Plasma endotoxin and concentrations of stable metabolites of prostacyclin, thromboxane A2, and prostaglandin E2 in postpartum dairy cows

The presence of endotoxin in plasma and patterns of stable metabolites of prostacyclin (PC), thromboxane A2 (TXA2) and prostaglandin E2 (PGE2) were determined during the first postpartum estrous cycles in sixteen dairy cows. These included 8 cows with uterine infections which exhibited shortened luteal phases (SC) and 8 cows which had normal luteal phases (NC) after the first post partum ovulations. Endotoxin was consistently detected in all SC cows during the abbreviated estrous cycles while plasma samples of NC cows were free of endotoxin. Plasma concentrations of TXA2 metabolite was higher in SC cows (p less than 0.05) (1785-3452 pg/ml) compared to NC cows (723-1240 pg/ml). Similarly, plasma concentrations of PC metabolite was higher in SC cows (p less than 0.07) (423-1847 pg/ml) compared to NC cows (159-325 pg/ml). In contrast, plasma concentrations of PGE2 metabolite was higher in NC cows (p less than 0.05) (850-2219 pg/ml) compared to SC cows (455-628 pg/ml). The results of this study suggest that postpartum uterine infections mediate the release of prostaglandins from the uteri by means of the endotoxin and endotoxin appears to stimulate selectively the production of PC and TXA2 favoring early demise of corpora lutea formed after first postpartum ovulations in dairy cows.     

Absorption of Escherichia coli endotoxin (lipopolysaccharide) from the uteri of postpartum dairy cows

An experiment was conducted to test the hypothesis that Escherichia coli (E. coli ) endotoxin is readily absorbed from uteri of early postpartum cows and that the absorbed endotoxin provokes systemic relcase of prostaglandins. Eleven postpartum Holstein dairy cows (aged 3 to 7 yr) with normal puerperium were selected and divided into a treatment group (n=7), which received intrauterine infusions of E. coli endotoxin, and a control group (n=4), which received intrauterine infusions of 10 ml of saline on Days 5 and 20 post partum. Blood samples were collected once every 30 min for 6 h starting from the time of infusion. Harvested sera samples were analyzed for concentrations of stable metabolites of prostacyclin (PCM), prostaglandin F(2alpha) (PGFM), and thromboxane A(2) (TXB(2)). Plasma samples were qualitatively tested for the presence of endotoxin. Endotoxin was detected in the plasma samples of cows that received endotoxin on Day 5 post partum 4 h after the infusion. Endotoxin was not detected in any of the samples from control cows on Days 5 and 20 post partum or from treatment group cows on Day 20 post partum. Cows treated on Day 5 post partum showed increases in serum PGFM concentrations from 710 +/-64pg/ml to peak concentrations of 1223 +/- 47 pg/ml within 2 h, followed by a decline to baseline concentrations within 4 h. The amount of PGFM released in treated cows on Day 5 post partum was higher (P < 0.05) than in control cows on Day 5 or in treated and control cows on Day 20 post partum. Serum PCM concentrations increased from 156+/-24 pg/ml to peak concentrations of 1348+/-127 pg/ml within 1 h. The amount of PCM released in treated cows on Day 5 postpartum was higher (P< 0.05) than in control cows on Day 5 or in treated and control cows on Day 20 post partum. The TXB(2) concentrations increased from 315+/-38 pg/ml to peak concentrations of 5043 +/- 242 pg/ml within 1 h and fell to baseline concentrations within 5 h. The amount of TXB(2) concentrations released in treated cows on Day 5 post partum was significant (P < 0.05) compared with those of cows in the other groups. The results support the hypothesis that uteri of early postpartum cows are capable of absorbing endotoxin, and the absorbed endotoxin provokes changes in the serum concentrations of prostanoids.     

An integrative model of amino acid metabolism in the liver of the lactating dairy cow

The objective of this work was to construct a dynamic model of hepatic amino acid metabolism in the lactating dairy cow that could be parameterized using net flow data from in vivo experiments. The model considers 22 amino acids, ammonia, urea, and 13 energetic metabolites, and was parameterized using a steady-state balance model and two in vivo, net flow experiments conducted with mid-lactation dairy cows. Extracellular flows were derived directly from the observed data. An optimization routine was used to derive nine intracellular flows. The resulting dynamic model was found to be stable across a range of inputs suggesting that it can be perturbed and applied to other physiological states. Although nitrogen was generally in balance, leucine was in slight deficit compared to predicted needs for export protein synthesis, suggesting that an alternative source of leucine (e.g. peptides) was utilized. Simulations of varying glucagon concentrations indicated that an additional 5 mol/d of glucose could be synthesized at the reference substrate concentrations and blood flows. The increased glucose production was supported by increased removal from blood of lactate, glutamate, aspartate, alanine, asparagine, and glutamine. As glucose output increased, ketone body and acetate release increased while CO(2) release declined. The pattern of amino acids appearing in hepatic vein blood was affected by changes in amino acid concentration in portal vein blood, portal blood flow rate and glucagon concentration, with methionine and phenylalanine being the most affected of essential amino acids. Experimental evidence is insufficient to determine whether essential amino acids are affected by varying gluconeogenic demands.     

Effect of bacterial cell wall and lipopolysaccharide on arachidonic acid metabolism by caruncular and allantochorionic tissues from cows that calved normally and those that retained fetal membranes

Immunoactive eicosanoids may have a role in both placental separation and uterine involution in cattle. In the present study, we examined the effects of bacterial cell wall preparation and endotoxins on in vitro prostaglandin synthesis and arachidonic acid (AA) metabolism by caruncular and allantochorionic tissues. Placentomes were obtained about 6 h post partum from cows that delivered normally (n = 10) or those with retained fetal membranes (n = 4); the tissue explants were incubated for 6 h in the presence of labeled or nonlabeled AA. Prostaglandin F(2alpha) (PGF(2alpha)) and E(2) (PGE(2)) were measured by radioimmunoassay, and labeled AA metabolites were separated by reverse phase-high pressure-liquid chromatography. There was no effect of bacterial cell wall preparations or endotoxins on in vitro caruncular PGF(2alpha) secretion. However, bacterial products increased caruncular PGE(2) secretion in both cows that delivered normally and those with retained fetal membranes. For normal delivery cows caruncular tissue, bacterial product also increased leukotriene B(4) (LTB(4)) and decreased both thromboxane B(2) (TXB(2)) and hydroxy-eicosatetranoic acids (HETE) in vitro secretion. For the allantochorion, bacterial products increased in vitro PGF(2alpha) secretion only in cows that delivered normally and increased PGE(2) secretion essentially in cows with retained fetal membranes. In general, 6 keto PGF(1alpha) was the main metabolite secreted by both allantochorionic and carucular tissues. However, in cows with retained fetal membranes, PGE(2) became the most important metabolite secreted by allantochorion, especially in the presence of endotoxin. In conclusion, these results suggest that bacteria found in the early postpartum uterus or their endotoxin affect primarily caruncular and allantochorionic PGE(2) synthesis.     

Pathophysiology of Experimental Bovine Endotoxicosis: Endotoxin Induced Synthesis of Prostaglandins and Thromboxane and the Modulatory Effect of Some Non-Steroidal Anti-Inflammatory Drugs

Endotoxin-induced synthesis of thromboxane A2 (TXA2), prostacyclin (PGI2) and prostaglandin E2 (PGE2) was studied in 3 cows after intravenous E. coli endotoxin (055:B5–0.025 mg/kg b.w.) administration. Blood sampling and monitoring of clinical signs were performed from 2 h prior to until 6 h after endotoxin challenge. Blood samples were analyzed for stable hydrolysis products of TXA2 (TXB2), PGI2 (6-keto PGF) and PGE2 (bicyclic PGE2), biochemical and haematological parameters. In a similar experimental design the efficacy of the non-steroidal anti-inflammatory drugs (NSAID) flunixin meglumine (FM) and phenylbutazone (PB) in suppressing eicosanoid synthesis and clinical signs in response to endotoxin challenge was investigated. Two groups of cows, each comprising 2 animals, were treated with FM and PB prior to endotoxin challenge. It was observed that plasma concentrations of TXB2, 6-keto PGF and bicyclic PGE2 increased rapidly after endotoxin challenge. Concentrations were significantly elevated for hours and were correlated to the severity of clinical signs of endotoxicosis. Pretreatment with NSAID suppressed mediator production and alleviated clinical signs. The experiments suggest a certain pathophysiological role of TXA2, PGI2 and PGE2 for the early systemic ill-effects of bovine endotoxicosis.     

肠道需氧革兰氏阴性杆菌与门静脉血内毒素水平关系的初步探讨

本实验以普通 Webster 大鼠为动物模型,探讨肠道需氧革兰氏阴性杆菌(Gram ne-gative,G~-杆菌)与门静脉血内毒素的关系。以抗生素联合灌胃使大鼠肠道脱污染,降低肠道定植抗力,再以4种需氧 G~-杆菌混合液灌胃,行肠道再污染,然后再分别测定正常鼠(组),脱污染鼠(组)及再污染鼠(组)不同肠段和粪便需氧 G~-杆菌及相应鼠门静脉血内毒素水平。结果表明,肠道需氧 G~-杆菌的变化与相应门静脉血内毒素水平的变化基本一致.由此可见,上消化道需氧 G~-杆菌过生长,可能会成为门静脉血内毒素水平增加的原因之一。     

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。     

Splanchnic free fatty acid kinetics

These studies were conducted to assess the relationship between visceral adipose tissue free fatty acid (FFA) release and splanchnic FFA release. Steady-state splanchnic bed palmitate ([9,10-(3)H]palmitate) kinetics were determined from 14 sampling intervals from eight dogs with chronic indwelling arterial, portal vein, and hepatic vein catheters. We tested a model designed to predict the proportion of FFAs delivered to the liver from visceral fat by use of hepatic vein data. The model predicted that 15 +/- 2% of hepatic palmitate delivery originated from visceral lipolysis, which was greater (P = 0.004) than the 11 +/- 2% actually observed. There was a good relationship (r(2) = 0.63) between the predicted and observed hepatic palmitate delivery values, but the model overestimated visceral FFA release more at lower than at higher palmitate concentrations. The discrepancy could be due to differential uptake of FFAs arriving from the arterial vs. the portal vein or to release of FFAs in the hepatic circulatory bed. Splanchnic FFA release measured using hepatic vein samples was strongly related to visceral adipose tissue FFA release into the portal vein. This finding suggests that splanchnic FFA release is a good indicator of visceral adipose tissue lipolysis.     

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.     

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.     

Thromboxane production by perturbed bovine aortic endothelial cells in culture

Bovine aortic endothelial cells in culture were incubated with endotoxin. The amount of thromboxane A2 synthesized was then determined by a specific radioimmunoassay for thromboxane B2. After a lag of several hours the cells changed their shape and parallel to the change in cell shape release of thromboxane B2 occurred. At 24 h the amount of thromboxane B2 generated in response to endotoxin was 200-fold above baseline. Thromboxane B2 generation could be blocked by aspirin and the specific thromboxane synthetase inhibitor UK 37248. The endotoxin effect was dependent on protein and RNA synthesis as evidenced by the inhibitory action of cycloheximide (1.5 microM) and actinomycin D (2 micron).     

Metabolism of thromboxane B2 in the cynomolgus monkey.

[5,6,8,9,11,12,14,15-3H8]-Thromboxane B2 was injected into the saphenous vein of female cynomolgus monkeys, and blood samples were withdrawn from the contralateral saphenous vein. The compound was eliminated from the circulation with a half-life of about 10 min after an initial rapid disappearance. Some more polar products appeared with time, and also small amounts of material less polar than thromboxane B2; however, the dominating compound in all blood samples was unconverted thromboxane B2. About 45% of the given dose of tritium was excreted into urine in 48 hrs. Several metabolites of thromboxane B2 were found. The major urinary metabolite was identified as dinorthromboxane B2 (about 32% of urinary radioactivity). Unconverted thromboxane B2 was also found in considerable amounts (13% of urinary radioactivity). It is concluded that 1) dehydrogenation at C-12 is not a major pathway in the degradation of this compound, in contrast to metabolism at the corresponding C-15 alcohol group of prostaglandins; 2) after having gained access to the circulation, thromboxane B2 is the main circulating compound; however, assay of thromboxane B2 in plasma will be complicated or precluded by large artifactual production of the compound by platelets during sample collection.     

Hepatocyte heterogeneity in response to icosanoids. The perivenous scavenger cell hypothesis

1. The metabolic and hemodynamic effects of prostaglandin F2 alpha, leukotriene C4 and the thromboxane A2 analogue U-46619 were studied during physiologically antegrade (portal to hepatic vein) and retrograde (hepatic to portal vein) perfusion and in a system of two rat livers perfused in sequence. 2. The stimulatory effects of prostaglandin F2 alpha (3 microM) on hepatic glucose release, perfusion pressure and net Ca2+ release were diminished by 77%, 95% and 64%, respectively, during retrograde perfusion when compared to the antegrade direction, whereas the stimulation of 14CO2 production from [1-14C]glutamate by prostaglandin F2 alpha (which largely reflects the metabolism of perivenous hepatocytes) was lowered by only 20%. Ca2+ mobilization and glucose release from the liver comparable to that seen during antegrade perfusion could also be observed in retrograde perfusions; however, higher concentrations of the prostaglandin were required. 3. The glucose, Ca2+ and pressure response to leukotriene C4 (20 nM) or the thromboxane A2 analogue U-46619 (200 nM) of livers perfused in the antegrade direction were diminished by about 90% during retrograde perfusion. Sodium nitroprusside (20 microM) decreased the pressure response to leukotriene C4 (20 nM) and U-46619 (200 nM) by about 40% and 20% in antegrade perfusions, respectively, but did not affect the maximal increase of glucose output. 4. When two livers were perfused antegradely in series, such that the perfusate leaving the first liver (liver I) entered a second liver (liver II), infusion of U-46619 at concentrations below 200 nM to the influent perfusate of liver I increased the portal pressure of liver I, but not of liver II. At higher concentrations of U-46619 there was also an increase of the portal pressure of liver II and with concentrations above 800 nM the pressure responses of both livers were near-maximal [19.6 +/- 0.8 (n = 7) cm H2O and 16.5 +/- 1.1 (n = 8) cm H2O for livers I and II, respectively]. There was a similar behaviour of glucose release from livers I and II in response to U-46619 infusion. When liver I was perfused in the retrograde direction, a significant pressure or glucose response of liver II (antegrade perfusion) could not be observed even with U-46619 concentrations up to 1000 nM. 5. Similarly, the perfusion pressure increase and glucose release induced by leukotriene C4 (10 nM) observed with liver II was only about 20% of that seen with liver I.(ABSTRACT TRUNCATED AT 250 WORDS)     

Trichinella spiralis: vascular recirculation and organ retention of newborn larvae in rats

The recirculation of Trichinella spiralis newborn larvae was studied in inbred AO rats. Newborn larvae collected after in vitro incubation of adult T. spiralis worms for 2 or 24 hr were injected into rats through the tail vein or hepatic portal vein. Blood samples from the femoral vein, hepatic portal vein, and abdominal aorta were collected at intervals from 1 min to 24 hr after larval injection. Newborn larvae of both ages (24 hr or 2 hr old) persisted in femoral vein blood for less than or equal to 5 hr after injection, but they could be detected in portal vein blood by 24 hr after injection. The injection of larvae into a tail vein or the portal vein did not influence the pattern of larval circulation, although there was a 1-5 min delay in newborn larval appearance time after injection into the portal vein. Transcapillary migration through tissue and back to the circulation was evident in the appearance of newborn larvae in the thoracic duct lymph up to 24 (occasionally 48) hr after tail vein injection of newborn larvae. During the course of a natural primary infection, no evidence for trapping of larvae in the mesenteric lymph node could be found despite direct larval migration through this organ. Injected newborn larvae were retained in the lungs, and small numbers could be recovered 24 hr after intravenous injection. We conclude that a proportion of newborn larvae recirculates within the vasculature for several hours; a smaller population extravasates but can reenter the circulatory system via the lymphatics. Furthermore, some newborn larvae are found in organs rich in capillaries up to 24 hr after their entry into the blood.     

Plasma endotoxin and concentrations of stable metabolites of prostacyclin, thromboxane A2, and prostaglandin E2 in postpartum dairy cows

The presence of endotoxin in plasma and patterns of stable metabolites of prostacyclin (PC), thromoxane A₂ (TXA₂) and prostaglandin E₂ (PGE₂) were determined during the first postpartum estrous cycles in sixteen dairy cows. These included 8 cows with uterine infections which exhibited shortened luteal phases (SC) and 8 cows which had normal luteal phases (NC) after the first post partum ovulations. Endotoxin was consistently detected in all SC cows during the abbreviated estrous cycles while plasma samples of NC cows were free of endotoxin. Plasma concentrations of TXA₂ metabolite was higher in SC cows (p<0.05) (1785–3452 pg/ml) compared to NC cows (723–1240 pg/ml). Similarly, plasma concentrations of PC metabolite was higher in SC cows (p<0.07) (423–1847 pg/ml) compared to NC cows (159–325 pg/ml). In contrast, plasma concentrations of PGE₂ metabolite was higher in NC cows (p<0.05) (850–2219 pg/ml) compared to SC cows (455–628 pg/ml). The results of this study suggest that postpartum uterine infections mediate the release of prostaglandins from the uteri by means of the endotoxin and endotoxin appears to stimulate selectively the production of PC and TXA₂ favoring early demise of corpora lutea formed after first postpartum ovulations in dairy cows.     

Metabolism of thromboxane B2 in the cynomolgus monkey

[5,6,8,9,11,12,14,15-³H₈]-Thromboxane B₂ was injected into the saphenous vein of female cynomolgus monkeys, and blood samples were withdrawn from the contralateral saphenous vein. The compound was eliminated from the circulation with a half-life of about 10 min after an initial rapid disappearnace. Some more polar products appeared with time, and also small amounts of material less polar than thromboxane B₂; however, the dominating compound in all blood samples was unconverted thromboxane B₂.About 45% of the given dose of tritium was excreted into urine in 48 hrs. Several metabolites of thromboxane B₂ were found. The major urinary metabolites was identified as dinorthromboxane B₂ (about 32% of urinary radioactivity). Unconverted thromboxane B₂ was also found in considerable amounts (13% of urinary radioactivity).It is concluded that 1) dehydrogenation at C-12 is not a major pathway in the degradation of this compound, in contrast to metabolism at the corresponding C-15 alcohol group of prostaglandins; 2) after having gained access to the circulation, thromboxane B₂ is the main circulating compound; however, assay of thromboxane B₂ in plasma will be complicated or precluded by large artifactual production of the compound by platelets during sample collection.     

克伦特罗对绵羊肝脏氮、挥发性脂肪酸和葡萄糖流量的影响

目的 :探讨克伦特罗 (CL)影响机体物质代谢的有关肝脏机制。方法 :利用多血管导管技术在 4只绵羊上测定CL (0 .8mg kgbw)对其肝脏氮、挥发性脂肪酸 (VFA)和葡萄糖流量的影响。结果 :CL处理期绵羊血中尿素氮昼夜流量始终低于对照期 ,肝静脉及门静脉处尿素氮平均水平分别下降 16 .86 % (P <0 .0 1) ,15 .5 1% (P <0 .0 1)。CL使肝静脉多肽水平下降 ,其平均流量下降 38.71% (P <0 .0 1) ,而门静脉处多肽流量变化不明显。CL还使门静脉处VFA流量有较大幅度的提高 ,其中乙酸平均流量增加 19.49% (P <0 .0 1) ,而肝静脉处VFA的昼夜水平变化不明显。此外 ,CL可使肝静脉中葡萄糖流量有较大幅度的提高 ,其葡萄糖平均流量上升 2 5 .96 % (P <0 .0 1)。门静脉血中葡萄糖循环水平也相应提高。结论 :CL可通过增加对肝脏氮的储留 ,促进肝脏对VFA的吸收和利用及提高肝脏中葡萄糖的异生从而促进机体的物质代谢     

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     

Renal blood flow in normal dogs and in dogs with experimental liver cirrhosis following the acute continuous infusion of endotoxin

The purpose of this study was to determine if the renal circulation of normal and cirrhotic dogs behave similarly in response to an acute endotoxin infusion. Endotoxin was administered as a slow continuous infusion (13-26 micrograms/min) to a total of 20 normal dogs through the femoral vein, portal vein, or into the left renal artery. In each case, there was an initial increment in renal blood flow, of the order of 46%, while arterial blood pressure was actually declining. After 8-20 min, blood flow fell as perfusion pressure declined further. The initial increment in renal perfusion was not due to a hyperthermic response following the endotoxin. When similar doses were given to five dogs with chronic biliary cirrhosis and ascites, the biphasic response in renal perfusion was not observed, rather blood flow declined as perfusion pressure declined. When normal dogs were infused with bilirubin, bile salts, noradrenaline, and angiotensin in pressor doses, the subsequent infusion of endotoxin still produced the usual biphasic response in renal perfusion. Chronic elevation of portal pressure (but not acute elevation), volume contraction by diuresis or hemorrhage, and the infusion of bile intravenously, all abolished the biphasic response in renal perfusion and reproduced in normal dogs the response to endotoxin observed in cirrhotic dogs. Investigation of the factors causing the initial decrease in intrarenal vascular resistance in normal dogs following the endotoxin infusion implicated a role for histamine, kinins, and prostaglandins. We conclude there is a fundamental difference in the response of the renal circulation of normal and cirrhotic dogs to an endotoxin infusion, which may depend on failure of this latter group to release one or more humoral agents. This difference may be due to elevated portal pressure, a decreased effective arterial blood volume, or the products of bile having access to the circulation in cirrhotic dogs.