THE ROLE OF ENDOTHELIN-1 AS A MEDIATOR OF THE PRESSURE RESPONSE AFTERAIR-EMBOLISM IN BLOOD-PERFUSED LUNGS

Objective: It is well known that lung embolism is associated with an i ncrease in pulmonary vascular resistance. Since the mech anisms of pul monary vascular reactions during embolism are still unclear, the aim o f this study was to investigate the potential involvement of endotheli n-l (ET-1) and thromboxane A(2) (TXA(2)) as mediators of the pulmonary artery pressure (PAP) increase after embolism using the selective ETA receptor antagonist LU135 252 [1], the ETB receptor antagonist BQ788 [2], and the cyclooxygenase inhibitor diclofenac. Design: Prospective experimental study in rabbits. Setting: Experimental laboratory in a u niversity teaching hospital. Subjects: 36 adult rabbits of either sex. Interventions: The experiments were performed in 36 isolated and vent ilated rabbit lungs which were perfused with a buffer solution contain ing 10% of autologous blood. Embolism was induced by the injection of 0.75 mi air into the pulmonary artery. Measurements and results: PAP a nd lung weight, reflecting edema formation, were continuously recorded . Perfusate samples were drawn intermittently to determine TXA(2) and ET-1 concentrations. Air injection resulted in an immediate increase i n PAP up to 22.8 +/- 1.4 mm Hg at 2.5 min (control, n = 6), which was parallelled by an enhanced generation of TXA(2). No relevant edema for mation occurred during the observation period. Pretreatment with the E TA receptor antagonist LU135 252 significantly reduced the pressure re action after air embolism (p < 0.001) whereas the ETB receptor antagon ist BQ788 (Iz = 6) was without marked effects. The administration of d iclofenac (n = 6) did not alter the PAP increase 2.5 min after embolis m, but significantly re duced the pressure reaction during the further observation period (p < 0,001). The application of LU135 252 and dicl ofenac together (it = 6) also significantly reduced the PAP increase f rom 2.5 min during the total observation period (p < 0.001). Conclusio ns: The acute pressure reaction after air embolism is mainly mediated via ET-1 by an ETA receptor related mechanism, TXA(2) seems to maintai n this reaction for a longer time.