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Biomedical subjects

B O Howden

Publications and source records attributed to B O Howden.

At least 19 recordsLinked to original sources
PubMed2002

Oral buprenorphine and aspirin analgesia in rats undergoing liver transplantation.

The objective of this study was to establish effective postoperative analgesia for Dark Agouti rats undergoing liver transplantation with minimal additional stress due to handling and no adverse effect on transplant outcome. Oral administration of buprenorphine (0.5 mg/kg/dose) or aspirin (100 mg/kg/dose) in raspberry-flavoured gelatine were compared to controls receiving no treatment or plain gelatine. The drugs were presented five times: immediately on recovery from anaesthesia and at 12 h intervals thereafter. All rats underwent right nephrectomy and replacement of their liver by an arterialized liver isograft preserved optimally for 24 h. All groups had reversible hepatic damage, lost weight and demonstrated severely reduced dark cycle activity after surgery. Neither treatment appeared to ameliorate the loss of body weight that probably reflected hepatic insufficiency during the first week as well as pain and surgical stress. In the second week, when liver function was 'normal', rats began to regain weight at the pre-transplant rate. Aspirin treatment significantly increased activity during the first and second dark cycles after surgery, whereas buprenorphine significantly increased activity during the second dark cycle only. Neither drug had any apparent adverse effects on the rats or on graft function. Postoperative oral administration of aspirin should be incorporated into future programmes of liver transplantation in rodents. More effective treatment in the immediate postoperative period may require oral administration of analgesia prior to surgery or a single subcutaneous injection of an analgesic agent on completion of surgery in addition to postoperative oral administration of aspirin.

Activity Cycles↗
PubMed2001

Heart preservation with celsior solution improved by the addition of nitroglycerine.

BACKGROUND: Preservation of rat hearts was extended to 16 hr when nitroglycerine (NTG) was added to colloid-free University of Wisconsin solution (MUW). This study examined the effectiveness of Celsior solution (CEL) and whether adding NTG to CEL would improve and extend cardiac preservation. METHODS: Two studies were conducted: (a) 9-hr preservation with either CEL or MUW, (b) 16-hr preservation with CEL, CEL+NTG, or MUW+NTG. Rat heart isografts were flushed and stored at 0 degrees C before heterotopic transplantation with an indwelling externalized intraventricular balloon-tipped catheter. One and 7 days after transplantation, quantitative functional studies were performed. RESULTS: After 9-hr preservation, all (6/6) grafts preserved with MUW beat for 7 days, whereas only 1/6 hearts preserved with CEL continued to beat. After 16-hr preservation, 6/10 CEL+NTG hearts beat for 7 days compared with 7/8 MUW+NTG hearts; none of the hearts preserved with CEL survived. Function was similar in CEL+NTG and MUW+NTG groups on day 1 (left ventricular developed pressure (LVDP): CEL+NTG=64+/-16, MUW+NTG=104+/-16 mmHg; maximum dP/dt: CEL+ NTG=2024+/-551, MUW+NTG=3582+/-513 mmHg/sec) and day 7: (LVDP: CEL+NTG=126+/-25, MUW+NTG=177+/-24 mmHg; maximum dP/dt: CEL+NTG=3835+/-848, MUW+ NTG=5639+/-670 mmHg/sec). Function in both groups improved significantly (P<0.05) on day 7 compared with day 1. CONCLUSIONS: Celsior was not as effective as MUW for rat heart preservation. The addition of NTG to both CEL and MUW provided similar effective preservation for 16 hr. NTG should be added routinely to both solutions.

Adenosine↗
PubMed2001

Influence of buprenorphine analgesia on post-operative recovery in two strains of rats.

The objective of this study was to establish an effective post-operative analgesic regimen for Sprague-Dawley (SD) and Dark Agouti (DA) rats. Buprenorphine (0.01 or 0.05 mg/kg), a partial mu opioid agonist, was administered subcutaneously immediately on completion of a standardized surgical procedure, involving anaesthesia, laparotomy and visceral manipulation. Two of the four treatment groups and the saline control group received a second injection 9 h later. Behavioural observations by three independent observers provided no information in assessing pain in this model. All rats lost weight, consumed less food and water after surgery. On the first day, both SD and DA rats receiving buprenorphine lost less weight than untreated control groups. Using weight loss as an efficacy criterion, low-dose buprenorphine, given once or twice, provided effective analgesia in SD rats. A higher single dose provided no additional benefit and a second dose was detrimental, reducing body weight and food intake. In DA rats, the high dose, given twice, appeared to be more effective than the lower dose. All DA cage cohorts consumed < 10% pre-operative food despite buprenorphine treatment, suggesting a higher dosage may be necessary. However, all SD and 80% DA rats who received no buprenorphine gained body weight on the second day, whereas most of the buprenorphine-treated rats continued to lose weight for another 2 days, despite increased food consumption by both strains. Buprenorphine may adversely affect intestinal function over a number of days due to its enterohepatic circulation; this effect may be more severe in DA rats. Adverse metabolic effects of buprenorphine and other opioids may preclude their use in the future if it can be shown that non-steroidal anti-inflammatory drugs (NSAIDs) provide equally effective analgesia.

Age Factors↗
PubMed2000

Liver preservation: a comparison of celsior to colloid-free University of Wisconsin solution.

INTRODUCTION: Celsior (CEL) was formulated specifically for heart preservation. Recently some preliminary reports have suggested that CEL is also effective for liver preservation. In this study liver preservation with CEL was compared to colloid-free University of Wisconsin solution (MUW). METHODS: Arterialized rat liver isografts were flushed and stored for 24 hr at 0 degrees C in CEL or MUW before orthotopic transplantation. Plasma albumin, bilirubin, glucose, aspartate aminotransferase, and alkaline phosphatase were measured 1, 2, 3, 7, 14, 21, and 28 days after surgery. RESULTS: All recipients of MUW-preserved livers survived, none of the recipients of CEL-preserved grafts lived beyond 3 days. On day 1, AST was raised in all rats but rats receiving CEL-preserved liver grafts were also markedly hypoglycemic, hypoalbuminemic and had elevated alkaline phosphatase. CONCLUSION: Celsior is not an effective solution for long-term liver preservation in its present composition.

Adenosine↗
PubMed1999

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

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, and this has been confirmed in studies in which 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. RESULTS: The postglomerular filtered albumin is returned to the blood supply by a high-capacity pathway that transports this albumin at a rate of 1830 +/- 292 micrograms/min.rat kidney (N = 14, mean +/- SEM). This pathway has been identified under physiological conditions in vivo and in the isolated perfused kidney. The pathway is specific for albumin, as it does not occur for horseradish peroxidase. The pathway is inhibited in a nonfiltering kidney. The pathway is also inhibited by ammonium chloride (an agent that inhibits tubular protein uptake but does not alter glomerular size selectivity) and by albumin peptides (which compete for the tubular albumin receptor). 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↗
PubMed1998

Studies in a modified auxiliary abdominal rat heart transplantation model: preservation with colloid-free University of Wisconsin solution.

BACKGROUND: Current clinical heart preservation is still limited to 6 hours. A suitable heart transplantation model to rapidly screen the effectiveness of new solutions is essential. This study examines a new screening test-a modification of the conventional abdominal rat heart transplantation model that overcomes its serious limitation of lack of quantitative evaluation of function. METHODS: Rat hearts, with an externalized intraventricular balloon-tipped catheter, were transplanted immediately (controls) or flushed and stored in colloid-free University of Wisconsin solution in ice for 6, 9, or 12 hours before transplantation. One and 7 days later this catheter was connected to a pressure transducer and a calibrated syringe. Heart rate, maximum developed pressure, and maximum rate of left ventricular pressure rise were determined. Grafts were prepared for histologic study on day 7. RESULTS: All preserved hearts commenced beating within 2 minutes (controls beat within 20 seconds). On day 1 the heart rate and chamber stiffness (deltaP/deltat) were similar in all groups. The 9- and 12-hour-preserved hearts had significantly (p < 0.05) diminished developed pressure and contractility. On day 7 contractility and developed pressure improved in 9- and 12-hour-preserved grafts. There was extensive muscular atrophy and necrosis, with extensive cellular infiltrate in the 9- and 12-hour-preserved grafts; other grafts showed no damage. CONCLUSION: This quantitative model provides an ischemia-related gradation of function and greater discrimination than conventional methods. It has refuted previous studies suggesting effective preservation for 20 hours and demonstrated that functional testing is essential in evaluating preservation regimens.

Adenosine↗
PubMed1998

Modified technique of abdominal heart transplantation in the rat.

BACKGROUND: A rapid, reproducible screening model is essential for evaluation of novel preservation regimens. This study describes a modification of the abdominal rat heart transplantation model reducing anastomosis time and allowing quantitative assessment for 7 days. METHODS: Hearts, obtained from inbred Dark Agouti rats, were arrested and stored in cold colloid-free University of Wisconsin solution until transplantation. The Dark Agouti recipient underwent a left nephrectomy. The donor left common carotid artery was anastomosed to the recipient left renal artery with a "sleeve" anastomosis. The "cuffed" donor left pulmonary artery was inserted into the left renal vein. Study 1 examined continuing viability by daily palpation and morphologic study by examination of hematoxylin and eosin-stained sections on days 4 or 90. Study 2 examined quantitative assessment of cardiac function in the anesthetized recipient. The model was further modified by introducing an externalized, fluid-filled, balloon-tipped catheter into the left ventricle. RESULTS: The new technique allowed vascular anastomoses to be completed in 5 to 12 minutes, minimizing rewarming of the graft. Most (25 of 28) grafts beat for 90 days, and 80% of these showed normal structure. There was evidence of myocyte damage or arteriosclerosis in 5 of 25 at 90 days and in 4 of 17 at 4 days. Cardiac function parameters were similar in consecutive runs and did not change between days 1 and 7. CONCLUSION: This abdominal rat heart transplant model is quick and easy to perform, minimizes warm ischemia, and is suitable for both short- and long-term studies. Quantitative parameters, assessed by use of an in situ intraventricular balloon-tipped catheter, are reproducible and maintained for 7 days.

Animals↗
PubMed1995

The effect of ureteric stenting on the function and morphology of long-term rat renal allografts.

In the development of a reliable model for chronic rejection in rat renal allografts, the effect of modifying the ureteric anastomosis was tested. Rats, tolerized by pretreatment with two donor blood transfusions under Cyclosporin A, received renal allografts with either sewn or stented ureter. Control groups received isografts or underwent uninephrectomy with insertion of ureteric stents. For the first 6 days after transplantation, serum creatinine and urea values were lower in allograft recipients with stented ureters than in the group with sewn ureters. The method of ureteric anastomosis did not affect the long-term incidence of abnormal function. Allograft morphology was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis as well as vascular changes. Glomerulosclerosis was absent in controls and increased with time in the allografts. Two hundred days after transplantation all allograft recipients with sewn ureters exhibited some glomerulosclerosis, in half of these kidneys more than 25% of glomeruli were affected. Only 33% recipients of allografts with stented ureters exhibited some glomerulosclerosis and less than 20% of glomeruli were affected. The stented ureteric anastomosis provides a reliable method, a reduction of the technical failure rate, a reduction of the incidence of hydronephrosis, allows more accurate assessment of early renal function and may be of importance in reducing the occurrence and prevalence of glomerulosclerosis in the long-term allografts.

Animals↗
PubMed1995

A reproducible model of chronic rejection in rat renal allografts.

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 66% after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.

Animals↗
PubMed1993

Development of chronic injury and nature of interstitial infiltrate in a model of chronic renal allograft rejection.

A model of chronic renal rejection in the Dark-Agouti to Albino-Surgery rat combination is described. In a number of cases, the original allograft was replaced by a second Dark-Agouti allograft. Seventy-five percent of rats experienced early episodes of rejection that subsided spontaneously. Second allografts had better initial renal function. Variable degrees of tubular atrophy, interstitial fibrosis, vascular damage, glomerulosclerosis, deposition of humoral mediators, and mononuclear leukocyte infiltrate were observed in all long-term allografts. Chronic damage increased with time, and was less severe in second allografts. At 5 days, total interstitial infiltrate was similar to that seen in unmodified rejection, but there was a significant increase in CD4+ cells and a decrease in ED2 and IL-2R expression. Subsequently, the total interstitial infiltrate decreased with time, although it remained significantly higher than in isografts and residual kidneys from uninephrectomized rats. No significant decrease over time was seen in numbers of CD4+ and CD45RC+ cells. The latter had a marked focal distribution after 100 days. Total leukocyte infiltrate was similar in original and second allografts, but there were changes in the proportions of leukocyte subpopulations, including significantly lower numbers of CD45RC+ cells in the latter. The persistence of CD45RC+ cells throughout the course of chronic rejection and their lower numbers in the second allografts favors a role for these cells in the development of chronic injury. The model of chronic renal allograft rejection characterized in this study will be valuable in further studies of the mechanisms of injury in this pathology.

Animals↗