Hepatic Blood Flow Rate Research Articles

Inhibition of nitric oxide synthesis enhances d-galactosamine-induced acute liver injury

Nitric oxide (NO), a potent vasodilator, also mediates a variety of physiological processes. We investigated the role of endogenous NO on d-galactosamine ( d-Galn)-induced liver injury. Sixteen rats were divided into four treatment groups; (a) d-Galn plus N ω -nitro- l-arginine ( l-NNA), (b) d-Galn plus N ω -nitro- d-arginine ( d-NNA alone, and (d) d-NNA alone. d-Galn was administrated intraperitoneally at a dose of 1000 mg/kg at time 0, and arginine derivatives were administrated intraperitoneally at a dose of 40 mg/kg at the same time and at 8 h intervals. After 48 h, regional hepatic blood flow and serum levels of aspartate aminotransferase and alanine aminotransferase were measured. Serum levels of AST and ALT in rats treated with d-Galn plus l-NNA were significantly higher than those in rats treated with d-Galn plus d-NNA. Regional hepatic blood flow in rats treated with d-Galn plus l-NNA was significantly decreased compared with those in rats treated with d-Galn plus d-NNA. Treatment with d-NNA and l-NNA alone had no adverse effects on serum AST and ALT levels and regional hepatic blood flow. These results suggest that endogenous NO has a protective effect on d-Galn-induced liver injury through a maintenance of hepatic microcirculation.

Lidocaine extraction by the in vivo and isolated perfused pig liver

Hepatic lidocaine elimination is increasingly being used to assess hepatic function. Although the isolated liver is extensively used as a model of in vivo function, it is necessary to determine whether this is a suitable model for in vivo lidocaine elimination. Fourteen male pigs (22-25 kg) were divided into two groups. Seven were anesthetized, and catheters and perivascular flow probes placed for transhepatic sampling and hepatic arterial and portal venous flow measurement. Sampling was performed at hourly intervals to determine hepatic function and plasma composition. Hepatic lidocaine elimination was determined during the second hour of a lidocaine infusion (1.41 mg.kg-1.min-1 for 10 min, then 0.165 m.kg-1.min-1), during which time the mean hepatic blood flow rates, plasma acid base status and body temperature were measured so that these could be emulated in the isolated perfused liver experiments. Seven male pigs were then anesthetized and the liver resected and cannulated for isolated liver perfusion. Hepatic arterial and portal venous blood flow and perfusate temperature were set to the mean in vivo values, and hepatic function and perfusate composition assessed at corresponding times. Hepatic lidocaine elimination was determined at a similar hepatic inflow whole blood concentration (+/- 5 micrograms.ml-1) to that in vivo over the second hour of lidocaine administration (40 mg bolus, then 2.8 mg.min-1). Lidocaine extraction ratio in vivo (0.61 +/- 0.04) [mean +/- SEM] and ex vivo (0.63 +/- 0.02) was similar, as was hepatic blood clearance (381 +/- 70 vs 363 +/- 16 ml.min-1) and hepatic blood intrinsic clearance (1132 +/- 280 vs 1069 +/- 109 ml.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of hyperosmotic solutions on the hepatic blood flow,

The present study was undertaken in order to measure the effect of hyperosmotic solutions on portal and hepatic blood flow. In five anaesthetized pigs without arterial blood supply to the liver, portal blood flow rate was measured (electromagnetic flowmeter) during 5 min lasting intravenous infusions of hyperosmotic galactose (50%, 84-100 ml) and mannitol (25%, 100 ml), with physiological saline (100 ml) as control. Portal blood flow increased to a peak value of (39% [P = 0.06] galactose and 37%, [P = 0.06], mannitol) soon after stop of the hyperosmotic infusion. For galactose the change ended somewhat earlier than for mannitol. Saline induced a minor increase (15%). Similarly, increments of, on average, 144% of the hepatic blood flow rate was seen in six patients with cirrhosis, following infusion of hyperosmotic galactose, the increase being more pronounced than in the pigs. The causes for these osmotic effects are not known, but they have to be taken into consideration in studies of the portal and hepatic blood flow.

P-329 - The effect of SA3443 on hepatic blood flow in rats

P-329 - The effect of SA3443 on hepatic blood flow in rats

Simple validation for the hepatic venous cannula implanted chronically in conscious rats

A method for the detection of vena caval contamination in blood taken from hepatic venous cannulas in conscious rats was described. The procedures included 1) bolus injection of tritiated water (50 microCi) through a cannula into the abdominal inferior vena cava and 2) continuous blood sampling (less than 0.2 ml) from the hepatic venous cannula for 2 min into a 180-cm piece of Tygon tubing, starting concurrently with tracer injection. The washout of tritium was determined from samples in 15-cm sections of Tygon tubing. Because circulation from the inferior vena cava to the hepatic vein is interceded by the systemic circulation, the washout of tritium from a valid hepatic venous cannula should resemble the pattern determined elsewhere in the systemic circulation. In the current study, the reference systemic washout was determined in the superior vena cava of a group of rats similarly injected with tritiated water in the inferior vena cava. The maximum of tritium washout derived from a valid hepatic venous cannula should fall in the range encompassed by one standard deviation of the mean of the maximum of the reference (1,400 to 1,930 cpm/sample). The maximum of the washout pattern derived from the invalid cannula, which lay adjacent to the site of injection, was expected to exceed this range. On the basis of these criteria, hepatic blood flow (HBF) was determined by sulfbromophthalein (BSP) extraction in groups of rats with valid and invalid cannulas. HBF in rats with valid hepatic venous cannulas was 2.58 +/- 0.15 in the conscious state and 2.76 +/- 0.26 ml.min-1.g wet wt-1 in the ketamine-anesthetized state.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of feeding on hepatic and portal blood flow in sheep

Changes in total hepatic and portal blood flow rates with feeding were observed during 24 hr in sheep by means of the para-aminohippuric acid (PAH) dilution method because there is little quantitative information on changes in blood passing through the liver. Blood flow rates in both veins increased significantly (P < 0.05) after the beginning of feeding while hepatic arterial blood flow tended to increase but was not statistically significant. Total blood volume passing through the liver was 4303 ± 2331/d (93.6 ± 7.21/kg BW/d) with contributions of hepatic arterial and portal venous blood being 21% and 79% of total daily hepatic blood flow in sheep, respectively.

Enhancement of Portal Pressure Reduction by the Association of Isosorbide–5–Mononitrate to Propranolol Administration in Patients With Cirrhosis

This study investigated whether oral doses of isosorbide-5-mononitrate, a preferential venous dilator that decreases portal pressure, could enhance the effects of propranolol on portal hypertension. Taking part in the study were 28 patients with cirrhosis and portal hypertension. Twenty patients (group 1) had hemodynamic measurements in baseline conditions after beta-blockade by intravenous administration of propranolol and after receiving oral doses of isosorbide-5-mononitrate. The remaining eight patients (group 2) were given oral isosorbide-5-mononitrate while receiving chronic propranolol therapy. In group 1, propranolol significantly reduced portal pressure (estimated as the gradient between wedged and free hepatic venous pressures) from 21.5 +/- 3.9 to 18.6 +/- 4.2 mm Hg (-13.7%, p less than 0.001), azygos blood flow (-38%, p less than 0.001), hepatic blood flow (-12.8%, p less than 0.05), cardiac output (-24.5%, p less than 0.001) and heart rate (-18.4%, p less than 0.001) without significant changes in mean arterial pressure. Addition of oral isosorbide-5-mononitrate caused a further and marked fall in portal pressure (to 15.7 +/- 3.1 mm Hg, p less than 0.001), without additional changes in azygos blood flow but with significant additional reductions in hepatic blood flow (-15.5%, p less than 0.05), cardiac output (-11.5%, p less than 0.001) and mean arterial pressure (-22%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of regional blood flow in abdominal organs and other structures in normal female rats and in rats with TAA-induced chronic liver injury using 99mTc labelled HSA-microsphere technique

A method for simultaneous determination of cardiac output and regional blood flow distribution in a chronically instrumented, unrestrained rat preparation for different experimental conditions (i.e. conscious, free movement; general anesthesia) and in an experimental chronic liver injury model is described. The use of a modified radioactive microsphere reference sample method using 99mTc labelled HSA-microspheres provides valid measurements of cardiac output [255 +/- 21.6 ml/(min.kg b.wt.)] and of the determined blood flow rates of abdominal organs (with separate determination of arterial and portal-venous hepatic blood flow rates; the latter by means of arterial blood flow measurement of the gastrointestinal tract and the spleen), the myocard, the adrenals, the kidneys, and various brain regions. Furthermore, it is demonstrated that this measuring approach with chronical preparation can also advantageously be used in pharmacological or pathogenetical studies, especially because of the simple measuring equipment and the comparatively low costs that offer a broader application.

Oxygen consumption by portal vein-drained organs and by whole animal in conscious growing swine.

A method was developed to measure simultaneously the O2 consumption (VO) by the whole animal and by the hepatic portal vein-drained organs (PVDO), including the gastrointestinal tract, spleen, and pancreas in conscious 3.5- to 4-month-old swine. The method was used to determine (i) the effect of feeding on hepatic portal vein blood flow rate (Qpv) and VO by PVDO and by the whole animal, and (ii) the significance of PVDO on the oxidative demand in the pig. Chronic cannulas were placed in the hepatic portal vein, carotid artery, and ileal vein. The Qpv was determined by an indicator dilution technique employing continuous constant infusion of 1% p-aminohippuric acid into the ileal vein. The VO2 by PVDO was estimated by multiplying Qpv by arterial-portal vein O2 difference measured with an arterial-venous O2 difference analyzer connected to the carotid artery and portal vein cannulas. Whole animal VO2 was measured with an open circuit indirect calorimeter. In seven pigs (3.5- to 4-month-old, 37.4 +/- 0.8 kg) trained to be fed once daily, feeding (1.2 kg of feed mixed with 1.2 liter of H2O) caused postprandial (6 hr) Qpv to increase more than 34 +/- 15% above the preprandial value of 34.5 +/- 4.2 ml.min-1.kg-1 body wt. The postprandial VO2 by PVDO was elevated more than 46 +/- 12% above the value of 1.52 +/- 0.20 ml.min-1.kg-1 body wt observed during the preprandial period. Whole animal VO2 increased 45 +/- 9 and 33 +/- 7% above the preprandial value of 6.23 +/- 0.57 ml.min-1.kg-1 body wt for the first 6 hr and the 7 to 12 hr after feeding, respectively. Although PVDO represent only 5% of body weight, they used 25% of whole body VO2. The study clearly illustrates the significance of PVDO on the whole animal oxidative demand in conscious growing swine.

Cardiac output, renal blood flow and hepatic blood flow in rats with glycerol-induced acute renal failure.

Cardiac output (CO), renal blood flow (RBF) and hepatic blood flow (HBF) were measured by the microsphere method before (control) and at 4 and 10 h after the induction of acute renal failure by intramuscular injection of glycerol in water-drinking, long-term saline-drinking and long-term captopril (converting enzyme inhibitor)-drinking rats. At 4 h after glycerol injection, CO, RBF and HBF significantly decreased in all three groups. At 10 h after glycerol injection, CO, RBF and HBF recovered to 88% of the respective control levels in only the saline-drinking rats, whereas CO, RBF and HBF further decreased to 53, 38 and 58% of the control levels, respectively in the captopril-drinking rats. At this time, not only acute renal failure but also hepatic disorder developed in the water-drinking and captopril-drinking rats as indicated by elevations of serum creatinine, urea nitrogen, alanine aminotransferase and other blood chemistry levels. The development of acute renal failure was not suppressed by captopril, but by long-term saline load. Thus, we conclude that the decrease in CO is an important variable of the early decrease in renal and hepatic perfusion in glycerol-induced acute renal failure, and that the early recovery of HBF as well as RBF may play an important role in preventing the development of acute renal failure.

The inhibitory effects of cimetidine on elimination and distribution of propranolol in rats.

We studied the effects of cimetidine on the pharmacokinetics, blood and tissue distribution and plasma protein binding of propranolol in rats. The plasma disappearance of propranolol after a 10 mg/kg intravenous injection and oral administration were fitted to a two compartment open model. In the cimetidine treated rats, the area under concentration curve after an intravenous injection (AUCiv) was increased by 64% and the plasma total body clearance (Cltot) and the rate constant at the terminal phase (beta) were decreased by 38% and 33% of those of the non-treated rats, respectively. The area under the concentration curve after oral administration (AUCpo) was increased by 62% and the plasma oral clearance (Clpo) was decreased by 39% by cimetidine treatment, whereas the bioavailability (F) was not changed. The hepatic blood flow rate (Qh) and the product of the plasma unbound fraction and the hepatic intrinsic clearance (fp x Clint,h) calculated from Cltot and Clpo were decreased by 30% and 39%, respectively. The blood-to-plasma concentration ratio (Rb) and the tissue-to-plasma concentration ratio (Kp) of propranolol were not affected by cimetidine treatment, while the binding constant (Kb) in plasma was decreased by 45%. The plasma unbound fractions (fp) of propranolol were increased by 25-70% in the in vivo plasma concentration range (0.1-1.0 microgram/ml) resulting in the decrease of tissue-to-plasma unbound concentration ratio (Kp,u) in lung, heart, spleen, brain and muscle. Cimetidine was shown to have the inhibitory effects on elimination and distribution of propranolol in rats.

Interspecies differences in pharmacokinetics of an antiallergic agent, 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1,4-diazepin-1-yl)benzimidazole difumarate (KG-2413) after intravenous administration to rats, guinea pigs and dogs.

Interspecies differences in the pharmacokinetics of an antiallergic agent, 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1,4-diazepin-1-yl)benzimid azole difumarate (KG-2413) after intravenous administration were investigated in rats, guinea pigs and dogs. The disappearance of unchanged KG-2413 base was described by biexponential curves in all three animal species. The areas under the plasma concentration-time curves (AUC) in rats, guinea pigs and dogs were 218, 421 and 369 ng.h/ml, respectively, at a dose of 2 mg/kg. The volume of distribution in rats was comparable to that in dogs, and was about three times greater than that in guinea pigs. This might be due to the difference in the unbound fractions of KG-2413 base in plasma (fu), that is, the values of fu in rats, dogs and guinea pigs were 0.607, 0.603 and 0.189, respectively. The first-order elimination rate constant from the central compartment (kcl) in dogs were smaller than those in rats and guinea pigs. Total body clearances (CLtot) of KG-2413 base in rats and guinea pigs were comparable to the hepatic blood flow rate (Q) of each animal. Assuming that KG-2413 base is only eliminated in the liver, relatively rapid metabolism of KG-2413 base occurred in the liver of rats and guinea pigs. In dogs, extrahepatic elimination was suggested because the value of CLtot seemed to be greater than that of Q.

Absorption kinetics of dietary hydrolysis products in conscious pigs given diets with different amounts of fish protein. 2. Individual amino acids.

1. Concentrations of amino acids (AA) in blood obtained from arterial and portal permanent catheters were measured together with the portal hepatic blood flow-rate during a post-prandial period of 8 h, in nine conscious pigs (initial mean body-weight 49.3 (SEM 1.8) kg) receiving experimental meals (500, 600 or 1000 g) at 3-4 d intervals from 6-8 to 20 d after the surgical implantation of the catheters and electromagnetic flow probe. The semi-synthetic starch-based diets contained variable amounts of fish meal giving crude protein (nitrogen x 6.25; CP) concentrations (g/kg) of 80 (seven meals), 120 (seven meals), 160 (five meals) and 240 (three meals). 2. During the post-prandial period, variations in the individual blood AA concentrations were parallel to those of total amino-N (Rérat et al. 1988) to a greater or lesser extent according to the AA considered. Portal concentrations, which always exceeded arterial ones (except for glutamic acid and glutamine), increased quickly and, after a peak, returned slowly to reach initial values (small intake) or above (large intake) after 8 h. 3. Relations between amounts of each AA appearing during 8 h after the meal and amounts ingested were characterized by a highly significant linear regression (with the exceptions of glutamic acid and cystine). There were also close and significant relations between amounts of AA absorbed during the first 2 and 4 h after the meal and the amounts ingested. 4. For a mean intake of 90 g CP, aromatic AA showed the highest hourly absorption coefficients (about 0.10/h), and sulphur-AA (0.07/h), lysine (0.07/h) and arginine (0.056/h) the lowest ones. Alanine was synthesized (amounts absorbed within 8 h exceeding those ingested) at the expense of glutamic acid (absorption coefficient 0.01/h). 5. For a given period of time, the AA absorption coefficients decreased with increasing intake, but not in the same proportions for all AA, resulting in an enrichment (lysine, arginine, serine, proline) or depletion (branched-chain AA, histidine) of the absorbed mixture. 6. Some substances of the urea cycle were synthesized in rather large amounts in the gut wall (for a mean level of intake of 90 g CP: citrulline 2.41 g/8 h, ornithine 1.09 g/8 h). Blood glutamine was taken up by the gut wall in larger amounts (4.28 g/8 h).

Absorption kinetics of dietary hydrolysis products in conscious pigs given diets with different amounts of fish protein. 1. Amino-nitrogen and glucose.

1. Concentrations of amino-nitrogen, glucose, reducing sugars and lactic acid in blood obtained from arterial and portal permanent catheters were measured together with the portal hepatic blood flow-rate during a post-prandial period of 8 h in twenty unanaesthetized pigs (initial mean body-weight 52.3 (SEM 0.9) kg) receiving experimental meals (200-1000 g) at 3-4 d intervals from 6-8 to 20 d after surgical implantation of the catheters and electromagnetic flow probe. The semi-synthetic starch-based diets contained variable amounts of fish meal given crude protein (nitrogen x 6.25; CP) concentrations (g CP/kg) of 80 (seven meals), 120 (twenty-two meals), 160 (six meals) and 240 (nine meals). 2. After the meal the concentration of amino-N increased with increasing levels of protein intake and increased more in the portal than in the arterial blood. There were significant relations between amounts of amino-N appearing in the portal blood at various time-intervals after the meal and the level of protein intake. Values for the ratio, amount absorbed within 8 h: amount ingested (absorption coefficient: 0.633 for a mean intake of 13.4 g N) decreased with increasing level of protein intake. 3. There was a rise in glycaemia after the meal, increasing with the amount of carbohydrate eaten, and this was more marked in the portal than in the arterial blood. There were also significant relations between amounts of glucose absorbed and amounts of starch ingested. However, the appearance of glucose in the portal blood was less marked than that of amino-N since the absorption coefficient within 8 h was lower (0.504 for a mean intake of 291 g reducing sugars). This was most probably due to a larger uptake of glucose by the intestinal cell wall. 4. Amounts of lactic acid appearing in the portal vein during the post-prandial period did not depend on amounts ingested; they ranged from 3 to 1.6 g/h from the 1st to the 8th hour after the meal.

Femur fracture with associated soft-tissue injury produces hepatic ischemia. Possible cause of hepatic dysfunction.

Clinical studies demonstrate that early débridement and operative fixation of femur fractures in multiply injured patients lowers both the incidence and severity of hepatic failure. Perhaps the single most important determinant of hepatic function is nutrient hepatic perfusion. This study compares systemic and hepatic blood flow in rats that have sustained femur fractures with or without associated soft-tissue injury. Femur fracture without soft-tissue trauma resulted in a hyperdynamic state with normal blood flow distribution at 24 hours after injury and normal hemodynamics at 48 hours. When femur fracture was associated with soft-tissue trauma, the elevated cardiac output at 24 hours was not matched by a proportionately elevated hepatic blood flow. In this latter group, the cardiac output was normal at 48 hours, but the hepatic perfusion defect remained. Retained fracture fragments, hematoma, and injured and necrotic soft tissue may serve as a stimulus leading to a pathologic reduction in hepatic perfusion.

Kinetics of hepatic alanine uptake and urea synthesis in pigs.

The kinetics of hepatic alanine uptake and urea synthesis in relation to sinusoid alanine concentration was investigated in seven anesthetized pigs weighing 63 kg, using liver vein catheterizations. Each experiment consists of four steady-state periods of 40 min with alanine concentrations in the range of 0.4-27 mmol/l. The process rates were measured as the products of transhepatic concentration gradients and hepatic blood flow rate, determined by indocyanine green. The data suggest that both processes follow saturation kinetics, that there exists a sinusoidal concentration of alanine below which net removal is limited, and that urea synthesis consists of two components: one alanine independent and one depending on alanine concentration according to Michaelis-Menten kinetics. The kinetic parameters were estimated iteratively by the maximum likelihood method. The maximum rate of alanine uptake was 1.13 +/- 0.74 mmol.min-1.kg liver wt-1 (mean +/- SD), the alanine concentration resulting in half-maximum alanine uptake rate was 1.69 +/- 0.99 mmol/l, and the removal-limiting alanine concentration was 0.27 +/- 0.09 mmol/l. The maximum rate of urea-N synthesis was 1.49 +/- 0.87 mmol.min-1.kg liver wt-1, the alanine concentration resulting in half-maximum urea-N synthesis rate was 2.32 +/- 1.11 mmol/l, and the alanine concentration-independent urea-N synthesis rate was 0.13 +/- 0.10 mmol.min-1.kg liver wt-1.

Clinical Pharmacokinetics of Ethanol

The pharmacokinetics of ethanol after typical doses are described by a 1-compartment model with concentration-dependent elimination. The volume of distribution estimated from blood concentrations is about 37 L/70 kg. Protein binding of ethanol has not been reported. Elimination is principally by metabolism in the liver with small amounts excreted in the breath (0.7%), urine (0.3%), and sweat (0.1%). Metabolism occurs, principally by alcohol dehydrogenase, in the liver to acetaldehyde. Models of ethanol input and absorption are crucial to the description and understanding of the effects of ethanol dose on bioavailability. Little attention has been paid to evaluation of potential models. First-pass extraction of ethanol is predicted to be dependent on hepatic blood flow and ethanol absorption rate, with a typical extraction ratio of 0.2. The overall elimination process can be described by a capacity-limited model similar to the Michaelis-Menten model for enzyme kinetics. The maximum rate of elimination of ethanol (elimination capacity or Vmax is 8.5 g/h/70 kg. This would be equivalent to a blood ethanol disappearance rate of 230 mg/L/h if metabolism took place at its maximum rate. The elimination rate is half of the elimination capacity at a peripheral blood ethanol concentration (Km) of about 80 mg/L. Ethanol is readily detectable in expired air. The usual blood:expired air ratio is 2300:1 and breath clearance at rest is 0.16 L/h. The renal clearance of ethanol is 0.06 L/h and sweat clearance is 0.02 L/h. The use of a zero-order model of ethanol elimination has been widespread although the limitations of this model have been known for a long time. Much of the published work on ethanol pharmacokinetics must be regarded with suspicion because of this assumption.

The pharmacokinetics of meperidine in acute trauma patients.

Traumatic injury has the potential to alter the hepatic clearance and hence the efficacy and toxicity of drugs by a variety of mechanisms. These include changes in hepatic microsomal enzyme activity, hepatic blood flow rate, and plasma protein binding. Unfortunately, there have been few pharmacokinetic studies in trauma patients. Thus, few data are available to provide guidance in drug regimen design for these individuals. Meperidine clearance was therefore evaluated in patients with traumatic injury and an effort was made to identify physiologic and/or clinical predictors of clearance which could facilitate initial dosage selection. Meperidine total body clearance (TBC) was determined on 12 occasions at steady state following IM administration of meperidine to nine severely injured nonseptic trauma patients with normal renal and hepatic function. TBC of this drug averaged 684 +/- 206 ml/min (mean +/- SD) and was highly correlated with ideal body weight (IBW) (r2 = 0.735; F = 27.75; n = 12; p less than 0.01). The serum concentration of the acute phase reactant protein, alpha 1 acid glycoprotein (AGP), which binds meperidine and many other basic drugs increased strikingly in an apparent linear manner at a rate of 27 mg/dl/day up to 9 days after the traumatic event (r2 = 0.828; F = 42.30; n = 12; p less than 0.01). However, this increase in binding protein concentration was not associated with an alteration in meperidine TBC as has been reported for other drugs. It is concluded that IBW may be a useful guide initial dosage selection of meperidine in acute trauma patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose Absorption and Hepatic Gluconeogenesis in Dairy Cows Fed Diets Varying in Forage Content

One dry and four lactating Holstein cows were prepared with chronic catheters in the mesenteric, hepatic and portal veins and used to study glucose absorption and hepatic gluconeogenesis. The dry cow was used in a preliminary assessment of the methods. In the main experiment high concentrate and high forage diets, providing equal energy intake, were delivered in hourly portions from an automatic feeder as total mixed rations. A few data were collected with the high concentrate ration fed ad libitum in early lactation. A few additional observations were made with limited feed intake by using the same cows subsequent to the main experiment. Portal and hepatic vein blood flow rates were determined by using para-aminohippuric acid. Glucose entry rates were significantly higher during ad libitum feeding of the high concentrate diet than during feeding of the two diets with restricted intake. There was no difference between high concentrate and high forage diets when fed at equal energy intakes. Net glucose appearance in portal blood was demonstrated. Data from this study and from the literature were used to develop general relationships between digestible energy intake and 1) portal vein blood flow, 2) rate of portal appearance of glucose and 3) total splanchnic glucose entry rate.

Systemic and splanchnic hemodynamic disturbances in conscious rats with experimental liver cirrhosis without ascites.

Rats with CCl4-induced cirrhosis of the liver show histological and clinical features that closely resemble those of the disease in humans. Metabolic cages were used and hemodynamic studies (15-micrograms radioactive microspheres) were performed on 10 conscious, nonascitic, cirrhotic rats and in 10 control rats. Compared with control animals, cirrhotic rats showed lower sodium excretion (0.80 +/- 0.07 vs. 1.01 +/- 0.07 meq/day), total solute excretion (12.52 +/- 0.79 vs. 19.38 +/- 3.7 mosmol/day), and increased aldosterone excretion. No differences were observed in urinary epinephrine and norepinephrine excretion. Cirrhotic rats showed also slight hypotension, increased cardiac output (48.97 +/- 3.94 vs. 26.97 +/- 2.3 ml X min-1 X 100 g-1) without tachycardia, and decreased total peripheral resistance, which was mainly attributed to reduced renal and skeletal muscle resistances with increased blood flow throughout these areas. Cirrhotic rats showed increased hepatic vascular resistances by both portal and arterial inputs with portal hypertension (16.15 +/- 1.01 vs. 9.60 +/- 0.77 cmH2O) but without differences in total hepatic blood flow or portal-systemic shunt rate with respect to control rats. Plasma renin content was not significantly different between the groups of rats. From these data it can be concluded that nonascitic, cirrhotic rats show a hyperdynamic circulatory state, which seems to be caused by a peripheral vasodilation of unknown mechanism; portal-systemic shunting does not seem to be a necessary condition for the hyperdynamic status at this early stage of the hemodynamic disturbances.