肝缺血再灌注后肝内血流动力学的变化

目的探讨肝脏缺血再灌注（I／R）后肝内分流（IHSF）和功能性肝血流（FHBF）的变化。方法健康雄性SD大鼠l2只，作右侧颈动脉、颈静脉插管；开腹后，经回结肠静脉作门静脉插管，分别用以输血、输液、给药、留样、检测等。大鼠经部分肝I／R制模后，随机分为2组（每组6只）：（1）正常对照组（对照组），术中只分离肝周围韧带，不作肝门阻断及再灌注。（2）缺血再灌注组（1／R组，实验组），进行45min的肝门阻断及60min的再灌注。然后两组均经门静脉输注D一山梨醇（10mmol／L，0．2mL／min），2min后同时取颈动脉、门静脉、肝静脉血各1mL。测定门静脉血流量（PVF）、肝动脉血流量（HAF）。计算肝脏山梨醇摄取率、FHBF和IHSF。结果两组PVF，HAF及总肝血流量（THBF）无明显统计学差异；与对照组比较，I／R组肝脏山梨醇摄取率和FHBF减少，IHSF增加（P〈0．01）。结论肝I／R后，肝内血流动力学变化表现为肝内门一体分流开放，功能性肝血流减少。     

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.     

Intraoperative hemodynamic investigations during portacaval shunt

We studied the hemodynamics of hepatic blood flow before and after creation of portacaval shunts in 28 patients. Electromagnetic flow recordings were used to measure hepatic arterial flow (HAF) and portal venous flow (PVF) with respect to total hepatic blood flow (THBF). No correlation between PVF and portal pressure was found, but PVF was directly related to liver function. The concept that patients with low PVF tolerate shunts better (with respect to postoperative course and encephalopathy) than those with high PVF was not supported. Our investigations suggest the existence of a compensatory mechanism that tends to maintain THBF by increasing HAF following creation of a shunt. This compensatory increase occurs only in those patients with good liver function and normal or enlarged livers.     

Effect of dopamine infusion on hemodynamics after hepatic denervation

BACKGROUND:. The effects of dopamine (DA) on systemic hemodynamics are better understood than its effects on hepatic hemodynamics, especially after liver denervation occurring during liver transplantation. Therefore, a porcine model was used to study DA's effects on hemodynamics after hepatic denervation. MATERIALS AND METHODS: Fifteen pigs underwent laparotomy for catheter and flow probe placement. The experimental group (n = 7) also underwent hepatic denervation. After 1 week, all pigs underwent DA infusion at increasing doses (3-30 mcg/kg/min) while measuring hepatic parameters [portal vein flow (PVF), hepatic artery flow (HAF), total hepatic blood flow (THBF = HAF + PVF), portal and hepatic vein pressures] and systemic parameters [heart rate (HR), mean arterial pressure (MAP)]. RESULTS: There was a significant increase in HAF from baseline to the 30 mcg/kg/min DA infusion rate (within-subjects P < 0.01), but the differences between the two groups were not significant. PVF and THBF showed large effects (increases) with denervation, but the increase in flow with DA infusion was not present after denervation. Perihepatic pressures were unchanged by denervation or DA. Heart rate differed significantly between the control and denervated animals at baseline, 3, 6, 12 (all P < 0.05), and 30 mcg/kg/min DA (P = 0.10). Control vs denervation MAP at baseline was 100 +/- 4 vs 98 +/- 4 Torr and at 30 mcg/kg/min it was 110 +/- 3 vs 101 +/- 5 mm Hg. CONCLUSIONS: Hepatic flows tended to be higher after denervation. HAF showed similar increases with DA in both control and denervation groups. Increases in PVF and THBF with DA infusion were not present after denervation. HR was significantly decreased and MAP tended to be lower after denervation. The HR and MAP response to DA was similar in both groups. Therefore, both denervation and DA infusion have an effect on systemic and hepatic hemodynamics.     

脾切除贲门周围血管离断术后肝脏血流动力学和储备功能的变化

目的 研究脾切除贲门周围血管离断术后肝脏血流动力学及肝功能储备的变化.方法 对2006年6月至2007年8月在四川大学华西医院行脾切除贲门周围血管离断术的连续30例乙肝后肝硬化患者通过感应器连续测定手术中的门静脉压力梯度;运用彩色多普勒分别测最术前和术后肝动脉血流量、门静脉血流量、肝动脉阻力指数,通过术前和术后吲哚青绿试验分别测得有效肝血流量及ICGR15.结果 本组30例患者的门静脉压力梯度在开腹后为(19±4)mm Hg,结扎脾动脉后为(14±4)mm Hg,脾切除后为(14±3)mm Hg,贲门周围血管离断术后为(12±4)mm Hg,有逐渐下降的趋势.术后门静脉血流餐由(42±14)ml/s降至(16±8)ml/s,而肝动脉血流量代偿性增加.术后有效肝血流量由(0.48±0.10)L/min增至(0.56±0.10)L/min,而ICGR15由22%±8%减至18%±4%.结论 脾切除贲门周围血管离断术后,尽管门静脉压力梯度及门静脉血流量减少,但肝功能储备至少在术后短期内是得到了改善的.     

Intraoperative flow measurement of native liver and allograft during orthotopic liver transplantation in children

Hepatic hemodynamic changes during liver transplantation (OLT) in children have not yet been studied. We measured intraoperative portal vein flow (PVF) and hepatic arterial flow (HAF) (mL/min) in 53 children and 58 grafts during OLT. Flows were measured in the native organ and in the allograft. In the native liver, PVF and HAF are similar; after transplantation they return to the physiological situation. No flow differences were seen between whole and partial grafts. Among the 8 (14%) portal vein thromboses, PVF was lower in both the native liver and the graft than in the no thrombosis group (P < .05). PVF <5 mL/min/kg was a risk factor to develop PV thrombosis. No graft loss occurred in 3 cases without PVF at the time of OLTs despite the observation that repermeabilization was not possible. In 4 patients with PVF <5 mL/min/kg, after tying a spontaneous spleno-renal shunt (n = 3) or performing a porto-renal vein anastomosis (n = 1), PVF reached >20 mL/min/kg, avoiding thrombosis. In conclusion, PVF and HAF measurements during pediatric OLT may predict patients at high risk for development of PV thrombosis.     

Optimal portal venous circulation for liver graft function after living-donor liver transplantation

BACKGROUND: Previous studies have shown poor outcome after living-donor liver transplantation (LDLT) as a result of excessive portal venous pressure (PVP), excessive portal venous flow (PVF), or inadequate PVF. We investigated optimal portal venous circulation for liver graft function after LDLT in adult recipients retrospectively. METHODS: Between June 2003 and November 2004, 28 adult patients underwent LDLT in our institution. We modulated PVP under 20 mmHg in these 28 cases by performing a splenectomy (n=4) or splenorenal shunt (n=1). The PVF and PVP were measured at the end of the operation. Compliance was calculated by dividing PVF by PVP. RESULTS: PVF and compliance showed a significant inverse correlation with peak billirubin levels after LDLT (r = -0.63: r=-0.60, P<0.01), and with peak international normalized ratio after LDLT (r=-0.41: r=-0.51, P<0.05). Compliance was higher in right-lobe graft with middle hepatic vein cases (148+/-27 ml/min/mmHg), and lower in left-lobe graft cases (119+/-50 ml/min/mmHg). CONCLUSIONS: Liver graft function was better when PVF and graft compliance were higher and PVP was maintained under 20 mmHg.     

The Relationship between Portal Venous and Hepatic Arterial Blood Flow. I. Experimental Liver Transplantation

The relationship between the changes in portal venous and hepatic arterial blood flows, in the liver is a much disputed question, it has tremendous significance in the practice of transplantation, and an explanation has been available since 1981, when Lautt published the so-caled “adenosine washout theory”. According to our earlier observations the decrease of portal pressure or flow consistently led to an increase in hepatic artery flow. At the same time changes in hepatic artery flow or pressure seemed to produce only inconsistent effects on the portal circulation. In the present experiments liver transplantation (OLTX) was carried out on mongrel dogs by Starzl''s method. Electromagnetic flow probes were placed on the hepatic artery and the portal vein before removal of recipient’s liver, and after completion of all vascular anastomoses to the newly inserted liver, during the recirculatory phase of OLTX. The flow probes were connected to a Hellige electromagnetic flowmeter, portal venous and systemic arterial pressures were also recorded.The control HAF was 241±23 ml/min, the average PVF was 517±47 ml/min before removal of the recipients''s liver. In the recirculatory phase the HAF increased, by 71±12% (p < 0.001). The PVF decreased in most animals after OLTX. The decrease was in average –40.2±3.5% (p < 0.001). The THBF calculated by adding the HAF and PVF showed a small, but not significant decrease during recirculation.The systemic arterial pressure decreased slightly and portal vein pressure rose in most animals after OLTX. There was a substantial increase in portal inflow resistance and prehepatic arteriolar resistance and a decrease in hepatic artery resistance. The decrease of PVF after OLTX can be explained by progressive fluid accumulation in the liver parenchyma and increased sinusoidal and portal inflow resistance. The prolonged and continuous increase in hepatic artery flow during the recirculatory phase of OLTX may be due to the decrease of portal flow. The exact mechanism, by which a change in portal flow leads to arteriolar dilatation, can be most probably explained by the “adenosine washout theory” of Lautt.     

Prospective Evaluation of Intraoperative Hemodynamics in Liver Transplantation with Whole,Partial and DCD Grafts

The interaction of systemic hemodynamics with hepatic flows at the time of liver transplantation (LT) has not been studied in a prospective uniform way for different types of grafts. We prospectively evaluated intraoperative hemodynamics of 103 whole and partial LT. Liver graft hemodynamics were measured using the ultrasound transit time method to obtain portal (PVF) and arterial (HAF) hepatic flow. Measurements were recorded on the native liver, the portocaval shunt, following reperfusion and after biliary anastomosis. After LT HAF and PVF do not immediately return to normal values. Increased PVF was observed after graft implantation. Living donor LT showed the highest compliance to portal hyperperfusion. The amount of liver perfusion seemed to be related to the quality of the graft. A positive correlation for HAF, PVF and total hepatic blood flow with cardiac output was found (p = 0.001). Portal hypertension, macrosteatosis >30%, warm ischemia time and cardiac output, independently influence the hepatic flows. These results highlight the role of systemic hemodynamic management in LT to optimize hepatic perfusion, particularly in LDLT and split LT, where the highest flows were registered.     

肝硬变患者门腔静脉分流术前后胰高血糖素水平的动态观察

目的 研究肝硬变门静脉高压症患者行门腔静脉分流术后血浆胰高血糖素水平的变化。方法 应用放射免疫分析法测定了１６例肝硬变门静脉高压闰行门腔静脉分流术和１６例对照组患者血浆Ｇｌｃ水平。     

Portacaval shunt and inferior vena cava preservation in orthotopic liver transplantation

The aim was to study the advantages of the use of a temporary portacaval shunt (PCS) with inferior vena cava (IVC) preservation during the piggyback technique for the anhepatic phase of orthotopic liver transplantation (OLT) performed in cirrhotic patients. Two groups of cirrhotic patients who underwent OLT with piggyback technique were compared; one with a PCS (n = 57) and the other, without PCS (n = 54). Patients with fulminant hepatitis, retransplantation, portal thrombosis, and previous portosystemic shunts were excluded. In both groups graft reperfusion was achieved by simultaneous arterial and venous revascularization. Donor, recipient, and surgical characteristics were similar in both groups. The PCS group had a significantly higher portal venous flow (PVF) than the no-PCS group (773 +/- 402 mL/min vs 555 +/- 379 mL/min, P = .004). Therefore, two subgroups were studied; the high PVF subgroup A (>800 mL/min), mean 1099 +/- 261 mL/min, and the low PVF subgroup B (<800 mL/min), mean 433 +/- 423 mL/min. Subgroup A, who were treated with PCS, required fewer blood transfusions and displayed better postoperative renal function; whereas, no differences were observed among subgroup B patients with versus without PCS. In conclusion, the use of a temporary PCS with piggyback technique during OLT in cirrhotics has advantages in patients who still maintain a high portal venous flow.     

Liver circulation and oxygen metabolism during short time ligation and the hepatic artery in the dog

The changes of liver circulation and liver oxygen metabolism during and after one hour hepatic artery ligation (HAL) were studied in eight mongrel dogs. At the end of the HAL period total hepatic blood flow (THBF) was reduced from 115.6 +/- 5.5 ml/min . 100 g liver tissue to 68.0 +/- 3.7 ml/min . 100 g or 59% of the initial value. The portal venous blood flow was reduced from 83.1 +/- 3.4 to 58.8 +/- 3.7 ml/min . 100 or 82% of the initial value and the liver oxygen consumption was reduced from 4.1 +/- 0.2 ml/min . 100 g to 3.1 +/- 0.3 ml/min . 100 g or 76% of the initial value. The changes in portal venous blood flow and liver oxygen consumption were reversible following reopening of the hepatic artery. The clinical importance of a reduced portal venous blood flow and liver oxygen consumption following HAL and the possibilities to increase the portal venous blood flow are discussed.     

Azygos venous blood flow in portal hypertension

Azygos venous blood flow estimated by the continuous thermodilution method was measured in 48 patients with portal hypertension. In patients with cirrhosis, azygos venous blood flow was 326 +/- 139ml/min (mean SD) and was significantly higher than in patients without portal hypertension (163 +/- 61ml/min). In patients with idiopathic portal hypertension and extrahepatic portal obstruction, azygos venous blood flow was 411 +/- 227ml/min and 328 +/- 85ml/min respectively. Azygos venous blood flow was significantly correlated with the hepatic venous pressure gradient but neither with cardiac output nor with size of esophageal varices. In eleven cirrhotic patients, azygos venous blood flow and other hemodynamic parameters were measured before and after the nonshunting operation of esophageal transection, splenectomy and esophagogastric devascularization. Azygos venous blood flow and hepatic venous pressure gradient were significantly reduced after operation. On the other hand, cardiac output did not change significantly after surgical procedure. Relatively high postoperative azygos venous blood flow indicates its important role in the postoperative collateral circulation.     

Enhanced hepatic portal blood flow induced by prostaglandin E1 following liver transplantation in pigs

Portal venous blood flow (PVF), hepatic arterial blood flow (HAF), and systemic arterial pressure (SAP) were examined after prostaglandin E₁ (PGE₁) was injected into the vena cava superior (VCS) of liver-transplanted pigs. The injection of PGE₁ at 0.2 g/kg/min for 2 min on the day of transplantation and 3 days later produced an increase in PVF without causing any change in HAF or SAP, the response in PVF being dose-dependent. However, no reliable change in PVF, HAF, or SAP was seen when the same dose of PGE₁ was administered 7 days after transplantation. Furthermore, no significant difference was noted among the values for PVF and total hepatic blood flow (THF) during the experimented days, although the HAF value had increased markedly 3 days after transplantation. These findings suggest that PGE₁ is effective in increasing PVF in the liver transplanted condition; however, the hepatic circulatory improvement attributed to this agent would be limited to the first few days following transplantation.     

The effects of intravenously infused catecholamines on hepatic blood flow in conscious dogs with experimental obstructive jaundice

This study was conducted to examine how the effects of dopamine and dobutamine on hepatic blood flow were influenced by obstructive jaundice in a conscious canine model. Prior to biliary obstruction, portal venous blood flow (PVF) increased in response to the infusion of either dopamine or dobutamine: dopamine infused at 8 g/kg per min produced an increase of 19±0% in PVF, while dobutamine infused at 16 g/kg per min produced an increase of 30±2%. Although hepatic arterial blood flow (HAF) decreased dose-dependently in response to the infusion of dopamine, no significant change was observed in HAF in response to any dose of dobutamine. Obstructive jaundice attenuated or completely abolished the PVF-increasing effect of dopamine, whereas it did not significantly alter the effect of dobutamine on hepatic blood flow. In dogs with obstructive jaundice, dopamine at 16 g/kg per min produced a decrease of 17±3% in PVF. These findings suggest that dobutamine is more effective than dopamine for increasing hepatic blood flow in patients with obstructive jaundice.     

Hyperperfusion syndrome in small-for-size livers

BACKGROUND: Portal hyperperfusion in small-for-size livers might seriously impair postoperative liver regeneration. Using an experimental model, we investigated splenectomy as a measure to reduce portal blood flow and its impact on postoperative recovery following extended liver resection. METHOD: Wistar rats underwent partial (90%) hepatectomy with or without splenectomy under temporary inflow occlusion (30 min). In addition to 10-day survival rate, laser Doppler flowmetry of hepatic blood flow and fluorescence microscopic analysis of hepatic microcirculation were performed to assess the effect of splenectomy on initial microvascular reperfusion of liver remnants. RESULTS: While postischemic perfusion failure was comparable between both groups, portal blood flow was significantly reduced after simultaneous splenectomy (3.5+/-0.4 vs. 5.4+/-0.4 ml/min). Moreover, red blood cell velocity and volumetric blood flow were reduced in splenectomized animals. These animals experienced lower AST levels (421+/-36 vs. 574+/-73 U/l) and a significantly increased survival rate, reaching 6.6+/-1.3 vs 2.6+/-0.8 days. CONCLUSION: Simultaneous splenectomy significantly reduced the risk for postoperative hyperperfusion syndrome in small-for-size livers. Shear-stress-induced liver injury was diminished due to a significant reduction of portal venous blood flow, which positively influenced postoperative regeneration resulting in significantly higher survival.     

Amino acids protects against renal ischemia-reperfusion injury and attenuates renal endothelin.1 disorder in rats

To investigate nephroprotective effects ofa mixture of 8 L-amino acids on renal ischemia-reperfusioninjury and its effects on renal endothelin-1 (ET-1).     

Auxiliary liver transplantation with flow-regulated portal vein arterialization offers a successful therapeutic option in acute hepatic failure – investigations in heterotopic auxiliary rat liver transplantation

Heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) was proposed in acute hepatic failure (AHF). However, clinical results of PVA are controversial because of lacking standardized flow-regulation. In rats, we examined HALT with flow-regulated PVA in AHF. Group A: HALT with flow-regulated PVA and 85% resection of the native liver to induce AHF [acute experiments (n = 8), killing after 7 days (n = 8) and after 6 weeks (n = 11)]. Group B: 85% liver-resection (n = 10). The average blood-flow in the arterialized portal vein in HALT achieved normal values (1.7 +/- 0.4 ml/min/g liver-weight). After reperfusion, the diameters of the sinusoids (6.4 +/- 0.6 microm), the postsinusoidal venules (31.1 +/- 3.3 microm) and the intersinusoidal distance (17.9+/-0.7 microm) also achieved normal values. The functional sinusoidal density amounted to 335 +/- 48/cm. The 6-week survival was nine of 11 with excellent liver function (Quick's value: 110% +/- 7.8%). The hepatobiliary radioisotope scanning with (99mTc) ethyl hepatic iminodiacetic acid (EHIDA) showed no significant differences between the native livers and grafts. The hepatocellular morphology was regular, apart from low-grade necroses in two grafts. The grafts' sinusoidal endothelial cells did not show any morphological changes. In group B, however, all rats died from AHF within 6 days. HALT with flow-regulated PVA achieved good results regarding microcirculation, morphology and function and can reliably bridge AHF.     

Endothelin-1 and big-endothelin concentrations are elevated in liver graft tissue during cold storage and reperfusion

Endothelin (ET) and its precursor big-ET were synchronously analyzed by RIA in liver biopsies and systemic plasma during porcine orthotopic liver transplantation (OLT) before graft harvesting (phase A), after cold storage (phase B), and early (phase C) and late reperfusion (phase D). Tissue and plasma concentrations were correlated with length of survival and reperfusion. Increased tissue ET/big-ET levels were already detected during phase B (ET: 46 +/- 20; big-ET: 245 +/- 119 pg/mg cytosolic protein) and remained elevated in phase C (ET: 49 +/- 16; big-ET: 306 +/- 144 pg/mg) compared to baseline (ET: 32 +/- 13; big-ET: 185 +/- 164 pg/mg; p < 0.05). In phase D, a rapid concentration decline was detected (ET: 36 +/- 26; big-ET: 163 +/- 138 pg/mg). Systemic ET levels were elevated in phase B (3.4 +/- 3.0 pg/ml), C, (2.8 +/- 1.2 pg/ml) and D (2.6 +/- 2.0 pg/ml), compared to baseline (1.7 +/- 1.1 pg/ml; p < 0.05). ET/big-ET kinetics in liver tissue and systemic plasma showed analogous characteristics. Intrahepatic ET accumulation during storage and early reperfusion could be of relevance for harvest-related disturbances of hepatic microcirculation.     

PGE1 reduces injury in hepatic allografts following preservation.

Prostaglandins of the E series have been shown to decrease renal and hepatic ischemic injury as well as improve hepatic function in patients with primary nonfunction following transplantation. We wished to determine the effect of prostaglandin E1 (PGE1) on hepatic allograft reperfusion injury in the isolated perfused rat liver (IPRL) model. Livers were harvested from adult male Sprague-Dawley rats and the bile duct, portal vein, and suprahepatic vena cava were cannulated. Control livers were placed immediately on the IPRL apparatus and perfused for 2 hr with a blood-Kreb's solution. Group A and B allografts were stored for 8 hr in heparinized lactated Ringer's solution at 4 degrees C. Group A livers were then perfused with a PGE1 infusion at 0.1 micrograms/kg/min while B livers received a placebo infusion of NS at the same rate. Temperature, pH, and inflow pressures were kept constant. Oxygen consumption, portal flow, and resistance were calculated for each group and found not to be statistically different. LDH, SGOT, superoxide anion (SOA), and bile flow were measured at 30-min intervals. At the end of the 2-hr perfusion, the placebo Group B (N = 5) had LDH, SGOT, and SOA higher than those of either Group A (N = 5) or control (N = 4) livers. The difference between Group A and Group B was significant for SGOT and SOA (P less than 0.05). Bile flow was highest in the control group (24.2 +/- 1.8 microliters/g/30 min).(ABSTRACT TRUNCATED AT 250 WORDS)