Hepatic Arterial Blood Research Articles

Effects of bromocryptine on hepatic blood volume responses to hepatic nerve stimulation in cats.

Arterial pressures, portal pressures, and hepatic blood volumes were recorded after hepatic denervation in cats anesthetized with pentobarbital. Bromocryptine (50 micrograms/kg) lowered arterial pressure but did not significantly change portal pressure or hepatic blood volume. However, both portal pressure and hepatic blood volume responses to hepatic nerve stimulation were significantly depressed after bromocryptine especially at low frequencies of stimulation. Responses to intraportal infusions of norepinephrine were significantly impaired only at the highest dose. The inhibitory effect of bromocryptine on the neural responses may, therefore, involve a presynaptic inhibition of norepinephrine release, but the mechanism requires further study. These data provide further support for the hypothesis that drugs which impair hepatic venous responses to sympathetic stimuli cause significant impairment of postural reflexes and orthostatic hypotension during clinical use.

Blockage of the hepatic-artery blood flow by biodegradable microspheres (Spherex®) combined with local hyperthermia in the treatment of experimental liver tumors in rats

The effect of local hyperthermia and a simultaneous blockage of the hepatic-artery blood flow by degradable starch microspheres (Spherex) was studied in a model of liver cancer in Wistar rats. Six days after each rat was inoculated with a cell suspension (NGW) in the central liver lobe, the rats were randomly allocated into four groups. The first group served as control, the second was treated with hyperthermia, the third by degradable starch microspheres (DSM) intraarterially, and the fourth with a combination of hyperthermia and DSM intraarterially. Tumor volumes were measured at laparotomy on days 0, 7, and 14. Temperature fluctuations in the tumor correlated well with those in the liver tissue, but were 2 degrees-4 degrees higher. The infusion of DSM did not change the pattern significantly. The tumor volumes were homogeneous between the groups at the start of treatment. The tumor growth was significantly reduced compared with the control group at day 7 in group III (P less than 0.05) and group IV (P less than 0.01) but only in group IV at day 14 (P less than 0.05). No differences in survival were found. Local hyperthermia concurrent with a blockage of the nutritional tumor blood flow seems to offer a more prominent and lasting tumor-growth inhibition.

Systemic Distribution of Blood Flow in Swine While Awake and During 1.0 and 1.5 MAC Isoflurane Anesthesia with and Without 50% Nitrous Oxide

To examine the effects of isoflurane on systemic distribution of cardiac output, organ/tissue blood flow was measured in 11 isocapnic pigs using 15-micrometer diameter radionuclide-labeled microspheres injected into the left atrium. Measurements were made on each pig during five of the following six conditions; awake (control); 1.0 MAC (1.45% end-tidal)isoflurane anesthesia; 1.5 MAC (2.18% end-tidal) isoflurane anesthesia; 0.95% end-tidal isoflurane and 50% N2O anesthesia equivalent to 1.0 MAC; 1.68% end-tidal isoflurane and 50% N2O anesthesia equivalent to 1.5 MAC; and 50% N2O administration. The order of anesthetized steps was randomized. A period of 60 min was interposed between anesthetized steps to allow pigs to recover towards control values. Mean aortic pressure decreased in a dose-related manner during isoflurane anesthesia, whereas cardiac output decreased only during 1.5 MAC isoflurane anesthesia and heart rate remained unchanged. The addition of N2O attenuated the hypotensive effects of isoflurane and cardiac output was maintained near control values because of increased heart rate. Brain blood flow increased in a dose-dependent manner with isoflurane anesthesia, but myocardial blood flow exhibited a dose-related decrease. The addition of 50% N2O to maintain the same total MAC anesthesia resulted in a larger increase in brain blood flow especially at 1.5 MAC, while myocardial blood flow was maintained near control value. Rate-pressure product and myocardial blood flow at 1.5 MAC anesthesia were higher when N2O was used with isoflurane. While blood flow and fraction of cardiac output going to the adrenal glands were unaltered during isoflurane-N2O anesthesia, blood flow increased at 1.5 MAC isoflurane anesthesia. Splenic blood flow and splenic fraction of cardiac output were increased at both MAC levels of isoflurane as well as isoflurane-N2O anesthesia whereas blood flow to the stomach, small intestine, diaphragm, skeletal muscle, and adipose tissue decreased from control values. Renal, hepatic arterial, and cutaneous blood flow remained unaltered. Fifty percent N2O in the presence of a residual end-tidal isoflurane concentration of 0.20% caused heart rate to increase from control levels, while cardiac output and mean aortic pressure were unaltered. Brain blood flow increased by 27% above control values, but perfusion in the myocardium, adrenal glands, spleen, kidneys, liver, and skin was unchanged. Stomach, small intestine, skeletal muscle, and diaphragm blood flows decreased from control values, whereas perfusion of adipose tissue increased.

Perinodular arteriolar plexus in liver cirrhosis. Scanning electron microscopy of microvascular casts

The blood supply to regenerative nodules in liver cirrhosis was studied by scanning electron microscopy of microvascular casts. Cirrhotic nodules are surrounded by many arterioles with rich anastomoses that form a perinodular arteriolar plexus: these arterioles connect with sinusoids in the nodules. The portal vein branches, on the contrary, are distorted and compressed by connective tissue. These findings illustrate how the regenerative nodules in liver cirrhosis are mainly nourished by hepatic arterial blood via a perinodular arteriolar plexus.

Furosemide vasodilates the canine gastrointestinal tract.

The ability of furosemide to induce vasodilation in the canine gastrointestinal system was studied by quantitative flowmetry. Blood flow and conductance increased maximally by 60 per cent in the stomach and duodenum and by 80 per cent in the small and large intestine. Vasodilation was evident at 2.4 mg/kg furosemide and higher. The onset of vasodilation occurred at 24 to 30 seconds and was maximal at 36 seconds in the stomach, at 66 seconds in the duodenum, at 78 to 84 seconds in the small intestine, and at 90 seconds in the large intestine. Hepatic arterial, splenic, and renal blood flows were unchanged. Simultaneous arteriovenous sampling from the small intestine indicated that the increased blood flow was not associated with increased O2 consumption. However, CO2 addition to the venous effluent decreased by 70 per cent. These data indicate that furosemide has a vasodilatory action on the gastrointestinal tract due either to a delayed effect on the vascular smooth muscle cell or on anaerobic bowel wall metabolism. The CO2 data are compatible with, but do not prove, stimulation of secretion of HCO3- by the intestinal mucosa.

Arterial and portal blood supply in cirrhosis: a functional evaluation

The uptake of (125)I albumin microaggregates (U-(125)I-AMA) from portal blood, during a single passage through the hepatic reticuloendothelial system, has been found to be generally decreased in cirrhosis. To investigate if a similar phenomenon occurs for the colloid flowing through the hepatic artery, the U-(125)I-AMA was first calculated in normal dogs after injection of a mixture of (51)Cr red blood cells ((51)Cr-RBC) and (125)I-AMA into the hepatic artery by comparing hepatic indicator dilution curves (IDC) obtained with both indicators. In nine dogs, the U-(125)I-AMA from hepatic artery blood was generally over 90%, as previously reported for the same colloid flowing through the portal vein in another group of normal dogs. This approach was then applied in nine patients with alcoholic cirrhosis who underwent combined umbilicoportal vein, hepatic vein, and hepatic artery catheterisation because of severe portal hypertension. Hepatic indicator dilution curves were obtained in the nine patients after injection of a mixture of (51)Cr-RBC and (125)I-AMA into the portal vein and the hepatic artery. The U-(125)I-AMA from portal and hepatic artery blood was measured by comparing (51)Cr-RBC and (125)I-AMA hepatic IDC. U-(125)I-AMA varied between 5.2 and 90.5% after portal vein injection and between 13.7 and 90.1% after hepatic artery injection; not difference was found between paired values. In all patients the extraction of indocyanine green (E-ICG) was calculated during a continuous infusion and significant correlations were found between E-ICG and U-(125)I-AMA from portal blood (r=0.931; p <0.001) or from hepatic artery blood (r=0.861; p <0.005). The decreased uptakes can be related to intrahepatic shunts or sinusoidal changes responsible for ineffective phagocytosis and restricted access of dye to parenchymal cells. These data indicate that in cirrhosis the hepatic artery and portal vein blood is cleared of colloid and ICG in a similar fashion and suggest nearly identical blood supply to the regenerative nodules by the hepatic artery and portal vein. Thus U-(125)I-AMA from hepatic artery or portal vein blood, as well as the E-ICG, may be used to estimate the functional hepatic blood supply in cirrhosis; this may prove to be useful in the prognosis of patients before portacaval shunts.

Epinephrine-induced hepatic potassium movements before and after adrenergic blockade.

The epinephrine-induced loss and subsequent uptake of K+ by the liver was studied by measuring hepatic arterio-venous K+ differences and splanchnic blood flows in anesthetized dogs with chronically implanted portal vein catheters and celiac and superior mesenteric artery flow probes. When epinephrine was administered intraportally, neither alpha- nor beta-adrenergic blockade, singly or in combination, had significant effects upon the hyperkalemic or the hypokalemic phases in either hepatic venous or systemic arterial blood. It was concluded that the movements of K+ into and out of the liver caused by epinephrine are not mediated by the classical adrenergic receptors as defined by inhibition by specific blocking agents.

Hepatic balances of glucose and insulin in response to physiological increments of endogenous insulin during glucose infusions in dogs.

Hepatic glucose uptake was measured in dogs in relation to physiological increments of plasma insulin levels under steady state conditions. Endogenous insulin secretion was stimulated by the infusion of small glucose loads, achieving normoglycaemia or mild hyperglycaemia. The measurement of hepatic arterial and portal venous blood flows allowed calculation of the relationships between net hepatic balances of insulin and glucose, the magnitude of insulin extraction by the liver and the hepatic sensitivity to physiological levels of insulin. During normoglycaemia, small glucose loads (2 and 4.5 mg/min. kg) reduced hepatic glucose output without a concomitant increase of the estimated total glucose utilization. No changes in arterial or hepatic venous plasma insulin levels occurred. Portal venous plasma insulin alone rose under the influence of the glucose stimulus. In the presence of hyperglycaemia, the liver further reduced its glucose output. Infusions of 11.3 mg/min. kg glucose resulted in reversal of hepatic glucose output to a net uptake of glucose. However, due to the large amounts of insulin emerging from the liver, peripheral tissue glucose utilization was significantly increased. A strong inverse correlation existed between arterial glucose concentration and hepatic glucose output as well as between portal venous plasma insulin level and hepatic glucose output. The net hepatic balance of insulin was promptly raised in response to the glucose perfusions, even when normoglycaemia was maintained. A highly significant, inverse correlation was demonstrated between net hepatic balance of insulin (i.e. net uptake of insulin by the liver) and hepatic glucose output. Hepatic insulin extraction ratio and hepatic plasma insulin clearance increased during glucose administration but no evident relationship to portal venous plasma insulin levels was found. These data suggest that insulin rather than glucose is the primary agent responsible for the reversal of the hepatic gradient of glucose in vivo.

Blood flow measurement with the spillover technique during intra-arterial drug infusions.

The spillover technique of measuring blood flow was used in dogs to estimate changes in the mesenteric, hepatic, and renal arterial blood flows following the infusion of vasoactive drugs. Spillover flow values agreed with blood flow measurements obtained with an electromagnetic flowmeter within ±8%. The technique was used with satisfactory results in patients treated with intra-arterial drug injections.

Measurement of Liver Blood Flow in the Infant Monkey

Liver blood flow in infant monkeys (M speciosa) was measured with both the fractional clearance flow rate technique and the microsphere technique in an attempt to evaluate these methods comparatively and to quantitate liver blood flow in the newborn nonhuman primate. Cardiac output, blood volume and regional hepatic arterial, splenic, gastrointestinal, pancreatic and mesenteric blood flows were determined. With the fractional clearance technique mean liver sinusoidal blood flow was 35.2 ml/min or 1.48 ml/min/g of liver; this represents 26.3% cardiac output. With the microsphere method mean liver blood flow was 23.8 ml/min or 1.02 ml/min/g of liver; this represents 18.0% cardiac output. In these infants the mean cardiac output was 190 ml/min/kg body weight and the mean blood volume was 92.4 ml/kg.

Effect of acetylsalicylic acid on the liver response to endotoxin.

SummaryGeneral responses of the dog to a lethal intravenous injection of endotoxin have been previously reported. The present investigation was devised to study the mechanism of the canine liver response to endotoxin. Experiments were carried out on an in situ liver preparation with controlled hepatic arterial and portal venous blood flows. Fifty mg acetylsalicylic acid/kg administered intravenously prior to endotoxin injection prevented the decrease in mean systemic arterial pressure and obliterated the constriction observed in both hepatic artery and hepatic vein in animals given endotoxin alone. The mechanism of action of acetylsalicylic acid is unknown.

The intrahepatic distribution of portal venous and arterial blood

Summary The distribution of arterial and portal venous blood within the liver, and within the cephalad and distal areas of each liver lobe, was investigated. The working hypothesis was based on the capacity of the reticuloendothelial system (RES) lining the liver sinusoids to remove iodine 131 -labeled, heat-denaturated human serum albumin, injected directly into the hepatic artery and portal vein. The distribution was calculated as percentage dose cleared per lobe and per gram liver tissue in the cephalad and distal areas of each liver lobe. The distribution pattern and clearance efficiency values, obtained after alternate injection of each component, were used as an index for the distribution of arterial and portal venous blood at the sinusoid level. The changes in distribution and clearance efficiency after simultaneous injection and acute and chronic ligation of each component were used for the determination of the portal vein—hepatic artery relationship. Our results indicate that each component has a specific intrahepatic distribution affected only by severe changes in arterial circulation. Portal venous blood was spread evenly throughout the liver sinusoids with a slight cephalad concentration, while arterial blood was concentrated mainly in the cephalad areas. The pattern of portal venous circulation changed when hepatic arterial blood was prevented from entering the liver, whereas the pattern of arterial blood distribution was not affected by changes in portal venous flow. Clearance efficiency values increased after chronic portal vein ligation and decreased after hepatic artery ligation, implying that the arterial flow is capable of compensating for the absence of portal venous blood and constitutes the predominant component of the afferent circulation.

EFFECT OF A SMALL, CIRCUMSCRIBED HEPATIC NECROSIS ON SERUM AND HEPATIC ENZYME ACTIVITIES.

A small focal necrosis of the liver was produced without affecting the general condition of dogs by injecting 20 ml. 69% sodium and methylglucamine diatrizoates into a catheter wedged in a hepatic vein. This was associated with a decreased enzyme activity of the injured tissue as compared with normal liver and correspondingly increased levels of serum glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactic dehydrogenase (LDH), and sorbitol dehydrogenase (SDH) activities in both hepatic venous and peripheral arterial blood. By 72 hr. after injury, when regeneration was seen histologically, the enzyme activities, markedly depressed in the injured areas, were returning to normal. The increase of serum enzyme activity appears to be quite rapid during the first few minutes after hepatic injury and there is a slow secondary rise during the first hour thereafter. By 24 hr. the serum enzyme activities returned to near normal. The enzyme activities in the peripheral arterial blood were not significantly different from those in the hepatic venous blood. Transient elevations of serum enzyme activities were also noticed in human subjects who underwent diagnostic wedge hepatic venography.

Intrahepatic vascular pathways.

Experiments were carried out on dogs, cats and rabbits. Under anæsthesia fine polythene cannulæ were inserted so that injections of acetylcholine and catechol amines could be made into the portal venous, the systemic venous and the hepatic arterial systems. Carotid arterial pressure was recorded. Much larger amounts of acetylcholine were needed when injected into the portal vein than when injected into the hepatic artery to produce the same response in arterial pressure. With adrenaline and noradrenaline the difference between the two hepatic circulations was much less marked, except in some rabbits. In more than half the experiments in which it was carried out, cooling or section of the hepatic branch of the cœliac plexus altered the blood pressure response to drugs injected into the hepatic circulation, the arterial and portal systems being affected differently. Changes evoked by nerve cooling were reversible. Ganglionic blockade with hexamethonium bromide, and sympathetic blockade with choline 2:6 xylyl ether bromide or bretylium, also affected the intrahepatic circulation of blood, as did stimulation of the sympathetic nerve from the cœliac plexus. It was concluded that portal venous and hepatic arterial blood may, under some circumstances, flow through different pathways which are under autonomic control.

Hepatic vascular response to norepinephrine.

Norepinephrine injected into the femoral vein or inferior vena cava in doses ranging from 1 to 10 µg/kg produced a prompt and definite decrease in hepatic blood flow; this response was, in general, more pronounced with increasing doses. Femoral venous injections also produced a prompt increase in arterial blood pressure followed by a decreased portal venous pressure and portal-hepatic venous pressure gradient. The calculated hepatic venous resistance increased, reaching a maximum at about 60 sec after injection. When the identical doses were injected into the portal vein in the same animals under comparable conditions, the arterial blood pressure and hepatic blood flow responses were delayed in time and attenuated in amount. However, within 10–15 sec of injection the portal venous pressure and portal-hepatic venous pressure gradient increased. The calculated hepatic venous resistance increased more rapidly after intraportal norepinephrine injection.

Amino Acids in Arterial and Hepatic Venous Blood of Patients with Laennec's Cirrhosis

Summary Simultaneous hepatic venous and femoral arterial blood specimens were obtained in 14 patients with Laennec's cirrhosis and in 2 subjects with normal liver function. The amino acid patterns of the blood specimens were compared by means of paper chromatography. The most consistent differences between the arterial and hepatic venous blood specimens were a posthepatic fall in a-alanine and a rise in glutamic acid. The pre- and posthepatic blood amino acid differences varied considerably among subj ects in the fasting state, but were not appreciably changed by decreases in liver blood flow induced by injections of Pitressin. In 2 subjects the differences between arterial and hepatic venous blood were greatly changed by an amino acid infusion and by milk ingestion, respectively. The 1 patient with a much greater hepatic venous glutamic acid concentration than any of the other subjects had Korsakoff's psychosis.

Measurement of hepatic glucose output and hepatic blood flow in response to glucagon.

Arterial, portal and hepatic venous glucose concentrations and hepatic blood flow were simultaneously measured in nine dogs in the postabsorptive state, and after intravenous administration of glucagon. A marked rise in hepatic venous glucose concentration occurred promptly after glucagon administration. This rise coincided with a mean increase in estimated hepatic blood flow of approximately 100%. This increase in hepatic blood flow following the administration of glucagon was regularly observed in all animals; the increase in blood flow ranged from 41 to 204% in this series. Hepatic glucose output was calculated by multiplying the portal-hepatic vein gradient by the hepatic blood flow. The mean hepatic glucose output of the series increased from base line of 73 mg/min. to a maximum of 381 mg/min. in response to glucagon.