The effects of vasopressin and its analogues on the liver and its disorders in the critically ill

Asfar, Pierre; Radermacher, Peter; Calès, Paul; Oberti, Frédéric

doi:10.1097/mcc.0b013e328335a35b

Cited by 11 publications

(7 citation statements)

References 56 publications

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“…Because of its strong vasoconstrictor effect, concerns have been raised about vasopressin use and its impact on splanchnic circulation with a fear of splanchnic ischaemia [30] and liver dysfunction [31]. These arguments were turned down with experimental studies.…”

Section: V1a Agonists and Splanchnic Circulationmentioning

confidence: 99%

Vasopressin and its analogues in shock states: a review

Demiselle

Fage

Radermacher

et al. 2020

Ann. Intensive Care

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Activation of arginine-vasopressin is one of the hormonal responses to face vasodilation-related hypotension. Released from the post-pituitary gland, vasopressin induces vasoconstriction through the activation of V1a receptors located on vascular smooth muscle cells. Due to its non-selective receptor affinity arginine-vasopressin also activates V2 (located on renal tubular cells of collecting ducts) and V1b (located in the anterior pituitary and in the pancreas) receptors, thereby potentially promoting undesired side effects such as anti-diuresis, procoagulant properties due to release of the von Willebrand's factor and platelet activation. Finally, it also cross-activates oxytocin receptors. During septic shock, vasopressin plasma levels were reported to be lower than expected, and a hypersensitivity to its vasopressor effect is reported in such situation. Terlipressin and selepressin are synthetic vasopressin analogues with a higher affinity for the V1 receptor, and, hence, potentially less side effects. In this narrative review, we present the current knowledge of the rationale, benefits and risks of vasopressin use in the setting of septic shock and vasoplegic shock following cardiac surgery. Clearly, vasopressin administration allows reducing norepinephrine requirements, but so far, no improvement of survival was reported and side effects are frequent, particularly ischaemic events. Finally, we will discuss the current indications for vasopressin and its agonists in the setting of septic shock, and the remaining unresolved questions.

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Section: V1a Agonists and Splanchnic Circulationmentioning

confidence: 99%

Vasopressin and its analogues in shock states: a review

Demiselle

Fage

Radermacher

et al. 2020

Ann. Intensive Care

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“…As far as we know, this is the first investigation describing increased expression of this receptor in the splanchnic vascular territory of rats with cirrhosis, laying the rationale to explain the preferential splanchnic vasoconstrictor activity of AVP, AVP analogues, and V 1a -AVP agonists in cirrhosis. 39 In summary, the results of this study indicate that vasopressin 1a receptor partial agonism safely reduces portal hypertension after acute administration and subchronically increases sodium excretion and decreases ascites in experimental cirrhosis. These results indicate that V 1a -AVP receptor partial agonism could be a useful pharmacological treatment in decompensated patients with cirrhosis.…”

Section: Discussionmentioning

confidence: 58%

“…In support of this finding, the results of mRNA expression and protein abundance of AVPR1a confirm the increase of this receptor in the mesenteric tissue of animals with cirrhosis. As far as we know, this is the first investigation describing increased expression of this receptor in the splanchnic vascular territory of rats with cirrhosis, laying the rationale to explain the preferential splanchnic vasoconstrictor activity of AVP, AVP analogues, and V 1a ‐AVP agonists in cirrhosis …”

Section: Discussionmentioning

confidence: 99%

Vasopressin 1a receptor partial agonism increases sodium excretion and reduces portal hypertension and ascites in cirrhotic rats

Fernández‐Varo

Oró

Cable³

et al. 2015

Hepatology

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Patients and rats with cirrhosis and ascites have portal hypertension and circulatory dysfunction. Synthetic arginine vasopressin (AVP) receptor agonists able to induce systemic and mesenteric vasoconstriction have shown their usefulness in reducing portal pressure (PP) in this condition. We assessed the potential therapeutic value of a new V 1a -AVP receptor partial agonist with a preferential splanchnic vasoconstrictor effect (FE 204038) in rats with cirrhosis and ascites. The hemodynamic effects of cumulative intravenous doses of FE 204038, terlipressin, or vehicle were investigated. Mean arterial pressure and PP were continuously recorded and cardiac output and systemic vascular resistance (SVR) assessed at 30-minute intervals for 90 minutes. Urine volume, urine osmolality, and urinary excretion of sodium and creatinine were measured in basal conditions and following twice-daily subcutaneous doses of FE 204038 or vehicle. PP, mean arterial pressure, cardiac output, SVR, and ascites volume were also measured after 6 days. The expression of an array of vasoactive genes was assessed in the thoracic aorta and the mesenteric circulation of control rats and rats with cirrhosis and ascites. FE 204038 dose-dependently decreased PP, did not modify mean arterial pressure, and increased SVR. The effect of the V 1a -AVP receptor partial agonist on PP was associated with an improvement in urine volume and urinary excretion of sodium during the first day of treatment. SVR was higher and cardiac output and ascites volume were lower in rats with cirrhosis and ascites treated with FE 204038. V 1a -AVP receptor expression in rats with cirrhosis and ascites was markedly enhanced in the mesenteric circulation compared to the thoracic aorta. Conclusion: FE 204038 increases sodium excretion and reduces portal hypertension and ascites in experimental cirrhosis. V 1a -AVP receptor partial agonism could be a useful pharmacological treatment in decompensated patients with cirrhosis. (HEPATOLOGY 2016;63:207-216) P atients with cirrhosis develop numerous clinical complications, among which ascites is one of the most important and constitutes a sign of poor prognosis.1,2 Ascites formation results from the homeostatic activation of endogenous sodium and water retaining systems in order to counteract the circulatory dysfunction developed by patients with advanced liver disease.3 One of the most prominent features of this circulatory dysfunction is the existence of marked splanchnic vasodilation and portal hypertension. Therapeutic strategies to correct portal hypertension and reduce mesenteric blood flow have focused on arginine vasopressin

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“…Terlipressin is a long-acting vasopressin analogue, used to manage acute variceal haemorrhage [4] and type 1 hepatorenal syndrome [5]. Action on V1a receptors in the splanchnic vascular bed reduces PV blood flow [6], but arterial vasoconstrictive properties are associated with serious adverse effects [7]. Compensatory increases in HA flow have been demonstrated in naïve porcine studies [8], but the effects of terlipressin on TLBF and HA flow in the context of chronic liver disease have not been reported previously.…”

Section: Introductionmentioning

confidence: 99%

Haemodynamic changes in cirrhosis following terlipressin and induction of sepsis—a preclinical study using caval subtraction phase-contrast and cardiac MRI

et al. 2020

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Objectives Effects of liver disease on portal venous (PV), hepatic arterial (HA), total liver blood flow (TLBF), and cardiac function are poorly understood. Terlipressin modulates PV flow but effects on HA, TLBF, and sepsis/acute-on-chronic liver failure (ACLF)-induced haemodynamic changes are poorly characterised. In this study, we investigated the effects of terlipressin and sepsis/ACLF on hepatic haemodynamics and cardiac function in a rodent cirrhosis model using caval subtraction phase-contrast (PC) MRI and cardiac cine MRI. Methods Sprague-Dawley rats (n = 18 bile duct–ligated (BDL), n = 16 sham surgery controls) underwent caval subtraction PCMRI to estimate TLBF and HA flow and short-axis cardiac cine MRI for systolic function at baseline, following terlipressin and lipopolysaccharide (LPS) infusion, to model ACLF. Results All baseline hepatic haemodynamic/cardiac systolic function parameters (except heart rate and LV mass) were significantly different in BDL rats. Following terlipressin, baseline PV flow (sham 181.4 ± 12.1 ml/min/100 g; BDL 68.5 ± 10.1 ml/min/100 g) reduced (sham − 90.3 ± 11.1 ml/min/100 g, p < 0.0001; BDL − 31.0 ± 8.0 ml/min/100 g, p = 0.02), sham baseline HA flow (33.0 ± 11.3 ml/min/100 g) increased (+ 92.8 ± 21.3 ml/min/100 g, p = 0.0003), but BDL baseline HA flow (83.8 ml/min/100 g) decreased (− 34.4 ± 7.5 ml/min/100 g, p = 0.11). Sham baseline TLBF (214.3 ± 16.7 ml/min/100 g) was maintained (+ 2.5 ± 14.0 ml/min/100 g, p > 0.99) but BDL baseline TLBF (152.3 ± 18.7 ml/min/100 g) declined (− 65.5 ± 8.5 ml/min/100 g, p = 0.0004). Following LPS, there were significant differences between cohort and change in HA fraction (p = 0.03) and TLBF (p = 0.01) with BDL baseline HA fraction (46.2 ± 4.6%) reducing (− 20.9 ± 7.5%, p = 0.03) but sham baseline HA fraction (38.2 ± 2.0%) remaining unchanged (+ 2.9 ± 6.1%, p > 0.99). Animal cohort and change in systolic function interactions were significant only for heart rate (p = 0.01) and end-diastolic volume (p = 0.03). Conclusions Caval subtraction PCMRI and cardiac MRI in a rodent model of cirrhosis demonstrate significant baseline hepatic haemodynamic/cardiac differences, failure of the HA buffer response post-terlipressin and an altered HA fraction response in sepsis, informing potential translation to ACLF patients. Key Points Caval subtraction phase-contrast and cardiac MRI demonstrate: • Significant differences between cirrhotic/non-cirrhotic rodent hepatic blood flow and cardiac systolic function at baseline. • Failure of the hepatic arterial buffer response in cirrhotic rodents in response to terlipressin. • Reductions in hepatic arterial flow fraction in the setting of acute-on-chronic liver failure.

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The effects of vasopressin and its analogues on the liver and its disorders in the critically ill

Cited by 11 publications

References 56 publications

Vasopressin and its analogues in shock states: a review

Vasopressin and its analogues in shock states: a review

Vasopressin 1a receptor partial agonism increases sodium excretion and reduces portal hypertension and ascites in cirrhotic rats

Haemodynamic changes in cirrhosis following terlipressin and induction of sepsis—a preclinical study using caval subtraction phase-contrast and cardiac MRI

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