Effect of endotoxemia on hepatic portal and sinusoidal blood flow in rats

A decrease in liver blood flow leads to dysfunction of hepatocytes and Kupffer cells, with subsequent local and systemic liberation of proinflammatory mediators that may maintain systemic inflammatory response syndrome (SIRS) and may lead to multiple organ dysfunction syndrome (MODS). There is only limited knowledge on the hepatic micro- and macrocirculation during sepsis or endotoxemia. Therefore, the aim of our study was to investigate alterations in hepatic portal blood flow (PBF) and sinusoidal blood flow (SBF) during endotoxemia. In male Wistar rats endotoxemia was induced by continuous infusion of 2 mg/kg/h lipopolysaccharides from Escherichia coli 026:B6 immediately after baseline measurements (n = 8). The control group (n = 8) received an equivalent volume of Ringer's solution. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), PBF, and SBF were measured at baseline and 60 and 120 min after induction of endotoxemia. PBF was measured using an ultrasonic flow probe that was positioned around the portal vein. SBF was detected by in vivo videomicroscopy of the left liver lobe. In the LPS group MAP decreased, but CO remained at baseline values. During endotoxemia PBF decreased significantly from 23 +/- 3 to 15 +/- 4 mL/min (60 min) and 16 +/- 3 mL/min (120 min). SBF also significantly decreased to 68.5% (60 min) and 57.1% (120 min) of baseline value. Our results demonstrate that during early endotoxemia hepatic macro- and microcirculatory perfusion is significantly decreased despite unchanged CO. This early reduction of hepatic perfusion might be caused by an increased hepatic vessel resistance as a consequence of liberation of vasoconstrictive mediators or/and by a decrease in intestinal perfusion.     

Comparison of Near-Infrared Spectroscopy and Laser Doppler Flowmetry for Detecting Decreased Hepatic Inflow in the Porcine Liver

Hepatic artery and portal vein thrombosis are devastating complications of partial liver transplantation. Early detection of inflow complications is important, as re-reconstruction can salvage the graft. Near-infrared spectroscopy or laser Doppler flowmetry can be used to detect tissue oxygenation or microcirculation on the liver surface. The aim of this study was to examine which of these two methods better detects changes in hepatic inflow. Sangen-strain pigs (n = 5) were used. The tips of the near-infrared spectroscopy and laser Doppler flowmetry probes were placed separately on the surface of the right liver. Inflow to the liver was controlled during the following seven conditions: control (not clamped), half- and totally clamped portal vein, half- and totally clamped hepatic artery, and half- and totally clamped portal vein and artery. Tissue blood flow was calculated using laser Doppler flowmetry. Oxyhemoglobin, deoxyhemoglobin, and the tissue oxygenation index were measured and calculated using a near-infrared spectroscopy system. The tissue blood flow and oxygenation index could not be used to differentiate between the half-clamped portal vein, half-clamped hepatic artery, and totally clamped portal vein conditions. The oxyhemoglobin minus deoxyhemoglobin value was significantly decreased after half or total clamping of the portal vein or hepatic artery (p <. 001 for each condition). The findings of the present study indicate that near-infrared spectroscopy was more sensitive than Doppler flowmetry for detecting changes in hepatic tissue inflow from the liver surface.     

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.     

Alterations in intrahepatic hemodynamics of the harvested porcine liver

Hemodynamic properties of a donor liver, during initial reperfusion, are associated with the degree of graft preservation injury and have been proposed to correlate with subsequent markers of liver function. In the present study, hepatic hemodynamics, that is, portal venous pressure, hepatic vascular resistance, and compliance (vascular distensibility), were characterized (1) in situ before porcine livers were manipulated, (2) after these same livers were isolated and perfused within a bypass circuit, and (3) on reperfusion after 2 hours of cold ischemia. Hepatic vascular resistance was determined in each of these three states from the portal vein pressure response to differing hepatic blood flows. In addition, the response of the same livers to norepinephrine and nitroprusside was evaluated in each condition. In the in situ and isolated perfused liver, portal venous pressure increased only modestly despite doubling of hepatic flows. After cold ischemia, the pressure response to higher flows was significantly greater and much less of a reduction in hepatic vascular resistance was noted than in studies prior to cold ischemia. Unlike livers prior to cold ischemia, the pressure response to norepinephrine was attenuated following cold ischemia. The response to nitroprusside, however, remained intact reducing the portal pressure to that of in situ livers. Therefore the portal hypertension that follows cold ischemia appears to be largely provoked by the preservation injury and not by surgical manipulation or the bypass circuit. This increment in portal pressure is responsive to a nitric oxide donor. Presented in part at the Fortieth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Fla., May 16–19, 1999.     

Ischemia and hepatic reperfusion: Is it possible to reduce hepatic alterations?

Our aim was to evaluate liver damage after ischemia and reperfusion, and at the same time test the effectiveness of some drugs in preventing these alterations. For this study, we utilized 50 rats divided into four groups: three underwent hepatic ischemia through occlusion of the portal vein and hepatic artery for 30 min, and one underwent a sham operation. In all groups, hepatic enzymes and bilirubine were tested at 2 h, 3 h, 4 h, 24 h, and 30 h. The drugs utilized were: L-arginine, donor of nitric oxide, and L-canavanine, inhibitor of nitric oxide synthase (NOS). Our data showed that the drugs tested could make an improvement in hepatic function after ischemia/reperfusion, preventing its damage. These preliminary results could suggest a clinical application in order to prolong ischemic period during liver transplantation or liver resection in cirrhotic patients.     

Experimental evaluation of the effects of the intraportal administration of cyclic guanosine monophosphate on ischemia/reperfusion in the porcine liver

This study was done to examine the protective effects of cyclic guanosine monophosphate (cGMP), a second messenger of nitric oxide, for ischemia/reperfusion injury of the liver, since it is known to induce vasodilatation and to inhibit platelet aggregation. Using an experimental model of porcine liver ischemia, 8-bromoguanosine 3′,5′ monophosphate, a cGMP analog, was continuously administered into the portal vein before ischemia and after reperfusion 30 min for each in the cGMP group (n=6). Saline water was administered in the same way in the control group (n=6). The cardiac output (CO), mean arterial blood pressure (MAP), portal venous flow (PVF), hepatic arterial flow (HAF), hepatic tissue blood flow (HTBF), and hepatic tissue cGMP level were determined. Hepatic enzymes and the bile discharge were also assessed as indicators of hepatic function. The hepatic tissue cGMP level was significantly higher, and PVF, HTBF, and the bile discharge were significantly greater in the cGMP group, while there were no remarkable differences between the groups with CO, MAP, HAF, and hepatic enzymes. In conclusion, the continuous supplementation of cGMP into the portal vein was found to be beneficial for preserving both the hepatic circulation and, consequently, the hepatic function of after warm ischemia of porcine liver.     

The effects of olprinone (a phosphodiesterase III inhibitor) on hepatic vascular bed in a porcine model of endotoxemia

Decreased hepatic blood flow, and impaired hepatic oxygen delivery caused by endotoxin, result in hepatic metabolic deterioration followed by liver dysfunction and multiple organ failure. Among phosphodiesterase III inhibitors, only olprinone increases hepatosplanchnic blood flow. We evaluated the effects of olprinone on systemic hemodynamics, hepatic circulation, and hepatic oxygen delivery in a porcine model of endotoxemia. Fifteen pigs received a continuous infusion (1.7 microg. kg(-1). h(-1)) of endotoxin (lipopolysaccharide [LPS]) via the portal vein for 240 min. Seven of these pigs received olprinone infusion (0.3 microg. kg(-1). min(-1)) via a central vein from t = 150 min to t = 240 min, whereas the eight remaining pigs served as LPS controls. Continuous infusion of LPS caused significant reductions in hemodynamic variables and a significant increase in arterial lactate. After the administration of olprinone during the LPS infusion, portal venous flow and hepatic oxygen delivery were increased and were higher than in the LPS group. Furthermore, olprinone prevented any further increase in arterial lactate. We conclude that the administration of olprinone halted the disturbances in the hepatic circulation, especially in portal venous flow and hepatic oxygen delivery, in a porcine model of endotoxemia. IMPLICATIONS: Endotoxin is a causative factor in peripheral vascular failure, resulting in a hemodynamic depression that includes a reduction in liver blood flow. The administration of olprinone (phosphodiesterase III inhibitor) improves the liver blood flow circulation in a porcine model of endotoxemia.     

Influence of Enteral Nutrition-induced Splanchnic Hyperemia on the Septic Origin of Splanchnic Ischemia

Escherichia coli endotoxin via portal vein administration were grouped according to whether they were fed enterally via a jejunostomy or given a placebo. Systemic hemodynamics; portal vein, hepatic, and superior mesenteric artery blood flow; hepatic and intestinal microcirculation; hepatic tissue PO ₂ ; intestinal pHi; and hepatic energy charge were assessed before, during, and after endotoxin infusion as well as during and after enteral or placebo feeding. All splanchnic hemodynamic parameters revealed a statistically significant decline ( p = 0.001) during the endotoxin shock period relative to the baseline. After enteral feeding all parameters exhibited a statistically significant increase ( p = 0.001) relative to the placebo group. The results of this study led us to suggest that enteral nutrition reverses the lipopolysaccharide infusion-induced splanchnic ischemia.     

Increased shear stress-released NO and decreased endothelial calcium in rat isolated perfused juxtamedullary nephrons

BACKGROUND: Nitric oxide is an important vasodilator released from endothelial cells by the calcium-dependent endothelial nitric oxide synthase (NOS). We considered it important to investigate how shear stress/perfusion pressure influenced endothelial cell calcium concentration, nitric oxide release, and autoregulation of the afferent arteriole, since this arteriole controls glomerular filtration rate (GFR) and renin release. METHODS: We used an isolated perfused juxtamedullary nephron preparation and measured calcium with Fura 2, nitric oxide with 4-amino-5 methylamino-2', 7'-difluorescein (DAF-FM) and diameter with an imaging system. A mathematical model was applied to calculate changes in nitric oxide concentration and shear stress/wall tension during perfusion with and without erythrocytes at perfusion pressures varying from 50 to 150 mm Hg. RESULT: Cell-free perfusion increased nitric oxide concentration and abolished autoregulation; addition of erythrocytes or l-arginine analog N-nitro-l-arginine methyl ester (L-NAME) decreased nitric oxide concentration and reinstated autoregulation. Elevated perfusion pressure/elevated shear stress increased nitric oxide release and surprisingly decreased the endothelial cell calcium concentration, with perfusion pressure increase from 50 to 150 mm Hg, using blood perfusion endothelial calcium concentration decreased from 186 +/- 39 to 76 +/- 25 nmol/L and with cell-free perfusion from 116 +/- 33 to 56 +/- 21 nmol/L. CONCLUSION: Nitric oxide scavenging by erythrocytes has a high impact on arteriolar nitric oxide concentration and autoregulatory response. Nitric oxide measurements in endothelial cells of the afferent arteriole showed that increased perfusion pressure/shear stress increased nitric oxide release, while simultaneously endothelial cell calcium concentration decreased, possibly indicating a feedback control of this calcium by nitric oxide release.     

Estimation of the relative liver perfusion using two methods of radionuclide angiography in the patients with hemodynamic disorders in the portal system

The aim of this study is the assessment of the relative arterial and venous contribution to the total liver blood flow (hepatic perfusion index-HPI), with two methods (S1 and S2), and estimation of their value. With this correction, HPI nonsignificantly increases (p>0.05) in all the groups of patients, with a very high correlation between the HPI (S1) and HPI (S2) values (p<0.01). In comparison to the portal perfusion in controls, values were significantly (p<0.01) lower in chronic active hepatitis and liver cirrhosis and differed between themselves (p<0.01). In the groups of cirrhotic patients with esophageal varices, sclerosated esophageal varices, recanalized umbilical vein, portal thrombosis and cavernous portal vein, portal perfusion was lower (p<0.01) than in controls, chronic active hepatitis and liver cirrhosis without collaterals. Both angioscintigraphic methods are useful for the estimation of the disturbances in the portal system. Because of the more exact estimation of the liver perfusion, S2 is recommended.     

Tumor Necrosis Factor-α, Interleukin-1β and Nitric Oxide: Induction of Liver Megamitochondria in Prehepatic Portal Hypertensive Rats

Abstact It has been shown that portal hypertension in the rat causes microvesicular hepatocytic fatty infiltration. Formation of megamitochondria (MG) is one of the most prominent alterations in steatosis. Because nitric oxide (NO), tumor necrosis factor-α (TNFα), and interleukin-1β (IL-1β) impair mitochondrial function, these mediators have been studied in prehepatic portal hypertensive rats to verify their coexistence with MG and therefore with steatosis. Male Wistar rats were divided into two groups: a control group (n = 7) and a group with partial portal vein hgation (n = 19) at 6 weeks of evolution. TNFα and IL-1β were quantified in liver by enzyme-linked immunosorbent assay, and NO was measured in the portal vein, suprahepatic inferior vena cava, and infrahepatic inferior vena cava by the Griess reaction. In portal hypertensive rats, the-serum concentration of NO of hepatic origin increases (132.10 ± 34.72 vs. 52.44 ± 11.32 nmol/ml; p < 0.001), as do TNF-α (2.02 ± 0.20 vs. 1.12 ± 0.43 μmol/mg protein) and IL-1β (18.95 ± 2.59 vs. 5.48 ± 1.70 μmol/mg protein) (p = 0.005) in the liver. The most frequent hepatic histologic findings are the presence of MG (p < 0.001), steatosis, and hyperplasia. An increase in hepatic release of NO, TNFα and IL-Iβ with MG formation is produced in rats with portal hypertension. Therefore these proinflammatory mediators and this morphologic mitochondrial alteration could both be involved in the etiopathogenesis of steatosis.     

一氧化氮在大白鼠肝硬变门静脉高压症中的作用

为探讨一氧化氮在肝硬变形成过程中的作用，我们通过观察一氧化氮合成酶在正常鼠和肝硬变、门静脉高压症大鼠肝脏的分布，同时测定了门静脉血亚硝酸盐／硝酸盐离子水平，并监测两组动物的血液动力学指标。结果发现：正常鼠肝脏的一氧化氮合成酶染色阴性，肝硬变鼠肝脏的再生假小叶内肝细胞的一氧化氮会成酶染色为强阳性；两组动物门静脉血的亚硝酸盐／硝酸盐离子的浓度分别为９．８±３．２ｕｍｏｌ／Ｌ，２６．７±６．８ｕｍｏｌ／Ｌ，差异有极显著性意义（Ｐ＜０．０１）；肝硬变大鼠的门静脉压力、门静脉血流量显著高于正常大鼠（Ｐ＜０．０５），而内脏血管阻力显著低于正常大鼠（Ｐ＜０．０５）。结果提示：一氧化氮在肝细胞的损伤及肝硬变门静脉高压的血液动力学改变中起重要作用。     

The Effects of Nitric Oxide Supplementation and Inhibition on Bacterial Translocation in Bile Duct Ligated Rats

Obstructive jaundice promotes bacterial translocation from the gut, but the role of nitric oxide is controversial in this process. We studied the effects of nitric oxide synthase substrate, L-arginine, and nitric oxide synthase inhibitor, NG-nitro-¿-arginine methyl ester, on bacterial translocation in bile duct ligated rats. The animals were randomized into five groups; control, sham, common bile duct ligation alone, nitric oxide inhibition, and nitric oxide supplementation. Obstructive jaundice was performed with common bile duct ligation. ¿-arginine or NG-nitro-¿-arginine methyl ester was injected once daily for 14 days. Blood bilirubin level, liver histology, and bacterial translocation to the mesenteric lymph nodes as well as to the liver were assessed. The ¿-arginine supplemented group had the lowest bacterial translocation rate, but the most prominent hepatic fibrosis. Nitric oxide inhibition increased bacterial translocation to the mesenteric lymph nodes. Therefore, the administration of nitric oxide donor or inhibitor acts as a significant regulatory factor for bacterial translocation in obstructive jaundice.     

Hepatic and portal vein blood flow during carbon dioxide pneumoperitoneum for laparoscopic hepatectomy

Background: Laparoscopy under carbon dioxide (CO₂) pneumoperitoneum has many advantages. However, the risks of CO₂ pneumoperitoneum during laparoscopic hepatectomy (LH) have not been defined. Methods: The hemodynamics of the hepatic vein were examined during CO₂ pneumoperitoneum both pre- and posthepatectomy in eight pigs. Portal blood flow was measured with Doppler ultrasound during laparoscopic cholecystectomy in 10 human patients. Results: Experimentally, elevated intraabdominal pressure (IAP) with CO₂ insufflation produced significant increases in CO₂ partial pressure and echogenicity of the hepatic vein in the posthepatectomy group. Clinically, elevated IAP caused significant narrowing of the portal vein and significant decreases in portal blood velocity. The mean portal flow was significantly decreased with elevation of IAP >10 mmHg. Conclusions: LH with CO₂ pneumoperitoneum may lead to embolism caused by CO₂ bubbling through the hepatic vein. Elevated IAP may cause a decrease in hepatic blood flow and induce severe liver damage, especially in patients with poor liver function. Gasless laparoscopy using abdominal wall lifting should be employed in LH to avoid the risks of CO₂ embolism and liver damage. Received: 28 March 1997/Accepted: 12 September 1997     

Recovery of graft circulation following percutaneous transluminal angioplasty for stenotic venous complications in pediatric liver transplantation: assessment with Doppler ultrasound

Percutaneous transluminal angioplasty was performed for venous stenosis after living related liver transplantation in three children. Two of them had hepatic vein stenosis and one had stenosis of both the hepatic and portal veins. Progressive development of ascites and deterioration of liver function were found in all cases. Serial Doppler ultrasound studies showed that the flow velocity in the hepatic vein gradually decreased with a flattened velocity waveform, followed by a decrease in portal blood flow. After a successful hepatic vein angioplasty, the velocity in the hepatic and portal veins increased and the Doppler waveform in the hepatic vein became pulsatile in two cases. In the remaining case, a remarkable recovery of both graft perfusion and clinical findings was achieved via combined hepatic vein and portal vein angioplasty. We conclude that balloon angioplasty is an effective alternative to surgery for post-transplant vascular stenosis and that Doppler ultrasound is useful in monitoring graft circulation.     

Functional Hepatic Flow Can Predict the Hepatic Reserve Function in Surgical Cirrhotic Patients

Aim: To evaluate hepatic reserve function by monitoring functional hepatic flow in cirrhotic patients admitted for surgical treatments. Methods: Thirty-seven biopsy-proved cirrhotic patients with portal hypertension and 10 healthy volunteers entered the study. Eleven were Child-Pugh class A, 18 class B, and 8 class C. Eight patients undergone Transjugular intrahepatic portosystemic shunt (TIPS), 10 were submitted to the combination of TIPS and portal-azygous disconnection, 10 were treated with surgical portal-azygous disconnection, and 9 were treated with the combination of portal-azygous disconnection and spleno-renal shunt. The functional hepatic flow (FHF) and total hepatic flow (THF) were determined by means of modified hepatic clearance of D-sorbitol combined with duplex Doppler color sonography. Portal pressure was measured directly by portal vein catheterization. Results: Portal blood flow, hepatic artery flow, and THF significantly increased in cirrhotic patients compared to the controls, while FHF was significantly reduced. Both portal pressure and FHF decreased in cirrhotic patients submitted to TIPS, the combination of TIPS and portal-azygous disconnection, or the combination of portal-azygous disconnection and spleno-renal shunt (p <.05). FHF decreased significantly in patients treated with TIPS compared to other patients (p <.01). The portal pressure decreased in patients treated with portal-azygous disconnection while FHF maintained no changes (p >.05). Conclusions: Monitor of FHF in cirrhotic patients is valuable to predict different hepatic reserve function in patients receiving different surgical operations.     

Direct measurement of hepatic blood flow during living donor liver transplantation in children

Background

The changes in liver blood flow associated with living donor liver transplantation (LDLT) in children have not yet been studied. The aim of the present study was to investigate changes in hepatic hemodynamics before and after pediatric partial liver transplantation.

Methods

In 7 pediatric recipients with congenital cholestasis and native liver Child-Pugh classes B and C, portal vein flow (PVF) and hepatic arterial flow (HAF) were measured using an ultrasonic transit time flow meter before removal of the native liver and after transplantation and compared with donor left PVF and donor left HAF.

Results

The mean portal contribution to total hepatic blood flow was markedly decreased in the recipient native liver compared with that in the donor (69% ± 15% vs 32% ± 15%; P = .0003) and after reperfusion changed to almost the same ratio as that in the donor liver (73% ± 18%; P < .0001).

Conclusion

The extreme imbalance between PVF and HAF that is common in implanted partial liver in adult LDLT recipients was not observed in pediatric LDLT. After transplantation of an appropriately sized liver graft, the portal contribution to total liver blood flow normalized to the value for normal liver.     

Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression

OBJECTIVE: To investigate the degree and mechanism of hepatic sinusoidal injury in different graft sizes in right lobe live donor liver transplantation (LDLT). SUMMARY BACKGROUND DATA: Liver grafts from living donors are likely to be small-for-size for adult recipients. Graft injury after reperfusion is common, but the mechanism and degree of injury remain unclear. The hepatic sinusoidal injury in different graft sizes and its relationship with portal hemodynamics and intragraft gene response at the early phase after reperfusion have not been studied in right lobe LDLT. METHODS: From May 2000 to November 2001, 40 adults receiving right lobe LDLT had portal pressure measured continuously before and after reperfusion. Liver biopsies were taken before and after reperfusion for detection of vasoregulatory genes (endothelin-1 and endothelial nitric oxide synthase) and heat shock genes (heat shock protein 70 and heme oxygenase-1), and electron microscope examination. Blood samples from the portal vein and suprahepatic inferior vena cava were taken for the measurement of plasma nitric oxide level. RESULTS: The recipients were grouped according to the ratio of graft weight to estimated standard liver weight: group 1 (n = 10), less than 40%; group 2 (n = 21), 40% to 60%; and group 3 (n = 9), more than 60%. The portal pressures recorded after reperfusion in group 1 were significantly higher within 30 minutes of reperfusion than those in groups 2 and 3. After reperfusion, the intragraft endothelin-1 mRNA level in group 1 increased by 161% of the basal level but decreased by 31.5% and 62% of the basal level in groups 2 and 3, respectively. The intragraft mRNA level of heme oxygenase-1 in groups 1 and 2 decreased by 75.5% and 25.3% of the basal level respectively but increased by 41% of basal level in group 3. The intragraft protein level of heat shock protein 70 decreased by 50 ng/mL after reperfusion in group 1 but increased by 12.4 ng/mL and 0.6 ng/mL in groups 2 and 3, respectively. The portal vein plasma nitric oxide level decreased more significantly after reperfusion in group 1 than in group 2. Electron microscope examination of liver biopsies in group 1 showed tremendous mitochondrial swelling as well as irregular large gaps between the sinusoidal lining cells. There were two hospital deaths in group 1 and none in the other two groups. CONCLUSIONS: Patients implanted with grafts less than 40% of standard liver weight suffered from transient portal hypertension early after reperfusion. The phenomenon was accompanied by intragraft upregulation of endothelin-1 and ultrastructural evidence of sinusoidal damage. The transient portal hypertension after reperfusion, subsequent endothelin-1 overexpression, and plasma nitric oxide level reduction, together with downregulation of heme oxygenase-1 and heat shock protein 70, may account for the small-for-size graft injury.     

Novel nitric oxide donor (FK409) ameliorates liver damage during extended liver resection with warm ischemia in dogs

BACKGROUND: Nitric oxide attenuates ischemia-reperfusion injury by maintaining organ circulation through its actions as a vasoregulator, an inhibitor of platelet aggregation, and an attenuator of leukocyte adhesion. Otherwise, the harmful effects of enhanced nitric oxide production induced by inducible nitric oxide synthase mediate ischemia-reperfusion injury. FK409 has been characterized as a spontaneous nitric oxide donor. The aim of this study was to evaluate the effects of FK409 on extended liver resection with ischemia using a canine model. STUDY DESIGN: Adult mongrel dogs were subjected to 60 minutes of warm ischemia by partial inflow occlusion. After reperfusion the nonischemic lobes were resected and the remnant liver function was evaluated. The dogs were divided into two groups: the control group (n = 7) and the FK409 group (n = 6), which was given FK409 through the portal vein. RESULTS: The hepatic tissue blood flow, serum liver enzymes levels, and serum endothelin-1 level after reperfusion were significantly better in the FK409 group than in the control group. Electron microscopy demonstrated that endothelial cells and Ito cells were well-preserved in the FK409 group. The 3-day survival rate was statistically better in the FK409 group (67%) than in the control group (14%). CONCLUSIONS: FK409 appears to have protective effects during extended liver resection with ischemia.     

Retrograde Arterial Flush of the Liver Graft in Living Donor Liver Transplantation

ABSTRACT?

Formal hepatic arterial flush to preserve the liver graft in living donor liver transplantation (LDLT) is not recommended by most transplant centers because direct cannulation may injure the intima of the hepatic artery. The authors describe a method of retrograde arterial flush of the liver graft without arterial cannulation by hepatic venous outflow occlusion (HVOO) in LDLT. First, we proved no backflow of the hepatic artery without HVOO by portal flush to pig livers. Then we used HVOO on 15 LDLT cases (Group HVOO). The results were compared with those of 24 counterpart LDLT cases (Group non-HVOO) without hepatic artery flush. The two-week posttransplantational liver functions were not different between two groups except that the day-three and day-seven serum bilirubin levels were lower in Group HVOO (day-three total bilirubin: 4.99 ± 4.04 mg/dl versus 7.65 ± 4.33 mg/dl, p =.016; day-seven total bilirubin: 5.06 ± 5.02 mg/dl versus 9.57 ± 6.09, p =.005). The rates of vascular complications, six-month graft survival, and biliary anastomotic stricture in Group HVOO were 0, 93.3, and 13.3% respectively, which were not different from those of Group non-HVOO. In summary, to avoid intima injury, the retrograde arterial flush of liver graft by HVOO is safe in LDLT. The short-term results showed the effect of decreasing early functional cholestasis but the long-term benefits need further evaluation, especially with regards to biliary anastomotic complications.