.01), and then decreased to the same level as the control group, where Q (LLL)/Q (T) remained unchanged. Cardiac output increased during hypercapnia (p < 0.01), resulting in increased oxygen delivery (p < 0.01), despite decreased PaO(2) (p < 0.01)(.) CONCLUSIONS: Hypercapnic acidosis does not potentiate HPV, but rather transiently weakens HPV, and does not affect endogenous NO production in either hypoxic or hyperoxic lung regions.

Distant effects of nitric oxide inhalation in endotoxemic pigs.

OBJECTIVE: Inhalation of nitric oxide (INO) has distant effects. By a blood- borne factor, INO down-regulates endogenous nitric oxide production in healthy pig lungs, resulting in vasoconstriction in lung regions not directly reached by INO. The aim of this study was to investigate whether INO has distant effects in endotoxemic pig lungs. The hypothesis was that INO down-regulates endogenous NO production in lung regions not reached by INO. DESIGN: Prospective, randomized animal study. SETTING: University hospital research laboratory. SUBJECTS: Twenty-two pairs of domestic pigs. INTERVENTIONS: Cross-circulation was established in 22 pairs of anesthetized pigs. Nine pairs received endotoxin (control group) and 13 pairs received endotoxin, with one pig inhaling NO (80 ppm) and one pig receiving blood from that pig (NO-blood recipient group). MEASUREMENTS AND MAIN RESULTS: NO in exhaled air, NO synthase activity in lung tissue, endothelin-1 in the blood, ETA and ETB receptor immunoreactivity in lung tissue, vital parameters, and blood gases were measured. Endotoxin per se increased NO in exhaled air by 100% compared to baseline (control group). In the NO-blood recipient group, i.e., pigs receiving blood from the NO-inhaling pigs, NO in exhaled air increased by 300% (p = .03). The Ca-dependent NO synthase activity was higher in these pigs (p = .02), indicating increased endogenous NO production. The ET B receptor immunoreactivity was higher in the NO-blood recipient group (p = .004). CONCLUSIONS: As opposed to findings in healthy pigs, INO in endotoxemic pigs causes an increase in endogenous NO production in lung regions not reached by INO. Increased NO production in nonventilated lung regions may cause vasodilatation, counteracting the INO-induced increase in blood flow to the ventilated lung regions.

Central hemodynamics during lung recruitment maneuvers at hypovolemia, normovolemia and hypervolemia. A study by echocardiography and continuous pulmonary artery flow measurements in lung-injured pigs.

OBJECTIVE: The impact of lung-recruitment maneuvers on heart function at different volemic levels has not been studied in detail. We therefore investigated the effect on central hemodynamics of lung recruitment maneuvers at hypovolemia, normovolemia and hypervolemia in experimental lung injury. DESIGN: Randomized, controlled, cross-over experimental study. SETTING: Animal laboratory at a university hospital. PARTICIPANTS: Eleven anesthetized and lung-lavaged pigs. INTERVENTION: The animals were randomized to 10-s lung recruitment maneuvers followed by 30-s maneuvers (40 cm H(2)O airway pressure) or vice versa, performed under hypovolemia, normovolemia and hypervolemia. MEASUREMENTS AND MAIN RESULTS: Left-ventricular end-diastolic diameter and cardiac output were measured before, during, and 1 min and 5 min after the lung recruitment maneuver and left-ventricular eccentricity index was calculated for before and during the maneuver. Cardiac output and left-ventricular end-diastolic diameter (within parentheses) decreased significantly during both the 10-s and 30-s lung recruitment maneuvers at hypovolemia, by a mean of 89% (35) and 92% (33), at normovolemia by 75% (33) and 86% (32), and at hypervolemia by 56% (32) and 64% (43), respectively. At hypovolemia, cardiac output was increased above baseline 1-5 min following the 30-s maneuver. Left-ventricular eccentricity index increased significantly during the maneuver, indicating right ventricular dysfunction. CONCLUSIONS: In this animal lung injury model, lung recruitment maneuvers significantly decreased left-ventricular end-diastolic volume and cardiac output at hypovolemia. Hypervolemia did partly counteract this compromise. In addition, a marked right-ventricular dysfunction during the maneuver was found.