Indomethacin pretreatment in continuous positive-pressure ventilation.

The purpose of the study was to investigate the possible involvement of prostaglandins (PG) and thromboxanes (TX) in the cardiovascular and pulmonary changes associated with the use of continuous positive-pressure ventilation (CPPV). Indomethacin (IND), an inhibitor of PG cyclo-oxygenase, was used to block the synthesis and release of PG and TX in the lung after alveolar stretch with CPPV. Groups of dogs received CPPV (buffer group) or CPPV + IND 5 mg/kh iv (CPPV + IND). Pulmonary edema or alveolar hemorrhage was evident in 5 of 6 buffer animals. This damage was also manifested by a 50% decrease in lung compliance. However, IND appeared to block development of lung tissue damage in 5 of 6 CPPV + IND dogs and compliance remained normal. A 52% lowering of cardiac index (CI) in the buffer group paralleled a 71% reduction of left ventricular dP/dt max (first derivative of left ventricular pressure). Peak transmural right heart filling pressure decreased only 15%. in contrast, the 38% decrement of CI in the CPPV + IND animals was coupled with a 98% reduction in filling pressure, but only a 25% decrease in dP/dt max. CPPV-induced changes may have been related, in part, to the release of cytotoxic negative inotrope(s) from damaged alveolar membranes because IND pretreatment blocked this damage.