The dose-dependent action of naloxone on systemic and portal circulation in acute blood loss in rats

Using the method of contact luminescent biomicroscopy of the liver and the intestine coupled with the ultrasonic measurement of systemic blood pressure, blood flow velocity in the portal vein and hepatic artery it has been established that in rats with acute decompensatory hemorrhage naloxone increases blood pressure and improves the state of protal macro and microcirculation only after i. v. injection of large dose (5 mg/kg). Naloxone does not influence the dynamics of acute compensatory hemorrhage and the development of the posthemorrhagic microcirculatory disturbances (local microstases, microthromboses, erythrocyte aggregation).     

ACTH inhibits the development of primary decompensation of the systemic and portal circulation in acute blood loss in rats]

Using the method of contact luminescent biomicroscopy of the liver and intestine coupled with the measurement of systemic blood pressure by micromanometer and ultrasonic registration of blood flow velocity in portal vein and hepatic artery it has been established that in rats with acute decompensatory hemorrhage fragments of ACTH (1-24) and (4-10) improve the state of portal macro- and microcirculation and increase the life span 2-3-fold. ACTH does not influence the dynamics of acute compensatory hemorrhage and the development of the posthemorrhagic microcirculatory disturbances (local microstases, microthromboses, erythrocyte aggregation).     

Hepatic neovascularization after partial portal vein ligation: novel mechanism of chronic regulation of blood flow

The present study was undertaken to investigate hepatic microcirculatory response following partial portal vein ligation (PPVL) in rats. Portal pressure was markedly increased 2-6 wk after PPVL, but no significant reduction in sinusoidal perfusion and hepatocellular injury were detected. However, marked neovascularization was observed in PPVL rats using intravital microscopy and scanning electron microscopy (SEM). Extremely high red blood cell velocity (2,000-4,900 microm/s) was seen in these vessels. Injection of fluorescein sodium via the carotid artery revealed that the neovessels originated from the hepatic arterial vasculature. This was further confirmed by clamping the common hepatic artery and phenylephrine injection from the carotid artery. These vessels maintained sufficient flow after massive sinusoidal shutdown elicited by the portal infusion of endothelin receptor B agonist IRL-1620. SEM also showed extensive neovascularization at the hilum. Additionally, clamping the portal vein decreased sinusoidal perfusion only by 9.5% in PPVL, whereas a 71.2% decrease was observed in sham. These results strongly suggest that the liver maintains its microcirculatory flow by vascular remodeling from the hepatic arterial vasculature following PPVL.     

Effect of portal hypertension on splenic blood flow,intrasplenic extravasation and systemic blood pressure

We have previously shown that intrasplenic fluid extravasation is important in controlling blood volume. We proposed that, because the splenic vein flows in the portal vein, portal hypertension would increase splenic venous pressure and thus increase intrasplenic microvascular pressure and fluid extravasation. Given that the rat spleen has no capacity to store/release blood, intrasplenic fluid extravasation can be estimated by measuring the difference between splenic arterial inflow and venous outflow. In anesthetized rats, partial ligation of the portal vein rostral to the junction with the splenic vein caused portal venous pressure to rise from 4.5 +/- 0.5 to 12.0 +/- 0.9 mmHg (n = 6); there was no change in portal venous pressure downstream of the ligation, although blood flow in the liver fell. Splenic arterial flow did not change, but the arteriovenous flow differential increased from 0.8 +/- 0.3 to 1.2 +/- 0.1 ml/min (n = 6), and splenic venous hematocrit rose. Mean arterial pressure fell (101 +/- 5.5 to 95 +/- 4 mmHg). Splenic afferent nerve activity increased (5.6 +/- 0.9 to 16.2 +/- 0.7 spikes/s, n = 5). Contrary to our hypothesis, partial ligation of the portal vein caudal to the junction with the splenic vein (same increase in portal venous pressure but no increase in splenic venous pressure) also caused the splenic arteriovenous flow differential to increase (0.6 +/- 0.1 to 1.0 +/- 0.2 ml/min; n = 8). The increase in intrasplenic fluid efflux and the fall in mean arterial pressure after rostral portal vein ligation were abolished by splenic denervation. We propose there to be an intestinal/hepatic/splenic reflex pathway, through which is mediated the changes in intrasplenic extravasation and systemic blood pressure observed during portal hypertension.     

Combined Hepatic Vein, Umbilicoportal Vein, and Superior Mesenteric Artery Catheterization in Portal Hypertension: Estimation of the Portal Fraction of Total Hepatic Blood Flow in Cirrhotic Patients

Hemodynamic data were obtained in 13 cirrhotic patients with severe portal hypertension, undergoing combined hepatic vein, umbilicoportal vein, and superior mesenteric artery catheterization. The relative clearance of indocyanine green, the portohepatic gradient (difference between the free portal venous pressure and the free hepatic venous pressure), and the estimated hepatic blood flow were measured. The portal fraction (PF) of total hepatic blood flow was calculated in all patients using indicator dilution curves obtained from the portal bifurcation, a right hepatic vein, and when possible a left hepatic vein (six cases) after injection of ⁵¹Cr-labeled red blood cells (⁵¹Cr RBC) into the superior mesenteric artery. Flows were overestimated because of loss of indicator through spontaneous portosystemic shunts; however, the ratio between hepatic and portal indicator dilution curves can be used to calculate the portal fraction of total hepatic blood flow since no extrahepatic shunts existed after the bifurcation of the portal vein (as shown on portography). In 10 patients, 15 series of curves were calculable and the PF varied between 30.1 and 100% (mean ± SE: 71.1 ± 6.2%). In the three other patients, only delayed activity from recirculation was detected from portal and hepatic vein samples and PF was 0%; in these three cases, portography and arteriography revealed spontaneous portacaval shunting with reverse and/or stagnant circulation in the portal vein. In the 13 patients, no correlation existed between PF and the relative clearance of indocyanine green or the portohepatic gradient, parameters generally used as indices of severity in cirrhosis. In 10 patients, no correlation was found between PF and the estimated hepatic blood flow.     

Effects of endothelin and vasopressin on portal pressure of rats

Endothelin is a vasoconstrictor peptide which has recently been isolated and sequenced from the vascular endothelial cells. It was reported to increase blood pressure in vivo and produce a prolonged contraction with a slow onset in vitro. The purpose of this study was to investigate whether endothelin can lower the portal pressure as another endogenous vasoconstriction peptidevasopressin (AVP) can. Heart rate, systemic blood pressure, portal pressure, and portal vein blood flow were measured. Effects of endothelin on these parameters were compared with those of AVP. Endothelin 10(-10) mol/Kg significantly decreased all of the parameters mentioned. At the higher dose (5 x 10(-10) mol/Kg), however, the portal pressure and blood pressure were increased and portal vein blood flow was unchanged. On the other hand, AVP decreased the portal pressure and portal vein blood flow but elevated the systemic blood pressure. In vitro experiments revealed that endothelin contracted both tail artery and portal vein of rat and vasopressin contracted only tail artery. We concluded that although both are endogenous vasoconstricting peptides, endothelin and AVP affect differently on arterial and venous vascular beds as well as on portal pressure.     

Transport of amino acids in the splanchnic bed by blood plasma and blood in the preruminant calf]

Three preruminant calves were fitted with catheters in portal and hepatic veins and in a mesenteric artery. Two electromagnetic flowmeter probes were clipped around the portal vein and the hepatic artery. The calves were fed either a diet with a low (L) or a high (R) abomasal emptying rate for dietary proteins. Blood flow and free amino acid levels in plasma (P) and blood (S) were determined before the morning meal and during the following 7 h. In the portal vein, for most amino acids P/S ratios were correlated to the net amino acid balance of the digestive tract measured in plasma. By contrast in the hepatic vein, these ratios were mainly correlated to hepatic balance measured in whole blood. Correlations between digestive tract and hepatic balance calculated using either plasma or whole blood pool were different for some amino acids. This suggests that amino acid exchange between plasma and blood cells is low and absorbed amino acids are mainly transported to the liver by plasma, whereas whole blood rather than plasma is concerned in amino acid exchanges in the liver.     

Intraportal glucose infusion and pancreatic islet blood flow in anesthetized rats

The aim of the study was to evaluate whether a selective increase in portal vein blood glucose concentration can affect pancreatic islet blood flow. Anesthetized rats were infused (0.1 ml/min for 3 min) directly into the portal vein with saline, glucose, or 3-O-methylglucose. The infused dose of glucose (1 mg. kg body wt(-1). min(-1)) was chosen so that the systemic blood glucose concentration was unaffected. Intraportal infusion of D-glucose increased insulin release and islet blood flow; the osmotic control substance 3-O-methylglucose had no such effect. A bilateral vagotomy performed 20 min before the infusions potentiated the islet blood flow response and also induced an increase in whole pancreatic blood flow, whereas the insulin response was abolished. Administration of atropine to vagotomized animals did not change the blood flow responses to intraportal glucose infusions. When the vagotomy was combined with a denervation of the hepatic artery, there was no stimulation of islet blood flow or insulin release after intraportal glucose infusion. We conclude that a selective increase in portal vein blood glucose concentration may participate in the islet blood flow increase in response to hyperglycemia. This effect is probably mediated via periarterial nerves and not through the vagus nerve. Furthermore, this blood flow increase can be dissociated from changes in insulin release.     

Diminished hyperaemic response of the hepatic artery to portal venous occlusion (the buffer response) in Asian hybrid minipigs: a comparison of the response to that observed in dogs

The hyperaemic response of the hepatic artery to portal vein occlusion (the buffer response) and the action of exogenous adenosine upon hepatic artery blood flow was studied in Asian hybrid minipigs as a potential alternative experimental model to that previously developed in dogs. Adenosine produced a dose-dependent hepatic artery vasodilatation, but of lesser extent than that observed in dogs. A greatly diminished buffer response was observed in the pigs compared to that seen in dogs, and could not be replicated consistently. The adenosine uptake inhibitor dipyridamole did not potentiate responses to adenosine or the buffer response. It is concluded that the minipig is an unsuitable alternative model for the study of the hepatic artery buffer response.Abbreviations bw body weight - DPD dipyridamole - GDV gastroduodenal vein - HA hepatic artery - PV portal vein - PVO portal venous occlusion - PVP portal venous pressure - SE standard error     

脾切除及贲门周围血管离断术对肝硬化门静脉高压患者肝脏血流动力学的影响及其术后门静脉血栓形成的因素分析

目的:探讨脾切除及贲门周围血管离断术对肝硬化门静脉高压患者肝脏血流动力学的影响,并分析患者术后门静脉血栓形成的危险因素。方法:选择2016年1月-2017年12月在我院进行脾切除及贲门周围血管离断术的96例肝硬化门静脉高压患者,于术前、术后1d、3d、7d采用彩色多普勒超声对患者的肝脏血流动力学指标进行动态监测。统计术后7d内患者门静脉血栓的发生率,并将患者分为血栓组(n=28)和无血栓组(n=68),对两组患者的一般资料、手术指标、彩色多普勒超声监测指标等进行单因素分析,并采用Logistic多因素回归分析门静脉血栓形成的危险因素。结果:患者在术前、术后1d、3d、7d时的门静脉内径、最大流速、血流量呈逐渐降低的趋势,肝动脉内径、最大流速、血流量呈逐渐升高的趋势,且各时间点间两两比较差异有统计学意义(P0.05)。术后7d内有28例患者出现门静脉血栓,发生率为29.17%。血栓组和无血栓组患者在性别、年龄、体质量指数、手术时间、术前门静脉流速比较差异无统计学意义(P0.05);血栓组患者Child-Pugh分级为B级比例、术中出血量、脾质量、腹水量、术前门静脉内径均高于无血栓组,术后门静脉内径、术后门静脉流速均低于无血栓组(P0.05)。经Logistic多因素回归分析显示,患者术后门静脉内径、术后门静脉流速是门静脉血栓形成的危险因素(P0.05)。结论:行脾切除及贲门周围血管离断术的肝硬化门静脉高压患者术后进行肝脏血流动力学监测,有助于患者术后的疗效判断,且术后门静脉内径、术后门静脉流速是门静脉血栓形成的危险因素。     

肝硬化患者肝脏门静脉血流与肝叶萎缩之间关系的研究

目的:探讨肝硬化患者肝脏右叶、左叶体积变化,检测肝硬化患者门静脉血流情况,分析二者之间的关系,以及门静脉血流与肝功能之间关系。方法:本研究纳入54例肝硬化患者和40例正常人,采用超声多普勒方法分析这些受试者的肝脏体积和门静脉主干及左右分支的内径、血流速、流量数据,并通过静脉血检测白蛋白、胆红素、胆碱酯酶水平等评估患者肝功能水平。结果:肝硬化组平均年龄46.3岁,男性32例,其中child A级患者16例,child B级患者27例,child C级患者11例;正常对照组平均年龄41.8岁,男性24例。肝硬化组患者右左肝叶之比明显低于正常对照组(p<0.05),门静脉内径和血流量明显高于正常对照组(p<0.05).随着child分级升高,门静脉血流量也明显升高。肝硬化组门静脉右支血流量明显低于左支血流量(p<0.05);此外肝硬化患者门静脉右支和左支血流量之比明显低于正常人群门静脉右左支之比(p<0.05);而且肝硬化患者门静脉右左支血流量之比与右左肝叶具有明显的相关性与右左肝叶之比具有明显的相关性(r=0.64,p<0.05)。结论:评估肝硬化病人门静脉血流情况,对于判断肝脏病理变化程度,评价治疗效果,以及选择治疗方案方面都具有重要的临床价值     

Pulmonary circulation in embolic pulmonary edema

The ultrasonic method was used in acute experiments on cats with open chest under artificial lung ventilation to obtain blood flow in low-lobar pulmonary artery and vein, the blood pressure in pulmonary artery, as well as the left atrial pressure in fat (olive oil) and mechanical (Lycopodium spores) pulmonary embolism. It is shown that pulmonary embolism produces the decrease in the blood flow in pulmonary artery and vein, the increase of the pressure in pulmonary artery and left atria, the increase of lung vessels resistance. The decrease is observed of systemic arterial pressure, bradycardia, and extrasystole. After 5-10 min the restoration of arterial pressure and heart rhythm occur and partial restoration of blood flow in pulmonary artery and vein. In many experiments the blood flow in vein outdoes that in the artery--it allows to suppose the increase of the blood flow in bronchial artery. After 60-90 min there occur sudden decrease of systemic arterial pressure, the decrease of the blood flow in pulmonary artery and vein. The pressure in pulmonary artery and resistance of pulmonary vessels remain high. Pulmonary edema developed in all animals. The death occurs in 60-100 min after the beginning of embolism.     

Splanchnic glucagon kinetics in exercising alloxan-diabetic dogs.

The purpose of this study was to define the relationship between arterial immunoreactive glucagon (IRG) and IRG that perfuses the liver via the portal vein during exercise in the diabetic state. Dogs underwent surgery >16 days before the experiment, at which time flow probes were implanted in the portal vein and the hepatic artery, and Silastic catheters were inserted in the carotid artery, portal vein, and hepatic vein for sampling. Dogs were made diabetic with alloxan injected intravenously approximately 3 wk before study (AD) or were studied in the nondiabetic state (ND). Each study consisted of a 30-min basal period and a 150-min moderate-exercise period on a treadmill. The findings from these studies indicate that the exercise-induced increment in portal vein IRG can be substantially greater in AD compared with ND, even when arterial and hepatic vein increments are not different. The larger IRG gradient from the portal vein to the systemic circulation in AD dogs is a function of a twofold greater increase in nonhepatic splanchnic IRG release and a fivefold greater hepatic fractional IRG extraction during exercise. In conclusion, during exercise, arterial IRG concentrations greatly underestimate the IRG levels to which the liver is exposed in ND, and this underestimation is considerably greater in dogs with poorly controlled diabetes.     

Role of the hypothalamus in regulating liver circulation

In acute experiments on nembutal anesthetized dogs stimulation of anterior hypothalamus elicited changes in the hepatic artery blood flow, which followed those of arterial pressure; the vascular resistance remaining unchanged. The stimulation of medial and posterior hypothalamus led to decrease in flow and increase in the resistance of the hepatic artery. In most cases of hypothalamic stimulation the portal blood flow diminished, portal pressure and vascular resistance increased. The opposite reactions were observed during stimulation of sympathoinhibitory area, paraventricular and lateral hypothalamic nuclei. The conclusion is made that the hypothalamus participates in integrative and differential control of the hepatic circulation.     

Simultaneous sampling of portal, hepatic and systemic blood during intragastric loading and tracer infusion in conscious pigs

A surgical model for catheterization at multiple sites has been developed for use in long-term metabolic studies. For blood sampling, catheters were inserted into the portal and hepatic veins and the common carotid artery. The hepatic vein catheter was inserted from the margin of a liver lobe and led through the venous system, until the tip was close to the bifurcation with the inferior vena cava. A new technique was developed to ensure correct placement of the hepatic vein catheter using the specific extraction of indocyanin-green over the liver during surgery. Gastrostomy was performed using a Pezzer catheter. Catheters in the artery and hepatic and portal veins were patent for blood withdrawal for up to 4 weeks, and thus allowed repeated metabolic studies. Studies were performed in conscious animals familiar with the experimental situation.     

Daily metabolism and hepatic balance studies of plasma cortisol and aldosterone in the preruminant calf

Intestinal and hepatic catabolism of cortisol and aldosterone were studied in the calf using blood samples from the mesenteric artery and portal and hepatic veins collected over 24 h, the hepatic blood flow being continuously recorded during this period. The total hepatic blood flow remained broadly constant over the 24 h, although meals were followed by decreasing flow in the portal vein and by increasing flow in the hepatic artery. The intestinal tract catabolizes cortisol as intensively as the liver (both 13% of cortisol reaching the organ). The part played by the gut and the liver in the catabolism of aldosterone were also equivalent (both 30% of aldosterone reaching the organ). This 24-h study demonstrated that a constant ratio existed between secretion and catabolism of cortisol while the hepatic balance of aldosterone seemed to be modified during the night.     

肝硬化患者肝脏门静脉血流与肝叶萎缩之间关系的研究

目的：探讨肝硬化患者肝脏右叶、左叶体积变化,检测肝硬化患者门静脉血流情况,分析二者之间的关系,以及门静脉血流与肝功能之间关系。方法：本研究纳入54例肝硬化患者和40例正常人,采用超声多普勒方法分析这些受试者的肝脏体积和门静脉主干及左右分支的内径、血流速、流量数据,并通过静脉血检测白蛋白、胆红素、胆碱酯酶水平等评估患者肝功能水平。结果：肝硬化组平均年龄46.3岁,男性32例,其中childA级患者16例,childB级患者27例,childC级患者11例;正常对照组平均年龄41．8岁,男性24例。肝硬化组患者右左肝叶之比明显低于正常对照组（p〈0．05）,门静脉内径和血流量明显高于正常对照组（p〈0．05）．随着child分级升高,门静脉血流量也明显升高。肝硬化组门静脉右支血流量明显低于左支血流量（p〈0．05）;此外肝硬化患者门静脉右支和左支血流量之比明显低于正常人群门静脉右左支之比（p〈0．05）;而且肝硬化患者门静脉右左支血流量之比与右左肝叶具有明显的相关性与右左肝叶之比具有明显的相关性（r=0．64,p〈0．05）。结论：评估肝硬化病人门静脉血流情况,对于判断肝脏病理变化程度,评价治疗效果,以及选择治疗方案方面都具有重要的临床价值     

A portal-arterial glucose concentration gradient as a signal for an insulin-dependent net glucose uptake in perfused rat liver

Since in the usual perfusion of isolated rat liver via the portal vein an insulin-dependent increase of hepatic glucose uptake could not be demonstrated, the possibility was considered that hepatic glucose uptake might not be a function of the absolute concentration of this substrate but of its concentration gradient between the portal vein and the hepatic artery. Therefore a new method was established for the simultaneous perfusion of isolated rat liver via both the hepatic artery (20-35% flow) and the portal vein (80-65% flow). When glucose was offered in a concentration gradient, 9.5 mM in the portal vein and 6 mM in the hepatic artery, insulin given via both vessels caused a shift from net glucose release to uptake. This insulin-dependent shift was not observed when glucose was offered without a gradient or with an inverse gradient, 6 mM in the portal vein and 9.5 mM in the hepatic artery. Using a portal-arterial glucose gradient as a signal the liver might be able to differentiate between endogenous and exogenous glucose.     

不同入肝血流阻断方式对荷瘤小鼠肝功能影响的实验研究

目的:探讨不同血流阻断方式对荷瘤小鼠肝细胞功能的影响。方法:选择昆明小鼠24只随机分为三组,正常对照组(Suspe-nded operation,SO)、肝门阻断组(Occlusion of the portal triad,OPT)、保留肝动脉持续阻断门静脉(Occlusion of portal vein,OPV)各8只。采用门静脉注射肿瘤的方法建立肝癌模型,建模后3天采用阻断范围为左外叶和中叶、阻断时间为60分钟的入肝血流阻断方式,复流后5天后,通过测量3组对肝脏的缺血再灌注损伤程度以及病理学变化来评价不同血流阻断方式对肝细胞功能影响的程度。结果:门静脉注射小鼠肝癌细胞8天后,对照组测量小鼠正常丙氨酸氨基转移酶(ALT)值为66.5±22.3 IU/L,OPT组值为276.3±80.5 IU/L,OPV组值为89.6±28.4 IU/L,两组比较有统计学差异(P0.01);对照组测量小鼠正常天冬氨酸氨基转移酶(AST)值为301.3±126.7 IU/L,OPT组值为1126.4±285.5 IU/L,OPV组值为438.6±150.7 IU/L,两组比较有统计学差异(P0.01),病理组织学OPV组肝细胞损伤程度明显较OPT组轻。结论:保留肝动脉持续阻断门静脉可以减轻荷瘤小鼠肝脏的缺血再灌注损伤。     

Influence of vasoactive intestinal polypeptide (VIP) on splanchnic and central hemodynamics in healthy subjects

The influence of VIP, a potent vasodilator, on central hemodynamics, splanchnic blood flow and glucose metabolism was studied in six healthy subjects. Teflon catheters were inserted into an artery, a femoral vein and a right-sided hepatic vein. A Swan-Ganz catheter was introduced percutaneously and its tip placed in the pulmonary artery. Determinations of cardiac output, systemic, pulmonary arterial and hepatic venous pressures as well as splanchnic blood flow were made in the basal state and at the end of two consecutive 45 min periods of VIP infusion at 5 and 10 ng/kg/min, respectively. Arterial blood samples for analysis of glucose, FFA, insulin and glucagon were drawn at timed intervals. VIP infusion at 5 ng/kg/min resulted in an increase in cardiac output (55%) and heart rate (25%) as well as a reduction in mean systemic arterial pressure (15%) and vascular resistance (45%). With the higher rate of VIP infusion heart rate tended to rise further while cardiac output and arterial pressure remained unchanged. At 15 min after the end of VIP infusion the above variables had returned to basal levels. Splanchnic blood flow and free hepatic venous pressure did not change significantly. Arterial concentrations of glucose, FFA, insulin and glucagon increased during VIP infusion. At 15 min after the end of infusion the glucose levels were still significantly higher than basal (20%). Net splanchnic glucose output did not change in response to VIP infusion. It is concluded that VIP exerts a potent vasodilatory effect resulting in augmented cardiac output and lowered systemic blood pressure and vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)