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Biomedical subjects

B Howden

Publications and source records attributed to B Howden.

17 recordsLinked to original sources
PubMed1999

Improved cardiac preservation by the addition of nitroglycerine to colloid-free University of Wisconsin solution (MUW).

BACKGROUND: This study examines whether the addition of nitroglycerine, a known coronary vasodilator and nitric oxide donor, to colloid-free University of Wisconsin solution will improve and extend cardiac preservation. METHODS: Rat hearts were flushed and stored in colloid-free University of Wisconsin solution with or without the addition of nitroglycerine for 12, 16 or 20 hours at 0 degrees C before heterotopic transplantation with an indwelling externalized intraventricular balloon-tipped catheter. One and 7 days after transplantation of the heart the catheter was connected to a pressure transducer and quantitative functional studies were performed. RESULTS: After 12 hours preservation with nitroglycerine in colloid-free University of Wisconsin solution 6/6 grafts continued to beat for 7 days compared to 3/6 without nitroglycerine. After 16 hours preservation the addition of nitroglycerine 5/7 hearts continued to beat for 7 days compared to 0/6 without nitroglycerine (p < .05). Only 1/6 hearts beat for 7 days after 20 hours preservation with nitroglycerine. On Days 1 and 7, the left ventricular developed pressure (LVDP), contractility (max dP/dt) and rate of relaxation (peak -dP/dt) of 12 hour preserved hearts was better (p < .05) when nitroglycerine was present. The function of hearts preserved with the addition of nitroglycerine was similar after 12 and 16 hours preservation. CONCLUSION: Nitroglycerine is a valuable additive to colloid-free University of Wisconsin solution, extending effective preservation of the rat heart to 16 hours and significantly improving left ventricular function after 12 and 16 hours preservation. The addition of nitroglycerine, however, did not extend preservation to 20 hours.

Adenosine↗
PubMed1989

The importance of the hepatic artery in rat liver transplantation.

The hepatic artery is important in preventing biliary ischemia and obstruction after bile duct reconstruction or orthotopic liver transplantation in the rat. A technique of orthotopic liver transplantation in the rat with reestablishment of the arterial inflow is described, suitable for studies in immunology and preservation. Reestablishment of both venous and arterial inflow is required to minimize biliary complications. General survival, hepatic cellular function, and biliary drainage are all improved by rearterialization. In all these features, the rat illustrates characteristics applicable to human liver transplantation. The vital requirement of the adequacy of blood supply to the bile duct in liver transplantation surgery in all species is highlighted by these findings, which indicate clearly the importance of an arterial blood supply in rat liver transplantation and bile duct surgery.

Animals↗
PubMed1988

The thigh flap: an osteomyocutaneous free-flap model in the rat.

A new experimental model for free-flap transfer has been developed in the rat. This "thigh flap" is an osteomyocutaneous free flap of bone (femur), muscle (thigh), and skin (groin) based on the femoral vessels. The flap is harvested from the left groin and thigh of an inbred female rat and is transferred to a subcutaneous pocket in the left groin of a male rat of the same inbred strain. The femoral vessels supplying the flap are anastomosed end-to-end with the femoral vessels of the recipient. Thirty flaps have been transferred, with 5 technical failures. Three of the remaining 25 flaps developed necrosis within 24 hours. The other 22 flaps remained viable until the rat was sacrificed at 7 days. The survival rate of the thigh flap was thus 88 percent. The model is suitable for use in metabolic, vascular, and immunologic studies of composite free flaps.

Animals↗
PubMed1987

Glomerular epithelial cell lesions in rat renal isografts.

Visceral glomerular epithelial cell lesions--microvillus formation, loss of foot processes, osmiophilic inclusion droplets, balloon-like malformation of cell processes, degeneration, necrosis, and loss of cell processes from capillary basement membranes--are found in rat renal isografts 1 mth after transplantation. The lesions, which are most readily recognized in perfusion-fixed material, are essentially focal, affecting neither all glomeruli, nor all cells in any glomerulus, bear no relation to the degree of interstitial nephritis in the graft, and are associated with albuminuria and with focal capillary sclerosis in some glomeruli. They are not restricted to renal isografts but are found in aging rats, in different experimental models of glomerular disease and in clinical glomerular disorders, again in association with proteinuria and glomerulosclerosis. It is therefore proposed that glomerular epithelial cell damage increases capillary permeability and impairs maintenance of the integrity of the capillary wall, leading to proteinuria and focal glomerulosclerosis.

Animals↗
PubMed1987

Rat pancreas preservation for transplantation.

This study has shown that phosphate-buffered sucrose is a suitable preserving solution for the cold storage of rat pancreata for 24 hours. Isotonic citrate does not appear to be as effective a preserving solution under these conditions. Preservation of endocrine function is evident, but preservation of exocrine function is effected by obstruction or occlusion of the ductocystostomy, which may occur some time after transplantation and may not be related to transplant conditions.

Amylases↗
PubMed1986

Cyclosporine and the ischemic rat kidney.

The effects of cyclosporine (CsA) on renal function and morphology have been studied in the rat after unilateral nephrectomy and warm renal ischemia. There is evidence of an enhanced CsA nephrotoxic effect after unilateral nephrectomy alone and of an additive or synergistic effect of CsA and renal ischemia upon renal function and morphology. These enhanced effects are most evident after longer periods of ischemia (60 min) and with higher doses of CsA (25 mg/kg/day). The findings may be relevant to clinical practice and suggest that the nephrotoxic effects of CsA upon the donor kidney may be greatest when there is coincident renal damage from other causes.

Animals↗
PubMed1986

Glomerular damage after kidney preservation.

Severe proteinuria occurs during isolated organ perfusion of kidneys removed from SD and DA rats and subjected to 24-hr cold preservation. In both strains increased glomerular permeability was associated with changes in glomerular visceral epithelial cells, particularly cytoplasmic edema and detachment of cells from capillary basement membranes. Foot processes were intact and staining for sialoglycoprotein was retained. The changes were compatible with survival of the isograft kidney after transplantation, but moderate proteinuria was found in some rats after one month. Protein loss in the urine during isolated organ perfusion is very much less in kidneys subjected to 4-hr cold preservation, and the glomerular epithelial cells are normal or show only minimal cytoplasmic edema on electron microscopy. The experiment shows that significant damage to glomeruli may occur during preservation prior to transplantation, and the model itself can be usefully exploited to determine the relation between increased glomerular permeability to albumin and the associated changes in the glomerular capillary wall.

Animals↗
PubMed1985

The influence of the contralateral kidney upon recovery from unilateral warm renal ischemia.

Unilateral warm renal ischemia of 90 min duration was induced in rats and the contralateral normal kidney was removed either immediately or after 1, 2, 4 or 14 d. Contralateral nephrectomy at 2, 4, 14 d increased survival and modified the functional and morphological events of the recovery period. Optimal recovery was obtained by 4 d delay. When contralateral nephrectomy was delayed by 14 d, scarring of the ischemic kidney was more severe suggesting that regeneration of damaged nephrons was impaired when renal homeostasis was sustained by the contralateral kidney. Such biphasic and inverse effects of normal kidney tissue are likely to be important determinants of the natural history of severe unilateral renal damage.

Animals↗
PubMed1984

Studies in renal preservation using a rat kidney transplant model: II. The effect of reflushing with citrate.

This study investigated the possible beneficial effects of reflushing renal grafts with isotonic citrate solution. Rat kidneys were initially flushed with isotonic citrate or with Hartmann's solutions at O C. After 2 hr, half the kidneys of each group were reflushed with isotonic citrate; 22 hr later, all kidneys were transplanted into rats of the same inbred strain. All animals receiving kidneys flushed with Hartmann's solution died, whereas reflushing such kidneys with isotonic citrate significantly ameliorated the deleterious effects of Hartmann's solution. All animals receiving citrate-flushed kidneys survived with relatively good renal function and morphology. However, reflushing itself is not a beneficial procedure and is only of value where an ineffective preserving solution has been used to flush the kidneys initially. There is evidence that some of the adverse effects of flushing develop in the renal medulla.

Animals↗
PubMed1983

Studies of renal preservation using a rat kidney transplant model. Evaluation of citrate flushing.

Rat kidneys were flushed with isotonic citrate solution, hypertonic citrate solution, or Collins's C2 solution, and were stored hypothermically for 24 hr before transplantation into another rat of the same inbred colony. The number of animals surviving for one month was greatest with isotonic-citrate-flushed kidneys (82%), and least with Collins's C2 solution (27%). Functional and morphological damage after transplantation was consistently greater in Collins's-flushed grafts, as compared with citrate-flushed grafts. Best results were attained with the isotonic-citrate flushed grafts. Seven days after contralateral nephrectomy all surviving animals had elevated serum creatinine and urea concentrations, along with decreased creatinine clearance, and they had secreted large volumes of dilute urine. Renal function was best in animals with isotonic-citrate-flushed grafts. After one month, significant improvement in urine osmolality, creatinine clearance, and serum creatinine had occurred only in the rats with citrate-flushed grafts. There were no significant differences between the citrate groups. All surviving rats had some residual renal cortical damage, but severe interstitial nephritis (greater than 30%) was much less frequent in the citrate groups.

Animals↗
PubMed1983

Recovery of renal function after warm ischemia. I. The effect of chlorpromazine and phenoxybenzamine.

The effects of treatment with chlorpromazine (4 mg/kg) and phenoxybenzamine (1 and 5 mg/kg) on renal function and morphology after warm ischemia and contralateral nephrectomy were studied. Chlorpromazine pretreatment by intravenous injection 15 min before warm ischemia of 60 min resulted in the survival of all animals (cf. 75% in untreated group), with better renal function in the first week. Necrosis of the proximal convoluted tubule and ultimate residual cortical damage were less severe than in the untreated groups. Chlorpromazine was also beneficial after 75 min warm ischemia, although mortality was not reduced. Administration of chlorpromazine just prior to revascularization was ineffective, suggesting that sufficient concentration of the drug must be present in the kidney during the ischemic period or immediately after revascularization. Chlorpromazine probably protects the proximal tubular cells from ischemic damage. Phenoxybenzamine (1 mg/kg) was ineffective when administered 15 min before warm ischemia. A higher (5 mg/kg) dosage of the drug proved to be detrimental.

Animals↗
PubMed1980

Evaluation of citrate flushing solution using the isolated perfused rat kidney.

The isolated rat kidney perfused at 37 C with dialyzed bovine serum albumin (6.5 g/100 ml) in Krebs-Henseleit buffer was used to examine why a hypertonic citrate flush permits rapid recovery of renal function after storage. The composition of the original hyperosmolar citrate solution was varied so that the roles of osmolality, magnesium, and citrate could be evaluated. All kidneys were flushed with the test solutions and stored for 24 hr in the test solutions at 0 C. The citrate flushing solution requires both the citrate anion and magnesium for efficacy. Hyperosmolality does not enhance its action, an isosmolar solution is more effective. Citrate can be replaced by a nonmetabolizable analogue, tricarballylate, if the solution is suitably buffered. The mechanism of action of citrate is still uncertain, it does not seem primarily to act as a metabolic fuel or inhibitor.

Animals↗
PubMedDate not supplied

The return of glomerular filtered albumin to the rat renal vein--the albumin retrieval pathway.

BACKGROUND: Recent studies have demonstrated that the normal glomerular capillary wall (GCW) is not charge selective to albumin. This means that albumin flux across the GCW is high. This has been confirmed in studies where albumin uptake by the tubules has been inhibited. Therefore, there must be a high capacity postglomerular retrieval pathway in normal kidneys that returns filtered albumin back to the blood supply. METHODS: This study identifies the presence of glomerular filtered albumin in the renal vein from the analysis of the decrease of radioactivity in the venous effluent after the injection of a pulse of tritium labeled albumin into the renal artery in vivo and in the isolated perfused kidney (IPK). RESULTS: The glomerular filtered albumin is returned to the blood supply by a high capacity pathway that transports this albumin at a rate of 1830+/-292 microg/min rat kidney (n= 14) (mean+/-SEM). This pathway has been identified under physiological conditions in vivo and in the IPK. The pathway is specific for albumin as it does not occur for horseradish peroxidase (HRP). The pathway is inhibited in a non-filtering kidney. The pathway is also inhibited by NH4Cl, an inhibitor of protein uptake. CONCLUSIONS: The high capacity retrieval pathway for albumin is most likely associated with transtubular cell transport. It is also apparent that most albuminuric states could be accounted for by the malfunctioning of this pathway without resorting to any change in glomerular permselectivity.

Albumins↗
PubMedDate not supplied

Effects of dopamine on renal function in the rat isolated perfused kidney.

The renal effects of dopamine, the dopamine antagonist spiperone and the combination of dopamine and spiperone were examined in the isolated perfused rat kidney preparation. Studies were carried out at constant perfusion pressure and the following were measured at 10 min intervals for 1 h: perfusate flow; GFR (3H-inulin); urine flow rate; sodium, potassium and kallikrein excretion; perfusate renin concentration; perfusate and urinary-dopamine levels. Low-dose dopamine infusion (6 X 10(-10) mol/min) resulted in significant diuresis, natriuresis and kaluresis but little change in GFR. These effects were blocked by spiperone (10(-10) mol/min) which had no significant effects when infused alone. At a higher dose (10(-8) mol/min) dopamine significantly increased urine flow alone; this too was reversed by spiperone. Dopamine had no significant effects on perfusate flow, renin release or kallikrein excretion. Perfused control kidneys excreted amounts of dopamine (328 pmol/h, s.e.m. = 57, n = 6) far in excess of kidney dopamine content (49 pmol/g, s.e.m. = 6, n = 32). Renal handling of infused dopamine was dose-related; the fraction of the administered dose taken up and/or metabolized by the kidney on the higher dose infusion was considerably less than on the lower dose (40%, s.e.m. = 3 vs. 82%, s.e.m. = 6) while more was excreted (13%, s.e.m. = 3 vs. 2%, s.e.m. = 1). These studies indicate that dopamine at low doses can produce diuresis, natriuresis and kaluresis independently of extrarenal or haemodynamic influences and not mediated by renal renin or kallikrein systems. The kidney also exhibits a saturable capacity for dopamine uptake and/or metabolism.

Animals↗