Effects of exchange transfusion with perfluorochemical emulsions on hepatic oxygen supply and blood flow in the rat

Summary Exchange-transfusion to hematocrit 20 with isotonic perfluorochemical (PFC) emulsions containing 3% hydroxyethylstarch (HES) in rats breathing 100% oxygen produced significant reductions of hepatic PO₂ and blood flow in comparison to rats hemodiluted with isotonic 3% or 6% HES solution. The results indicate that PFC and/or emulsifiers were associated with adverse effects on liver blood supply.This work was supported by a grant from the Kentucky Affiliate of the American Heart Association.     

Changes in plasma enzyme concentrations in response to blood substitution with perfluorocarbon emulsion in the conscious rat

The effects of near total blood replacement with the proprietary perfluorocarbon (PFC)-based emulsion, Fluosol-DA 20%, on plasma concentrations of 2 enzymes, lactate dehydrogeanse (LDH) and alkaline phosphatase (ALP), have been examined in conscious, chronically catheterized rats. A pronounced fall in both plasma LDH (p less than 0.05) an ALP (p less than 0.01) occurred in response to exchange-transfusion. However, at 6 h following blood replacement, plasma concentrations of both enzymes had risen to values significantly greater than those measured immediately before perfusion. The observed changes in plasma LDH and ALP after blood replacement with Fluosol-DA indicated alterations in normal functioning of tissues from which these enzymes originate.     

Preliminary purification and dosages of the erythropoietic factor from ox-spleen.

The administration of ox-spleen homogenate, whether in rats made polycythemic by blood transfusion or in mice polycythemic by hypoxia, elicited a significant stimulatory effect on the rate of erythropoiesis. This activity remained unchanged even if the spleen, before being homogenized, was exhaustively washed with isotonic buffer pH 7.4 up to the total blood elimination.     

The role of volume expansion,of prostaglandins and catecholamines in the development of acute renal failure

Summary A single injection either of isotonic or hypertonic saline solutions protected rats against acute renal failure (ARF) induced with glycerol. This protection was accompanied by increased urinary prostaglandin E (PGE) concentration. On the contrary, a single s.c. injection either of hypotonic saline or isotonic glucose solution, which did not increase urinary PGE concentration, or depletion of the endogenous catecholamines, using reserpine, did not protect the animals against acute renal failure.The authors wish to thank Miss Sylvie Bompis and Miss Ermione-Loukia Ghikas for their technical assistance and Mr Richard Irvine B.A. for his help with the English.     

Suppression of the immune response by drugs interfering with the metabolism of serotonin

The work was based on the assumption that neurohumoral control of the immune response, particularly in stressed animals, involves central serotoninergic mechanisms. Rats immunized with sheep erythrocytes were stressed by repeated restraints and/or treated with a precursor of serotonin (5-hydroxytryptophan, 5-HTP) or with an inhibitor of serotonin synthesis (parachlorophenylalanine, PCPA). As expected, repeated stresses reduced the plaque-forming cell (PFC) response. Treatment with 5-HTP also reduced the PFC response, and potentiated the immunosuppressive effect of stress. This was accompanied by increased metabolism of serotonin in the brain, as indicated by increased concentration of its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in cerebral tissue. Treatment with PCPA also suppressed the PFC response, but this suppression was accompanied by decreased levels of brain serotonin and of 5-HIAA. Plasma corticosterone levels were elevated in rats treated with PCPA. It seems that putative central effects of PCPA on serotoninergic regulation of the immune response were outweighed by its effects on corticosterone secretion and/or on lymphoid cells.     

Suppression of the immune response by drugs interfering with the metabolism of serotonin

Summary The work was based on the assumption that neurohumoral control of the immune response, particularly in stressed animals, involves central serotoninergic mechanisms. Rats immunized with sheep erythrocytes were stressed by repeated restraints and/or treated with a precursor of serotonin (5-hydroxytryptophan, 5-HTP) or with an inhibitor of serotonin synthesis (parachlorophenylalanine, PCPA). As expected, repeated stresses reduced the plaque-forming cell (PFC) response. Treatment with 5-HTP also reduced the PFC response, and potentiated the immunosuppressive effect of stress. This was accompanied by increased metabolism of serotonin in the brain, as indicated by increased concentration of its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in cerebral tissue. Treatment with PCPA also suppressed the PFC response, but this suppression was accompanied by decreased levels of brain serotonin and of 5-HIAA. Plasma corticosterone levels were elevated in rats treated with PCPA. It seems that putative central effects of PCPA on serotoninergic regulation of the immune response were outweighed by its effects on corticosterone secretion and/or on lymphoid cells.     

Antidiuretic hormone involvement in the release of alpha-melanocyte-stimulating hormone by hyperosmotic stimuli

In the normal Wistar rat, the plasma alpha-MSH level was raised by hypertonic saline injection (as compared with control rats injected with isotonic saline). No such rise in alpha-MSH followed hypertonic saline administration in the Brattleboro (hereditary diabetes insipidus) animal (compared to isotonic saline injected controls). It is suggested that, in the rat, endogenous antidiuretic hormone is involved in the secretory response of the pars intermedia to osmotic stimuli.     

Action of diphenylhydantoin on chromosomes

The effect of diphenyl hydantoin, (DPH) a nonbarbituate anticonvulsant drug, on chromosomes and fertility was tested in cultured human lymphocytes, mouse fertility, and rat maternal marrow chromosomes and fetal development. Whole human blood from 5 male and 5 female subjects was cultured for 68 hours with phytohemagglutinin, then incubated for 2 hours in isotonic salts with .05-.3 mg per ml DPH, .02 mcg per ml colchicine, or .4 mg per ml sodium diethylbarbiturate. The mean number of metaphases per 1000 stimulated cells was 10.0 in controls, 40.3 with colchicine, 27.9 with diethylbarbiturate, and 30.5 with .25 mg DPH per ml. Both diphenylbarbiturate and DPH produced linear dose effect curves. These results were demonstrated not to be due to urea, since there were no differences in urea content, with a 2 hour urease micromethod. Mouse fertility was totally inhibited in 6 virgin mice given .1mg DPH daily for 10 days compared to 41 pups both of 6 control mice. In 6 pregnant rats given 25 mg DPH per 100 gm/orally 4 times daily for 2 days on gestation Days 7 and 8, there were 5 rats with all fetuses resorbed and 1 rat with 3 living and several resorptions. 6 controls had 6-14 normal fetuses each. 50 metaphase plates from each rat's femoral marrow and each fetus were examined 2 hous after injecting .3 mg colchicine per 100 gm. 30% of the metaphase cells from treated females and fetuses showed strongly contracted chromosomes and reduced number os "pulverized" chromosomes. These phenomena may have been due to inhibition by DPH of folic acid metabolism which is involved in purine synthesis.     

Renal response to acute saline loading in Sabra hypertension-prone and -resistant rats

The renal handling of an oral isotonic saline load was studied in hypertension-prone (SBH), hypertension-resistant (SBN) and the parental Sabra (SB) rats. The diuretic and natriuretic response of SBH rats was unequivocally diminished, thus lending further support to the concept of impaired salt handling in hypertension.     

Renal response to acute saline loading in Sabra hypertension-prone and-resistant rats

Summary The renal handling of an oral isotonic saline load was studied in hypertension-prone (SBH), hypertension-resistant (SBN) and the parental Sabra (SB) rats. The diuretic and natriuretic response of SBH rats was unequivocally diminished, thus lending further support to the concept of impaired salt handling in hypertension.This work was supported in part by a grant from Bayer AG, FRG.     

Antidiuretic hormone involvement in the release of α-melanocyte-stimulating hormone by hyperosmotic stimuli

Summary In the normal Wistar rat, the plasma -MSH level was raised by hypertonic saline injection (as compared with control rats injected with isotonic saline). No such rise in -MSH followed hypertonic saline administration in the Brattleboro (hereditary diabetes insipidus) animal (compared to isotonic saline injected controls). It is suggested that, in the rat, endogenous antidiuretic hormone is involved in the secretory response of the pars intermedia to osmotic stimuli.     

Respiratory control in liver mitochondria of rats hosting the walker 256 carcinoma tumor.

The decrease in the respiratory control ratio of mitochondria is a first order process when these organelles are incubated in isotonic sucrose. Furthermore, the initial respiratory control ratios and the rates of loss in respiratory control in liver mitochondria from rats hosting the Walker 256 carcinoma are not significantly different form the same properties of mitochondria from untreated animals.     

Increase in Na+, K+ -ATPase enzyme units in liver and kidneys from essential fatty acid deficient rats.

(3H)-Ouabain binding to liver and kidney preparations was utilized to estimate the number of Na+, K+-ATPase enzyme units in livers and kidneys from rats fed 2% corn oil supplemented or fat-free diets. The specific (3H)-ouabain binding in liver and kidney preparations from fatty acid deficient rats was increased approximately 40%, but the affinity of the binding sites for ouabain (Kd-value) remained unchanged. The increased concentration of Na+, K+-ATPase enzyme units observed in the essential fatty acid deficient rats may contribute to the reduced body fat accumulation and elevated heat production observed in these animals.     

Partial pancreatectomy in rats causes an impairment of the glucose-induced stimulation of pancreatic islet blood flow

Summary Adult rats were subjected to either a sham operation (S-rats) or a 60% partial pancreatectomy (P-rats). Both P- and S-rats were normoglycemic and normoinsulinemic after surgery. Four weeks later, the animals were injected i.v. with 1 ml of either 0.9% (w/v) saline or 30% (w/v) D-glucose, and after 5 min whole pancreatic blood flow (PBF) and islet blood flow (IBF) were measured, using a microsphere technique. In the saline-injected P-rats both PBF and IBF values were, higher than in S-rats (p<0.001 for both values). Administration of glucose had no effects on PBF in either S- or P-rats when compared to saline-injected animals. IBF was, however, markedly increased (p<0.01) by glucose in S-rats in comparison with saline-injected S-rats, whilst no difference in IBF was observed between glucose- and saline-injected P-rats. The fraction of PBF diverted through the islets (fIBF) was approximately 10% in S-rats and 20% in P-rats. Glucose increased fIBF in S-rats, but had no effect in P-rats. In conclusion, in S-rats a glucose-stimulated insulin release is accompanied by an increase in IBF, but this is not observed in P-rats.     

Partial pancreatectomy in rats causes an impairment of the glucose-induced stimulation of pancreatic islet blood flow

Adult rats were subjected to either a sham operation (S-rats) or a 60% partial pancreatectomy (P-rats). Both P- and S-rats were normoglycemic and normoinsulinemic after surgery. Four weeks later, the animals were injected i.v. with 1 ml of either 0.9% (w/v) saline or 30% (w/v) D-glucose, and after 5 min whole pancreatic blood flow (PBF) and islet blood flow (IBF) were measured, using a microsphere technique. In the saline-injected P-rats both PBF and IBF values were higher than in S-rats (p less than 0.001 for both values). Administration of glucose had no effects on PBF in either S- or P-rats when compared to saline-injected animals. IBF was, however, markedly increased (p less than 0.01) by glucose in S-rats in comparison with saline-injected S-rats, whilst no difference in IBF was observed between glucose- and saline-injected P-rats. The fraction of PBF diverted through the islets (fIBF) was approximately 10% in S-rats and 20% in P-rats. Glucose increased fIBF in S-rats, but had no effect in P-rats. In conclusion, in S-rats a glucose-stimulated insulin release is accompanied by an increase in IBF, but this is not observed in P-rats.     

Renin activity in rat choroid plexi: effects of water-deprivation and hypovolemia

Choroid plexus contains components of a renin-angiotensin system that could regulate hydration. Hypovolemia or 48 h water deprivation did not change choroidal renin-like activity; but under identical assay conditions, brain perfusion with cold isotonic sucrose containing EDTA and PMSF increased enzyme activity 3-4-fold.     

Effect of blood pH on anionic ferritin transport through rat aortic endothelium.

Acute lowering of blood pH between 7.4 and 6.9 in rats by ventilation with 10 or 20% CO2 does not increase the passage of ferritin molecules across the aortic endothelium. These results do not rule out alteration of endothelial permeability to anionic macromolecules in local circulatory disturbances when blood pH drops to levels much lower than 6.9.     

Effet de quelques anesthésiques sur le flux sanguin de la muqueuse gastrique,chez le Rat

Summary Effects of ether, nembutal or urethane anaesthesia on gastric secretion and mucosal blood flow (MBF) are studied in the Rat; these 3 anaesthetics alter neither volume nor total acidity of juice, but free acidity and proteolytic activity are more importance after ether anaesthesia; MBF is highest in nembutal anaesthetized rats; therefore nembutal is the best anaesthetic for studies of digestive physiology or pharmacology.     

L-arginine and pancreatic islet blood flow in anesthetized rats

The aim of the present study was to see if L-arginine, which induces insulin release and is a precursor of the endothelial-derived relaxing factor nitric oxide, affects whole pancreatic and/or islet blood flow. For this purpose, anesthetized male Sprague-Dawley rats were injected intravenously with either saline or L-arginine (25, 100 or 250 mg/kg body weight). All doses of arginine caused a slight increase in blood glucose concentration, while the highest dose (250 mg/kg body weight) also increased insulin concentration. However, no changes in either mean arterial blood pressure, whole pancreatic or islet blood flow could be discerned with any of the doses of arginine used. It is concluded that insulin release is not necessarily associated with an increased islet blood perfusion.     

Hemodynamic studies in acute venous stasis edema in rats

An increase in venous pressure in the rat tail is known to result in acute edema. Acute venous stasis edema of the rat tail was induced by applying a force-controlled banding of standard tension (200 g) proximally for a period of 6-12 h. The hemodynamic changes of acute venous stasis edema were evaluated using non-invasive plethysmography, fluorescence angiography, computer thermography and invasive radioactive microsphere techniques. It is shown here that reduction of tail circulation to 40% of the control value is followed by prolonged vascular disorder characterized by genesis of reversible edema, increased total blood flow to the tail and decreased local cutaneous blood flow, without affecting the general hemodynamics. The cutaneous circulation (decreased blood flow) seems to be principally involved in the edemogenic response, whereas the deeper vessels (hyperemia) may or may not play a determinant role in acute experimental venous stasis edema in rats.