Endothelin-1 blockade corrects mesenteric hypoperfusion in a porcine low cardiac output model.
OBJECTIVE
To study the importance of endothelin-1-induced vasoconstriction in a model of acute and maintained low cardiac output, by investigating regional changes within the mesenteric and particularly the intestinal mucosal circulation.


METHODS
Prospective, controlled animal study.


METHODS
University-affiliated research laboratory.


METHODS
Thirteen fasted, anesthetized, mechanically ventilated landrace pigs.


RESULTS
Cardiac output, portal venous blood flow, renal arterial flow, jejunal mucosal microcirculation by laser Doppler flowmetry, jejunal capnotonometry (Pco2 gap), and jejunal mucosal oxygenation (tPo2) were monitored. Cardiac tamponade was established to reduce portal venous blood flow to a preset end point at two thirds of baseline. Measurements were made at baseline, after 90 mins of cardiac tamponade, and 90 mins after the administration of the combined endothelinA/endothelinB antagonist tezosentan at 1 mg.kg-1.hr-1 during tamponade in seven animals. Six animals served as time controls and received only the vehicle. Cardiac tamponade decreased portal venous blood flow, renal arterial flow, and laser Doppler flowmetry, whereas the Pco2 gap increased. The change in tPo2 failed to gain statistical significance (p =.08). Administration of tezosentan during tamponade restored portal venous blood flow and laser Doppler flowmetry to baseline values, increased tPo2 above baseline, and decreased Pco2 gap. No effect on renal arterial flow was observed. Investigated variables remained unchanged in control animals after induction of cardiac tamponade.


CONCLUSIONS
Endothelin-1 blockade in acute cardiac failure improves mesenteric, but not renal, perfusion, illustrating the regional importance of endothelin-1-induced vasoconstriction. Importantly, endothelin-1 blockade restored mucosal blood flow and oxygenation, which might be particularly interesting considering the implications for maintenance of mucosal barrier integrity in low output states.
Burgener
D
D
Division of Gastroenterology and Hepatology, Geneva University Hospital, 1211 Geneva 4, Switzerland. dominique.burgener@hcuge.ch
Laesser
M
M
Treggiari-Venzi
M
M
Oi
Y
Y
Jolliet
P
P
Strasser
S
S
Hadengue
A
A
Aneman
A
A
D000818:Animals; D001784:Blood Gas Analysis; D002303:Cardiac Output, Low / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D005260:Female; D006439:Hemodynamics; D006863:Hydrogen-Ion Concentration; D008297:Male; D010092:Oximetry; D010477:Perfusion; D011725:Pyridines / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D011725:Pyridines; D013777:Tetrazoles; D014665:Vasodilator Agents; C120582:tezosentan