Acute pulmonary hypertension after cardiopulmonary bypass in pig: the role of endogenous endothelin.
BACKGROUND
Acute pulmonary hypertension occurring after cardiopulmonary bypass can be a cause of post-operative morbidity and mortality. The purpose of this study was to investigate whether bosentan, a non-peptidic mixed endothelin antagonist affected the pulmonary hypertension induced by experimental cardiopulmonary bypass.


METHODS
Pigs were anesthetized and instrumented to determine hemodynamic measurements. Pigs were randomized to receive either 3 mg/kg bolus + 7 mg/kg per h bosentan (n = 8) or saline (n = 7). All pigs underwent 90 min of cardiopulmonary bypass and were further observed for a 120-min period.


RESULTS
In the control group, cardiopulmonary bypass induced a dramatic pulmonary hypertension (+78 +/- 13%, P < 0.005) and accompanied an increase of pulmonary vascular resistance (+228 +/- 50%, P < 0.005), whereas, in the treated group, bosentan completely prevented these deleterious effects of cardiopulmonary bypass with only a moderate decrease of systemic vascular resistance (-19 +/- 14.6%, P < 0.05).


CONCLUSIONS
The present findings support the hypothesis that endogenous endothelin is a mediator of acute pulmonary hypertension occurring after cardiopulmonary bypass. Bosentan, a mixed endothelin antagonist completely prevented pulmonary hypertension after cardiopulmonary bypass and may, therefore, have therapeutic applications in the management of patients following cardiac surgery.
Carteaux
J P
JP
Laboratoire de Chirurgie Experimentale, Faculte de Medecine de Nancy, France. jp.carteaux@chu-nancy.fr
Roux
S
S
Siaghy
M
M
Schjöth
B
B
Dolofon
P
P
Bechamps
Y
Y
Mertes
P M
PM
Villemot
J P
JP
D000208:Acute Disease; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000077300:Bosentan; D002315:Cardiopulmonary Bypass; D019332:Endothelin-1 / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013552:Swine
D000959:Antihypertensive Agents; D019332:Endothelin-1; D013449:Sulfonamides; D000077300:Bosentan