Portal Vein Cannulation Research Articles

Percutaneous transhepatic pancreatic islet cell transplantation in type 1 diabetes mellitus: radiologic aspects.

To report our experience with percutaneous transhepatic pancreatic islet cell transplantation in patients with type 1 diabetes mellitus. Between March 1999 and May 2002, 34 patients underwent 68 islet cell transplantation procedures. Patients with C-peptide-negative type 1 diabetes were selected on the basis of poor metabolic control (hypoglycemia or lability) despite compliance with optimal medical therapy. Islet cells were isolated from brain-dead donors. Access to the portal vein was gained from a right percutaneous transhepatic approach, and islet cells were infused with intermittent pressure monitoring. Twenty patients underwent two transplantations, seven patients underwent three transplantations, and seven patients underwent one transplantation. Complications during and after the procedure and postprocedural diabetic status were monitored. Successful portal vein cannulation and islet cell infusion were achieved in all cases. Fluoroscopy was used as the primary guidance modality in 58 of 68 (85%) procedures, and ultrasonography was used in 10 of 68 (15%). Total recorded fluoroscopy time varied from 0.6 to 103 minutes, with a median of 6.9 minutes. Potentially serious complications occurred in six of 68 (9%) procedures. Two patients developed portal venous thrombosis, and with subsequent anticoagulation therapy, one of the two developed an expanding hepatic hematoma that required surgery. Clinically important hemorrhage occurred in four patients, three of whom required blood transfusions. Of 26 patients who received completed transplants, all became insulin independent, and 81% (21 of 26) remained insulin free at 1 year. The percutaneous transhepatic approach for the implantation of islet cells into the portal vein is a safe procedure, and together with use of current cell separation techniques and an immunosuppressive regimen, offers a marked advance in the treatment of type 1 diabetes mellitus.

Gene Transfer into the Liver of Nonhuman Primates with E1-Deleted Recombinant Adenoviral Vectors: Safety of Readministration

Preclinical studies were designed to investigate the safety of recombinant adenoviruses infused into the portal vein of adult rhesus monkeys, as well as the safety and efficacy of readministration of these agents. The vectors used were recombinant adenoviruses, the E1 region of which was replaced with a marker gene expression cassette. Four 3- to 5-kg rhesus monkeys underwent portal vein cannulation, and infusion of escalating doses of recombinant first-generation vector. Serial sequential liver biopsies were performed, and necropsies were performed out to 14 months. X-Gal histochemical analysis of the liver showed evidence of dose-dependent increased gene transfer throughout the liver. Quantitative analysis of histopathology showed that portal inflammation was also present in transduced livers, and occurred in a dose-dependent manner. Severe toxicity, including mortality, was noted at the highest dose of vector. Readministration of a second vector was associated with the same degree of toxicity as the first vector, but prompted a much more vigorous neutralizing antibody response. The data suggest that intraportal administration and readministration of recombinant adenoviral E1-deleted vectors are feasible and safe. Vector administration at the highest dose (1 x 10(13) particles/kg) was associated with severe clinical and biochemical toxicity, and significant gene expression was associated with transaminitis. Readministration of vector is safe, but gene transfer is limited by the presence of neutralizing antibody.

Hepatic Portal Vein Cannulation for Infusion and Blood Sampling in Freely Moving Rats

Chronic portal vein cannulation in the rat is an important technique to study secretory rates of hormones from the endocrine pancreas. Moreover, it can be used for studying the effects of enteric hormones and pharmaca on behavioral and physiological processes. This article contains an extensive description of a cannulation technique of the portal vein that has many advantages over those reported so far in the literature, and that was very successful in several behavioral and physiological studies during the last decade.

Perivascular and intralesional tissue necrosis after hepatic cryoablation: Results in a porcine model

Background . Cryosurgical ablation of malignant hepatic tumors is being increasingly used for definitive treatment of metastatic colorectal and primary hepatic tumors. The lack of tumor necrosis near vessels that results from inadequate freezing may contribute to local recurrence and thus limit the applications of this therapy. This study was designed to determine whether single-freeze cryoablation could cause necrosis of both the perivascular and intralesional hepatic parenchyma. Methods . Ten pigs were treated with one 15-minute cycle of cryoablation. Five additional animals were treated with overlapping cryolesions to simulate a double freeze. After 24 hours, animals underwent reoperation with portal vein cannulation and infusion of formalin. Serial sectioning and hematoxylin and eosin staining of cryolesions were performed. Results . Complete cell death was visualized within all cryolesions. There was no difference between once-or twice-frozen tissue. Vessels within or adjacent to cryolesions showed necrosis of hepatic tissue up to the vessel wall. No sections revealed incomplete necrosis of perivascular hepatic parenchyma. Conclusions . Single-freeze cryoablation results in necrosis of intralesional hepatic parenchyma without added benefit from repeat freezing. Complete necrosis of the perivascular tissue suggests that cryosurgical ablation can effectively cause necrosis immediately adjacent to vessels without concerns of incomplete ablation resulting from the heat sink effect.

Support perfusion for liver transplantation.

Addenbrooke's Hospital, Cambridge, UK, has had an ongoing orthotopic liver transplant programme since 1968. Various support bypass techniques have been used intermittently since 1977. In 1990 bypass was needed for 38% of adult liver transplants, and bypass standby was provided for a further 25%. Adult liver recipients (high-risk) are selected for bypass in accordance with a number of surgical and anaesthetic criteria in order to maximize patient benefit and minimize risk. Before the start of the operation two cannulae (8 or 10 Fg) are placed into left and right internal jugular veins and/or the left brachial vein for rapid volume replacement. Femoral and portal vein cannulation (16 to 22 Fg) can quickly be achieved for splanchnic venous drainage to a heparin coated Biomedicus bypass system. This technique provides flows of 1.5 to 2.5 litres per minute with modest perfusion pressures (around 120mmHg) and provides adequate surgical venous decompression and circulatory support during the anhepatic phase.

A new catheter to simplify portal vein cannulation for adjuvant cytotoxic liver perfusion following resection of rectal cancer

Evidence from randomised clinical trials suggests that adjuvant cytotoxic liver perfusion with 5-fluorouracil following resection of colorectal carcinoma may improve survival in some patients. Various methods of cannulating the portal vein or a tributary at the time of surgery have been described. We describe a simple method of accessing the portal venous circulation via a tributary in the small bowel mesentery, employing a new type of polyurethane catheter. The technical details are discussed with reference to previous literature.

Simple and safe method for operative cannulation of the portal vein.

A method of portal vein cannulation via the omental vasculator is described. This mode of vascular access, which requires only five or ten minutes of additional operating time, can be used for adjuvant or therapeutic portal vein infusion of chemotherapy.

Inhibition of galactosamine cytotoxicity in an in vivo/in vitro hepatocellular toxicity model

A combined in vivo/in vitro model of galactosamine hepatotoxicity was employed to test whether previously reported cytoprotective actions of cystamine administration on galactosamine-induced hepatic injury in vivo could be attributed to a direct action of cystamine on toxicant-challenged hepatocytes. In this model, male Sprague-Dawley rats received a 400 mg/kg galactosamine challenge via intraperitoneal injection 1 hr prior to portal vein cannulation for hepatocyte isolation. Isolated cells are established in monolayer culture and galactosamine-induced cellular injury is then expressed over the ensuing 24–48 hr in culture. Consistent with the biochemical basis of galactosamine-induced hepatocellular injury in vivo, cytotoxicity could be prevented by in vitro uridine treatments within 3 hr of the in vivo galactosamine challenge, but not when added 12 hr later. Cystamine, in contrast, exhibited a cytoprotective effect even when added to cultures 12 hr after the in vivo toxicant challenge. Post-toxicant cytoprotection by cystamine in vitro was concentration dependent and did not produce an alteration of hepatocyte nonprotein sulfhydryl content. Post-toxicant cytoprotection by uridine and cystamine in this in vivo/in vitro model of toxicity were fully consistent with in vivo protection from galactosamine-induced necrosis by these agents. This model eliminates potential “extrahepatic” mechanisms for cystamine's hepatoprotective effect and demonstrates a direct cytoprotective action on galactosamine-challenged hepatocytes.

Method for chronic portal vein infusion in unrestrained rats

Surgical procedures for the chronic cannulation of the portal and the femoral veins in the rat are described. The surgical procedure for portal vein cannulation is delicate and requires practice, but has proven useful for chronic drug administration. Cannulation of the femoral vein was less involved and cannula patency was extended by proper cannula preparation and placement. This dual cannulation of the rat allowed infusion of racemic mephenytoin into the portal vein and blood collection from the femoral vein for characterizing blood concentrations of the individual isomers. Chronic portal vein drug infusions may provide a useful approach to studies of time-dependent change in hepatic metabolism and stereoselective first-pass drug elimination in unrestrained animals.

SYMPATHETIC TONE MODULATES PORTAL VENOUS PRESSURE IN ALCOHOLIC CIRRHOSIS

Sixteen alcoholic cirrhotic patients with portal hypertension were studied before and after 2·5 μg/kg intravenous clonidine. In six patients portal venous pressure was assessed simultaneously by wedged hepatic vein and transhepatic portal vein cannulation. Wedged hepatic vein pressure accurately reflected portal venous pressure both before and after clonidine (r = 0·912 and 0·940; p <0·01). In all the other ten patients, sympathetic tone, measured by total plasma noradrenaline spillover, was high (755 ± 123 ng/min; normal 296 + 29 ng/min). It fell significantly after clonidine (378 ± 95 ng/min; p <0·01). This fall was associated with a decrease in corrected wedged hepatic vein pressure (18·6 ± 1·1 to 13·4±0·5 mm Hg; p <0·01) but no change in estimated hepatic blood flow (934±94 to 976±102 ml/min), indicating a fall in postsinusoidal hepatic vascular outflow resistance. Clonidine-induced changes in mean arterial pressure and cardiac output were independent of the change in portal venous pressure. The results suggest that in alcoholic cirrhosis there is a labile component of hepatic vascular resistance which is partly under sympathetic nervous control and is thus potentially sensitive to pharmacological control.

Treatment of unresectable hepatocellular carcinoma : Results of a randomized controlled trial

AbstractMost patients with hepatocellular carcinoma present late with unresectable disease and, to date, an effective and safe palliative treatment has not been found. From December 1971, to December 1981, a randomized controlled trial was conducted to evaluate the following treatments against a control group receiving only symptomatic therapy (group I) : hepatic dearterialization (group II), hepatic artery ligation and cannulation for infusion of chemotherapeutic agents (group III), hepatic artery ligation and portal vein cannulation for chemotherapeutic agents infusion (group IV), and external irradiation (group V). Response to various treatments was assessed with respect to symptomatic relief and duration of survival. A total of 166 patients with histologically confirmed tumor confined to the liver were studied. All patients had similar preoperative general status and biochemical findings. Patients in group IV had the best symptomatic improvement; 58.6% responded to some degree. Hepatic artery ligation intraportal infusion (group IV) offered significantly longer survival than infusion via the intra‐arterial route (group III) (p = 0.023). However, when compared with the control group, the survival times in the 4 treatment groups were not significantly different. Hepatic dearterialization (group II) had the highest 7‐day mortality rate, 33.3%. The results of this trial suggested that none of the modalities of treatment studied offered patients with unresectable hepatocellular carcinoma any better survival and symptomatic palliation than did symptomatic treatment alone.

A simplified method for chronic portal vein cannulation in the rat

A simple technique is described for chronic cannulation and repeated blood sampling from the portal vein of the conscious undisturbed rat. The method employs a straight cannula and allows precise location of the tip. Blood flow in the portal vein is not obstructed. The present technique was used in combination with chronic cannulation of the superior vena cava. Simultaneous blood sampling from the two cannulas was successfully carried out at fifteen minute intervals over six hour periods. The system and the sampling were well tolerated by the rats.

Intestinal absorption of vitamin D sterols: Differential absorption into lymph and portal blood in the rat

Radiolabeled vitamin D sterols (5 nmol) were administered intraduodenally (in fat emulsion) into conscious rats with mesenteric lymph fistula and portal vein cannulation. The rats were kept for 4 h in restraining cages, and lymph and blood samples were collected at half-hour intervals. Vitamin D3 was absorbed mostly into the mesenteric lymph (6.5% of administered dose vs. < 1%/4 h into the portal blood). 1,25-Dihydroxyvitamin D3 was absorbed mainly into the portal blood (~7%/4 h and only 1.6%/4 h into the mesenteric lymph). 25-Hydroxyvitamin D3 had a similar rate of absorption into the lymph and portal vein (5%/4h and 7%/4 h, respectively). Vitamin D3 absorption started after 2 h, whereas the more hydroxylated metabolites were more rapidly absorbed and appeared in the lymph and portal blood within the first half-hour. In the lymph the vitamin D sterols were transported mainly on chylomicrons and lipoproteins (> 50%), whereas in blood less than 20% were associated with plasma lipoproteins. In rats where lymph was not diverted, the increment of lymphatic contribution was observed in plasma levels for all vitamin D sterols. The absorbed sterols in lymph and blood were mostly unchanged with the exception of 25-hydroxyvitamin D3, about one-third of which underwent esterification during absorption into the mesenteric lymph. We conclude that 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3, in particular, are absorbed directly into portal blood independent of fat absorption, and thus may be prescribed as oral supplements in most patients with fat malabsorption.

Orthotopic rat liver transplantation after long-term preservation by continuous perfusion with fluorocarbon emulsion.

Isolated rat livers have been stored for up to 25 hr using a continuous pulsatile perfusion technique with and without fluorocarbon emulsion oxygen carrier in the perfusate. After preservation, orthotopically isografted livers can maintain recipient animals in good health. The longest surviving animal is alive at 12 months. A prosthetic cuff technique for the portal vein anastomosis was specially developed for this experimental series. It has simplified vascular anastomosis after the portal vein cannulation that is required for machine preservation of the donor liver. We believe that the described method in the rat liver isograft model might be useful for studies of liver preservation.

Liver perfusion technique using inexpensive nonbinding medium for first-pass metabolism studies of drugs

A rat liver perfusion technique which employs an inexpensive nonbinding medium has been developed and evaluated for first-pass drug kinetic studies. The perfusate consisted of a modified Krebs-Henseleit solution containing sucrose to minimize edema. The medium was aerated with 5% CO 2 in O 2 before flowing through the liver in a single pass at 3.8–4.0 ml min per gram liver. Bile flow rate peaked at 10.8 μl min 20 min after portal vein cannulation and declined to 7.8 μl min 2 hr after cannulation. Liver resistance remained steady at about 70 μb per ( ml min ) per liver. Some muscopic changes as well as a reduction in the dry/ wet weight ratio were detected in the liver after 2 hr of perfusion. However, a test of the perfused liver with 14C-imipramine indicated that these changes are not serious enough to substantially impair the metabolism and elimination of xenobiotics during at least the first 90 min of perfusion. Since the perfusate passes only once through the liver, drugs can be administered at a constant rate until steady state conditions are approximated. Hence, this technique not only allows the hepatic first-pass effect to be easily determined, but also permits the ready detection of pathways of metabolism and/or elimination affected by controlled changes in experimental protocol, such as the introduction of a second drug.