Redistribution Of Organ Blood Flow Research Articles

Arterial ammonia levels in cirrhosis are determined by systemic and hepatic hemodynamics, and by organ function: a quantitative modelling study

Hyperammonaemia is a common complication of chronic liver failure. Two main factors are thought to underlie this complication: a loss of hepatic detoxification function and the development of portosystemic shunting. However, few studies have tried to quantify the importance of portosystemic shunting. Here, we used a theoretical approach to test the hypothesis that the development of portosystemic shunting is sufficient to cause hyperammonaemia in cirrhosis. Two mathematical models are developed. The first one describes the main vascular resistances of the circulation and is used to provide scenarios for the distributions of organ blood flow in cirrhosis, which are necessary to run the second model. The second model predicts arterial ammonia levels resulting from ammonia metabolism in gut, liver, kidney, muscle and brain, and the distribution of organ blood flow. The fraction of gastrointestinal blood flow shunted through collaterals was estimated to be 41% in mild cirrhosis, 69% in moderate and 85% in severe cases. In the second model, the redistribution of organ blood flow associated with severe cirrhosis was sufficient to cause hyperammonaemia, even when the hepatic detoxification function and the ammonia production were set to normal. The model indicates that the development of portosystemic shunting in cirrhosis is sufficient to cause hyperammonaemia. Interventions that reduce the fraction of shunting may be future targets of therapy to control severity of hyperammonaemia.

PTU-010 Computational model predicts that portosystemic shunting is key to the development of hyperammonaemia in liver cirrhosis

IntroductionHyperammonaemia occurs in patients with advanced cirrhosis, which is also associated with a major redistribution of blood flow (hyperdynamic circulation). Previous investigations have sought to explain hyperammonaemia on the basis...

Thoracic Epidural Anesthesia Attenuates Endotoxin-induced Impairment of Gastrointestinal Organ Perfusion

Systemic inflammation can be associated with a redistribution of organ blood flow and a decrease in gastrointestinal perfusion. Regional sympathetic blockade by means of thoracic epidural anesthesia (TEA) has been shown to improve intestinal microcirculation during systemic inflammation. This study tests the hypothesis that during systemic inflammation, TEA attenuates the impairment of gastrointestinal organ perfusion without compromising blood flow to vital organs. Eighteen rats were anesthetized, hemodynamically monitored, and mechanically ventilated with room air. By using fluorescent microspheres, organ perfusion was quantified at baseline, 30 min after the start of epidural infusion of either 2% lidocaine (TEA) or normal saline (control), and after 60 and 120 min of intravenous Escherichia coli lipopolysaccharide infusion in TEA and control animals. Blood pressure initially was lower in TEA animals, but it was comparable to controls during endotoxemia. Gastrointestinal organ perfusion significantly decreased after 120 min of endotoxemia in the controls but not in the TEA animals (-23 +/- 27% vs. -6 +/- 26%, mean +/- SD, P < 0.05). Perfusion of the vital organs such as the heart, brain, liver, and kidneys was comparable between controls and TEA after 120 min of endotoxemia. TEA attenuates the impairment of gastrointestinal organ perfusion during endotoxemia. Hence, the protective effects of TEA on intestinal microcirculation during endotoxemia may be due to a higher total organ blood flow compared with endotoxemic control animals. Furthermore, in the course of endotoxemia, TEA provides hemodynamic stability and does not compromise blood flow to vital organs.

REVERSAL OF MEDETOMIDINE INDUCED SEDATION BY ATIPAMEZOLE IN SHEEP

S391 INTRODUCTION: Medetomidine is a highly selective alpha-2 agonist with sedative properties. The alpha-2 antagonist, atipamezole, reverses medetomidine induced sedation in animals. Sedative doses of alpha-2 agonists may change cardiac output and organ blood flow. The aim of this study was to investigate changes in cardiac output and organ blood flow induced by medetomidine and reversed by atipamezole in sheep. METHODS: With the approval of the Animal Care Committee, we studied 8 sheep. Animals were chronically instrumented with catheters in the left atrium, femoral artery and vein and a thermodilution pulmonary artery catheter. Medetomidine was infused in the femoral vein using a computer-controlled infusion pump targeting plasma levels of 0, 0.8, 1.6, 3.2, 6.4 and 12.8 ng/ml for 20 minutes each, followed by a 5 minute infusion of atipamezole (170 ug/kg). Hemodynamic values and organ blood flow (using coloured microspheres) were measured just prior to medetomidine infusion (baseline), at the end of each of the 5 medetomidine infusion steps, and 30 minutes after administration of atipamezole. Data were analyzed by repeated measures ANOVA followed by Dunnett's test. P<0.05 was considered significant. Data are mean +/- SD RESULTS: All animals fell asleep during medetomidine infusion and awoke within 5 minutes from the start of atipamezole infusion. Medetomidine (12.8 ng/ml) increased mean arterial pressure (MAP) from 107 +/- 10 to 134 +/- 16 mmHg, systemic vascular resistance (SVR) from 1310 +/- 207 to 3467 +/- 1299 dynes[center dot]s[center dot]cm-5, decreased heart rate from 96 +/- 14 to 67 +/- 23 bpm and cardiac output (CO) from 6.3 +/- 1.0 to 3.3 +/- 0.7 l/min. Blood flow decreased in heart, brain, kidney, skeletal muscle and intestine but increased in liver (Table 1). After atipamezole SVR and MAP returned to baseline, CO remained below baseline at 5.8 +/- 1.1 l/min and HR increased above baseline to 124 +/- 33 bpm. Blood flow increased to above baseline values in skeletal muscle but remained significantly below baseline in heart, brain and kidney (Table 1).Table 1: Percentage changes from baseline in organ blood flowDISCUSSION: Atipamezole did not reverse medetomidine induced reduction in cardiac, cerebral and renal blood flow. However, skeletal muscle blood flow increased to above baseline values. These results in sheep imply that high doses of alpha-2 agonists reversed by antagonists may cause considerable redistribution of organ blood flow in humans.

The brain of the asphyxiated fetus--basic research.

The question whether asphyxia may be harmful to the brain of the fetus and newborn is largely related to the gestational age. Experimental studies on chronically prepared fetal sheep suggest that the resistance to asphyxia associated with maturity is not only related to structural changes in the fetal brain during development. Also, maturational changes of the sympathetic nervous system seem to be involved, which provide the neurohumoral basis for an effective circulatory and metabolic centralization to ensure intact survival of asphyxia (Jensen and Berger, 1991). This review will summarize the peculiarities of the fetal circulation, the redistribution of organ blood flow during hypoxaemia and asphyxia and its changes during development. Finally, it will focus on direct effects of asphyxia on the fetal brain. Future work in this field will have to concentrate on the important question how the fetal brain can be protected against the adverse effects of asphyxia.

Effects of dopamine on liver blood flow in children with congenital heart disease

A reduction in liver function is common after cardiac operations, particularly in children with preexisting cardiac failure. The etiology is multifactorial, but the redistribution of organ blood flow that occurs during cardiopulmonary bypass implicates ischemia as one of the principal causes of injury. Dopamine hydrochloride is known to have specific effects on the renal circulation, and the aim of this study was to investigate its effects on hepatic perfusion. Eight children with congenital heart disease were studied 6 hours after the end of cardiopulmonary bypass when they were fully rewarmed and hemodynamically stable. Using noninvasive auricular densitometry, we determined the percent disappearance rate of indocyanine green as an index of liver blood flow both before and 1 hour after commencing an infusion of dopamine at 4 micrograms.kg-1.min-1. Results showed an increase of approximately 31% in the percent disappearance rate of indocyanine green with the addition of low-dose dopamine (4 micrograms.kg-1.min-1) (p < 0.01). Dopamine may have a therapeutic role in increasing hepatic perfusion and minimizing any loss in liver function.

The effects of congenital heart disease and cardiac surgery on liver blood flow in children.

Children with congenital heart disease may have some degree of hepatic impairment, with further impairment developing shortly after surgical correction of the cardiac defect. The redistribution of organ blood flow that occurs during cardiopulmonary bypass implicates ischaemia as one of the principal causes of injury. The aim of this study was to measure liver blood flow in children with congenital heart disease and to determine both the effects of cardiopulmonary bypass and the consequences of corrective surgery. Indocyanine green clearance and auricular densitometry, were used in 31 children. In 83% we demonstrated a reduced liver blood flow, with a mean percentage disappearance rate (PDR) of 12.9% (SEM +/- 1.2). This finding was unrelated to the patient's age, the type of congenital heart defect or the presence or absence of cyanosis. During cardiopulmonary bypass, hepatic perfusion was further reduced in 77% of children, by an average of 67%, out of proportion with the iatrogenic reduction in total body flow. Six hours after surgery, liver blood flow had increased significantly above preoperative levels (p < 0.001; t-test) to approximately normal values with a mean PDR of 20.4% (SEM +/- 1.5).

Redistribution of organ blood flow after hemorrhage and resuscitation in full-term piglets: J Pediatr Surg 1994; 29/8: 1097–1102

0 Newborn piglets (aged 1 to 2 days and 7 to 14 days) were used to study (1) the redistribution of organ blood flow after a 25% acute blood loss and (2) the response to resuscitation with shed blood (20 mL/ kg), crystalloid (normal saline [NS] or lactated Ringer’s [LR]; 60 mL/ kg), and colloid (Dextran-40, 20 mL/kg). Hemodynamic parameters showed little differences in the response to hemorrhage and resuscitation. The two age groups had no significant differences in parameters or blood flow (results combined). The animals maintained flow to the heart and central nervous system (CNS) and had significantly decreased flow to the kidneys and splanchnic organs. In the gastrointestinal tract, the small intestine was affected most severely, with a significant decrease in blood flow, especially to the mucosa. In all organ systems, Dextran 40 restored blood flow to levels significantly above the baseline. Shed blood and crystalloid restored flow to organs sustaining decreased flow, but crystalloid did not restore flow to the baseline level in the kidney and all segments of the gastrointestinal tract. Copyright Q 1994 by W.B. Saunders Company

Redistribution of organ blood flow after hemorrhage and resuscitation in full-term piglets

Newborn piglets (aged 1 to 2 days and 7 to 14 days) were used to study (1) the redistribution of organ blood flow after a 25% acute blood loss and (2) the response to resuscitation with shed blood (20 mL/kg), crystalloid (normal saline [NS] or lactated Ringer's [LR]; 60 mL/kg), and colloid (dextran-40, 20 mL/kg). Hemodynamic parameters showed little differences in the response to hemorrhage and resuscitation. The two age groups had no significant differences in parameters or blood flow (results combined). The animals maintained flow to the heart and central nervous system (CNS) and had significantly decreased flow to the kidneys and splanchnic organs. In the gastrointestinal tract, the small intestine was affected most severely, with a significant decrease in blood flow, especially to the mucosa. In all organ systems, Dextran 40 restored blood flow to levels significantly above the baseline. Shed blood and crystalloid restored flow to organs sustaining decreased flow, but crystalloid did not restore flow to the baseline level in the kidney and all segments of the gastrointestinal tract.

Distribution of systemic blood flow during anoxia in the turtle, Chrysemys scripta

Hypoxia causes a reflex redistribution of regional blood flow in mammals that maintains delivery of oxygen to vital organs such as the brain during periods of decreased oxygen availability. The present study was performed to test if this response is developed in lower vertebrates. Regional organ blood flow and arterial blood gases were measured during normoxia (room air) and anoxia (nitrogen breathing) in anesthetized turtles, Chrysemys scripta. Organ blood flow was measured by the distribution of radioactive microspheres injected into the left atrium. The concentration of the microspheres in the organ is directly related to the blood flow rate. By knowing the reference blood flow rate, the reference microsphere concentration, and the total counts in the tissue, the tissue blood flow rate can be calculated. Anoxia caused a redistribution of blood flow away from the kidneys and splanchnic bed the brain. Coronary blood flow and skeletal muscle blood flow remained constant. Brain blood flow increased approximately 260%. Blood flow to the kidneys and stomach was reduced approximately 50%. Blood flow to the pancreas, small intestine, and liver decreased almost to zero. The observation of anoxia-induced reflex redistribution of organ blood flow in a lower vertebrate suggests that this mechanism could be characteristic of vertebrates in general.

Cardiac output and redistribution of organ blood flow in hypermetabolic sepsis.

Cardiac output (CO) and the distribution of blood flow were studied in chronically catheterized conscious rats during sustained (4 days) sepsis. Septicemia was induced by intraperitoneal administration of a pooled fecal inoculum, and tissue blood flow and CO were determined daily with 15-micron radioactive microspheres. Mean arterial blood pressure (MABP, 113 +/- 2 mmHg), CO (244.5 +/- 11.4 ml X min-1 X kg-1), and total peripheral resistance (TPR, 1.36 +/- 0.07 mmHg X ml-1 X min) were stable in control rats over the 4 days postinoculation. Septic animals showed a consistent tachycardia with MABP significantly reduced only on days 3 and 4 (86 +/- 4 mmHg). A hyperdynamic response to sepsis was indicated by an elevated CO (27%) and similarly reduced TPR on day 2. The calculated stroke volume averaged 0.22 +/- 0.01 ml/beat and did not vary over time or between the two groups. There was a 40-70% increase in blood flow to the heart, spleen, adrenal glands, and small intestine, and a greater than sixfold increase in hepatic arterial blood flow. The sustained elevation of coronary blood flow, observed in septic animals, was independent of myocardial work and is consistent with impaired myocardial function. Pancreas, stomach, and skeletal muscle blood flow was consistently compromised (24, 39, and 52%, respectively) during sepsis. Blood flow in other organs remained unchanged over time. Sepsis-induced changes in the fractional distribution of blood flow to various organs were similar to those described for absolute flow. (ABSTRACT TRUNCATED AT 250 WORDS)