Na restriction blunts expansion of plasma volume and ameliorates hyperdynamic circulation in portal hypertension

Genecin, Paul; Polio, John; Groszmann, R. J.

doi:10.1152/ajpgi.1990.259.3.g498

Cited by 15 publications

(9 citation statements)

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“…We decided on this diet by taking into account the study design, which included patients without ascites and their poor compliance with a low-sodium diet for a long time. It had been shown in portal-hypertensive rats 20 and in cirrhotic patients 6 that restriction of sodium produces a significant reduction in plasma volume and improves the hyperdynamic circulation associated with cirrhosis. In this trial, treatment with spironolactone probably did not result in additional effects because the administered amount of sodium blunted a more pronounced decrease of plasma volume.…”

Section: Discussionmentioning

confidence: 99%

Nadolol plus spironolactone in the prophylaxis of first variceal bleed in nonascitic cirrhotic patients: A preliminary study

Abecasis¹

2003

Hepatology

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Treatment with ␤-blockers fails to decrease portal pressure in nearly 40% of cirrhotic patients. Recent studies have suggested that treatment with spironolactone reduces pressure and flow in the portal and variceal systems. This trial was designed to assess if nadolol plus spironolactone is more effective than nadolol alone to prevent the first variceal bleeding. One hundred patients with medium and large varices who had never bled and were without ascites were included in a prospective, randomized, multicenter, double-blind, placebo-controlled trial. The patients were randomized into 2 groups: 51 received nadolol plus placebo (N ؉ P) and 49 received nadolol plus spironolactone 100 mg/d (N ؉ S). Hepatic venous pressure gradient (HVPG) and activity of the renin-aldosterone system (plasma renin activity/plasma aldosterone levels) were measured in 24 patients. There were no significant differences in the appearance of variceal bleeding and ascites between groups at a mean follow-up of 22 ؎ 16 months. However, analyzing both complications together, the incidence was significantly higher in the N ؉ P group than in the N ؉ S group (39% vs. 20%; P < .04). Clinical ascites was also higher in patients in the N ؉ P group than in the N ؉ S group (21% vs. 6%; P < .04). Significant increases in plasma renin activity and plasma aldosterone levels were only observed in patients in the N ؉ S group (P < .01). The cumulative probabilities of remaining free of bleeding and ascites were similar in both groups after 70 months of follow-up. In conclusion, these results suggest that nadolol plus spironolactone does not increase the efficacy of nadolol alone in the prophylaxis of the first variceal bleeding. However, when bleeding and ascites were considered together, the combined therapy effectively reduced the incidence of both portal-hypertensive complications. A t present, nonselective ␤-adrenergic blockers (␤-blockers) are the drugs of choice to prevent the first variceal bleeding in cirrhotic patients with large esophageal varices. 1 Previous studies have shown that reduction of the hepatic venous pressure gradient (HVPG) to less than 12 mm Hg or a decrease in HVPG greater than 20% from basal values protects against variceal hemorrhage. However, such a decrease in portal pressure could be achieved in only 20% of patients receiving ␤-blockers. 2 Moreover, 40% of treated patients do not have reduced portal pressure despite adequate ␤-blockade. 3 Therefore, the addition of drugs to ␤-blockers has been investigated to achieve effective reductions in portal pressure in a greater proportion of patients. 4 Recent data have shown that spironolactone significantly lowers portal and variceal pressures by reducing plasma volume and splanchnic blood flow. 5-9 Plasma volume depletion improves the hyperdynamic circulatory state associated with the development and maintenance of portal hypertension. 10,11 However, a correlation could not be shown between the decrease in circulating plasma volume and the decrease in HVPG. 5,6,8 It has been sugge...

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Section: Discussionmentioning

confidence: 99%

Nadolol plus spironolactone in the prophylaxis of first variceal bleed in nonascitic cirrhotic patients: A preliminary study

Abecasis¹

2003

Hepatology

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“…The hyperdynamic circulatory syndrome of advanced cirrhosis is linked to both total blood volume expansion 5,30 and arterial vasodilation, 3,4 which mainly involves the splanchnic area. 31 Both events are owing to the combined effects of various pathophysiological factors.…”

Section: Discussionmentioning

confidence: 99%

Autonomic dysfunction and hyperdynamic circulation in cirrhosis with ascites

et al. 1999

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Patients with advanced cirrhosis frequently show hemodynamic abnormalities. Autonomic dysfunction (AD) is also common and, owing to the importance of autonomic function in cardiovascular homeostasis, it may be involved in the pathogenesis of the hyperdynamic circulation. We, therefore, evaluated the hemodynamic status and autonomic function in 30 patients with cirrhosis, most of them with an advanced stage of the disease. Autonomic function was assessed with 7 cardiovascular tests exploring the vagal or sympathetic function. Each test was scored from 1 to 3 (normal, borderline, altered). Cardiac index (CI) was measured by an echocardiogram. Twenty-four (80%) patients showed an AD, this being definite in 14 (47%) patients. A vagal dysfunction (VD) was found in 19 patients (63%), this being definite in 11 patients (37%), and a sympathetic dysfunction (SD) in 7 patients (definite in 3 [10%] patients). The patients with AD showed a faster heart rate (P ‫؍‬ .021), lower indicized peripheral vascular resistance (P ‫؍‬ .013), and increased CI (P ‫؍‬ .004) than patients without AD whereas mean arterial pressure did not differ. Similar results were seen by grouping patients according to the VD. AD score was directly correlated with heart rate (r ‫؍‬ 0.53; P ‫؍‬ .002) and CI (r ‫؍‬ 0.45; P ‫؍‬ .016), and inversely correlated with peripheral vascular resistance (r ‫؍‬ 0.46; P ‫؍‬ .013). Even closer correlations were found with vagal score. AD (mainly VD) may be involved in the pathogenesis of the hyperdynamic circulatory syndrome of patients with advanced cirrhosis. (HEPATOLOGY 1999;30:1387-1392.)Hyperdynamic circulation is a common and long-recognized feature of patients with advanced cirrhosis, 1 consisting of elevated cardiac rate and output and reduced peripheral vascular resistance, so that arterial pressure is tendentially or frankly reduced. The clinical importance of this disorder was shown by subsequent studies, showing that the alterations of systemic hemodynamics, renal function, and vasoactive systems are prognostic indicators even more accurate than the tests exploring liver function. 2 The setting of the hyperdynamic circulatory syndrome is the pathogenetic background of complications such as renal sodium and water retention and hepatorenal syndrome. 3 Splanchnic blood pooling, opening of portal-systemic collaterals, and arterial vasodilation, as well as a compensatory increase in blood volume, are the causative events of the hyperdynamic circulatory syndrome. 4,5 The pathogenesis of arterial vasodilation is still debated. It has been proposed that an overproduction of a variety of vasorelaxant agents, such as histamine, adenosine, gut-derived peptides and endothelial cell-derived vasodilators, and bile acid retention reduce the responsiveness of the vascular bed to endogenous vasoconstrictor stimuli. 4,6 The autonomic nervous system plays a central role in modulating cardiac performance and vasomotor activity. The presence of an autonomic dysfunction (AD) in cirrhosis has been clearly shown through different...

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“…On day 1, TPR of PVL rats decreased markedly, achieving significantly lower values than those of sham-operated rats (4.18 * 0.21 mm Hg*rnin.ml-'. 100 gm vs. 5.19 k 0.16 mm H g . m i n .…”

Section: Systemic Hemodynamics and Portal Pressurementioning

confidence: 92%

“…Plasma volume ( P, ) determination was performed by measuring the albumin-distribution space using an isotopic dilution technique (5,9). An intravenous injection of 12SI-albumin (0.03 to 0.05 pCi) was performed through a PE-50 catheter (Clay Adams).…”

Section: Plasma Volumementioning

confidence: 99%

Temporal relationship of peripheral vasodilatation, plasma volume expansion and the hyperdynamic circulatory state in portal-hypertensive rats

1992

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Peripheral vasodilatation and plasma volume expansion are required to generate the hyperdynamic circulatory state observed in portal hypertension. To determine which of these factors is the initial event and to assess their temporal relationship with the development of hyperdynamic circulation, we sequentially measured plasma volume (by 125I-albumin dilution), cardiac index (by thermodilution), mean arterial pressure (by catheterization), superior mesenteric and iliac arterial flows (by Doppler flowmetry) and calculated total and regional peripheral resistances in portal-hypertensive rats. Experimental groups were studied from day 1 through day 4 after partial portal-vein ligation (n = 110) or sham operation (n = 111). Decreased total peripheral resistance was detected within a day of portal-vein ligation (4.18 +/- 0.21 mm Hg.min.ml-1 x 100 gm vs. 5.19 +/- 0.16 mm Hg.min.ml-1 x 100 gm; p less than 0.01). Plasma volume increased significantly on day 2 (4.31 +/- 0.07 ml.100 gm-1 vs. 3.86 +/- 0.04 ml.100 gm-1; p less than 0.05). Cardiac index and regional blood flows increased in parallel with plasma volume elevation. On day 4, maximum values of plasma volume (4.49 +/- 0.08 ml.100 gm-1 vs. 3.73 +/- 0.03 ml.100 gm-1) coincided with fully developed hyperdynamic circulation, as shown by a significant elevation in cardiac index (32.3 +/- 0.6 ml.min-1 x 100 gm-1 vs. 25.5 +/- 1.2 ml.min-1 x 100 gm-1), iliac and mesenteric blood flow. On day 1, vasodilatation was present in the iliac arterial circulation. In contrast, the superior mesenteric artery vascular bed showed vasoconstriction in response to the protal outflow block.(ABSTRACT TRUNCATED AT 250 WORDS)

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Na restriction blunts expansion of plasma volume and ameliorates hyperdynamic circulation in portal hypertension

Cited by 15 publications

References 0 publications

Nadolol plus spironolactone in the prophylaxis of first variceal bleed in nonascitic cirrhotic patients: A preliminary study

Nadolol plus spironolactone in the prophylaxis of first variceal bleed in nonascitic cirrhotic patients: A preliminary study

Autonomic dysfunction and hyperdynamic circulation in cirrhosis with ascites

Temporal relationship of peripheral vasodilatation, plasma volume expansion and the hyperdynamic circulatory state in portal-hypertensive rats

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