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Changes in the blood volume of the rabbit with age.

1. The changes in blood haemoglobin concentration, great vessel haematocrit value, red cell volume, plasma volume and total blood volume have been studied in rabbits from birth to 4 months of life.2. The plasma volumes were measured with [(131)I]human serum albumin and/or rabbit serum [(14)C]albumin. Red cell volumes were measured with [(51)Cr]-rabbit red blood cells. Blood volumes were also calculated from carbon clearance curves.3. The haemoglobin concentration and the great vessel haematocrit value fell during the first 11 days of life. The great vessel haematocrit value was then not significantly different from the value at 4 months; whereas the haemoglobin concentration fell further until 22 days, when it started to rise towards the concentration at 4 months.4. The true plasma volume could not be accurately measured during the first 48 hr of life by the injection of labelled albumin since it rapidly equilibrated with an extravascular albumin space. As the ratio of the whole body haematocrit to the great vessel haematocrit (F(cells)) did not appear to change with age the plasma volume at this time was best obtained by calculation from the red volume and corrected great vessel haematocrit.5. The blood volume fell significantly during the first 4 months of life due to significant falls in the red cell and plasma volumes.

Age Factors↗

Intrahepatic distribution of portal and hepatic arterial blood flows in anaesthetized cats and dogs and the effects of portal occlusion, raised venous pressure and histamine.

1. Radioactive microspheres were used to determine the distribution of arterial and portal flows within the liver. (141)Ce-microspheres and (51)Cr-spheres were given to allow two determinations of flow distribution in each animal and experiments are described to establish the accuracy and validity of the method.2. Mean flow/g to any lobe or segment of a lobe in a group of animals was not markedly different from the mean flow/g to the whole liver, and in general the liver was homogeneously perfused with both portal and arterial blood. However, in any one liver, some areas received a relatively greater flow (up to 300%) and some a relatively smaller flow (down to 50%) at the time the microspheres were given. The gall bladder received a much smaller portal flow/g than the parenchyma but its arterial flow/g varied widely in different animals.3. If portal flow to an area of parenchyma was reduced by occlusion of a branch of the portal vein, this area received a significantly increased arterial flow.4. An increase in hepatic venous pressure did not cause a significant change in the intrahepatic distribution of either arterial or portal flows in cats.5. In dogs, infusions of histamine into the portal vein caused a redistribution of portal flow away from the free ends of the lobes towards the hilar ends but the distribution between lobes did not change and there was no redistribution of arterial flow.

Animals↗

Comparison of the effects of hepatic nerve stimulation on arterial flow, distribution of arterial and portal flows and blood content in the livers of anaesthetized cats and dogs.

1. The responses to hepatic nerve stimulation were studied in cats and dogs anaesthetized with sodium pentobarbitone. In three series of experiments, hepatic arterial flow was recorded by an electromagnetic flowmeter, intrahepatic distributions of arterial and portal flows were studied by radioactive microspheres, and hepatic volume responses were measured by a plethysmographic method.2. In cats, nerve stimulation produced a frequency-dependent decrease in hepatic arterial flow which was not maintained and autoregulatory escape occurred. In dogs, the initial decrease in arterial flow was similar but escape did not occur and the vasoconstriction was well maintained.3. In both cats and dogs, stimulation of the hepatic nerves did not cause a redistribution of either arterial or portal flows within the liver. Autoregulatory escape in the liver of the cat was not associated with an intrahepatic redistribution of arterial flow and is best interpreted as relaxation of the same vessels which were initially constricted, due to increased production of a vasodilator factor.4. Stimulation of the hepatic nerves caused a marked frequency-dependent decrease in hepatic volume which was well maintained and the responses were similar in cats and dogs. The quantitative importance of the liver as a blood reservoir is compared in relation to other vascular beds and the concept of the blood volume reserve is discussed.

Animals↗

In vitro attachment of radioactive endotoxins to lysosomes.

The experiments reported here demonstrate that under certain conditions endotoxin can interact with lysosomes in vitro. After incubation of large granular fraction with (51)Cr-labeled antigen under the conditions required for acid hydrolytic activity, radioactivity was associated with the pellet after centrifugation. This effect can be inhibited by preincubation of the large granular fraction with unlabeled homologous or heterologous endotoxins. High resolution autoradiography showed that (14)C-labeled endotoxin was predominantly attached to the lysosomes contained in the large granular fraction. The mechanism of this interaction and its relationship to the toxic effect of endotoxins on lysosomes are discussed.

Animals↗

Fecal excretion of bile acids: a new technique for studying bile acid kinetics in patients with ileal resection.

The fecal elimination and enterohepatic circulation of bile acid was studied in 11 patients. 10 patients with varying degrees of ileal disease or resection and 1 patient with pancreatic insufficiency and no ileal disease. A new technique was employed which involved the nearly simultaneous administration of cholic acid-(14)C and a nonabsorbable marker. (51)CrCl(3). Each individual stool specimen was collected for 36-96 hr and analyzed separately. Assay of the radioactivity of each isotope allowed the accurate determination of an excretion rate for both cholic acid and (51)Cr. The difference between these rates was used to calculate an absorption coefficient for cholic acid. In addition, bile acid concentration measured by the steroid dehydrogenase technique, and the water content of each stool was determined. THE PATIENTS WERE DIVIDED INTO GROUPS DEPENDING UPON HOW MUCH SMALL INTESTINE WAS RESECTED OR DISEASED: six patients with less than 100 cm of ileal resection or disease (group A), and five patients with more than 100 cm of ileal disease or resection (group B). The (51)Cr excretion rate was similar in the two groups, but cholic acid-(24)C excretion rates were significantly more rapid in group B than in group A. The cholic acid absorption coefficient was essentially normal in the patient with pancreatic insufficiency, moderately decreased in group A patients, and extremely low or zero in group B patients. It was inversely related to the length of intestine diseased or resected. Daily fecal bile acid excretion was normal to twice normal in group A patients and 2-8 times normal in group B patients. In all patients with ileal disease or resection, there was a direct correlation between fecal bile acid, fecal mass, and fecal water. Each millimole of additional bile acid in the stool was associated with an increase in stool water of 11 moles (P < 0.01). These studies show that the kinetics of bile acids in the enterohepatic circulation can be accurately studied in patients with extensive ileal resection. The regular relationship between fecal bile acid and fecal mass and water suggests, but does not prove, a critical role of bile acid in determining stool water.

Administration, Oral↗

Quantitative studies of the delivery of hepatic-synthesized bilirubin to plasma utilizing -aminolevulinic acid-4- 14 C and bilirubin- 3 H in man.

After the simultaneous intravenous administration of unconjugated bilirubin-(3)H and delta-aminolevulinic acid-4-(14)C, the plasma disappearance curves of unconjugated bilirubin-(3)H and the plasma appearance curves of biosynthesized unconjugated bilirubin-(14)C have been defined in seven patients, three of whom had acute intermittent porphyria (AIP). The incorporation of (14)C into plasma unconjugated bilirubin, derived by an analysis which involves deconvolution of the two plasma curves, varied between 13.1 and 23.5% (mean 19.3%) of the injected dose in the nonporphyric patients and between 5.4 and 13.6% (mean 8.3%) of the injected dose in the porphyric patients. In five of the patients, the stercobilin-(14)C specific activity in a pooled specimen of feces was measured, enabling the following further values to be calculated: (a) the total (14)C radioactivity incorporated into bilirubin (21.0 and 25.3% [mean 23.2%] of the injected dose in two of the nonporphyric patients and between 8.5 and 25.3% [mean 14.2%] of the injected dose in the porphyric patients), and (b) the proportion of hepatic synthesized bilirubin delivered directly to plasma in the unconjugated form (between 0.520 and 0.904; mean for nonporphyric patients 0.712; mean for porphyric patients 0.614). The results demonstrate that a large proportion of bilirubin derived from hepatic hemes passes through the plasma in the unconjugated form before conjugation and secretion into bile.

Adult↗