Decrease In Hepatic Blood Flow Research Articles

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.

Portal hypertensive gastropathy in patients with cirrhosis

Portal hypertensive gastropathy is a recently recognized important complication of cirrhosis. In the present study, the clinical features, portohepatic hemodynamics, and hepatic function were investigated in a series of 47 patients with cirrhosis. Mild gastropathy was found in 15 patients (32%) and severe gastropathy in 17 patients (36%). The presence of gastropathy seemed to be independent of age, sex, cause of cirrhosis, or grade of gastroesophageal varices. However, severe gastropathy was associated with an increase in portal venous pressure gradient (vs. control, P < 0.01; vs. mild gastropathy, P < 0.01), an increase in hepatic sinusoidal resistance (vs. control, P < 0.01; vs. mild gastropathy, NS), and a decrease in hepatic blood flow (vs. control, P < 0.01; vs. mild gastropathy, NS). In addition, patients with severe gastropathy had impaired metabolic activity of the liver, which was assessed by intrinsic clearance of indocyanine green (vs. control, P < 0.01; vs. mild gastropathy, NS). These observations may have important therapeutic implications in patients with cirrhosis and portal hypertensive gastropathy.

Relationship between endothelin and thromboxane A 2 in rat liver microcirculation

In our previous study, we determined changes in hepatic blood flow using a Laser Doppler blood flow meter after i.v. injection of endothelin-1 (ET-1) or endothelin-3 (ET-3) at 2 nmol/kg in rats and found that ET-3 caused greater decreases in blood flow than ET-1. In the present study, we determined how the arachidonic acid cascade, mainly thromboxane A 2 (TXA 2), is related to ET-1 and ET-3 using indomethacin (INDO), which inhibits the biosynthesis of prostaglandin (PG), and OKY-046, a selective inhibitor of TXA 2 synthesis. In the first series of experiments, ET-1 and ET-3 were administered after inhibiting the biosynthesis of PG by s.c. injection of 2 mg/kg of INDO. While INDO failed to inhibit the slight decrease in hepatic blood flow induced by ET-1, it significantly inhibited the marked decrease in hepatic blood flow elicited by ET-3. In the next series of experiments, ET-1 and ET-3 were administered after administration of 20 mg/kg of OKY-046. OKY-046 showed no effects in animals treated with ET-1, as in those pre-treated with INDO, while it significantly inhibited the decreases in hepatic blood flow induced by ET-3. These findings suggest that ET-1 decreases hepatic blood flow due to its direct effects although to a lesser extent than ET-3, while ET-3 does so due not only to its direct effects but also to TXA 2-mediated effects. It is therefore likely that in addition to ET family peptides, PG-mediated mechanisms are involved in the regulation of hepatic microcirculation by ETs.

Oxygen-derived free radicals mediate liver damage in rats subjected to tourniquet shock.

The placement of rubber band tourniquets upon rat hind-limbs for 5 h followed by reperfusion of the extremities results in a severe form of circulatory shock characterized by hypotension and death within 24 h of tourniquet release. Oxidative damage to muscle tissue is an early consequence of hind-limb reperfusion on tourniquet release, yet this local damage does not explain the lethal hypotensive shock state which evolves within the next 24 h. Multiple system organ failure (MSOF), of as of yet unknown causes, is usually described in relation to several shock states. It has been suggested that injured or necrotic tissue may activate neutrophils, platelets, and the coagulation system leading to embolization in remote tissues. Effective decreases in hepatic blood flow have been observed in several forms of sepsis which precedes the biochemical evidence consistent with an ischemic insult of the liver. In support of our original hypothesis, that organ failure has its genesis in a primary perfusion abnormality with secondary ischemic organ injury, herein we have assessed the possibility that oxygen-derived free radicals are generated in the liver of rats after reperfusion of their hind-limbs on release of the tourniquets. We report on the protective effects of allopurinol (ALLO) and a mixture of superoxide dismutase (SOD) catalase (CAT) and dimethylsulfoxide (DMSO) on liver free sulfhydryl content (SH), thiobarbituric acid-reactive substances (TBARS), and on the release of aspartic acid (AsT) and alanine aminotransferase (AlT) activities, and of alkaline phosphatase during a 5 h tourniquet period and after 2 h of reperfusion of the hind-limbs. During the hind-limb ischemic period hepatis tissue SH levels remained essentially constant during the first hour (6.02 +/- 0.36 to 5.65 +/- 0.20 mumoles/g wet tissue), and decreased significantly, over and above the normal circadian decrease of liver glutathione levels, to 4.02 +/- 0.69 mumoles/g wet tissue after the third hour and remained lowered until tourniquet release. A further significant decrease (3.11 +/- 0.49 mumoles/g wet tissue) was observed after 2h of reperfusion. TBARS production remained constant during the 5 h hind-limb ischemic period (168.4 +/- 37.3 mumoles/g wet tissue) and rose by 55% to 261.7 +/- 55.8 mumoles/g wet tissue after 2 h of tourniquet release. ALLO, but not the SOD-CAT-DMSO combination, protected hepatic SH loss during the hind-limb ischemic insult, yet both offered protection after 2 h of tourniquet release.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of molsidomine, a long acting venous dilator, on portal hypertension

The present study investigated the effects of molsidomine, a predominant venous dilator which, contrary to organic nitrates, does not produce pharmacological tolerance on splanchnic and systemic hemodynamics in patients with cirrhosis. Twenty-seven cirrhotic portal hypertensive patients were studied prior to and up to 2 h after the oral administration of 2 mg of molsidomine (n = 11), 4 mg of molsidomine (n = 8) or placebo (n = 8). Molsidomine caused a significant reduction in the hepatic venous pressure gradient. The mean decrease at 60 min was -6.8 +/- 9% after 2 mg (p less than 0.05) and -15.4 +/- 12% after 4 mg (p less than 0.01). The decrease in the hepatic venous pressure gradient was maintained at 120 min: -11% after 2 mg (p less than 0.05) and -19% with 4 mg (p less than 0.01). This was associated with mild changes in azygos blood flow and with a significant decrease in hepatic blood flow (-17%, p less than 0.05). There was a moderate reduction in mean arterial pressure (-12.6% after 2 mg and -13.2% after 4 mg, p less than 0.01), which was due to a reduction in cardiac output, without any significant fall in systemic vascular resistance. Placebo administration did not change systemic or hepatic hemodynamics. This study shows that molsidomine causes a significant and sustained reduction in portal pressure in patients with cirrhosis, suggesting the potential role of this agent in the treatment of portal hypertension.

Propranolol Compared with Propranolol plus Isosorbide-5-Mononitrate for Portal Hypertension in Cirrhosis

To investigate whether isosorbide-5-mononitrate (Is-5-Mn) given with propranolol reduces hepatic portal pressure more than does propranolol alone in patients with cirrhosis. A randomized controlled trial. Fifty patients with cirrhosis and esophageal varices entered and 42 completed the study. Twenty-one patients received oral propranolol at increasing doses until their resting heart rate was reduced by 25%, and 21 patients received oral propranolol (on the same schedule) plus oral Is-5-Mn, 40 mg twice a day. Hepatic vein pressure gradient, liver function, and splanchnic and systemic hemodynamics before and after 3 months of continuous therapy. At 3 months, the hepatic venous pressure gradient decreased more (P less than 0.01) in patients given propranolol plus Is-5-Mn (19%, from 18.4 +/- 3.9 to 14.9 +/- 3.8 mm Hg; 95% CI, -2.4 to -4.5 mm Hg) than in those given propranolol alone (10%, from 18.2 +/- 3.5 to 16.3 +/- 3.1 mm Hg; CI, -1.1 to -2.7 mm Hg). The hepatic venous pressure gradient decreased by more than 20% of the baseline value in 10% of patients receiving propranolol, but in 50% of patients receiving combined therapy (P less than 0.02). There were statistically significant decreases in hepatic blood flow and the intrinsic clearance of indocyanine green after propranolol therapy, but not after combined therapy. The treatments caused similar reductions in azygos blood flow and cardiac output. The long-term combined administration of propranolol plus Is-5-Mn reduces portal pressure more than propranolol alone without adverse effects on hepatic perfusion and liver function. Whether this greater hemodynamic effect translates into better clinical efficacy should be determined in randomized controlled trials.

Effect of traditional Chinese herbal medicines on the pharmacokinetics of western drugs in SD rats of different ages. I. Aminophylline-Tin Chuan Tang and aminophylline-Hsiao Ching Long Tang.

The effect of the traditional Chinese herbal medicines (Tin Chuan Tang and Hsiao Ching Long Tang) on the serum concentrations and pharmacokinetics of aminophylline was examined in three different ages of SD rats. Each traditional Chinese herbal medicine was orally preadministered to SD rats for one week and then aminophylline was administered intravenously. The serum concentrations and pharmacokinetic parameters of theophylline were estimated by a two-compartment open model. The liver isolated after the last blood sampling was homogenized and the activity of hepatic cytochrome p-450 was determined. Significant difference was found in some pharmacokinetic parameters of theophylline such as K10, t 1/2, Cl and Vd for three different ages of SD rats without pretreatment with Chinese herbal drugs (p less than 0.05). However, pretreatment with Tin Chuan Tang or Hsiao Ching Long Tang did not affect the pharmacokinetic parameters of theophylline in three different ages of SD rats (p greater than 0.05). We also found that there was no correlation between age and activity of cytochrome p-450 of SD rats (p greater than 0.05). The decline in some pharmacokinetic parameters of theophylline in the elderly rats perhaps might be attributed to the decrease in hepatic blood flow and liver volume. It is concluded that there was no drug interaction between theophylline and Tin Chuan Tang or Hsiao Ching Long Tang in the different ages of SD rats.

Hepatic Organic Anion Transport Kinetics and Bile Flow during Short-Term Total Parenteral Nutrition in the Rabbit

Plasma disappearance of sulfobromophthalein (BSP) after an intravenous bolus (5 mg/kg) was determined in six lab chow-fed (LCF) rabbits and in six rabbits maintained on total parenteral nutrition (TPN) for 5 days. A common bile duct cannula enabled measurements of bile flow and biliary BSP excretion. Compartmental analysis of the biexponential plasma disappearance curve yielded three fractional transfer rates, plasma to liver (hepatic uptake), liver to plasma (reflux), and liver to bile (canalicular excretion). The transfer rates for hepatic uptake were 0.253 +/- 0.061/min for LCF and 0.147 +/- 0.040/min for TPN (P less than 0.01) and for the canalicular excretion of BSP were 0.038 +/- 0.019/min for LCF and 0.019 +/- 0.002/min for TPN (P less than 0.05). Model-computed rates for BSP excretion in bile over 60 min were lower with TPN (61%) than with LCF (80%); the measured excretory rates were 53% for TPN rabbits and 75% of injected dose for LCF animals. Basal biliary flow was reduced by 50% in the TPN group. With a two-compartmental model, assuming two pools and three transfer rates, we have demonstrated for the first time significant decreases in hepatic uptake and canalicular excretion of the organic anion BSP during TPN. A decrease in hepatic blood flow due to the enteral fast of TPN could have contributed in part to the decreased hepatic uptake. But, because the second exponent of the biexponential curve is independent of hepatic blood flow, the decrease in liver to bile transfer rate is a true approximation of a diminished canalicular excretory capacity during TPN. It is concluded that the movement of organic anions along the hepatic BSP/bilirubin transport system is impaired early during TPN.

Kinetics and hemodynamic effects of intravenous nicardipine modified by previous propranolol oral treatment

Intravenous nicardipine, 5 mg, was administered in two comparable groups of eight patients with chronic coronary artery disease but no clinical signs of heart failure. One group had received no previous treatment and served as a control group, and the other had received long-term treatment with large oral doses of propranolol. Blood concentrations of nicardipine were higher, and the area under the plasma concentration curve was greater in the group previously treated by propranolol. The total clearance of nicardipine was decreased in patients taking propranolol, without a change in the half-life of the drug. Typical hemodynamic responses, namely, a decrease in aortic pressure and in arterial resistances, were greater and more lasting in patients previously treated orally by propranolol. Filling pressure remained stable in both groups. The nicardipine infusion did not induce signs of dromotropic or inotropic negative effects in either group. The greater and more lasting hemodynamic effects of nicardipine in the group previously treated orally by propranolol do not seem to be related to an overall hemodynamic action of propranolol, but are probably due to higher nicardipine plasma levels, and may be caused by a decrease in hepatic blood flow induced by propranolol, with a consequent decrease in nicardipine clearance and by a smaller nicardipine volume of distribution in the propranolol group.

The Effect of Halothane on Morphine Disposition

The present study determined the effect of halothane on the disposition of morphine by defining the effect of halothane anesthesia on the systemic, renal, and hepatic clearance of the parent compound, morphine, and on the generation of the primary metabolite, morphine-3-glucuronide (M3G) in the dog. Unlabeled morphine, 3H-morphine, and 14C-morphine were simultaneously administered into the portal vein, femoral vein, and renal artery, respectively, first during pentobarbital anesthesia and second during halothane (1.5 MAC) anesthesia; blood samples were taken for estimation of unlabeled plasma morphine and M3G concentrations by high performance liquid chromatography (HPLC). 3H- and 14C-morphine concentrations and corresponding M3G concentrations were determined by dual-channel liquid scintillation counting of the eluant corresponding to the appropriate peak on the HPLC. The portal clearance of morphine was not altered by halothane. However, intravenous (iv) morphine clearance (CLs) decreased (P less than 0.05) by 40% from 963 +/- 131 to 579 +/- 91 ml/min during halothane anesthesia, accompanied by an increase (P less than 0.05) in half-life from 78 +/- 8 to 106 +/- 8 min. The reduction in CLs of morphine occurred putatively on the basis of a halothane-induced decrease in hepatic blood flow, whereas morphine metabolism, reflected by morphine portal (intrinsic) clearance, was not significantly decreased by halothane. There was no significant effect of halothane on the partial metabolic clearance of morphine to M3G, and the ratio of area under the plasma concentration-time curve (AUC)-M3G to AUC unchanged morphine was not significantly altered by halothane, indicating that morphine glucuronidation is unaffected by halothane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Beneficial Effect of Hepatic Arterialization on Hypogonadism in Male Rats with Portacaval Shunt

The effect of portacaval shunt (PCS) with and without hepatic arterialization (HA) upon the liver morphology, hemodynamics, and in relation to testicular weight, histology, and plasma sex steroid levels has been investigated in male rats. PCS rats showed a significant decrease in hepatic blood flow, body and liver weights, together with signs of severe hypogonadism. In contrast, in HA rats the increment in liver blood flow was associated with higher body and liver weights. In spite of total portal blood shunting, a beneficial effect on testicular morphology and an increase in plasma testosterone level were observed. In respect to plasma estradiol levels the intergroup differences could not be evaluated due to large individual variations. This was probably caused by the presence of cross-reactive plasma component(s) masking the level of endogenous estrogen. It is concluded that portosystemic shunting is not of primary importance in the etiology of PCS-related hypogonadism in the male.

Hepatic Involvement in Hereditary Hemorrhagic Telangiectasia

Hepatic Involvement in Hereditary Hemorrhagic Telangiectasia

水素ガスクリアランス法による肝組織血流量測定 実験的ならびに臨床的研究

In this study, the author intended to examine the validity of the inhaled hydrogen gas clearance method (i-H2) for determination of the hepatic blood flow (HBF), and also to show some applicabilities of the method in experimental animals and patients with liver diseases. Simultaneous determinations of HBF by i-H2 and electromagnetic flowmetry in rabbits revealed an excellent correlation between the values obtained by the two methods. Moreover, HBF in rabbits measured by i-H2 varied in parallel with that by thermocouple flowmetry or laser Doppler velocimetry after administration of norepinephrine, propranolol or glucagon. In carbon tetrachloride-treated rats, HBF measured by i-H2 correlated better with the severity of damage in the sinusoidal structure than the severity of hepatic cell injury or the serum levels of transaminases. HBF as determined by i-H2 was significantly decreased in acute hepatitis (AH), chronic inactive hepatitis (CIH), chronic active hepatitis (CAH), liver cirrhosis (LC) and fatty liver. Reduced HBF in AH returned to normal during recovery of the disease. The ratio of HBF in tumor/normal tissue was greater than 1.0 for hepatocellular carcinoma in contrast to the ratio of less than 1.0 for metastatic liver carcinoma. Propranolol caused a decrease in HBF by 31%, and vasopressin by 39% in patients with CIH or LC. In contrast, glucagon induced its increase by 65%, 35% and 17%, respectively, in patients with CIH, AH and LC.

Effect of acute umbilical cord compression on hepatic carbohydrate metabolism in the fetal lamb.

Although the liver plays a central role in glucose homeostasis in the adult, its importance in fetal glucose homeostasis during acute reductions of substrate delivery is unknown. To examine this, we studied eight fetal lambs at 121 +/- 2 d gestation. We placed catheters in the descending aorta, inferior vena cava umbilical vein and the left (n = 6) or right (n = 2) hepatic vein, and a balloon occluder around the umbilical cord. At least 4 d after surgery, before and during umbilical cord compression, we measured blood oxygen saturation, glucose, lactate, and Hb concentrations, and blood flows using the radiolabeled microsphere technique. Gluconeogenesis was assessed by infusion of [U14C]lactate. Reducing umbilical flow by 50-60% from a control value of 181 +/- 20 mL/min/kg (mean +/- SD) caused a dramatic decrease in hepatic blood flow from 332 +/- 99 to 94 +/- 77 mL/min/100 g (p less than 0.05). Oxygen delivery to the fetus fell by 50% and that to the liver by 73%. However, hepatic O2 consumption was maintained by increased extraction. Glucose delivery to the liver fell from 67 +/- 24 to 20 +/- 13 mg/min/100 g (p less than 0.001), but lactate delivery did not change. In spite of the maintenance of lactate delivery, net hepatic lactate uptake fell significantly from 3.3 +/- 1.7 to 1.4 +/- 0.9 mg/min/100 g (p less than 0.05). This could account, in part, for the increase of blood lactate concentration from 16 +/- 4 to 27 +/- 7 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

Portal blood velocity and flow in aging man.

The portal blood velocity and flow were measured by means of pulsed echo-Doppler in 60 normal subjects of 4 different age groups (less than or equal to 40, 41-55, 56-70, greater than or equal to 71 years). All subjects had normal routine liver function tests and no history of liver disease. Portal blood velocity decreased from 15.7 +/- 3.2 cm/s in younger subjects to 12.4 +/- 1.7 in subjects over 71 years (ANOVA: p = 0.005). Similarly portal blood flow decreased (p = 0.025). Both portal blood velocity and flow were inversely correlated with age (r = -0.583 and -0.505, respectively). No changes in portal vein diameter were observed. The age-related decline in portal flow may account for the decrease in hepatic blood flow previously documented in the elderly.

Pharmacokinetics of Bupivacaine after Short and Prolonged Infusions in Conscious Dogs

A conscious dog model was used to study pharmacokinetics of bupivacaine after a short infusion (SI) (15 min) and a prolonged infusion (PI) (24 hours). Bupivacaine was infused in six mongrel dogs at least 10 days after implantation of femoral arterial and venous catheters. Each dog received both the SI and the PI in a random crossover design at a one week interval. Bupivacaine concentration was measured in serum sampled during the SI, during the last hour of the PI, and at frequent intervals during eight hours after cessation of infusion. Indocyanine green (ICG) clearance also was measured during the last hour of the PI and 90 min after cessation of both the SI and the PI. The terminal half-life (T1/2Z) of bupivacaine increased after the PI compared with the SI, 167 +/- 86 vs 53 +/- 13 min, respectively (mean +/- SD; P less than 0.05), and total body clearance (Cl) decreased, 3.4 +/- 1.2 vs 9.5 +/- 4.5 ml.min-1.kg-1, (P less than 0.05), although the volumes of distribution (VZ and VSS) did not change. A decrease in hepatic blood flow did not cause the decrease in Cl because ICG clearance did not change during the three sets of measurements. Thus, the observed increase in T1/2Z and decrease in Cl after the PI as compared with the SI are due to a decrease in hepatic intrinsic clearance of bupivacaine. Differences in the kinetic profile of the two enantiomers of bupivacaine cannot be excluded as a cause. We conclude that the extrapolation of kinetic data of bupivacaine obtained after a short infusion (or a bolus injection) to prolonged dosage must be done with care.

Hemodynamic changes of systemic, hepatic, and splenic circulation following triglycyl-lysin-vasopressin administration in alcoholic cirrhosis.

Triglycyl-lysin-vasopressin is a long-acting vasopressin derivative which is under consideration for the treatment of acute variceal bleeding in cirrhosis. However, its splanchnic hemodynamic effects have not been investigated thoroughly. In 11 patients with alcoholic cirrhosis, systemic and splanchnic hemodynamics were evaluated before and 20-40 min after intravenous administration of 2 mg triglycyl-lysin-vasopressin. Following the drug administration, heart rate decreased by 10% and cardiac index by 22% on the average, respectively; mean arterial pressure increased by 14% and systemic vascular resistence index by 48%. Hepatic venous pressure gradient showed a marked and persistent fall, averaging 31%. Hepatic and splenic blood flow decreased by 31% and 56%, respectively. A significant correlation was found between the decrease in hepatic venous pressure gradient and in splenic blood flow. By contrast, the decrease in the hepatic venous pressure gradient was not significantly correlated to the decrease in hepatic blood flow or in cardiac index. We conclude that in patients with alcoholic cirrhosis, triglycyl-lysin-vasopressin decreases portal pressure as well as hepatic and splenic blood flows. The decrease in portal pressure was due to the decrease in splanchnic blood inflow and not to the decrease in cardiac index.

Computer simulation of portal venous shunting and other isolated hepatobiliary defects of the enterohepatic circulation of bile acids using a physiological pharmacokinetic model.

The effect of three isolated defects in the enterohepatic circulation of bile acids on the size and distribution of the bile acid pool, plasma bile acid levels and bile acid secretion into the intestine was simulated using a linear multicompartmental physiological pharmacokinetic model previously used to simulate these aspects of bile acid metabolism in healthy man. Stepwise increases in portal-systemic shunting (with a reciprocal decrease in hepatic blood flow) caused an exponential increase in systemic plasma concentrations of bile acids, but no other major changes in bile acid metabolism. When the effect of varying fractional hepatic extraction was simulated, it was found that the greater the fractional hepatic extraction, the greater the elevation observed for systemic plasma bile acid levels for a given degree of portal-systemic shunting. When total hepatic blood flow was restored to normal by simulating "arterialization," systemic plasma levels of bile acids decreased strikingly, yet remained elevated. For cholate with a fractional hepatic extraction of 0.9 and 100% portal-systemic shunting, arterialization caused a decrease from a 20-fold elevation to a 5-fold elevation. This simulation thus defined the effect of the presence of the portal venous system per se on plasma bile acid levels and also quantified the circulatory route by which substances reach the liver when portal-systemic shunting is present. An isolated defect in hepatic uptake of bile acids caused little change in overall bile acid metabolism other than modestly increased plasma levels. Loss of bile acid storage by the gallbladder caused the majority of the bile acid pool to move from the gallbladder compartments to the proximal small intestine during fasting but had little effect on the dynamics of the enterohepatic circulation during eating. The results of these novel simulations of isolated defects in bile acid transport should aid in the interpretation of the more complex changes in bile acid metabolism which are likely to occur in hepatic or biliary disease.

The use of quantitative perfusion fluorometry to measure relative tumor and liver blood flow after transient microembolization

Optimal chemotherapy delivery to the tumor depends on regional drug concentration, tumor perfusion, tissue drug uptake, and metabolism. Modulation of tumor blood flow has been used to improve tumor response to treatment. Transient microembolization is one method to alter regional blood flow, but its effects on relative changes in tumor and liver blood flow have not been previously measured. This study used quantitative perfusion fluorometry (QPF) to evaluate blood flow distribution in liver and tumor before and after hepatic arterial infusion of degradable starch microspheres (DSMs) in 10 New Zealand white rabbits. QPF was compared with radioactive xenon-133 washout, an established method for measuring blood flow. Xenon-133 was injected intraparenchymally and the clearance rate was measured allowing calculation of relative blood flow. QPF was then used to measure liver and tumor blood flow in a hepatic VX-2 tumor model after hepatic artery injection of DSMs. Initial tumor blood flow was 55% of liver flow. DSMs produced a significant and transient decrease in hepatic blood flow that was decreased to 40% of baseline after 25 min. Changes in relative hepatic blood flow after DSMs as measured by QPF correlated strongly with results obtained by xenon-133 washout ( R = 0.97, P < 0.01). Fluorometry's simplicity and reliability may be clinically useful to evaluate tumor blood flow characteristics.

Effects of continuous positive-pressure ventilation on hepatic blood flow and intrahepatic oxygen delivery in dogs.

The effect of mechanical ventilation with PEEP of 0, 10, and 20 cm H2O (continuous positive-pressure ventilation [CPPV]) on hepatic blood flow (HBF) and intrahepatic oxygen delivery was studied in 26 mongrel dogs anesthetized with fentanyl. Hepatic arterial and portal venous blood flow was measured by an electromagnetic flowmeter. CPPV caused a significant decrease in HBF, which was related to the PEEP level. A linear correlation was seen between HBF and cardiac output. Intrahepatic oxygen delivery decreased more than HBF and cardiac output. The reduced oxygen delivery was due mainly to the decrease in portal venous oxygen content.