The aim of this study was to investigate the influence of different strategies of blood volume restitution in the outcome of portal hypertension-related bleeding in anesthetized cirrhotic rats. Gastrointestinal hemorrhage was induced by sectioning a first order branch of the ileocolic vein in 38 cirrhotic rats (common bile duct ligation and occlusion). The subsequent hypovolemic shock was treated with no transfusion (n ؍ 17), moderate transfusion (50% of expected blood loss, 5 mL, n ؍ 11), and total transfusion (100% of expected blood loss, 10 mL, n ؍ 10). At the end of the blood transfusion period (minute 15), mean arterial pressure (MAP) partially recovered in rats receiving moderate transfusion or no transfusion but decreased in the 10-mL transfusion group (212 ؎ 43%, P < .05 vs. no transfusion and 5 mL transfusion). After transfusion, groups given no or 5 mL transfusion remained hemodynamically stable. However, rats receiving 10 mL transfusion continued to deteriorate with persistent bleeding and progressive fall in MAP (265 ؎ 12%; P < .05 vs. no transfusion and 5 mL transfusion). Collected blood loss was significantly greater in the 10-mL group (20.0 ؎ 1.5 g) than in groups given 5 mL (15.9 ؎ 2.8 g; P < .05) or no transfusion (13.2 ؎ 2.1 g; P < .05 vs. 10 mL and 5 mL transfusion). Survival in the no transfusion group was 47%. Rats given 5-mL transfusion had 64% survival. The worst survival was observed in the 10-mL transfusion group (0% survival; P < .05). We concluded that a transfusion policy aimed at completely replacing blood loss worsens the magnitude of bleeding and mortality from portal hypertensive-related bleeding in cirrhotic rats. On the contrary, moderate blood transfusion allowed hemodynamic stabilization and increased survival. Bleeding from esophageal varices is a frequent and severe complication of portal hypertension in patients with cirrhosis. An important part of the treatment of variceal bleeding is the general management of hypovolemic shock, in which blood volume replacement represents a crucial step. 1 However, there is little information on how blood volume restitution should be done. There is a general concern as to avoiding over transfusion, 1,2 since it is known that plasma volume expansion increases portal pressure in patients with portal hypertension. [3][4][5] The blood volume dependency of portal pressure is further illustrated by the fact that depletion of blood volume during hemorrhage or lymph drainage lowers portal pressure. 6 In addition, studies in portal hypertensive rat models have shown that blood volume restitution following a hemorrhage produces an increase of portal pressure beyond baseline values, which is not observed in normal rats, 4,5,7 suggesting that total blood volume restitution, even if not causing an expansion of the blood volume above prehemorrhage values, may have detrimental effects when correcting hypovolemia in portal hypertensive animals.The present study addressed these issues by investigating the effects of different schedules of blood volu...