Contractile response of femoral arteries in pigs with acute liver failure

Abstract

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 ± s x (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.

Endothelium-derived hyperpolarization factor (EDHF) is up-regulated in a pig model of acute liver failure

“…Another important finding in the present study was the lack of evidence for vascular hyporesponsiveness to phenylephrine. This observation is consistent with our recently published study, where we found no evidence of hyporesponsiveness to vasopressors in endothelium-denuded femoral arteries [10]. Such results may suggest that loss of vascular resistance in the early phase of ALF is caused by a profound endothelium-dependent vasodilation rather than a primary vascular hyporesponsiveness to vasopressors.…”

“…During the past 8 years, we have studied circulatory disturbances in pigs with ALF, and through different approaches have characterized the pathophysiologic patterns [6,10,19,20]. Our experimental data support the concept of a generalized vasodilation across all organs studied [19].…”

“…Accordingly, we chose a well-defined region in order to be able to explore our working hypothesis, which proposes the existence of a common vasodilatory pathway through which pathologic vasodilation is transmitted during the early phase of ALF. The femoral artery is a relative large conduit artery, and with this model we found a pathologic response to decreasing arterial log Phe blood pressure [6,10,19]. Accordingly, as proof of the principles, we set out to investigate the impact of different vasodilatory pathways on the development of pathological vasodilation in this model.…”

“…In this model, we recently studied endotheliumdenuded femoral arteries without finding any evidence of vascular hyporesponsiveness in vitro [10]. In the present study, we set out to explore the impact of endothelium-derived vasodilatory pathways on the development of hyperdynamic circulation in ALF.…”

The systemic inflammatory response syndrome is predictive of renal dysfunction in patients with non-paracetamol-induced acute liver failure

“…Moreover, the degree of portal hypertension rarely equates with that of hepatorenal syndrome in cirrhosis: the mean reported hepatic venous pressure gradient for patients with ALF and renal dysfunction is 14 mm Hg compared with 21 mm Hg for patients with hepatorenal syndrome 9 – 11. Secondly, animal studies imply that the systemic vasodilatation may be more generalised and not limited to the splanchnic circulation as occurs in cirrhosis 12 13. Pigs with ALF demonstrate reduced hind leg and renal vascular resistance, which contrasts with the femoral and renal vasoconstriction of hepatorenal syndrome 12 – 15.…”