Vascular and airway effects of endogenous cyclooxygenase products during lung inflation

The influence of lung inflation on lung elasticity and pulmonary resistance (RL) and on pulmonary and bronchial hemodynamics was examined in five anesthetized, mechanically ventilated adult sheep before and after treatment with the cyclooxygenase inhibitor indomethacin (2 mg/kg). Lung inflation was accomplished by increasing levels of positive end-expiratory pressure (PEEP). Measurements of pulmonary vascular resistance (PVR), bronchial blood flow (Qbr), and RL were obtained with a Swan-Ganz catheter, with an electromagnetic flow probe placed around the carinal artery, and by relating airflow to transpulmonary pressure (Ptp), respectively. Before indomethacin, increasing PEEP from 5 to 15 cmH2O increased mean lung volume (VL) to 135% (P less than 0.01), Ptp to 165% (P less than 0.005), and PVR to 132% (P less than 0.05) of base line and decreased mean Qbr (normalized for cardiac output) to 53% (P less than 0.05) of base line. Mean RL showed a tendency to decrease with a mean value of 67% of base line at 15 cmH2O PEEP. After indomethacin the corresponding values were 121% for VL, 155% for Ptp, 124% for PVR, 35% for Qbr, and 31% for RL. The PEEP-dependent changes were not different before and after indomethacin except for mean VL, which increased less (P less than 0.05) after indomethacin. The failure of indomethacin to modify PEEP-induced changes in RL, PVR, and Qbr was also present when these parameters were expressed as a function of Ptp. These findings suggest that the cyclooxygenase products elaborated during lung inflation reduce lung elasticity but fail to influence airflow resistance and pulmonary and bronchial hemodynamics.