Portal Vascular Resistance Research Articles

The transjugular stent implantation for the treatment of malignant portal and hepatic vein obstruction in cancer patients

The increase in portal vascular resistance is a significant complication of metastatic disease to the liver or locally advanced cancer, e.g., biliary cancer. This paper describes the successful palliative treatment of two cancer patients with portal hypertension presenting with the symptoms of tense ascites, mesenteric congestion, and severe variceal bleeding. By creating a stenttract between a hepatic vein and a main branch of the portal vein and/or by placing an extendable stent into the portal vein, the transjugular intrahepatic portosystemic stent-shunt (TIPS) technique was used to decompress the portovascular system. The TIPS-technique offers a new, safe and effective palliation for malignant portal hypertension. In both patients, the symptoms of the portal hypertension disappeared after the procedure. This was accompanied by a significant improvement of the patients performance status allowing an early ambulation. Our findings demonstrate the feasibility and effectiveness of the TIPS procedure as a minimal invasive treatment for portal vein decompression in selected tumor patients.

Effect of hepatic nerve stimulation and norepinephrine on the laser Doppler flux signal from the surface of the perfused rat liver.

The effect of hepatic nerve stimulation and norepinephrine (NE) on the laser Doppler signal from the surface of the perfused rat liver was tested. The livers from male Wistar rats were perfused in situ via the portal vein with Krebs-Henseleit buffer containing 20% bovine erythrocytes (37 degrees C, pH 7.4) and total liver blood flow (TLBF) was by timed collection of effluent. Portal vascular resistance (PVR) was calculated from the pressure difference across the liver. Linearity of laser Doppler flowmetry (LDF) with TLBF was confirmed in all preparations. Stimulation of the hepatic nerves (2 ms, 20 V) was performed at frequencies between 0.5 and 20 Hz (n = 11). NE was added to the buffer at concentrations between 10(-10) and 10(-6) M (n = 8). A stimulus-dependent rise in PVR occurred during hepatic nerve stimulation (basal, 3.11 +/- 0.26 dyn s cm-5) and NE administration (basal, 2.62 +/- 0.29 dyn s cm-5), with a maximum effect at 20 Hz (311 +/- 45%) and 10(-6) M (591 +/- 72%), respectively. Both LDF and TLBF fell during nerve stimulation and NE. A linear relationship (r = 0.99; p < 0.001) between change in TLBF (%) and LDF flux (%) was found for NE (10(-10) to 10(-6) M). During nerve stimulation, the fall in TLBF and LDF flux was linear with the logarithm of stimulus frequency and reached a maximum at 10 and 20 Hz, respectively. At a stimulus frequency of 20 Hz, the change in LDF was significantly different from the change in TLBF (p < 0.001). We conclude from our findings that during high-frequency hepatic nerve stimulation, LDF underestimates TLBF.

Pathophysiology and Treatment of Variceal Hemorrhage

Portal hypertension results from increases in portal flow and portal vascular resistance. Factors increasing portal blood flow are predominantly humoral. Resistance to portal flow has a fixed component due to distortion of the vasculature by cirrhotic nodules and a variable component that is related to vasoactive substances. Varices result from an increase in portal pressure. Factors predicting the risk of variceal bleeding include continued alcohol use, poor liver function, large varices, and red wale markings on varices at endoscopy. Octreotide is probably the drug of choice for pharmacologic management of bleeding esophageal varices. Propranolol has an established role in the prevention of variceal hemorrhage, and variceal band ligation may be the preferred endoscopic technique. Transjugular intrahepatic portosystemic shunts have emerged as an important treatment for patients in whom pharmacologic and endoscopic therapies have failed and are an effective bridge to liver transplantation.

Role of pentobarbitone anaesthesia and sympathetic tone in the haemodynamic effects of isosorbide dinitrate in rats with cirrhosis.

The haemodynamic effects of nitrovasodilators and their mechanisms of action on portal hypertension remain unclear. The splanchnic and systemic haemodynamic response to the infusion of isosorbide dinitrate (100 micrograms/kg per min), a nitrovasodilator, was investigated in cirrhotic rats. The role of the conscious state in the haemodynamic response to isosorbide dinitrate was examined using rats that were anaesthetized with pentobarbitone. The role of sympathetic tone in the haemodynamic response to isosorbide dinitrate was examined using rats pretreated with the ganglion blocker hexamethonium. Isosorbide dinitrate had no haemodynamic effects in conscious, unblocked normal and cirrhotic rats. Isosorbide dinitrate had no haemodynamic effects in normal and cirrhotic rats treated with hexamethonium. In normal anaesthetized rats, isosorbide dinitrate significantly decreased systemic vascular resistance (414 +/- 25 vs 290 +/- 26 dyn.s/cm-5 per 100 g). In cirrhotic anaesthetized rats, isosorbide dinitrate significantly decreased mean arterial pressure (98 +/- 6 vs 79 +/- 7 mmHg), systemic vascular resistance (318 +/- 30 vs 207 +/- 10 dyn.s/cm-5 per 100 g), portal pressure (14.0 +/- 1.0 vs 11.3 +/- 0.9 mmHg) and portal territory vascular resistance (1362 +/- 163 vs 1031 +/- 182 dyn.s/cm5 per 100 g). In conclusion, this study shows that the portal hypotensive effects of isosorbide dinitrate depend upon the alterations of vascular tone by pentobarbitone.

肝切除時における術中超音波ドプラ法を用いた門脈血管抵抗評価の試み

肝切除時における術中超音波ドプラ法を用いた門脈血管抵抗評価の試み

Effects of endothelin-1 on hepatic blood flow.

Endothelin-1 belongs to a family of potent vasoconstrictors, recently isolated from endothelial cells. Endothelin-1 has a variety of hepatic effects and hepatic clearance from the circulation is important. Elevated plasma concentrations of Endothelin-1 are found after orthotopic liver transplantation and in cirrhosis with ascites. This study in piglets on hepatic bloodflow was designed to compare differences in effects between central venous and intraportal injection of endothelin-1, and to evaluate effects of repeated injections. Central venous injection of endothelin-1 caused a larger reduction in portal vein flow, while intraportal injection caused a larger increase in portal vein pressure. Repeated injections resulted in a reduction in portal vein flow and an increase in portal vein vascular resistance.

Long-term management of variceal bleeding: the place of pharmacotherapy.

Portal hypertension is treated by reducing portal pressure in order to prevent esophageal variceal bleeding or recurrent bleeding. Because portal hypertension depends on both elevated portal tributary blood flow and intrahepatic vascular resistance, the pharmacologic therapy of this syndrome consists in reducing portal blood flow or vascular resistance, or both. The pharmacologic prevention of first bleeding or recurrent bleeding has been performed with nonselective beta-adrenergic antagonists (propranolol or nadolol). Certain controlled studies have shown that this type of drug significantly reduces the risk of first bleeding by approximately 40% in patients with esophageal varices. A meta-analysis showed that death due to bleeding was also significantly lower in the beta-blocker group than in the placebo group. Moreover, beta-blockers are effective in patients in both good and poor condition and with all types of cirrhosis. The efficacy of beta-blockers on the risk of recurrent bleeding is less clear, but these substances significantly decrease the risk of rebleeding, by approximately 30%. Recurrent bleeding in patients treated with beta-blockers is associated with the occurrence of hepatocellular carcinoma or lack of compliance. In conclusion, it is clear that different substances have portal hypotensive effects and can be used to treat or prevent complications of portal hypertension. However, other drugs should be tested, and other clinical studies are needed to identify good responders.

Modulation of the hyperdynamic circulation of cirrhotic rats by nitric oxide inhibition

The effects of NG-monomethyl-l-arginine (l-NMMA), an inhibitor of nitric oxide (NO) biosynthesis on the splanchnic and systemic circulation, were investigated in rats with cirrhosis induced by carbon tetrachloride. Portal hypertension in these rats was accompanied by decreased arterial blood pressure and peripheral vascular resistance as well as by splanchnic vasodilation with increased portal venous inflow and decreased splanchnic resistance. Intravenous bolus administration of l-NMMA (25 mg/kg) significantly increased systemic blood pressure and decreased cardiac output. l-NMMA also significantly increased systemic and splanchnic vascular resistance; whereas blood flow to the stomach, small intestine, colon, pancreas, mesentery, spleen, and kidney was decreased significantly. l-NMMA did not alter the portal pressure or porto-systemic shunting in these cirrhotic rats, yet portal vascular resistance increased, suggesting effects on the intrahepatic and collateral circulation. Pretreatment with l-arginine (300 mg/kg) prevented the hemodynamic changes induced by l-NMMA. These findings support the concept that local excess formation of NO contributes to changes in splanchnic circulation associated with portal hypertension in cirrhosis.

The actions of two sensory neuropeptides, substance P and calcitonin gene-related peptide, on the canine hepatic arterial and portal vascular beds.

1. The two peptides, calcitonin gene-related peptide (CGRP) and substance P (SP) were administered individually as bolus injections into the separately perfused hepatic arterial and portal vascular beds of the anaesthetized dog to assess their actions and relative molar potencies at these sites. 2. CGRP caused an immediate dose-related increase in hepatic arterial flow when injected close-arterially, reflecting a fall in resistance. This vasodilator effect was slightly increased by the prior administration of the selective beta 2-adrenoceptor antagonist, ICI 118,551. 3. On a molar basis, CGRP was more potent as an hepatic arterial vasodilator than the non-selective beta-adrenoceptor agonist, isoprenaline (Iso). 4. Intra-portal injection of CGRP also evoked hepatic arterial vasodilatation unaccompanied by other cardiovascular changes. 5. CGRP in doses up to 10 nmol had no effect on portal vascular resistance when administered intra-portally. 6. SP evoked a rapid, dose-related increase in hepatic arterial flow when injected intra-arterially. The molar ED50 for this hepatic vasodilatation was 40.2 fmol, significantly less than the ED50 for either CGRP or Iso. SP was the most potent hepatic arterial vasodilator yet examined. The vasodilator effect of SP was slightly potentiated by prior beta 2-adrenoceptor blockade. 7. SP caused hepatic arterial vasodilatation when administered by intra-portal injection; its absolute and relative potency was much reduced. 8. SP when injected intra-portally caused a graded increase in hepatic portal inflow resistance. The molar potency for this portal vasoconstriction was significantly greater than that for noradrenaline (NA); however, the maximum increase in portal resistance was significantly less to SP than to NA.9. In view of the location of the peptides CGRP and SP within the afferent innervation of the liver, it is proposed that they play an important function in controlling the hepatic microvasculature in response to sensory stimuli, particularly those arising from changes in portal blood composition secondary to change in metabolic activity within the gastrointestinal tract (GIT).10. Since the peptides are released from the GIT into the hepatic portal inflow, they may modify hepatic arterial blood flow, the extent of which is related to events within the GIT.

Effects of alpha 1 and beta-adrenergic antagonists and 5-hydroxytryptamine receptor antagonist on portal-systemic collateral vascular resistance in conscious rats with portal hypertension.

In order to study the acute effects of pharmacological agents on the vascular resistance of portal-systemic collaterals, a model of total portal vein occlusion with 100% portal-systemic shunts was developed in the conscious rat. The haemodynamic effects of several vaso-active substances were evaluated in this model and compared with those obtained after saline administration. Prazosin (0.5 mg), an alpha 1-adrenergic antagonist, significantly reduced mean arterial pressure by 29%, portal pressure from 13.8 +/- 1.0(mean +/- s.e.m.) to 10.1 +/- 0.4 mmHg and portal tributary blood flow (radioactive microspheres) from 13.6 +/- 2.1 to 11.7 +/- 1.2 mL/min. It also decreased portal-systemic vascular resistance from 95 +/- 16 to 73 +/- 9 dyn s/cm5 x 10(3). Propranolol (4 mg), a beta-adrenergic antagonist, significantly reduced mean arterial pressure by 12% and portal pressure from 15.5 +/- 1.2 to 13.3 +/- 0.9 mmHg while reducing portal tributary blood flow from 14.6 +/- 1.5 to 11.0 +/- 1.7 mL/min and increasing portal systemic collateral vascular resistance from 88 +/- 7 to 103 +/- 8 dyn s/cm5 x 10(3). Ketanserin (0.25 mg/kg), a 5-hydroxytryptamine receptor antagonist, reduced portal pressure from 15.8 +/- 1.0 to 13.3 +/- 0.7 mmHg at a dose that did not alter mean arterial pressure or portal tributary blood flow. It achieved this by reducing portal-systemic collateral vascular resistance from 90 +/- 14 to 74 +/- 13 dyn s/cm5 x 10(3). Saline had no significant effect on systemic and splanchnic haemodynamics. This study shows that ketanserin decreases vascular resistance of portal-systemic collaterals while propranolol increases it. Thus, it is suggested that collateral vascular resistance is accessible to pharmacological manipulation.

Pathophysiology of portal hypertension.

Portal hypertension is characterised by alterations in the splanchnic and systemic circulation associated with the development of portosystemic collateral channels, the most important of which are found in lower oesophagus and stomach. Bleeding from these gastro-oesophageal varices represents the major clinical complication and over the last decade there has been considerable interest in the pharmacological management of this condition. The factors underlying the development and maintenance of portal hypertension and the pathogenesis of variceal rupture are as yet not fully understood. Whilst an increase in portal vascular resistance, as a consequence of liver disease, appears to be the primary event in the majority of cases, increasing attention has focused on the potential importance of enhanced circulating levels of vasoactive compounds coupled with a proposed reduction in vascular sensitivity to endogenous vasoconstrictors. Consequently, portal hypertension is now being more widely considered as a multi-organ disorder associated with changes in blood flow within both systemic and splanchnic vascular beds. This article reviews the factors currently implicated in the development and maintenance of portal hypertension and considers the pathogenesis of variceal bleeding.

Active contractile and mechanical factors in the pathogenesis of portal hypertension

In order to study the relative contibution of active and mechanical factors to the increased intrahepatic portal vascular resistance (IHPVR) in portal hypertension (PH), CCl 4 -induced cirrhosis and two models of non-cirrhotic PH induced by feeding rats for 60 d with either vit. A (25000 lU/d) or by adding phenobarbitone (pbarb; 0.5 g/1) to their drinking water were investigated. The livers were isolated and perfused via the portal vein with Krebs-Henseleit buffer containing 2.5% BSA at a constant flow rate of 40 ml.min- 1 using a roller pump. Perfusion pressures were measured with an electronic transducer. To obtain a measure of the vascular tone the non-specific smooth muscle relaxant, papaverine (6.4 x 10 4 M) was added to the perfusate and the change in pressure was measured and the % change in portal vascular resistance (% ΔR) calculated. The perfusate flow rate was calculated in units of ml.min- 1 .g- 1 (dry wt). The IHPVR was calculated according to the formula R = P/F, where P is the perfusion pressure in mmHg and F is the flow /g dry wt liver. Comparison of portal venous pressure (PVP) in vivo, IHPVR in vitro, %ΔR elicited by papaverine and weights of livers of normal, cirrhotic (CCl 4 ), and non-cirrhotic (phenobarbitone and vitamin A fed) rats. Variable Normal Cirrh Pbarb Vit. A PVP (mmHg) in vivo 8.5±0.2 16.1±0.4 * 9.9±0.3 * 10.9±0.4 * (n = 25) (n = 25) (n = 8) (n = 6) IHPVR 0.29+0.02 0.49±0.04 * 0.41+0.04 * 0.39±0.06 # (mmHg.ml- 1 .min.g dry wt) (a =25) (0 = 25) (n = 8) (n = 6) Response to papay. (%ΔR) 4.7+1.2 13.1+1.6 * 5.7+1.5 6.9±0.6 (n = 6) (n = 6) (n = 8) (n = 6) Drv liver wt (g) 3.11+0.11 3.26±0.11 4.71+0.16 * 2.80±0.30 (n = 25) 0 = 25) (n = 8) (n = 6) All values are x ±SEM; * p # p Liver cells in pbarb treated rats showed a mean increase in size of 1.5x (p 4 -induced cirrhosis, approximately 20% of the increased resistance is attributable to an active pharmacologically reversible component and the remainder to mechanical impediment to flow through the liver.

Hepatic haemodynamics and microvascular architecture after portal venular embolization in the rat

To clarify the relationship between hepatic damage and alterations of hepatic microvascular architecture and haemodynamics following portal venule occlusion, the present study was performed in rats which had been injected into the portal vein with 700,000 plastic beads (30-35 microns in diameter). When the occluded segment of the portal venule was short, infarction did not occur because of the prompt development of vascular channels bypassing the obstructed venules. On the other hand, when the occluded segment was long, infarction usually occurred. In this case, formation of collateral vascular channels began as dilatation of the sinusoids in the vicinity of the occluded portal venules and increased in diameter and developed into new portal venules in 5 days. Increased portal vascular resistance after embolization was normalized after 5 days in parallel with the progression of reconstruction of vascular channels. Reduced bile production returned to a normal level 3 days after embolization. Necrotic tissue was resorbed completely and replaced by fibroblasts 5 days after embolization. These findings indicate that the development of infarct following portal venule occlusion depends on the length of the occluded segment, and that hepatic microvasculature has a great capacity for adaptation and rapid reconstruction of vascular channels which leads to speedy recovery from hepatic circulatory disturbances and resulting hepatic damage.

Mechanisms and consequences of portal hypertension.

Portal hypertension is characterised by alterations in the splanchnic and systemic circulation resulting in the development of portosystemic collateral channels, the most important of which are found in the lower oesophagus and stomach. The major clinical complication of gastro-oesophageal varices is bleeding and over the last decade there has been considerable interest in the pharmacological management of this complication. The factors currently implicated in the development of gastro-oesophageal varices in patients with cirrhosis include a) increased portal vascular resistance, b) splanchnic and systemic vasodilatation and c) changes in the lower oesophageal venous anatomy [palisade and perforating venous zones]. In a patient with gastrointestinal bleeding, endoscopic examination of the upper gastrointestinal tract will confirm the diagnosis of portal hypertension by confirming the presence of gastro-oesophageal varices. Cirrhosis is the most common aetiological factor for gastro-oesophageal varices, but imaging techniques, including Doppler ultrasound, computerised tomography and venous phase angiography, may be required to exclude extrahepatic portal venous obstruction from the differential diagnosis. Although the pathogenesis of variceal rupture remains unclear, several risk factors for variceal haemorrhage have been identified, including a) increased size, b) high intravariceal-portal pressure, c) increased varix wall tension characterised by the presence of red spots observed at endoscopy (particularly in large varices since wall tension is related to variceal size), and d) poor liver function. Although oesophagitis may be observed at endoscopy, an erosive mechanism is no longer considered to be of pathogenic significance. A high portal pressure in the immediate postbleeding period is now recognised as predictive of rebleeding. Periodic elevations in intravariceal pressure, associated with the release of enhanced endogenous vasoactive compounds, or beta-adrenergic-mediated stress-related increases in portal pressure, may contribute to the rupture mechanism. Consequently, portal hypertension is now being more widely considered as a multiorgan disorder associated with changes in blood flow within both systemic and splanchnic vascular beds. This article reviews the factors currently implicated in the development of portal hypertension and the approach to diagnosis. The pathogenesis of variceal bleeding will also be considered.

Changes in hepatic haemodynamics in rats with overt liver tumour

Overt liver tumour was induced in Fisher rats by intraportal administration of 1.6 x 10(7) Walker carcinosarcoma cells. Control groups of rats received similar volumes of dead cells or saline intraportally. All animals were studied at 3 weeks when overt tumour was present. The Hepatic Perfusion Index (HPI) was significantly raised in rats with overt tumour compared to both groups of control animals. Portal flow and portal venous inflow were significantly reduced in the presence of overt tumour but hepatic arterial flow did not alter. These observations suggest that the alteration in the HPI in the presence of overt tumour results from an alteration in portal venous flow and inflow even though the blood supply to the tumour is principally derived from the hepatic artery. The changes in hepatic haemodynamics in the presence of tumour were accompanied by a reduction in portal pressure, an increase in splanchnic vascular resistance and an increase in the degree of arteriovenous shunting through the liver. Portal vascular resistance was unchanged. These findings indicate that the presence of overt hepatic tumour results in gross derangements of hepatic blood flow. These changes must be taken into consideration when attempting to potentiate the delivery of cytotoxic drugs to hepatic tumour by manipulation of hepatic haemodynamics.

Recovery from hepatic necrosis following acute portal vein embolism with special reference to reconstruction of occluded vessels

We examined the morphological and haemodynamic changes in the livers of rats following acute obstruction of portal vein branches by the injection of agar into the portal vein. Histological and angiographic examinations of the liver were performed after measurements of portal vein pressure in vivo and portal vascular resistance by an isolated liver perfusion method. Portal vein embolism induced hepatic necrosis in the centrilobular and midzonal areas, which was rapidly resorbed and replaced by regenerated liver cells leaving no trace. This recovery from hepatic necrosis was closely related to recanalization of obstructed portal vein branches, which led to falls in both the elevated portal vein pressure and the increased portal vascular resistance following embolization.

Effects of Positive End-Expiratory Pressure on Splanchnic Circulation and Function in Experimental Peritonitis

Splanchnic and central hemodynamic effects of positive end-expiratory pressure (PEEP) were studied in anesthetized pigs using mechanical ventilatory assistance, with or without sepsis (fecal peritonitis). One hour after sepsis, PEEP (10 cm H2O) was applied (n = 6). Another group (n = 6) had sepsis without PEEP. In one group (n = 6) without sepsis, PEEP was applied after 1 hour, while a fourth group (n = 5), without sepsis or PEEP, served as a control. The group with PEEP and sepsis had reduced cardiac index, portal venous blood flow, and liver surface blood flow. The group with PEEP alone had reduced splanchnic circulation by increasing gastrointestinal vascular resistance, while the group with sepsis alone had increased portal vascular resistance. In a separate series with sepsis, intermittent PEEP, and vigorous fluid resuscitation, it was demonstrated that avoiding hypovolemia did not seem to protect from the PEEP effects on the splanchnic circulation. The combination of sepsis and PEEP was not additive on portal blood flow reduction but reduced bile production.

The role of pericentral fibrosis in experimental portal hypertension in rats

To clarify the relation of pericentral fibrosis to portal hypertension, measurements of portal vascular resistance in vitro and blood pressures of several key points in hepatic vascular pathways in vivo were undertaken in rats given dimethylnitrosamine. Administration of dimethylnitrosamine induced tortuosity and narrowing of the peripheral branches of the hepatic vein due to pericentral fibrosis. No significant change was produced in the sinusoids and the portal vein branches. The portal vascular resistance was increased and the portal vein pressure was elevated markedly. The blood pressure gradient was steep in the intrahepatic vein, but not in the intrahepatic portal vein or the sinusoids, as compared to control. These data suggest that deformation of the peripheral branches of the hepatic vein due to pericentral fibrosis causes a marked increase in vascular resistance in the intrahepatic hepatic vein, i.e. postsinusoidal portal hypertension.

PAF increases hepatic vascular resistance and glycogenolysis in vivo

Administration of platelet-activating factor (PAF) to portal venous circulation of anesthetized fed rats produced decreases in mean arterial pressure and increases in hepatic portal pressure and blood glucose concentration. These responses to PAF were dose dependent with ED50 values of 0.02-0.05 micrograms/kg and specific as lyso- and enantio-PAF did not reproduce effects of PAF. Specific PAF receptor antagonist SRI 63-675 (75 micrograms/kg) inhibited significantly these PAF (0.1 micrograms/kg)-induced responses in rats. Administration of prazosin (500 micrograms/kg) and propranolol (400 micrograms/kg) to rats abolished phenylephrine (50 micrograms/kg)-induced increases in mean arterial pressure, hepatic portal pressure, and blood glucose concentration but did not prevent PAF (1 microgram/kg)-induced alterations in these parameters. Glycogen phosphorylase alpha levels were increased significantly in livers of rats after administration of PAF (1 microgram/kg) or phenylephrine (50 micrograms/kg). Administration of prazosin and propranolol to rats inhibited phenylephrine- but not PAF-induced activation of hepatic glycogen phosphorylase. Hepatic adenosine 3',5'-cyclic monophosphate (cAMP) concentration was increased slightly by PAF, but these increases were eliminated by adrenergic blockade, suggesting that activation of hepatic glycogen phosphorylase by PAF is not dependent on increases in cAMP. Increases in hepatic portal pressure and blood glucose concentration in response to PAF (0.1 micrograms/kg) were not attenuated in adrenalectomized rats. Moreover, PAF (0.1 micrograms/kg) stimulated increases in hepatic portal pressure after administration of the ganglionic blocking agent chlorisondamine (2.5 mg/kg) to adrenalectomized rats. Administration of PAF (0.05 micrograms/kg) to rats instrumented with pulse Doppler flow probes produced decreases in hepatic arterial and portal vein blood flow and increases in hepatic arterial and portal vascular resistance. These observations provide direct evidence that PAF regulates hepatic hemodynamics and glycogenolysis in vivo. It is suggested that PAF plays an important role in regulating hepatic blood flow and supplying extrahepatic tissues with energy substrates by sympathetic-independent mechanism(s) after its release in acute pathophysiological situations.

Relationship between portal venous and hepatic arterial blood flows: spectrum of response

The relationship between portal tributary blood flow (PBF) and hepatic arterial blood flow (HAF) was studied in awake, unrestrained rats with the radiolabeled microsphere technique. Six distinct patterns of response emerged. In group A (PBF+, HAF 0), ethanol, acetate, glucagon, prostacyclin, and a mixed diet increased PBF without a change in HAF; in group B (PBF+, HAF+), adenosine and histamine increased both PBF and HAF; in group C (PBF 0, HAF+), isoflurane and triiodothyronine did not change PBF but increased HAF; and in group D (PBF-, HAF+), halothane and vasopressin decreased PBF and increased HAF. Acute partial portal vein ligation decreased PBF (56%) and increased HAF (436%). Hypoxia (7.5% O2) decreased PBF (28%) and increased HAF (110%). In group E (PBF+, HAF-), acute hepatic artery ligation increased PBF (35%) and reduced HAF (74%), while in group F (PBF-, HAF-), thyroidectomy reduced PBF and HAF (36 and 47%, respectively). All blood flow responses were accompanied by the expected changes in both portal tributary and hepatic arterial vascular resistances. The data suggest that the portal and hepatic arterial vascular territories have regulatory mechanisms that allow for independent changes.