Tezosentan normalizes hepatomesenteric perfusion in a porcine model of cardiac tamponade.
BACKGROUND
To investigate endothelin-1 (ET-1)-dependent hepatic and mesenteric vasoconstriction, and oxygen and lactate fluxes in an acute, fixed low cardiac output (CO) state.


METHODS
Sixteen anesthetized, mechanically ventilated pigs were studied. Cardiac tamponade was established to reduce portal venous blood flow (Q(PV)) to 2/3 of the baseline value. CO, hepatic artery blood flow (Q(HA)), Q(PV), hepatic laser-Doppler flow (LDF), hepatic venous and portal pressure, and hepatic and mesenteric oxygen and lactate fluxes were measured. Hepatic arterial (R(HA)), portal (R(HP)) and mesenteric (R(mes)) vascular resistances were calculated. The combined ET(A)-ET(B) receptor antagonist tezosentan (RO 61-0612) or normal saline vehicle was infused in the low CO state. Measurements were made at baseline, after 30, 60, 90 min of tamponade, and 30, 60, 90 min following the infusion of tesozentan at 1 mg/kg/h.


RESULTS
Tamponade decreased CO, Q(PV), Q(HA), LDF, hepatic and mesenteric oxygen delivery, while hepatic and mesenteric oxygen extraction and lactate release increased. R(HA), R(HP) and R(mes) all increased. Ninety minutes after tesozentan, Q(PV), LDF and hepatic and mesenteric oxygen delivery and extraction increased approaching baseline values, but no effect was seen on CO or Q(HA). Hepatic and mesenteric handling of lactate converted to extraction. R(HA), R(HP) and R(mes) returned to baseline values. No changes were observed in these variables among control animals not receiving tesozentan.


CONCLUSIONS
In a porcine model of acute splanchnic hypoperfusion, unselective ET-1 blockade restored hepatomesenteric perfusion and reversed lactate metabolism. These observations might be relevant when considering liver protection in low CO states.
Aneman
A
A
Department of Anesthesiology and Intensive Care, Sahlgrenska University Hospital, Göteborg, Sweden. anders.aneman@medfak.gu.se
Treggiari
M M
MM
Burgener
D
D
Laesser
M
M
Strasser
S
S
Hadengue
A
A
D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D002303:Cardiac Output, Low / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002305:Cardiac Tamponade / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004353:Drug Evaluation, Preclinical; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D007773:Lactates / Q000097:blood; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D013152:Splanchnic Circulation / Q000187:drug effects*; D034421:Sus scrofa; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007773:Lactates; D011725:Pyridines; D013777:Tetrazoles; D002245:Carbon Dioxide; C120582:tezosentan; D010100:Oxygen