The role of endothelin-1 as a mediator of the pressure response after air embolism in blood perfused lungs.
OBJECTIVE
It is well known that lung embolism is associated with an increase in pulmonary vascular resistance. Since the mechanisms of pulmonary vascular reactions during embolism are still unclear, the aim of this study was to investigate the potential involvement of endothelin-1 (ET-1) and thromboxane A2 (TXA2) as mediators of the pulmonary artery pressure (PAP) increase after embolism using the selective ETA receptor antagonist LU135252 [1], the ETB receptor antagonist BQ788 [2], and the cyclooxygenase inhibitor diclofenac.


METHODS
Prospective experimental study in rabbits.


METHODS
Experimental laboratory in a university teaching hospital.


METHODS
36 adult rabbits of either sex.


METHODS
The experiments were performed in 36 isolated and ventilated rabbit lungs which were perfused with a buffer solution containing 10% of autologous blood. Embolism was induced by the injection of 0.75 ml air into the pulmonary artery.


RESULTS
PAP and lung weight, reflecting edema formation, were continuously recorded. Perfusate samples were drawn intermittently to determine TXA2 and ET-1 concentrations. Air injection resulted in an immediate increase in PAP up to 22.8 +/- 1.4 mm Hg at 2.5 min (control, n = 6), which was parallelled by an enhanced generation of TXA2. No relevant edema formation occurred during the observation period. Pretreatment with the ETA receptor antagonist LU135252 significantly reduced the pressure reaction after air embolism (p < 0.001) whereas the ETB receptor antagonist BQ788 (n = 6) was without marked effects. The administration of diclofenac (n = 6) did not alter the PAP increase 2.5 min after embolism, but significantly reduced the pressure reaction during the further observation period (p < 0.001). The application of LU135252 and diclofenac together (n = 6) also significantly reduced the PAP increase from 2.5 min during the total observation period (p < 0.001).


CONCLUSIONS
The acute pressure reaction after air embolism is mainly mediated via ET-1 by an ETA receptor related mechanism. TXA2 seems to maintain this reaction for a longer time.
Institute of Anesthesiology and Operative Intensive Care Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany.
J
J
Schmeck
T
T
Koch
B
B
Patt
A
A
Heller
H
H
Neuhof
K
K
van Ackern
D000704:Analysis of Variance; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D004195:Disease Models, Animal; D004618:Embolism, Air / Q000209:etiology / Q000503:physiopathology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000032:analysis / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000494:pharmacology; D010477:Perfusion; D010666:Phenylpropionates / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology*; D011655:Pulmonary Embolism / Q000503:physiopathology*; D011743:Pyrimidines / Q000494:pharmacology; D011817:Rabbits; D011863:Radioimmunoassay; D013928:Thromboxane A2 / Q000032:analysis / Q000502:physiology*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010666:Phenylpropionates; D010880:Piperidines; D011743:Pyrimidines; D004008:Diclofenac; C107831:darusentan; C086539:BQ 788; D013928:Thromboxane A2