Selective inhibition of inducible nitric oxide synthase maintains haemodynamic stability without untoward consequences for hepatic function or morphology.
OBJECTIVE
To examine the effects of the inducible nitric oxide synthase inhibitor aminoethyl-isothiourea (AE-ITU) on haemodynamic measurements, and correlate these with hepatic morphology and function in a porcine model of endotoxaemia.


METHODS
Experimental study.


METHODS
15 juvenile pigs.


METHODS
Flow probes were placed around the hepatic artery and portal vein. Catheters were introduced into the portal and hepatic veins, pulmonary artery, and aorta. Infusion of AE-ITU was started one hour before that of endotoxin (study group n = 6); thereafter both substances were infused simultaneously until the end of the study (6 hours). The controls (n = 9) had endotoxin alone.


METHODS
Hepatic morphology assessed by light and electron microscopy; and hepatic integrity and function by transaminase activities and oxygen consumption. Systemic, pulmonary, and hepatic blood flow and pressure.


RESULTS
AE-ITU maintained systemic blood pressure (p < 0.05 compared with controls) without causing pulmonary hypertension. Neither hepatic morphology nor function were adversely influenced.


CONCLUSIONS
In endotoxaemia AE-ITU has a favourable haemodynamic profile which is achieved without impairment of hepatic function or morphology.
Gundersen
Y
Y
Institute for Surgical Research, Rikshospitalet, University of Oslo, Norway.
Saetre
T
T
Scholz
T
T
Hovig
T
T
Lilleaasen
P
P
Aasen
A O
AO
D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D019446:Endotoxemia / Q000473:pathology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D010101:Oxygen Consumption; D013552:Swine; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D000338:beta-Aminoethyl Isothiourea; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II