Portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient

Hepatocytes transplantation is viewed as a possible alternative or as a bridge therapy to liver transplantation for patients affected by acute or chronic liver disorders. Very few data regarding complications of hepatocytes transplantation is available from the literature. Herein we report for the first time a case of portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient. A patient affected by acute graft dysfunction, not eligible for retransplantation, underwent intraportal infusion of 2 billion viable cryopreserved ABO identical human allogenic hepatocytes over a period of 5 h. Hepatocytes were transplanted at a concentration of 14 million/ml for a total infused volume of 280 ml. Doppler portal vein ultrasound and intraportal pressure were monitored during cell infusion. The procedure was complicated, 8 h after termination, by the development of portal vein thrombosis with liver failure and death of the patient. Autopsy showed occlusive thrombosis of the intrahepatic portal vein branches; cells or large aggregates of epithelial elements (polyclonal CEA positive), suggestive for transplanted hepatocytes, were co-localized inside the thrombus.     

Effects of propranolol on hepatic haemodynamics in the cirrhotic and non-cirrhotic rat

The effects of systemic and intraportal administration of propranolol on hepatic haemodynamics were studied in cirrhotic and non-cirrhotic rats. In the non-cirrhotic rat systemic infusion of 4 micrograms (kg body wt)-1 min-1 propranolol significantly decreased portal pressure, wedged hepatic venous pressure, portal venous flow and liver blood flow without affecting heart rate. Similar changes were observed in the cirrhotic rat following an infusion of 2 micrograms (kg body wt)-1 min-1 propranolol. Higher rates of propranolol infusion produced greater reductions in portal pressure, wedged hepatic venous pressure, portal venous flow and liver blood flow in cirrhotic and non-cirrhotic rats but these changes were accompanied by a bradycardia. The reduction in portal pressure effected by propranolol was accompanied by an increased splanchnic vascular resistance. Intraportal injection of propranolol resulted in a rapid but transient fall in portal pressure. The decrease in portal pressure was sustained if propranolol was infused intraportally. The results indicate that propranolol effects a reduction in portal pressure via a combination of increased splanchnic vascular resistance, increased hepatic arterial resistance and reduced cardiac output. The observation that propranolol can significantly reduce portal pressure without affecting heart rate may be clinically important in the long-term management of portal hypertension. Furthermore, the rapid reduction in portal pressure following intravenous administration suggests that propranolol may be of value in the acute control of variceal haemorrhage.     

Effect of dopamine infusion (3-30 microg/kg/min) on hepatic hemodynamics

BACKGROUND: While dopamine produces well-characterized dose-dependent effects on systemic hemodynamics, there is a paucity of information regarding its effects on hepatic hemodynamics. Infusion rates above 10 microg/kg/min are reported to produce significant vasoconstriction and impair organ perfusion. Therefore, donors are sometimes considered unsuitable when higher doses of dopamine are in use. The aim of this study was to determine the effect of increasing doses of dopamine on hepatic hemodynamics in a nonanesthetized swine model. MATERIALS AND METHODS: Sixteen pigs were instrumented with indwelling catheters in a peripheral artery, peripheral vein, portal vein, and hepatic vein and flow probes around the portal vein and hepatic artery. After recovery, the following variables were measured 10 +/- 1 days postinstrumentation: hepatic arterial flow (HAF), portal venous flow (PVF), mean systemic arterial pressure (MAP), central venous pressure (CVP), portal venous pressure (PVP), hepatic venous pressure (HVP), heart rate (HR). Recordings were obtained at baseline and subsequently when dopamine was infused at rates of 3, 6, 12, 15, 21, and 30 microg/kg/min increasing at 1-h intervals. RESULTS: HAF and PVF increased linearly over the entire infusion range, to 69 and 13% over baseline, respectively (P < 0.001, P < 0.05). Total hepatic blood flow rose 23% over baseline at the 30 microg/kg/min dosage (P < 0.01). MAP increased linearly 13% over the range 12 to 30 microg/kg/min (P < 0.001). CVP, HVP, and PVP did not change significantly. HR decreased from 12 to 15 microg/kg/min (P < 0.01), then increased from 15 to 30 microg/kg/min (P < 0.05). CONCLUSION: These data show that dopamine infused at dosages of 3-30 microg/kg/min augments HAF, PVF, and THBF and that this effect is linear. These results suggest high-dose dopamine infusion does not disqualify a potential donor liver for transplantation.     

Morbidity associated with intraportal islet transplantation

INTRODUCTION: Complications associated with intraportal islet infusion have been reported. In this study, we analyzed the relationship between occurrence of complications and islet preparation characteristics/infusion technique. METHODS: We reviewed all intraportal islet infusions from 1992 to 2003. RESULTS: Sixteen islet autotransplantations were performed without infusion-related complications. The tissue volume injected was 13 +/- 11 mL with basal and peak portal pressures of 13 +/- 6 and 21 +/- 6 mm Hg. Seventy-seven intraportal islet allotransplantations were performed in 51 patients. Fifteen islet infusions were done by laparotomy during simultaneous islet/kidney transplantation without complication. Among 62 percutaneous transhepatic injections, nine complications (two portal branch thrombosis and seven intra-abdominal hemorrhages) were recorded. Rise in portal pressure was related to tissue volume injected (P <.05). Basal and peak portal pressures were 14 +/- 5 and 18 +/- 6 mm Hg in uncomplicated infusions, 14 +/- 9 and 18 +/- 9 mm Hg in the thrombosis group, and 13 +/- 7 and 18 +/- 5 mm Hg in the hemorrhage group (P >.05). Complications occurred only after percutaneous islet infusion (P <.03). CONCLUSIONS: Procedure-related morbidity of intraportal islet infusion is low. Changes in portal pressure are related to volume of tissue injected but do not seem to be associated with the occurrence of complications. Percutaneous infusion is a minimally invasive procedure, but this advantage must be balanced by the higher rate of complications.     

Portal venous 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion overcomes hyperinsulinemic suppression of endogenous glucose output

AMP-activated protein kinase (AMPK) plays a key role in regulating metabolism, serving as a metabolic master switch. The aim of this study was to assess whether increased concentrations of the AMP analog, 5-aminoimidazole-4-carboxamide-1-beta-D-ribosyl-5-monophosphate, in the liver would create a metabolic response consistent with an increase in whole-body metabolic need. Dogs had sampling (artery, portal vein, hepatic vein) and infusion (vena cava, portal vein) catheters and flow probes (hepatic artery, portal vein) implanted >16 days before a study. Protocols consisted of equilibration (-130 to -30 min), basal (-30 to 0 min), and hyperinsulinemic-euglycemic or -hypoglycemic clamp periods (0-150 min). At t = 0 min, somatostatin was infused and glucagon was replaced in the portal vein at basal rates. An intraportal hyperinsulinemic (2 mU . kg(-1) . min(-1)) infusion was also initiated at this time. Glucose was clamped at hypoglycemic or euglycemic levels in the presence (H-AIC, n = 6; E-AIC, n = 6) or absence (H-SAL, n = 6; E-SAL, n = 6) of a portal venous 5-aminoimidazole-4-carboxamide-ribofuranoside (AICAR) infusion (1 mg . kg(-1) . min(-1)) initiated at t = 60 min. In the presence of intraportal saline, glucose was infused into the vena cava to match glucose levels seen with intraportal AICAR. Glucagon remained fixed at basal levels, whereas insulin rose similarly in all groups. Glucose fell to 50 +/- 2 mg/dl by t = 60 min in hypoglycemic groups and remained at 105 +/- 3 mg/dl in euglycemic groups. Endogenous glucose production (R(a)) was similarly suppressed among groups in the presence of euglycemia or hypoglycemia before t = 60 min and remained suppressed in the H-SAL and E-SAL groups. However, intraportal AICAR infusion stimulated R(a) to increase by 2.5 +/- 1.0 and 3.4 +/- 0.4 mg . kg(-1) . min(-1) in the E-AIC and H-AIC groups, respectively. Arteriovenous measurement of net hepatic glucose output showed similar results. AICAR stimulated hepatic glycogen to decrease by 5 +/- 3 and 19 +/- 5 mg/g tissue (P < 0.05) in the presence of euglycemia and hypoglycemia, respectively. AICAR significantly increased net hepatic lactate output in the presence of hypoglycemia. Thus, intraportal AICAR infusion caused marked stimulation of both hepatic glucose output and net hepatic glycogenolysis, even in the presence of high levels of physiological insulin. This stimulation of glucose output by AICAR was equally marked in the presence of both euglycemia and hypoglycemia. However, hypoglycemia amplified the net hepatic glycogenolytic response to AICAR by approximately fourfold.     

Surgically induced unilateral pulmonary hypertension: time-related analysis of a new experimental model.

OBJECTIVE: Patients with irreversible pulmonary vascular obstructive disease caused by pulmonary hypertension due to congenital heart defects are considered either inoperable or only candidates to lung transplantation. This study evaluated an experimental model of surgically induced unilateral pulmonary hypertension. METHODS: In eight pigs, 2-months-old, the left pulmonary artery was divided at the origin and end-to-side anastomosed to the descending thoracic aorta through a left thoracotomy. In this way, increased pulmonary blood flow in the right lung and systemic perfusion pressure and oxygenation in the left lung were obtained. After an interval of 6-12 weeks the animals underwent cardiac catheterization and were then sacrificed. Histological examination was done on both the lungs. RESULTS: The mean left-to-right shunt through the left pulmonary artery diminished from 58.9+/-9.6% at the end of the procedure to 4.5+/-1.5% at the latest hemodynamic evaluation (P<0.01). Pressures and saturations remained identical in aorta and left pulmonary artery, without reduction (NS) with FiO(2)=1.0 ventilation; in the right pulmonary artery there was a mild elevation of the pressures, but still responsive (P<0.05) to FiO(2)=1.0 ventilation. Lung histology showed normal right pulmonary arteries, but irreversible vascular lesions like intimal fibrosis, medial hypertrophy, vascular occlusions, plexiform and dilatation lesions in all the left lungs. CONCLUSIONS: The lung exposed to systemic pressure and oxygenation develops irreversible vascular lesions typical of pulmonary vascular obstructive disease. The lung exposed to increased flow shows only mild elevation of the arterial pressure, remains responsive to oxygen vasodilatation, and displays normal histology.     

Effects of Intraabdominanlly Insufflated Carbon Dioxide and Elevated Intraabdominal Pressure on Splanchnic Circulation: An Experimental Study in Pigs

Background: Intraabdominally insufflated carbon dioxide (CO2) during laparoscopy may have a specific effect on splanchnic circulation that may be unrelated to the effects of increased intraabdominal pressure alone. Therefore, the influences of insufflation with CO2 versus air on splanchnic circulation were compared.

Methods: Pigs were chronically instrumented for continuous recording of mesenteric artery, portal venous, inferior vena cava, and pulmonary arterial blood flow and portal venous pressure. After induction of anesthesia, CO2 or air was insufflated in 14 and 10 pigs, respectively. With the pigs in the supine position, intraabdominal pressure was increased in steps of 4 mmHg up to 24 mmHg by graded gas insufflation.

Results: During air insufflation, mesenteric artery vascular resistance was unchanged, whereas mesenteric arterial blood flow decreased with increasing intraabdominal pressure. Shortly after CO3 insufflation to an intraabdominal pressure of 4 mmHg, mean arterial pressure, mesenteric arterial blood flow, and mesenteric arterial vascular resistance were increased by 21%, 12% and 9%, respectively. Subsequently, with the onset of CO2 resorption in the third minute, mean arterial pressure declined to baseline values and mesenteric arterial vascular resistance declined to 85% of baseline values, whereas mesenteric arterial blood flow continued to increase to a maximum of 24% higher than baseline values. At steady-state conditions during CO2 insufflation, mesenteric arterial blood flow was increased up to an intraabdominal pressure 相似文献   

Central haemodynamics in experimental acute pancreatitis.

OBJECTIVE: To investigate central haemodynamics in severe and mild acute pancreatitis in pigs. DESIGN: Randomised controlled experiment. SETTING: Animal laboratory, Finland. SUBJECTS: 24 domestic pigs weighing 21-27 kg. INTERVENTIONS: In 8 anaesthetised and mechanically ventilated pigs the pancreatic duct was cannulated and taurocholic acid was infused to induce severe acute pancreatitis. Eight animals received intraductal saline infusion and developed mild acute pancreatitis. Eight pigs were cannulated alone and served as controls. MAIN OUTCOME MEASURES: Cardiac index, heart rate, mean arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary arterial occlusion pressure, haemoglobin, arterial blood gases and acid base balance. RESULTS: Intraductally infused taurocholic acid rapidly induced severe necrotising acute pancreatitis as assessed both macroscopically and histologically. Histological changes of mild acute pancreatitis were seen in animals after intraductal saline infusion. Central haemodynamics, arterial blood gases, and acid base balances were stable throughout the study period in all groups. The main finding was haemoconcentration as indicated by the increase in arterial haemoglobin concentration in pigs with mild and severe acute pancreatitis. CONCLUSION: Haemoconcentration precedes central haemodynamic alterations in experimental acute pancreatitis.     

Central hemodynamic changes in experimental muscle crush injury in pigs

To investigate central and pulmonary hemodynamics in a standardized normovolemic experimental muscle injury model, 8 anesthetized and mechanically ventilated test pigs were intracavally infused with 100 ml of autologous muscle extract over a period of 100 min; 8 control pigs received Ringer's solution. The cardiac index decreased 20% and the heart rate decreased 10% within 30 min of starting the infusion in the muscle extract group and remained depressed. Mean arterial pressure increased significantly in both groups. The pulmonary capillary wedge pressure and central venous pressure remained relatively unchanged during the 5-hour study. A 2-fold increase in mean pulmonary arterial pressure and a nearly 4-fold increase in the pulmonary vascular resistance index was seen in the muscle extract infusion group, which however returned to normal. Arterial hemoglobin concentration and systemic vascular resistance index remained fairly stationary in both groups. Immediate significant decreases in both arterial oxygen saturation and arterial oxygen tension were observed in the muscle extract group, however both variables recovered towards the end of the experiment. A slight increase in arterial blood pH value was noted during the experiment. In conclusion, autologous muscle extract infusion causes decreases in heart rate and cardiac index, as well as a significant increase in pulmonary vascular tone and systemic hypoxemia, emphasizing the detrimental effects of skeletal muscle injury following severe trauma.     

Hepatic stimulator substance in extracts from regenerating porcine liver. Basic physiochemical properties

Previous studies in rats and dogs have implicated the liver as the source of some of the factors which are responsible for its regeneration. In the present study extracts from regenerating and normal livers were infused into the portal vein of pigs after a 15% partial hepatectomy. Thymidine kinase activity was measured on the 3rd and 4th days as an index of liver regeneration. An intraportal infusion of extracts from regenerating, but not normal, livers resulted in an increased regenerative response. The response was dose-related. The stimulator substance was stable when stored at -20 degrees C and could be precipitated by absolute ethanol.     

Extra-pulmonary effects of inhaled nitric oxide in swine with and without phenylephrine

We have compared the effects of inhaled nitric oxide (iNO) and i.v. nitroglycerin (ivGTN) on the haemodynamic response to phenylephrine- induced hypertension (PEHT) in anaesthetized pigs. PEHT did not change either pulmonary vascular resistance or gas exchange throughout all experiments. Both treatments lowered pulmonary arterial pressure to the same extent (-12.4% iNO; -13.7% ivGTN) and passively via an effect on left atrial pressure (-26.3% iNO; -31.4% ivGTN). Both treatments failed to reverse the decrease in renal blood flow (RBFc) induced by PEHT, but both increased urinary flow (UF) (+128% iNO; +148% ivGTN). IvGTN significantly increased plasma concentrations of nitrite and nitrate during (+22.7% arterial blood; +26.2% venous blood) and beyond the period of infusion (iNO: +6.4% and +4.9%, respectively). In four control pigs (no PEHT), iNO markedly increased RBFc (+109%), glomerular filtration rate (+72.5%) and UF (+68.7%). We conclude that iNO may have direct cardiac and renal effects, probably via intervention of NO carrier forms such as S-nitroso compounds.      

Pancreatic islet transplantation using the nonhuman primate (rhesus) model predicts that the portal vein is superior to the celiac artery as the islet infusion site

We've established a nonhuman primate islet allotransplant model to address questions such as whether transplanting islets into the gut's arterial system would more safely and as effectively support long-term islet allograft survival compared with the traditional portal vein approach. We reasoned that islets make up <2% of pancreatic cell mass but consume an estimated 20% of arterial blood flow, suggesting an advantage for the arterial site. Access to the arterial system is also easier and safer than the portal system. Pancreatectomized rhesus macaques were transplanted with allogeneic islets infused into either the portal vein (n = 6) or the celiac artery (n = 4). To prevent rejection, primates were given daclizumab, tacrolimus, and rapamycin. In five of six portal vein experiments, animals achieved normoglycemia without exogenous insulin. In contrast, none of the animals given intra-arterial islets showed even transient insulin independence (P = 0.048). Two of the latter animals received a second islet transplant, this time to the portal system, and both achieved insulin independence. Thus, intraportal islet transplantation under conventional immunosuppression is feasible in primates and can result in long-term insulin independence when adequate immunosuppression is maintained. Arterial islet injection, however, does not appear to be a viable islet transplantation technique.     

Increased spillover of norepinephrine to the portal vein during CO-pneumoperitoneum in pigs

BACKGROUND: Elevated intra abdominal pressure (IAP) during CO2-insufflation has been associated with increased catecholamine concentrations in plasma. We have previously indicated that this may be due to a regional increased spillover from the abdominal region. In this experimental study we investigated catecholamine spillover from the drainage area of the portal vein during CO2-pneumoperitoneum. Methods: Eight pigs under general anesthesia were investigated before and after CO2-pneumoperitoneum with an IAP of 15 mmHg. Regional spillover of catecholamines was determined by measuring plasma catecholamine concentrations and flow simultaneously. Plasma concentrations of catecholamines were measured from the portal and femoral veins, the pulmonary and carotid arteries. Flow data were collected with laser-Doppler transit time flow probes around the portal and femoral veins. Cardiac output was measured by the thermo-dilution technique. Estimated spillover was calculated by the veno-arterial difference multiplied by flow. RESULTS: We found a significant increase in estimated spillover of norepinephrine from the drainage area of the portal vein from 10 (-1.2, 78) ng x min(-1) to 27 (1.8, 475) ng x min(-1)[median (range)] (P = 0.05), but no change in estimated spillover of norepinephrine from the drainage area of the femoral vein. Plasma concentrations of norepinephrine increased in central venous and arterial blood. There was no significant change in epinephrine concentrations in arterial blood. CONCLUSION: Estimated norepinephrine spillover from the drainage area of the portal vein increased during CO2-pneumoperitoneum in pigs. This may indicate that the increased norepinephrine concentrations found in arterial plasma reflects a local activation of sympathetic nerves in the region of the portal drainage area.     

Distribution of Amniotic Epithelial Cells After Intraportal Infusion in a Rat Model

BackgroundHuman amniotic epithelial cells (hAECs) are increasingly gaining attention as novel sources for cell transplantation. In clinical practice, intraportal infusion is considered one of the leading approaches for transplantation; however, this has not yet been validated for in vivo transplantation of hAECs. Thus, this study aims to investigate the distribution of hAECs post intraportal infusion and compare this distribution with other cell administration routes.MethodsWistar/ST rats were divided into 4 groups (n = 3 for each) based on cell administration route: group 1, intraportal; group 2, the spleen; group 3, tail veins; and group 4, penile veins. Subsequently, hAECs (1 × 10⁷) stained with XenoLight DiR were infused into each recipient. Cell distribution was evaluated using an in vivo imaging system.ResultsDiR signals were detected in the rat livers of groups 1 and 2 with those in group 2 being much weaker than those in group 1. Necrosis of small intestine was observed in 2 cases in group 2. DiR signals were detected in the lungs in groups 3 and 4 because of systemic circulation; however, all the animals died within 20 minutes of infusions.ConclusionsIntraportal infusion is potentially applicable for safe and efficient transplantation of hAECs into the liver, whereas hAECs administration via the spleen carries a risk of thrombosis in a narrow portal vein system. Our results also indicate that hAECs administration via the systemic circulation could cause pulmonary embolism in clinical settings.     

Prostaglandin E(1) continuous hepatic arterial infusion in the treatment of postoperative acute liver failure: basic study on hepatic hemodynamics and clinical application

AIM: In the treatment of severe liver damage, it is of greater advantage to administer prostaglandin E(1) (PGE(1)) directly to the liver compared with systemic intravenous infusion, because of its high inactivation rate in the lungs. In comparison with intraportal infusion, hepatic arterial infusion is more advantageous because of its easier and safer accessibility. This study was designed to prove the superiority of hepatic arterial infusion to intravenous infusion. METHODS: Changes in hepatic hemodynamics and oxygen delivery accompanying PGE(1) infusion using both methods were investigated in pigs. In addition, continuous hepatic arterial infusion was applied in 3 cases of postoperative acute liver failure, for patients in whom other conventional treatments like plasma exchange failed to improve the functioning of the liver. RESULTS: Hepatic arterial flow increased significantly accompanying hepatic arterial infusion of PGE(1) at a rate of 0.1 microg/kg/min compared with intravenous infusion at the same rate in pigs. Such an increase resulted in elevation of total hepatic blood flow and oxygen delivery to the liver. Correspondingly, bile flow significantly increased accompanying hepatic arterial infusion of PGE(1). Continuous hepatic arterial infusion was applied in 3 cases of postoperative acute liver failure. The infusion was continued for 7-9 days at a rate of 0.01 microg/kg/min without any complications through heparin-coated catheters inserted via the femoral artery. Significant increase in bile flow was observed in 2 cases in whom bile was collected, serum total bilirubin began to decrease in all these 3 cases, and the patients recovered from acute liver failure. CONCLUSION: Hepatic arterial infusion of PGE(1) is very useful and effective in the treatment of acute liver failure.     

Angiotensin II mesenteric and renal vasoregulation: dissimilar modulatory effects with nitroprusside

BACKGROUND: The role of systemic arterial pressure for the vascular effects of angiotensin II (Ang II) and the interactions between Ang II and perfusion pressure-dependent local vascular control mechanisms are not well understood. This study addresses these aspects of exogenous Ang II in the mesenteric and renal regional circulations. METHODS: Ang II was infused in incremental doses (0-200 microg/h) in anesthetized instrumented pigs (n=10). Renal and portal blood flows were measured by perivascular ultrasound. In the second part of the study, sodium nitroprusside (SNP) was infused at doses titrated to keep mean arterial pressure constant, in spite of concurrent Ang II administration. RESULTS: Powerful dose-dependent vasoconstrictions by Ang II were found in renal and mesenteric vascular beds (at highest Ang II doses vascular resistances increased by 109% and 88% respectively). Ang II-induced vasoconstriction was fully inhibited in the mesenteric, but not in the renal circulation, during conditions of constant mean arterial pressures achieved by SNP infusion. CONCLUSIONS: Mesenteric, but not renal, vasoconstriction by Ang II was inhibited by pharmacological maintenance of perfusion pressure. This could reflect differences between these vascular beds as regards the importance of co-acting myogenic pressure-dependent vasoconstriction. Alternatively, as the drug chosen for pressure control, sodium nitroprusside, serves as a nitric oxide donor, the relative balance between nitric oxide-mediated vasodilation and Ang II-induced vasoconstriction could have regional differences.     

The effects of vasoactive drugs on hepatic blood flow changes induced by CO2 laparoscopy: an animal study.

Laparoscopic surgery is associated with systemic and splanchnic hemodynamic alterations. Recent data suggest that small-dose dobutamine may attenuate the reduction in splanchnic blood flow associated with increments in intraabdominal pressure. We conducted this study to analyze the effects of dopamine and dobutamine on the hepatic circulation in this setting. Twenty-one pigs were anesthetized and mechanically ventilated. A flow-directed pulmonary artery and carotid artery catheters were inserted. Perivascular flow probes were placed around the main hepatic artery and the portal vein. CO2 was insufflated into the peritoneal cavity to reach an intraabdominal pressure of 15 mm Hg. After 60 min, animals received dopamine (5 microg x kg(-1) x min(-1); n = 8), dobutamine (5 microg x kg(-1) x min(-1); n = 8), or saline (n = 5) for 30 min. Pneumoperitoneum induced significant increases in heart rate, mean arterial pressure, and systemic vascular resistance, with decreases in cardiac output and hepatic artery and portal vein blood flows. Dobutamine infusion, in contrast to dopamine, corrected, at least in part, cardiac output, systemic vascular resistance, and hepatic artery blood flow alterations, but neither drug restored total hepatic blood flow. IMPLICATIONS: Hepatic blood flow decreases during laparoscopic surgery. A small-dose infusion of neither dobutamine nor dopamine corrects the total hepatic blood flow impairment, but the former is able to restore the hepatic arterial blood supply in an animal model mimicking this condition.     

Systematic evaluation of nitric oxide, tetrahydrobiopterin, and anandamide levels in a porcine model of endotoxemia

PURPOSE: Using a lipopolysaccharide (LPS)-treated porcine model, we examined: (1) whether nitric oxide (NO), anandamide, and tetrahydrobiopterin (BH4) increased or not in early endotoxic shock; and (2) the location of the major site of production of these molecules, by comparing their concentrations in arteries and the portal and hepatic veins. METHODS: Ten pigs received an infusion of LPS at 1.7 microg x kg(-1)x h(-1) via the portal vein for 240 min. Consecutive changes in systemic hemodynamics, hepatosplanchnic circulation, and oxygen delivery were measured. Furthermore, the variable changes in the concentrations of nitrite and nitrate (NOx), anandamide, and BH4 were measured. To access the effects of surgery, anesthesia, and fluid management on BH4, an experiment without LPS infusion was performed in two other animals. RESULTS: Mean arterial pressure and cardiac index started to decrease at 60 min after LPS infusion. However, systemic vascular resistance remained unchanged. Total hepatic blood flow and hepatic oxygen delivery also decreased significantly. NOx and anandamide did not change during LPS infusion. BH4 values did not change without LPS infusion. However, BH4 values increased significantly in the arterial, portal, and hepatic circulation during LPS infusion, especially in the hepatic vein (from 136.8 +/- 27.5 to 281.3 +/- 123.2 mol/ml; P < 0.01). CONCLUSION: Our data suggest that the BH4 values were significantly increased in several organs, especially in the liver during endotoxic shock. Impaired cardiac output and decreased blood pressure appeared in the early phase of porcine endotoxemia. Longer-term observation of these parameters after LPS treatment should be performed as the next step in future studies.     

Experimental study of the effect of intraportal prostaglandin E1 on hepatic blood flow during reperfusion after ischaemia and hepatectomy.

BACKGROUND: Prostaglandin E1 (PGE1) has protective effects experimentally and clinically in individual models of hepatic ischaemia-reperfusion injury and of partial hepatectomy. The present study investigated the effects of intraportal administration of PGE1 on hepatic blood flow, systemic arterial pressure and long-term animal survival after 60 min of total liver ischaemia followed by 70 per cent partial hepatectomy in rats. METHODS: Total liver ischaemia was induced by occluding the hepatoduodenal ligament for 60 min. PGE1 0.5 microg per kg per min was infused intraportally for 15 min before inducing ischaemia and for 120 min after ischaemia in the treatment group. Normal saline was infused in the control group. During ischaemia 70 per cent partial hepatectomy was performed. Portal venous flow (PVF), peripheral tissue blood flow (PTBF) and hepatic artery flow were measured before and after ischaemia. Serum biochemical analysis was carried out at 1, 3 and 24 h, and 7 and 14 days; and liver histology at 1 and 24 h, and 7 days after reperfusion. Survival was followed for 1 year. RESULTS: Intraportal infusion of PGE1 significantly improved PVF and PTBF without affecting the systemic arterial pressure. Long-term survival was significantly higher in the PGE1 group. Serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase levels decreased significantly, and 2-h bile flow was significantly improved, in the PGE1 group. Histological examination revealed significant portal venous congestion, sinusoidal congestion, fatty degeneration and tissue necrosis 24 h and 7 days after reperfusion in the control group. CONCLUSION: PGE1 has a protective effect against liver damage when the liver is injured by warm ischaemia and reperfusion followed by partial resection.