Effect of volume expansion on hemodynamics, capillary permeability and renal function in conscious, cirrhotic rats

Abstract

General and splanchnic hemodynamics (radioactive microspheres), renal function, spontaneous and histamine-mediated vasopermeability and albumin distribution space were studied in conscious control and nonascitic cirrhotic rats, before and after a moderate and sustained saline infusion (3% of body weight per 30 min + repletion of urinary losses). In basal conditions, cirrhotic rats showed lower fractional sodium excretion than did control rats (0.09 +/- 0.01 vs. 0.15 +/- 0.01%, p less than 0.005). In addition, cirrhotic animals showed higher cardiac output (161.4 +/- 12.8 ml per min) and lower total peripheral resistance (0.63 +/- 0.05 mm Hg . min per ml) and mean arterial pressure (102.9 +/- 3.9 mm Hg) than did control rats (cardiac output: 89.0 +/- 7.6; total peripheral resistance: 1.31 +/- 0.11; mean arterial pressure: 117.5 +/- 5.11; p less than 0.005). No differences in portal-systemic shunt rate or vasopermeability between both groups were observed. After saline infusion, fractional sodium excretion increased to 4.31 +/- 0.16% in controls but only 2.11 +/- 0.02% in cirrhotic animals. In this group, cardiac output decreased by 49.6 +/- 5.1% whereas mean arterial pressure and total peripheral resistance increased by 7.1 +/- 0.6 and 112 +/- 10%, respectively. In control rats, no significant hemodynamic changes were observed. Blood gases did not change after expansion in any group. Saline infusion induced an increase in histamine-mediated vasopermeability in cirrhotic rats but not in control rats. Also albumin distribution space increased more in cirrhotic than in control animals. Heart weight was higher in cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Cirrhotic cardiomyopathy

“…From the mid-1980s to the early 1990s, several investigators showed that cardiac contractile reserve is diminished in different rat models of nonalcoholic cirrhosis [16][17][18][19]. Notable is the landmark study of Caramelo and colleagues [17], who infused saline into rats with carbon tetrachlorideinduced cirrhosis.…”

“…Notable is the landmark study of Caramelo and colleagues [17], who infused saline into rats with carbon tetrachlorideinduced cirrhosis. There was a 50% decrease in cardiac output despite a 112% increase in peripheral vascular resistance [17].…”

“…Notable is the landmark study of Caramelo and colleagues [17], who infused saline into rats with carbon tetrachlorideinduced cirrhosis. There was a 50% decrease in cardiac output despite a 112% increase in peripheral vascular resistance [17]. This suggests that the decreased cardiac contractile response observed in cirrhosis was due to cirrhosis per se rather than related to the damaging effects of alcohol on the myocardium as it had been claimed up to then.…”

Hepatorenal Syndrome

“…Under these conditions, it is hard to conceive that myocardial performance is impaired in patients with cirrhosis. This concept was challenged by studies that demonstrated decreased cardiac function in cirrhotic animals (33,34). In humans, Bernardi et al (35) evaluated cardiac function in 22 nonalcoholic patients with cirrhosis and demonstrated impaired myocardial contractility both at rest and on exercise that correlated with the degree of cirrhosis.…”

Cardiac dysfunction in spontaneous bacterial peritonitis: A manifestation of cirrhotic cardiomyopathy?

“…Gerbes et al found downregulated ␤-adrenergic receptor density in lymphocytes (thought to reflect cardiac ␤-adrenoceptors) from patients with decompensated cirrhosis, 4 while in the CCl 4 -rat model of cirrhosis, Caramelo et al found that volume infusions decreased cardiac output, thus indicating ventricular failure. 5 In 1990, we documented down-regulation of ventricular ␤-adrenoceptors in rats with biliary cirrhosis. 6 Since then, a large number of studies have incontrovertibly demonstrated that both patients and animal models with nonalcoholic cirrhosis show blunted cardiac inotropic and chronotropic responses to diverse stimuli such as exercise, drugs, hemorrhage, surgery, or other stresses (reviewed [7][8][9] ).…”