Portal Venous Flow Research Articles

Potentiation of responses to sympathetic nerve stimulation and vasoconstrictor agents by SK&F 103829 in the feline mesenteric circulation.

1. The amplification of vasoconstrictor effects of several agonists and sympathetic nerve stimulation, caused by 5-HT2 receptor activation, was studied in the autoperfused mesenteric circulation of anaesthetized cats. To produce long lasting and selective 5-HT2 receptor stimulation we used SK&F 103829 (2,3,4,5 tetrahydro-8[methyl-sulphonyl]-1H3-benzazepin-7-ol methensulphonate). We assessed that SK&F 103829 was a strong contractile partial agonist in isolated preparations of rat tail artery and calf pulmonary artery. 2. The intrinsic activity of SK&F 103829 with respect to 5-hydroxytryptamine (5-HT) was 0.8 in rat tail artery and 0.6 in calf pulmonary artery. SK&F 103829-induced contractile responses were surmountably antagonized by ketanserin with a potency expected from its affinity for 5-HT2 receptors. SK&F 103829 surmountably antagonized the effects of 5-HT in rat tail artery with a pKp of 5.8. 3. Concentrations of SK&F 103829 causing greater than threshold constrictions enhanced vasoconstrictor responses of sympathetic nerve stimulation, noradrenaline, angiotensin II, methoxamine and alpha, beta-methylene ATP in the mesenteric arterial bed. Increases in mesenteric arterial pressure by noradrenaline, observed in the presence of prazosin, were also potentiated by SK&F 103829. 4. Ketanserin prevented both the constrictor effect of SK&F 103829 and the SK&F 103829-evoked potentiation of the responses to noradrenaline and angiotensin II in the mesenteric arterial bed. Ketanserin, however, failed to abolish (once established) the SK&F 103829-evoked potentiation of the constrictor effects caused by both noradrenaline and angiotensin II. 5. Short lasting constrictor effects of 5-HT were reversed to dilator effects by SK&F 103829 in both the mesenteric arterial and venous bed, thereby revealing the existence of vasodilator 5-HT receptors.6. The main finding is consistent with a sensitization of the mesenteric arterial bed to vasoconstrictor responses mediated through alpha 1- and alpha2-adrenoceptors, angiotensin II receptors and purinoceptors by SK&F 103829-evoked activation of 5-HT2 receptors. This property, together with the direct constrictor effect of the mesenteric arterial bed suggest that SK&F 103829 can reduce portal venous flow thereby being a useful therapeutic principle for the treatment of portal hypertension.

Pathophysiology and Prognosis of Oesophageal Varices

The fundamental initiating factor in portal hypertension is an increase in resistance to portal venous flow. Portal venous pressure rises as a consequence, and collateral channels open to decompress the portal venous system. A number of secondary haemodynamic phenomena occur in animals and humans with portal hypertension. Systemic vascular resistance and mean arterial blood pressure fall and both cardiac output and splanchnic blood flow increase. Current theories suggest that increased vascular production of nitric oxide may have a principal role in the pathogenesis of these secondary haemodynamic changes. The most common causes of variceal bleeding are cirrhosis, schistosomiasis and extrahepatic portal venous obstruction. Varices develop in 90% of cirrhotic patients if follow-up is long enough. Bleeding from varices occurs in approximately 30% of patients followed up for 2-4 years, with mortality rates of 25% to 50% in those who bled. Prognosis is better in conditions where liver function is preserved, e.g. portal venous obstruction, schistosomiasis, etc.

Presence of pulsations and reproducibility of waveform recording in the umbilical and left portal vein in normal pregnancies.

Reproducibility and inter-observer variability of intra- and extra-abdominal umbilical venous flow velocity and left portal venous flow velocity as well as heart-synchronous waveform pulsations in these vessels were studied in 23 women at 34-38 weeks of normal pregnancy.Limited reproducibility, expressed by large intra-patient coefficients and limits of agreement between two observers, was established for all standardized recording sites. Pulsations, defined as negative venous deflections of at least 10% of the mean velocity, were demonstrated at all locations ranging from 19.6% of the measurements at the free-floating loop of the umbilical vein to 78.4% of the measurements at the left portal vein. The present study shows that the limited reproducibility of venous flow velocity waveforms should be taken into consideration, and that the presence of pulsations can be demonstrated in normal late pregnancy.

PORTAL MAGNETIC RESONANCE ANGIOGRAPHY

MR angiography has shown definite clinical use in the portal venous system. Methods have been developed for noninvasive assessment of portal venous anatomy and blood flow using a variety of techniques. Time-of-flight techniques for portal angiography and both time-of-flight and phase-contrast techniques for flow measurement are reviewed.

Effect of lidocaine onin Vivo hepatic function

Lidocaine is administered to assess donor or recipient liver function during hepatic transplantation. This study was performed to determine whether lidocaine administered at a constant concentration affected hepatic function or had demonstrable effects on hepatocellular ultrastructure. Fourteen pigs were randomly allocated to receive either a two-stage infusion of lidocaine hydrochloride or of saline. Transhepatic blood samples were taken and ultrasonic portal venous and hepatic arterial blood flow readings made on animals anesthetized with isoflurane in nitrous oxide. Liver biopsies were taken for histological analysis and determination of adenine nucleotide status prior to and after 2 hr of the two-stage infusion. A mean systemic constant plasma lidocaine concentration of 5.9 micrograms/ml was achieved during the second hour of infusion. There were no differences between the two groups in a large number of indices of hepatic function and plasma composition prior to and during the second hour of the respective infusions. Hepatic blood flow was also similar at these times. On histological examination there were no electron microscopic changes that could be specifically attributed to the administration of lidocaine. However, there were progressive changes with time. This study suggests that in anesthetized pigs a constant lidocaine concentration of about 6 micrograms/ml has no detrimental effect on hepatic function. Progressive hepatic ultrastructural changes occurred that could not be attributed to the administration of lidocaine. These may be the result of anesthetic administered or the surgery performed.

Diltiazem preserves hepatic gluconeogenesis following hemorrhagic shock.

Prolonged hemorrhagic shock is characterized by the progression from hyperglycemia to hypoglycemia and failure to respond to standard methods of resuscitation. Previous studies have shown that the transition to irreversible shock is accompanied by attenuation of hepatic gluconeogenic capacity and a rising level of intracellular calcium. Additionally, it has been observed that diltiazem improves survival following prolonged hemorrhagic shock in rats. We examined the effect of resuscitation containing diltiazem upon hepatic gluconeogenesis during early and late phases of hemorrhagic shock in a rat model. Fasted male Sprague-Dawley rats (250-350 g) were rapidly bled to a mean arterial pressure of 40 mm Hg for a period of 30 minutes (group A) or 120 minutes (group B). At the end of the hemorrhagic shock period, rats were randomized to resuscitation utilizing lactated Ringer's (LR) solution, or LR+diltiazem (DZ, 1.2 mg/kg). Following resuscitation, rats underwent laparotomy and in situ liver perfusion with an oxygenated 37 degrees C glucose-free Krebs solution via the portal vein. After equilibration, 5 mmol/L lactate and 0.5 mmol/L pyruvate were added to the perfusate as substrate and effluent samples collected. Serum glucose concentration and portal venous flow did not differ significantly between DZ and LR groups throughout the study periods. In group A, hepatic glucose production was significantly elevated in DZ animals when compared with controls (p < 0.05). A similar significant improvement in gluconeogenesis was observed following 120 minutes of hemorrhagic shock in group B (p < 0.05). Additionally, treated rats (DZ, both groups A and B) demonstrated improved gluconeogenic response to substrate when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Splenic Venous Flow Exceeding Portal Venous Flow at Doppler Sonography: Relationship to Portosystemic Varices

Splenic Venous Flow Exceeding Portal Venous Flow at Doppler Sonography: Relationship to Portosystemic Varices

Splenic venous flow exceeding portal venous flow at Doppler sonography: relationship to portosystemic varices.

The purpose of this study was to determine if the Doppler sonographic finding of hepatopetal flow in the splenic vein that exceeds hepatopetal flow in the portal vein is associated with portosystemic varices. Sixty-four patients with chronic liver disease were studied retrospectively. In 32 patients, splenic venous flow exceeded portal venous flow (S > P group); in 32 patients, portal venous flow exceeded splenic venous flow (P > S group). All patients were evaluated with Doppler sonography and CT of the upper part of the abdomen. Upper endoscopy was performed within 3 months of sonography in 44 of the 64 patients. In the S > P group, mean splenic volume was significantly larger (p = .02) than in the other group. The prevalence of varices as determined by CT in the esophageal, coronary, and peripancreatic regions was also higher in this group (p < or = .01). When esophageal varices were present, they were judged on the basis of their CT appearance to be massive in 50% of the S > P group and in 0% of the P > S group. Upper endoscopy revealed esophageal varices in 92% of the S > P group and in 55% of the P > S group (p < .005). Bleeding esophageal varices were noted in 75% of the S > P group and in 30% of the P > S group (p < .01). Patients with chronic liver disease and the Doppler sonographic finding of splenic venous flow that exceeds portal venous flow have an increased prevalence of portosystemic varices, which tend to be larger and more likely to bleed.

Evaluation of portal venous hypertension with cine phase-contrast MR flow measurements: high association of hyperdynamic portal flow with variceal hemorrhage.

Thirty-two patients with portal venous hypertension and endoscopically proved esophageal varices who were being evaluated for possible liver transplantation were studied with cine phase-contrast magnetic resonance (MR) imaging. Flow measurements in the main portal vein were obtained and associated with the presence of variceal hemorrhage within 2 years before the MR examination. Low (hypodynamic) flow was present in 22 patients, while high (hyperdynamic) flow was present in 10 patients. The presence of variceal hemorrhage was significantly associated with a high portal venous flow rate (P = .001), high variceal grade (P = .030), and Child class A or B (P = .003); however, only portal venous flow (P = .006) and variceal grade (P = .044) were found to be associated with variceal hemorrhage in a multiple logistic regression analysis. The portal venous flow rate was significantly higher among patients with Child class A or B disease compared with those with class C disease (median, 24.6 vs 8.0 mL/min.kg; P = .004).

Selective MR angiography of the liver.

Two-dimensional time-of-flight MR angiography was done with a 1.0 T whole-body imaging system. The 10 mm thick presaturation slab was positioned between two sagittal imaging slices of the liver. Images were obtained through the right lobe of the liver by moving the slab and slices together. Each image was acquired during a breath-holding interval of 16 s. Since the directions of the portal and hepatic venous flows are opposite to each other in the right lobe, these two venous systems could be visualized on separate images by the interleaved presaturation slab. On the reconstructed angiograms, separation between the two venous systems was complete and even the fourth and fifth branches were demonstrated clearly. These images facilitate clear understanding of the structure of the intrahepatic blood vessels. Although this technique is limited to volunteer studies and works only on the right lobe of the liver, it will provide valuable information for evaluating the location and vascular involvement in various liver diseases.

The effect of captopril on the superior mesenteric artery and portal venous blood flow in normal man.

1. Measurements of superior mesenteric artery and portal venous blood flow were made non-invasively along with systemic and other regional (cardiac index, forearm and cutaneous blood flow) vascular responses to acute ingestion of the ACE inhibitor captopril (50 mg) or placebo (50 mg vitamin C), in 12 healthy subjects while supine and during head-up tilt. 2. After captopril, superior mesenteric artery and portal blood flow rose markedly with a reduction in superior mesenteric artery vascular resistance. Supine blood pressure was unchanged but cardiac index and forearm blood flow rose; during head-up tilt, blood pressure fell in some subjects. 3. There was a rise in levels of plasma renin activity and a fall in levels of plasma angiotensin II after captopril. After placebo, there were no significant changes in splanchnic blood flow, systemic or other regional responses and in biochemical measurements, while supine. 4. Our studies indicate that captopril is a potent dilator of the splanchnic vascular bed and suggest that this action may contribute to its therapeutic effects. The studies indicate a role for angiotensin II in the control of this large vascular bed although other agents (bradykinin, prostacyclin) may contribute.

Interpretation of the Laser Doppler Flow Signal from the Liver of the Rat

It has been proposed that the laser Doppler flow (LDF) signal from the surface of the rat liver is almost exclusively a measure of hepatic arterial and not of total liver blood flow and therefore that LDF is not a suitable technique for the measurement of blood flow in the hepatic microcirculation. The objective of the present study was twofold: (i) to establish that liver blood flow is homogeneously distributed and (ii) to assess the behavior of the LDF signal during changes in hepatic perfusion. When 31Cr-labeled microspheres were injected into the portal vein ( n = 12), no significant differences in the relative flow (cpm/lobe to cpm/liver) to each of the liver lobes were found nor was there any difference in the ratio of flow to the outer 1-2 mm of lobe as compared to that to the "core" of the liver. Temporary occlusion of the hepatic artery and the portal vein caused ∼13% ( n = 7, P < 0.001) and ∼74% ( n = 7, P < 0.001) fall in LDF signal, respectively. Diversion of flow from the anterior to the posterior lobes ( n = 5) caused a 97.9 ± 21.1% (SD, P < 0.001) rise in LDF signal in the posterior lobes. Zero-flow LDF signal was found to represent 13.0 ± 4.1% of maximum. Hemorrhage (in 1.5-ml aliquots) was associated with a fall in mean arterial pressure (MAP) and LDF signals. A linear relationship between MAP and the LDF signal ( r > 0.9) was found. Reinfusion of blood caused both MAP and the LDF signal to return to normal. We conclude that (i) blood flow in rat liver is homogeneously distributed; (ii) the LDF signal from the liver surface responds in a manner predicted by conventional theories of hepatic hemodynamics during alteration, either independent or combined, in hepatic arterial and portal venous blood flow; and (iii) LDF may be used to measure relative changes in hepatic perfusion but problems associated with zero-flow signal and intersite variability preclude its quantification in absolute flow units.

Image-directed Doppler ultrasonography: a novel technique for the diagnosis of colorectal liver metastases.

Image-directed Doppler ultrasonography has been used to measure changes in hepatic arterial and portal venous blood flows in 22 controls and 88 patients with colorectal cancer. Doppler Perfusion Index, (DPI, ratio of hepatic arterial to total liver blood flow) and Doppler Flow Ratio (DFR, ratio of hepatic arterial to portal venous blood flow) of controls and patients with overt liver metastases were clearly separated (p < 0.0001). There was a significant reduction in the Hepatic Arterial Resistive Index (HARI) of patients with overt liver metastases (p < 0.0001). Percentage Hepatic Replacement (PHR) by metastases, measured using a computed tomography scanner, did not correlate with DFR or DPI. The results suggest that the measurement of hepatic perfusion changes using image-directed Doppler ultrasonography may be of value in the detection of small liver metastases.

Effects of PEEP on splanchnic hemodynamics and blood volume.

The effects of intermittent positive pressure ventilation with PEEP on splanchnic circulation and hepatic oxygen supply were studied in six beagles. PEEP of 0, 0.5 and 1.0 kPa (0, 5, 10 cmH2O, PEEP0, PEEP5 and PEEP10, respectively) of 30 min duration was applied in a random sequence. Hepatic arterial blood flow and portal venous blood flow were measured by electromagnetic flow meters. Blood volume changes in the splanchnic area were assessed from hepatic and splenic dimensions determined by sonomicrometry. PEEP5 and PEEP10 were associated with proportional decreases in both hepatic blood flow and cardiac output, while mean arterial pressure remained unchanged. Reflecting the decrease in hepatic blood flow, the hepatic oxygen supply decreased with the level of PEEP, and hepatic venous hemoglobin oxygen saturation was significantly less during PEEP10 (55.1 +/- 14.3%) than during PEEP5 (62.6 +/- 17.4%) and PEEP0 (62.3 +/- 11.9%). Hepatic venous and portal venous pressure increased with the level of PEEP. Hepatic dimensions increased by 7-8% and 16-19% during PEEP5 and PEEP10, respectively, but no significant changes in splenic dimension were observed. We conclude that PEEP5 and PEEP10 are accompanied by a decrease in hepatic blood flow and oxygen supply along with hepatic congestion.

Hepatic artery: effect of a meal in healthy persons and transplant recipients.

Thirty healthy volunteers and 12 liver allograft recipients (two with cirrhotic changes seen at microscopy) were given a standard meal. Doppler sonography of the right and left hepatic arteries, the superior mesenteric artery, and the portal vein was performed. The change in hepatic arterial resistance was evaluated with the resistive index (RI). After the standard meal, portal venous flow increased in both the healthy volunteers and allograft recipients (more so in the latter group). Superior mesenteric arterial RI decreased in all subjects. A postprandial increase in hepatic arterial RI, likely reflecting constriction of the hepatic artery, was seen in both groups. It was absent in the two patients with recurrent transplant cirrhosis. These results show the importance of examining hepatic arterial flow in the fasting subject, since high resistance after a meal may be falsely interpreted as a sign of disease. Absence of a postprandial change in resistance of the hepatic artery could signal abnormal liver function.

Volumetric flow rates in the portal venous system: measurement with cine phase-contrast MR imaging.

The purposes of this study were to (1) validate the accuracy of cine phase-contrast MR flow measurements within the portal vein, (2) develop a suitable protocol for using this method to measure volumetric flow rate in the portal venous system, and (3) use this protocol, with Doppler sonography as a reference, to measure portal venous flow in healthy volunteers and in patients with protal venous hypertension. Flow determinations were obtained in a model of fluid movement approximating blood-flow conditions in the portal venous system. A suitable protocol was based on consideration of the theoretical effects of (1) spatial resolution, (2) obliquity of the imaging plane to the direction of flow, and (3) signal-to-noise ratio of the signed quantitative velocity images (in three volunteers) on the accuracy and precision of flow measurements. This protocol was used to obtain cine phase-contrast MR images of the portal venous system in five volunteers and six patients. Values obtained with a flow phantom showed good accuracy of cine phase-contrast-measured vs actual volumetric flow rate (r = .995; p = .0001; MR rate = [0.94 x actual rate] + 65.6 ml/min; standard error of the y estimate = 67.3 ml/min). Velocity encoding and section thickness substantially influenced the signal-to-noise ratio of the velocity images, whereas flip angle and matrix size had only minimal effect. In volunteers and patients, portal volumetric flow rates determined by using MR images and Doppler sonography showed good correlation (r = .94; p = .0003). Our results indicate that cine phase-contrast MR imaging is a practical noninvasive method for measuring volumetric flow rates in the portal venous system.

Effects of Intraaortic Balloon Pumping on Portal Venous Flow

The effects of intraaortic balloon pumping (IABP) on portal venous flow were assessed using color Doppler echography. A total of 23 heart failure patients treated with IABP were assessed. Balloon inflation was timed to occur with every other cardiac contraction. The maximum, minimum, and mean flow velocity (Vmax, Vmin and Vmean, respectively) in the right portal vein were measured with the IABP ON and OFF, and the values compared. The Vmin with IABP ON and OFF was the same (11 +/- 5 cm/sec), whereas the difference between Vmax and Vmean was small for each patient. The velocities measured with IABP ON were larger than or equal to those with IABP OFF in all cases, however, except one. Thus, Vmax (22 +/- 8 cm/sec) and Vmean (17 +/- 6 cm/sec) with IABP ON were significantly larger (p 0.01) than those with IABP OFF (20 +/- 7 cm/sec and 16 +/- 6 cm/sec, respectively). The flow pattern of the portal vein was characteristically pulsatile either with IABP ON or OFF in most cases.

Blood flow in the portal vein: velocity quantitation with phase-contrast MR angiography.

Quantitative phase-contrast magnetic resonance (MR) angiography of the portal vein was prospectively evaluated in 79 fasting patients and 23 healthy volunteers. Images were obtained during a 12-second breath-hold acquisition in the coronal (n = 102) and axial (n = 11) planes. Pathologic correlation was available in 55 of 79 patients and included findings of cholangiocarcinoma, cirrhosis, hepatocellular carcinoma, hepatitis, and metastatic disease. Forty-one patients had correlative Doppler ultrasound (US) findings. MR and US findings correlated as to flow direction in all cases. In nine patients, Doppler US velocity measurements were available and closely correlated with MR findings. A comparison of axial and coronal portal venous phase-contrast measurements in 11 patients revealed no substantial difference with regard to the plane used. Quantitative phase-contrast MR angiography is a simple and rapid technique for the assessment of portal venous patency, flow direction, and flow velocity and, combined with high-resolution conventional MR imaging, may obviate the current use of both computed tomographic and US examinations.

A pharmacological analysis of prostaglandin E1 on portal blood flow after partial hepatectomy in rats.

Portal venous flow (PVF) and portal venous pressure (PVP) were examined after the jugular or portal injection of Prostaglandin E1 (PGE) in rats partially hepatectomized by either 40% or 66%. In the 66% hepatectomized animals, the jugular injection of PGE at 5.0 micrograms/kg/min produced an increase in PVF concomitant with a fall in systemic arterial pressure (SAP), while PVP remained unchanged. The portal injection of PGE at 0.5 micrograms/kg/min increased PVF to a level equivalent to that evoked by the jugular injection of 5.0 micrograms/kg/min PGE, without any change in SAP. PVP was reduced synchronistically with an increase in PVF. The PVF response to a portal injection of PGE at 0.5 micrograms/kg/min was not reproduced in liver intact rats. These results suggest that PGE is potent in increasing PVF in the partially resected condition of the liver and that the portal vascular bed is involved in this response.

Lidocaine decay and hepatic extraction in the Pig

Plasma lidocaine decay after injection was studied in five anaesthetized pigs and fitted to a two compartment open model. Derived pharmacokinetic parameters were employed to rapidly achieve plateau concentrations within 60 min of starting a two stage infusion of lidocaine hydrochloride. Hepatic extraction and clearance of lidocaine at steady state were determined in 10 pigs by transhepatic sampling and measurement of hepatic arterial and portal venous blood flow using perivascular ultrasonic flow probes placed at laparotomy. These data were compared with similar studies performed in man as well as the sheep, dog, monkey and cat. The lidocaine extraction ratio of 0.60 in the pig was found to be similar to that determined by others in man.