Abnormal pressor response to vasopressin in patients with cirrhosis: Evidence for impaired buffering mechanisms

Abstract

In patients with cirrhosis, vasopressin infusion induces sustained vasoconstriction and elevation of arterial pressure. The vasopressor effect could be caused by impairment of mechanisms normally aimed at buffering increases in arterial pressure (reflex bradycardia and decreases in arteriolar resistance). We studied the acute effects of continuous vasopressin infusion (0.4 IU/min) on systemic hemodynamics in seven patients with cirrhosis and in six patients without cirrhosis (controls). Vasopressin effects on systemic O2 consumption were also studied. In both groups, vasopressin infusion induced similar peak increases in arterial pressure, followed by similar decreases in heart rate and cardiac output. However, cirrhotic patients and controls differed 30 min after the start of vasopressin infusion. At 30 min, mean arterial pressure, diastolic arterial pressure and systemic vascular resistance remained significantly higher than preinfusion values in patients with cirrhosis. No decrease in systemic O2 consumption occurred in cirrhotic patients. In controls, at 30 min, mean arterial pressure and diastolic arterial pressure had returned to baseline. Systemic vascular resistance was not significantly higher than the preinfusion value and systemic O2 consumption had significantly decreased to below preinfusion values. We conclude that the vasopressor effect of vasopressin is abnormally sustained in patients with cirrhosis. This might be caused by insufficient buffering of vasopressin-induced arteriolar constriction rather than by abnormal vagal control of heart rate. In turn, as suggested by the lack of a decrease in systemic O2 consumption, persistent arteriolar constriction might be related to abnormally sustained sympathetic vascular tone in patients with cirrhosis.

Vasopressin: Mechanisms of action on the vasculature in health and in septic shock

“…The former has also been reported in dogs with baroreceptor denervation (99). Moreover, cirrhotic patients show an abnormally prolonged blood pressure response to vasopressin, and this has been ascribed to abnormal autonomic cardiovascular regulation (100). Vasopressin administration in septic shock does not produce the degree of bradycardia seen in normal individuals (40), suggesting impairment of normal baroreflexes.…”

Cirrhotic cardiomyopathy

“…Over the last 2 decades, there is accumulating evidence to suggest that the presence of cirrhosis per se is associated with significant cardiovascular abnormalities, irrespective of the cause of cirrhosis. These include resting increased cardiac output; decreased systemic vascular resistance [1]; reduced myocardial contractility or systolic incompetence, especially under conditions of stress, whether physiological [5], physical [6,7], or pharmacological [8]; increased thickness of the left ventricle [9][10][11], associated with diastolic dysfunction; and electrophysiological abnormalities [12][13][14]. This constellation of abnormalities has been termed cirrhotic cardiomyopathy [15].…”

Pathophysiological basis of pharmacotherapy in the hepatorenal syndrome

“…Most studies have focused on defects in the SNS, but several papers have emphasized the importance of vagal impairment for sodium and fluid retention [68,70]. Blood pressure responses to orthostasis are impaired, probably because of a blunted baroreflex function [71,72] and the cardiovascular responses to pharmacological stimulations with angiotensin II, noradrenaline and vasopressin are abnormal [73,74]. Captopril may, to some extent, correct vagal dysfunction in cirrhosis [68] and neuromodulation by the RAAS is also supported by data from Laffi et al, who recently reported that canrenone, an aldosterone antagonist, normalized cardiac responses to postural changes in compensated cirrhotic patients [72].…”