Blood Volume Restitution Research Articles

Subcapsular hepatic hematoma as a complication associated with ERCP: presentation of a case in a geriatric patient

Introduction: A 68-year-old female patient who began her condition with the presence of transfictive pain in the epigastrium, presenting pancreatitis diagnosed by tomographic, clinical and biochemical parameters, and later performing endoscopic retrograde cholangiopancreatography, subsequently with data compatible with hepatic sub capsular hematoma by tomography, in addition to presenting bilateral pleural effusion, the treatment of the hematoma was purely conservative. Radiological follow-up was performed during the following two weeks, evidencing progressive hemolysis of the hematoma. Discussion: Hepatic sub capsular hematoma is a rare complication of endoscopic retrograde cholangiopancreatography. The presentation of this type of complications is infrequent and little reported in literature, the exact mechanism by which it can occur is not yet known, however in several reports it is thought that the metallic guide produces accidental injury of a hepatic blood vessel and, consequently, produces a bleeding that accumulates under the hepatic capsule, producing pain in the right hypochondrium due to the distension of the same. In addition to the pain, the drop-in hemoglobin is a suspicion of this condition. In this case, the patient presented with hypovolemic shock, presenting prerenal kidney injury requiring renal replacement management, was managed with crystalloid solutions, blood transfusion, conservative management and serial tomographic controls. In addition to having a bilateral pleural effusion that did not merit interventionist management. The treatment of the hematoma reported by the majority of authors has been conservative with restitution of blood loss and volume, surgical treatment is reserved for cases with patient deterioration, hemodynamic instability and data of peritoneal irritation that can lead to a broken hepatic hematoma. Conclusion: The pathology of hepatic sub capsular hematoma is a rare complication of endoscopic retrograde cholangiopancreatography that its management will require supportive management and only merits surgical management if it ruptures.

MICROCIRCULATORY EFFECTS OF CHANGING BLOOD HEMOGLOBIN OXYGEN AFFINITY DURING HEMORRHAGIC SHOCK RESUSCITATION IN AN EXPERIMENTAL MODEL

Microvascular responses to blood volume restitution using red blood cells (RBCs) with modified hemoglobin (Hb) oxygen affinity were studied in the hamster window chamber model during resuscitation from hemorrhagic shock. Allosteric effectors inositol hexaphosphate and 5-hydroxymethyl-2-furfural were introduced into the RBCs by electroporation to decrease and increase Hb-oxygen affinity. In vitro P50s (partial pressure of oxygen at 50% Hb saturation) were modified to 10 and 50 mmHg (normal P50, 32 mmHg). Awake hamsters were subjected to hemorrhage of 50% of blood volume, followed by a shock period of 1 h, and then resuscitated with 25% blood volume with high or low P50 RBCs (hematocrit, 50%). After resuscitation, base excess was significantly lower than baseline in the high-P50 RBC group (HP50; 0.3 +/- 2 vs. 5.0 +/- 1.7 mM) and MAP was lower than baseline in the low-P50 RBC group (LP50; 93 +/- 6 vs. 109 +/- 6 mM). Arteriolar diameter and flow were significantly lower in the HP50. Functional capillary density in the HP50 was significantly lower than LP50 at 60 and 90 min after resuscitation. There was no significantly difference in arteriolar PO2. Tissue PO2, venular PO2, and oxygen delivery were higher in LP50 than in HP50. There was no significant difference in oxygen extraction. Oxygen extraction ratio (oxygen extraction/oxygen delivery) x 100 was significantly higher in HP50 than in LP50. These results suggest that lowering blood P50 in resuscitation provides improved microvascular function in comparison with higher P50.

Influence of resuscitation volume on blood cells TNF production in a murine model of haemorrhage

The influence of haemorrhage and resuscitation on Tumour Necrosis Factor (TNF) production by whole blood cultures under endotoxin (Escherichia coli LPS) stimulation was investigated in male BALB/c mice. Haemorrhagic shock was induced by removing 0.026 +/- 0.003 mL of blood/g via a cardiac puncture, resulting in a 50% decrease in arterial pressure and a metabolic adidosis. Animals were resuscitated successfully (normotensive) despite a residual base deficit and hyperlactatemia, 60 min after the haemorrhage by the restitution of shed blood volume (SBV) with or without an additional volume of crystalloid (Lactated Ringer's solution) equal to 50, 100 (isovolumetric resuscitation) or 200% of SBV. Pulmonary failure (hypoxia-hypercarbia) and myocardial injury (troponin I release) was observed in this last group. TNF production by whole blood cultures stimulated ex vivo by LPS was estimated 60 min after the end of resuscitation. Haemorrhage resulted in a 48-60% decrease in TNF production. This decrease so-called 'leukocyte deactivation' was not modified by the restitution of SBV with or without crystalloid except for isovolumetric resuscitation which resulted in the cytokine level returning to control in the absence of clear cardiopulmonary dysfunction. In the present murine model of haemorrhage, modifying resuscitation volume influences in vitro TNF production in whole blood cultures challenged by LPS.

Plasma protein and blood volume restitution after hemorrhage in conscious pregnant and ovarian steroid-replaced rats

We have previously shown that both plasma protein restitution and plasma volume restitution are significantly enhanced in female rats hemorrhaged during the proestrus phase of the estrous cycle. Estradiol and progesterone levels are markedly elevated during proestrus and also increase during pregnancy. The present studies were therefore designed to determine whether the ability to restore plasma protein and blood volume after hemorrhage is augmented during pregnancy and by chronically elevated estradiol levels. The response to moderate hemorrhage (22-23% blood loss) was evaluated in conscious pregnant rats during early and midgestation and compared with that of virgin female rats studied during metestrus. At 22 h posthemorrhage, plasma volume had increased to greater than basal levels, and blood volume was restored to 93 +/- 1% (metestrus), 91 +/- 2% (early pregnancy), and 98 +/- 2% (midgestation) of control (P > 0.05). Animals hemorrhaged during metestrus or early pregnancy restored the same amount of protein to the plasma as had been removed, whereas those hemorrhaged during midgestation restored nearly 50% more plasma protein than had been removed (P < 0.01). In ovariectomized animals with chronic steroid replacement that maintained plasma progesterone at metestrus levels (15 +/- 2 ng/ml) but raised plasma estradiol to twofold that of midgestation (22 +/- 3 pg/ml), the blood volume and plasma protein restitution responses to hemorrhage did not differ from those of ovariectomized animals with no steroid replacement. In summary, posthemorrhage restoration of plasma protein content is significantly augmented during midgestation, but not during early pregnancy. This augmented response cannot be attributed to chronic elevation of plasma estradiol levels alone.

Treatment of variceal bleeding in patients with cirrhosis of the liver

AbstractGastroesophageal variceal bleeding is a complication of liver cirrhosis with a mortality rate of 20% at 6 weeks. Initial treatment includes blood volume restitution, antibiotic prophylaxis, and administration of vasoactive drugs to decrease portal pressure with the aim to arrest the bleeding and prevent rebleeding. Effective drugs include terlipressin and somatostatin, which should be started at admission and maintained for 2–5 days. Early endoscopic diagnosis (<12 hours) is mandatory. If variceal bleeding is confirmed endoscopic elastic band ligation (or injection sclerotherapy if banding is not possible) should be administered, but vasoactive drugs should not be withdrawn. Failures of combined medical therapy (drugs plus endoscopic therapy) should be evaluated for transjugular intrahepatic portosystemic shunt or portosystemic shunt surgery.

Evolving Consensus in Portal Hypertension Report of the Baveno IV Consensus Workshop on methodology of diagnosis and therapy in portal hypertension

Portal hypertension is associated with the most severe complications of cirrhosis, including ascites, hepatic encephalopathy, and bleeding from gastro-esophageal varices. Despite the progress achieved over the last decades, the 6-week mortality associated with variceal bleeding is still in the order of 10–20%. Awareness of the difficulty inherent to the evaluation of diagnostic tools and the design and conduct of good clinical trials for the treatment of portalhypertensionhas led to theorganization, since1986,of a series of consensus meetings. The first one was organized by Andrew Burroughs in Groningen, The Netherlands [1]. After Groningen, other meetings followed, in Baveno in 1990 (Baveno I) [2] and in 1995 (Baveno II) [3,4], in Milan in 1992 [5], in Reston, USA, in 1996 [6], in Stresa in 2000 (Baveno III) [7,8], again in Baveno in 2005 (Baveno IV) [9,10], and in Atlanta in 2007 [11]. The aims of these meetings were to develop definitions of key events in portal hypertension and variceal bleeding, to review the existing evidence on the natural history, the diagnosis and the therapeutic modalities of portal hypertension, and to issue evidence-based recommendations for the conduct of clinical trials and the management of patients. All these meetings were successful and produced consensus statements on some important points, although some issues remained unsettled. To continue the work of the previous meetings, a Baveno V workshop was held on May 21–22, 2010. The workshop was attended by many of the experts responsible for most of the major achievements of the last years in this field. Many of them had attended the previous meetings as well. The main fields of discussion of the Baveno V workshop were the same as in Baveno I–IV, i.e. the definitions of key events concerning the bleeding episode and the therapeutic options in patients with portal hypertension. For each of these topics, a series of consensus statements were discussed and agreed upon. As in Baveno IV, whenever applicable, the level of existing evidence was evaluated and the recommendations were ranked according to the Oxford System [12] (i.e.: level of evidence from 1 = highest

Modulation différentielle des effets de la stimulation des récepteurs Toll-like 2 et 4 par l'état de choc hémorragique

Objective. – To investigate the influence of haemorrhagic shock in mice on ex vivo TNF production by whole blood cells (WBC) stimulated through Toll-like receptors (TLR) 4 and 2.Study design and animals. – Experimental study using BALB/c male mice.Methods. – Haemorrhage (0,026±0,003 ml/g) by transparietal cardiac puncture under general anaesthesia. Measurement of left intraventricular pressure through a direct subcostal cardiac puncture. Possible restitution of shed blood volume (SBV) in retroorbital venous plexus, 60 minutes following haemorrhage. Lethal exsanguination 120 minutes following general anaesthesia (Control group), cardiac puncture (Sham group), blood sample (Haemorrhage group), or 60 minutes following SBV retransfusion (SBV group). Cultures (24 hours) of whole blood from the exsanguination, alone or with Escherichia coli endotoxin (LPS, TLR 4) or with heat-killed Staphylococcus aureus Cowan (SAC, TLR 2). Assessment of TNF levels in the cultures supernatant (Elisa).Results. – Hemorrhage (~30% of calculated blood volume) resulted in arterial hypotension (–50%) which was reversed by SBV retransfusion. TNF production by LPS-stimulated WBC was reduced by haemorrhage (~–50%) with or without SBV retransfusion. TNF production by SAC-stimulated WBC remained unchanged.Conclusion. – The reduction of proinflammatory cytokines production by WBC stimulated with pathogen-associated molecular patterns is not a generalized phenomenon following murin haemorrhagic shock. It depends on the used stimulus and studied signalling pathways.

Treatment of variceal bleeding in patients with cirrhosis of the liver

Gastroesophageal variceal bleeding is a complication of liver cirrhosis with a mortality rate of 20% at 6 weeks. Initial treatment includes blood volume restitution, antibiotic prophylaxis, and administration of vasoactive drugs to decrease portal pressure with the aim to arrest the bleeding and prevent rebleeding. Effective drugs include terlipressin and somatostatin, which should be started at admission and maintained for 2–5 days. Early endoscopic diagnosis (<12 hours) is mandatory. If variceal bleeding is confirmed endoscopic elastic band ligation (or injection sclerotherapy if banding is not possible) should be administered, but vasoactive drugs should not be withdrawn. Failures of combined medical therapy (drugs plus endoscopic therapy) should be evaluated for transjugular intrahepatic portosystemic shunt or portosystemic shunt surgery.

Review article: definition and diagnosis in portal hypertension--continued problems with the Baveno consensus?

The goals of the Baveno workshops were to develop consensus definitions of key events related to portal hypertension and variceal bleeding, and to produce guidelines to facilitate the conduct and reporting of clinical trials. The consensus definitions concern the diagnosis of active bleeding, failure to control bleeding, the criteria to distinguish continuing bleeding from rebleeding, and the means of assessing failure to prevent rebleeding. The guidelines concern the timing of diagnostic endoscopy, the policy for blood volume restitution, the measures to prevent infection and encephalopathy, and the treatment options for acute bleeding, as well as primary and secondary prophylaxis. The intention of the experts who developed the guidelines was that, as feedback from their practical application develops, they should be adapted to better fit the practical needs. The applicability of the Baveno definitions has been evaluated in a study where the definitions of clinically significant bleeding, failure to control bleeding, the time frame for the acute bleeding episode and the definition of rebleeding were tested. The main criticism raised in this study was that tachycardia, one of the criteria that define failure to control bleeding, was misleading in 15% of patients who had the symptom but were not bleeding.

Effects of blood volume restitution following a portal hypertensive–related bleeding in anesthetized cirrhotic rats

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 (↓12 ± 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 (↓65 ± 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. (HEPATOLOGY 2001;33:821-825.)

Blood viscosity, hemodynamics and vascular hindrance in a rat model of acute controlled bleeding and volume restitution with blood or Haemaccel.

Hemorrhage and volume restitution with commercially available solutions is followed by reduced blood viscosity. Consequent hemodynamic changes may arise not only from the reduced viscosity itself but also from changes in vascular geometry induced by autoregulation processes. Vascular hindrance reflects the contribution of vascular geometry to flow. Our aim was to explore the possible effects of blood volume restitution with Haemaccel or blood, on regional blood flow and vascular geometry. Under ketamine anesthesia, blood was withdrawn at a rate of 0.3 ml/min for 15 min followed by 15 min of stabilization. The shed blood or Haemaccel was infused at the same rate and volume as used for withdrawal. Hemodynamic measurements were performed using radioactive microspheres. Blood viscosity was measured with an Ostwald viscometer. Vascular hindrance was calculated as the resistance/viscosity ratio. Volume replacement with Haemaccel (n=10), compared to blood (n=10), was followed by increased cardiac output and portal venous inflow (37.1 +/- 9.0 and 3.1 +/- 0.5 vs 25.9 +/- 6.8 and 2.2 +/- 0.9 ml x min(-1) x 100 g bw(-1), respectively; P<0.05), decreased viscosity (2.8 +/- 1.3 vs 3.7 +/- 1.3, respectively; P<0.01) and decreased peripheral and splanchnic arteriolar resistance (3.8 +/- 1.1 and 40.9 +/- 7.6 vs 5.2 +/- 1.7 and 61.1 +/- 29.5 mmHg x ml(-1) x min x 100 g bw, respectively; P<0.05). No significant differences between the groups were observed in vascular hindrance and cardiac output distribution. Volume replacement with Haemaccel, compared to blood, induced increase in systemic and splanchnic blood flows, reflecting mainly changes in viscosity and not in blood vessel geometry. These results suggest no significant difference in overall activation of autoregulation process between volume restitution with blood or Haemaccel.

Blood volume restitution during a portal hypertension-related bleedingin rats

Blood volume restitution during a portal hypertension-related bleedingin rats

Splanchnic and systemic haemodynamic response to volume changes in patients with cirrhosis and portal hypertension

We investigated the haemodynamic response to volume depletion and subsequent repletion in patients with cirrhosis and portal hypertension. Twelve patients with compensated cirrhosis and portal hypertension were included in the study. The haemodynamic changes occurring after removal of approx. 15% of the blood volume, and subsequently after isovolume repletion with colloid, were assessed. Baseline haemodynamic measurements showed increased cardiac output and a systemic vascular resistance at the lower limit of normal. The hepatic venous pressure gradient (HVPG) was increased, at 18 mmHg. After depletion, arterial pressure, cardiac output and all right-heart-sided pressures decreased, and systemic vascular resistance increased. HVPG decreased to 16.0 mmHg. All the above changes were statistically significant. After blood volume restitution, the haemodynamic values returned to baseline. In particular, an increase in HVPG was shown in four out of the twelve patients (two with ascites and two without), which was small in three of them. However, HVPG remained the same as or lower than the baseline in the other eight patients. Patients with cirrhosis and portal hypertension exhibit an abnormal haemodynamic response to blood volume depletion. After volume repletion, no increase in the portal pressure was noted in this group of patients as a whole, although four out of the twelve patients did show an increase, possibly due to extensive collateral circulation.

A423 Mixed oxygen saturation (SvO2) versus Cardiac filling pressures to monitor blood loss and volume restitution during acute hemorrhage under inhalation anesthesia

A423 Mixed oxygen saturation (SvO2) versus Cardiac filling pressures to monitor blood loss and volume restitution during acute hemorrhage under inhalation anesthesia

Female reproductive cycle influences plasma volume and protein restitution after hemorrhage in the conscious rat.

The present study was designed to test the hypothesis that gender and female reproductive cycle phase influence the restitution of blood volume following blood loss. The experiments were performed in conscious 9- to 11-wk-old Sprague-Dawley rats subjected to a slow hemorrhage of 19 ml/kg over 40 min. The effect of hemorrhage was compared in male rats and in female rats in either proestrus (Pro) or metestrus (Met). In comparison with either metestrus females or males, females hemorrhaged on the morning of proestrus showed a significantly larger overall decrease in percent hematocrit (Pro, -17 +/- 1; Met, -10 +/- 1; male, -13 +/- 1; mean +/- SE), increase in plasma volume (Pro, to 151 +/- 15% of initial volume; Met, 104 +/- 8%; male, 120 +/- 4%), and increase in total plasma protein content (Pro, to 164 +/- 14% of initial content; Met, 101 +/- 5%; male, 132 +/- 5%) over the 21-h posthemorrhage recovery period. Proestrus females also showed a larger increase in plasma osmolality during the first 2.5-h posthemorrhage than either metestrus females or males (P < 0.05). In addition, basal hematocrit and total blood volume (51Cr-tagged erythrocyte method) were higher in females studied on the morning of proestrus than in metestrus females. These results indicate that the female reproductive cycle is an important variable in basal blood volume regulation and in plasma protein and plasma volume restitution following blood loss.

The lymphatic circulation plays a dynamic role in blood volume and plasma protein restitution after hemorrhage.

The purpose of this study was to determine the contribution of the lymphatic circulation to blood volume and plasma protein restitution after hemorrhage. Splenectomized sheep were prepared with thoracic duct and vascular catheters. The day after surgery, thoracic duct lymph flow, thoracic duct lymph protein, plasma protein, mean arterial pressure, and blood volume were measured. After 12 h, awake sheep were either bled 25% of blood volume over 5 min (HEM; n = 6) or observed (SHAM; n = 5) and measurements were recorded for 48 h. In HEM, the thoracic duct protein return rate and thoracic duct lymph flow transiently decreased (0-.5 h) but were then equal to or greater than that in SHAM. In HEM, there was restitution of both blood volume and plasma protein mass approximately 12 h after hemorrhage. Both thoracic duct lymph flow and protein return rate are significant contributors to blood volume and plasma protein restitution after hemorrhage. These findings and the prior demonstration by the authors that lymphatic vessel pumping is increased after hemorrhage suggest a dynamic role for the lymphatic circulation in blood volume homeostasis after hemorrhage.

Impairment of blood volume restitution after large hemorrhage: a mathematical model.

A mathematical model tests possible mechanisms for the progressive failure of blood volume restitution seen after larger hemorrhages ( > 26%) with increasing changes in plasma osmolality. After 10% hemorrhage, the model requires a decrease in net hydrostatic capillary pressure, the release of solute into the extracellular space, and the release of Na+ and K+ from a bound pool in equilibrium with the interstitium to match the experimental data. The solute and released cations expand the interstitium to drive the restitution of volume and protein from 3 to 24 h. After 30% hemorrhage, the best prediction of the average experimental responses occurs when the Na(+)-K(+)-adenosinetriphosphatase (ATPase) in the cell membrane is inhibited by 38.7% from 0.8 to 3 h, and the proportionality between capillary pressure and blood volume is reduced by 68% from its value for 10% hemorrhage. When the change in plasma osmolality is doubled after 30% hemorrhage, an increase in the inhibition of the ATPase to 85% and extension of its duration to 24 h are necessary to match experimental findings. The associated defect in sodium transport may occur after large hemorrhage so that sodium and water move into cells. This response may oppose osmotically driven expansion of the interstitium and thus account for the failure of restitution.

Blood volume restitution and growth in fetal lambs after acute hemorrhage.

The effects of 15-50% fetal hemorrhage (at approximately 1%/min) were studied in 13 pregnant ewes at 130-135 days of gestation for up to 5 days posthemorrhage. The upper limit of acute blood loss appears to be approximately 45%, and the rate of restoration of blood volume decreases with the severity of hemorrhage, particularly with hemorrhage > 30-40%. The restoration of fetal blood volume was due primarily to the restoration of plasma volume; in the animals subject to 40-45% blood loss (n = 9), red cell mass was still only 69.1 +/- 3.9% of the prehemorrhage value at day 5 posthemorrhage. There appear to be two phases in the restoration of plasma: 1) plasma volume was restored by 2 h posthemorrhage and 2) the restoration of plasma protein mass occurred primarily from 2 to 24 h. There was a significant correlation between blood volume and plasma protein mass. However, the regression line for the posthemorrhage days was shifted significantly upward in relation to that for the hemorrhage day because of a significant rise of plasma protein concentration. This may be important for the maintenance of blood volume after hemorrhage. Finally, fetal growth rate was determined by comparing fetal weight estimated in utero (from blood volume) with birth weight in 12 nonhemorrhaged control fetuses and in the 9 fetuses subject to 40-45% hemorrhage. The average rate of growth per day was 1.57 +/- 0.34% and -1.82 +/- 1.02%, respectively. The latter value is not significantly different from zero, suggesting that the acute blood loss impaired fetal growth.

Changes in regional vascular resistance and blood volume after hemorrhage in fed and fasted awake rats

To determine whether fasting alters the response of blood flow to hemorrhage, blood flow was measured by radiolabeled microspheres before and after a 20 ml.kg-1.3 min-1 hemorrhage in fed and fasted chronically cannulated male Sprague-Dawley rats. Restitution of blood volume, as determined by dilution of hematocrit, was attenuated in fasted rats, although the responses of arterial blood pressure, heart rate, cardiac output, and total peripheral resistance were not significantly different. Fasting only affected resting blood flow in the bronchial artery and fat and had no effect on resting vascular resistance in any organ studied. In both fed and fasted rats, hemorrhage led to a significant fall in blood flow to the stomach, small intestine, cecum, colon, spleen, pancreas, kidney, bronchial artery, thymus, and muscle and a rise in blood flow to the adrenals. However, fasting did not significantly alter the response of flow or vascular resistance to these organs. Fasting did alter the blood flow response to hemorrhage in bone, fat, and the hepatic artery. These results demonstrate that 24 h of fasting does not affect the responses of blood flow and vascular resistance to hemorrhage in most organs, even though restitution of blood volume is attenuated.

Role of intestinal fluid in restitution of blood volume and plasma protein after hemorrhage in awake rats.

To determine whether food and/or water in the gastrointestinal tract affects restitution of blood volume and plasma protein after hemorrhage, fed and 24-h-fasted awake rats received a 20 ml.kg-1 x 3 min-1 hemorrhage, and restitution of blood volume was measured by Evans blue dye and dilution of hematocrit. Restitution of blood volume and plasma protein in fed rats was complete by 2-4 h. In contrast, restitution was severely attenuated in fasted rats and was not complete by 24 h. Because initial blood volume was significantly lower in the fasted rats (55.4 +/- 1.7 vs. 64.9 +/- 2.5 ml/kg in fed), the percent blood lost during hemorrhage was significantly greater (36 vs. 31%). However, the attenuated restitution was not the result of the larger hemorrhage, as fed rats receiving a 36% hemorrhage also restored blood volume completely by 4 h. In fasted rats, complete restitution of blood volume did occur when either water or food and water were given 4 h after hemorrhage. Gastrointestinal water content fell (from 65.5 +/- 4.8 to 47.9 +/- 1.6 ml/kg) 2h after hemorrhage in fed but not in fasted rats (33.5 +/- 2.4 to 30.6 +/- 2.5 ml/kg). These data suggest that gastrointestinal fluid is essential for complete restoration of blood volume in the awake rat.