Contractile response of femoral arteries in pigs with acute liver failure.
BACKGROUND
Acute liver failure (ALF) is characterized haemodynamically by a progressive hyperdynamic circulation. The pathophysiological mechanism is unknown, but impaired contractility of vascular smooth muscle may play an important role. The aim of this study was to evaluate the vascular response to stimulation with norepinephrine and angiotensin II in endothelium-denuded femoral artery rings.


METHODS
Norwegian Landrace pigs weighing 27.1 +/- 0.5 kg (mean +/- sx (standard error of the mean)) were used. ALF was induced by performing a portacaval shunt followed by ligation of the hepatic arteries (n = 6). Sham-operated animals served as controls (n = 5). Cumulative isometric concentration contraction curves were obtained after in vitro stimulation of the femoral artery rings with either angiotensin II (10(-13) - 10(-5) mol/L) or norepinephrine (10(-13) - 10(-3) mol/L).


RESULTS
Pigs suffering from ALF developed a hyperdynamic circulation with an increased cardiac index (P = 0.017) and decreased systemic vascular resistance index (P = 0.015). Studies of the hind leg revealed a decreased vascular resistance index and increased blood flow compared to sham-operated controls (P = 0.003 and P = 0.01, respectively). Angiotensin II caused a concentration-dependent contraction of the arterial segments, with no significant differences in vascular responses between the two groups. Maximum force generated did not differ (55 +/- 7 versus 56 +/- 7 mN, P = 0.95). Furthermore, there were no differences for norepinephrine in the cumulative concentration-response curves and the maximum contractile force was not significantly different (87 +/- 8 versus 93 +/- 16 mN, P = 0.55).


CONCLUSIONS
This study documents for the first time that there are no signs of endothelium-independent peripheral vascular hyporesponsiveness to angiotensin II and norepinephrine in pigs with ALF.
Ytrebø
L M
LM
Department of Digestive Surgery, University Hospital Northern Norway, Tromsø. larsmy@fagmed.uit.no
Ekse
S
S
Sen
S
S
Rose
C
C
Nedredal
G I
GI
Fuskevåg
O-M
OM
Jalan
R
R
Revhaug
A
A
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology*; D006334:Heart Function Tests; D006439:Hemodynamics / Q000502:physiology; D017114:Liver Failure, Acute / Q000150:complications*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D000804:Angiotensin II; D009638:Norepinephrine