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Biomedical subjects

J F McAnulty

Publications and source records attributed to J F McAnulty.

At least 19 recordsLinked to original sources
PubMed1999

The effect of quinacrine on oxidative stress in kidney tissue stored at low temperature after warm ischemic injury.

Rabbit kidney cortex tissue slices were made ischemic (37 degrees C) for 60 min and then either reperfused in warm (37 degrees C) oxygenated physiologic buffer for 210 min or placed in UW Na gluconate solution (+/- quinacrine; 100 micromol/L) for 18 h followed by warm aerobic reperfusion. Slices were sampled at intervals and analyzed for malondialdehyde (MDA) content by HPLC. Control (nonischemic) slices had no change in MDA content over the duration of the experiment. Hypothermic storage of nonischemic slices did not result in any increase in MDA during reperfusion. Ischemic slices showed significant increases in MDA content during the first 1.5 h of reperfusion and remained elevated for the remainder of the experiment. Hypothermic storage of warm ischemic kidney slices resulted in a significant decrease in MDA content during the storage period. However, MDA content in these slices increased during warm reperfusion and was significantly higher than that in nonischemic controls. Quinacrine added during hypothermic storage of warm ischemic slices significantly decreased slice MDA content during warm reperfusion, an effect which was lost by increasing the storage solution calcium content. This study shows that aerobic hypothermic storage can aid in reducing oxidative stress in warm ischemic kidney tissue during reperfusion. This study suggests that the effects of quinacrine are at the level of the mitochondrion and not as an antioxidant compound.

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PubMed1999

Effect of various short-term storage methods on viability of cancellous bone fragments.

OBJECTIVE: To determine effects of various storage methods on ex vivo viability of cancellous bone fragments. SAMPLE POPULATION: Cancellous bone fragments obtained from 4 New Zealand White rabbits. PROCEDURE: Cancellous bone fragments were stored for 3 hours on ice in 1 of 5 preservation solutions or in 0.9% NaCl. Fragments were then reperfused (37 C) in oxygenated physiologic buffer solution for 1 hour. Cellular viability in fragments was assessed by ethidium monoazide labeling and fluorescence microscopy. RESULTS: Viability in fresh cancellous bone ranged from 85 to 100% (mean+/-SEM, 88+/-7%). Storage of fragments significantly reduced viability. Viability in bone fragments stored at 22 C in blood-soaked sponges or 0.9% NaCl solution was 63.8+/-3 and 65.2+/-7%, respectively. Use of cold 0.9% NaCI solution reduced viability to 53.6+/-3%. Viability was significantly better for fragments stored in cold phosphate-buffered sucrose (70.4+/-2%) and EuroCollins (71.4+/-3%) solutions. After warm reperfusion, viability was best for fragments stored in cold phosphate-buffered sucrose (70.2+/-4%), EuroCollins (72.6+/-3%), or UW lactobionate solutions (69.6+/-3%), compared with those stored in cold 0.9% NaCl (47.6+/-3%) or hypertonic citrate (53.0+/-3%) solutions or blood-soaked sponges (57.2+/-3%). CONCLUSIONS: Hypothermic storage in solutions designed to prevent temperature-dependent cell injury were best for maintaining cancellous bone fragment viability. CLINICAL RELEVANCE: Hypothermia may be advantageous for use in storing cancellous bone fragments during procedures that dictate a prolonged period between harvest and placement of graft fragments.

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PubMed1998

The effect of calcium on hypothermia-facilitated resuscitation of warm ischemic kidney tissue slices: a role for the mitochondrial permeability transition pore?

This study examined the effect of varying the calcium (Ca) content of a solution used for aerobic hypothermic storage of rabbit kidney cortex tissue slices previously injured by 1-h warm ischemia. Ischemic slices were stored in UW Na-gluconate solution for 18 h at 5 degrees C with 0.5, 1.5, or 1.75 mM Ca (+/- quinacrine; 100 microM) followed by warm (37 degrees C) aerobic incubation in physiologic buffer for 3.5 h to simulate reperfusion. There was no effect of solution Ca concentration on tissue ATP (adenosine 5'-triphosphate) and nonesterified fatty acid (NEFA) content during reperfusion. However, recovery of slice ATP and NEFA content to control levels was seen with addition of quinacrine to hypothermic storage medium containing either 1.5 or 1.75 mM Ca but not with 0.5 mM Ca storage medium. Treatment of tissue slices with cyclosporine A (20 microM), an inhibitor of the mitochondrial Ca-induced permeability transition pore, abolished the resuscitative benefits of hypothermic preservation with quinacrine + 1.5 mM Ca. These results suggest that quinacrine exerts its effects on warm ischemic tissue during hypothermic storage via the mitochondrial permeability transition pore. An effect utilizing a pore-open state is probable but it remains unclear if quinacrine acts on the pore directly or gains access to the matrix space through the pore and exerts its effects via an unknown mechanism. These results indicate that resuscitative hypothermic storage methods may be able to use manipulation of the permeability transition pore as a valuable adjunct to pharmacologic treatments administered during hypothermia.

Adenosine Triphosphate↗
PubMed1997

The efficacy of antioxidants administered during low temperature storage of warm ischemic kidney tissue slices.

Accumulation of products of lipid peroxidation (malondialdehyde, conjugated dienes, lipid peroxides, and Schiff bases) was evaluated in rabbit kidney cortex slices made ischemic for 60 min followed by 18 h storage at 5 degrees C in UW Na gluconate solution and 210 min normothermic reoxygenated incubation. In addition, the effect of adding Trolox (1 mM), deferoxamine (1 mM), and ascorbate (1 mM) as supplemental antioxidants to the UW gluconate solution was evaluated. Lipid peroxidation was slightly increased after hypothermic storage compared to slices subjected to ischemia alone but was not significantly different than ischemic slices during subsequent incubation at normothermia. The addition of either deferoxamine or Trolox to the storage solution substantially reduced lipid peroxidation both during hypothermic storage and subsequent to normothermic incubation. Ascorbate had a mild prooxidant effect as a sole additive to the UW gluconate solution but was clearly prooxidant when combined with either deferoxamine or Trolox. These results suggest that supplemental antioxidants added to the UW gluconate solution under conditions analogous to machine perfusion preservation have a potential role in reducing oxidative stress in kidney tissues harvested after warm ischemia and that hypothermia may be a valuable adjunct to resuscitative therapeutic regimens developed for salvage of ischemic kidneys for transplantation.

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PubMed1996

Nephron sparing by partial median nephrectomy for treatment of renal hemangioma in a dog.

A 6-year-old neutered male Golden Retriever was admitted for evaluation of intermittent hematuria of 2 months' duration. A 3-cm heterogeneous mass causing distortion of the caudomedial aspect of the left kidney was detected via ultrasonography. Histologic examination of a renal tissue sample obtained by ultrasound-guided biopsy revealed a telangiectatic vascular plexus of unknown origin. Low glomerular filtration rate was identified by a modified exogenous creatinine clearance test. Excretory urography revealed a filling defect in the medial aspect of the caudal pole of the kidney, near the hilus. Because total renal function was low, a decision was made to perform nephron-sparing surgery involving resection of centrally located renal parenchymal and pelvic tissue by en bloc resection in the median plane, instead of radical nephrectomy. After surgery, the hematuria resolved and further decrease in renal function was not evident. Nephron-sparing surgery is a viable option for dogs with compromised renal function when there is concern that radical nephrectomy may precipitate uremia.

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PubMed1996

The effect of simple hypothermic preservation with Trolox and ascorbate on lipid peroxidation in dog kidneys.

Dog kidneys were preserved by simple hypothermic storage in UW-lactobionate organ preservation solution for 48 h and analyzed for evidence of lipid peroxidation. The antioxidant function of the UW solution was evident in stored kidney tissues which had significant reductions in conjugated dienes, lipid peroxides, and Schiff base content compared to fresh controls without vascular flushing. Aerobic incubation of kidney cortex homogenates at 37 degrees C for 60 min resulted in increases in conjugated dienes, lipid peroxides, and Schiff bases in UW-stored kidneys. Schiff base production was markedly higher in UW-stored kidneys during warm incubation than in controls. Addition of Trolox (200 microM) to UW solution resulted in significant reductions in Schiff base production during warm aerobic incubation after preservation. In contrast, adding ascorbate (1 mM) to UW solution potentiated oxidative stress during aerobic incubation, with significant increases in conjugated dienes, lipid peroxides, and Schiff bases which were only partially reversed by further addition of Trolox. Increased oxidative stress was correlated with decreased respiratory function (decreased uncoupled respiration rates and sensitivity to oligomycin inhibition) in aerobically incubated homogenates. This study showed that although the UW solution does have an antioxidant function during hypothermic preservation there remains an increased oxidative stress during warm reoxygenation even in optimally harvested kidneys. The antioxidant effect of the UW solution after preservation can be significantly enhanced using the water-soluble vitamin E analogue Trolox. Antioxidant supplementation of UW solution may be advantageous in preserving kidneys with increased oxidative stresses obtained from suboptimal donors in clinical practice.

Adenosine↗
PubMed1996

The effects of administering quinacrine during ultraprofound hypothermia on warm ischemic kidney cortex tissue.

Recent advances have led to increased use of ultraprofound hypothermia for cardiopulmonary bypass, organ preservation and trauma patients and have introduced the possibility of targeted pharmacologic intervention during the hypothermic period. In this study, rabbit renal cortex slices were used to examine the effect of administering quinacrine (100 microM) during hypothermia induced after a warm ischemic injury (60 min at 37 degrees C) on recovery of biochemical function during 3.5 hr of simulated warm reperfusion. In ischemic tissue slices, ATP content was reduced to near zero and only recovered about 50% by the end of reperfusion. Hypothermic storage of ischemic slices for 18 hr restored slice ATP content to about 80% of control levels but was followed by a decline during reperfusion to levels similar to ischemic slices. Administering quinacrine (100 microM) during 18 hr of hypothermic storage of ischemic slices resulted in a significant and sustained increase in slice ATP content during warm reperfusion. Slices stored at hypothermia only 3 hr with quinacrine had reduced swelling during reperfusion even though total ATP content was unaffected. Administering quinacrine (100 microM) only during reperfusion after ischemia or hypothermia did not affect tissue ATP content. This study showed that drug administration during hypothermic storage has potential therapeutic benefits for resuscitating tissues after warm ischemia and is more effective than the same drug given only during reperfusion. Tissue pretreatment was not required to obtain improved function in this study which suggests that future adaptations of these principles may have practical applications for specific clinical conditions where ischemic and reperfusion injury are significant factors.

Adenosine Triphosphate↗
PubMed1989

Repair of pectus excavatum by percutaneous suturing and temporary external coaptation in a kitten.

Severe pectus excavatum sternal deformity in a 3-month-old kitten was repaired by use of percutaneous circumcostal and circumsternal sutures to coapt the sternal deformity to an external splint made from thermoplastic material. One year after treatment, the kitten remained free of clinical signs of the disease or complications from the repair. The technique represents a conservative method of repair of pectus excavatum deformities in immature animals.

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PubMed1989

Successful five-day perfusion preservation of the canine kidney.

Over 20 years ago, successful 3-day-perfusion preservation of canine kidneys was obtained. Since then, consistent 5-day preservation has not been reported. In this study, we investigated how the perfusate calcium concentration affected both mitochondrial function and posttransplant viability in dog kidneys preserved for 5 days. Dog kidneys were preserved by machine perfusion (5 degrees C) using a hydroxyethyl starch-gluconate solution that contained either 0.0, 0.5, 1.5, or 5.0 mM calcium. Mitochondria isolated from preserved kidneys has a loss of respiratory control when either 0.0, 1.5, or 5.0 mM calcium were present. However, the use of a perfusate with 0.5 mM calcium preserved the mitochondrial function at levels equivalent to controls for 5 days. Transplantation of kidneys preserved for 5 days with 0.0 or 1.5 mM calcium yielded poor survival (0% and 17%, respectively). The use of a 0.5-mM calcium perfusate increased posttransplant survival to 63% (5 of 8 transplanted). Donor pretreatment of kidneys with chlorpromazine (2.5 mg/kg i.v.) did not improve the function of mitochondria isolated from preserved kidneys but did increase survival in the 1.5-mM calcium group to 67% (4 of 6 transplanted) and in the 0.5 mM calcium group to 100% (7 of 7 transplanted). This is the first report to document consistently successful 5-day preservation of canine kidneys and clearly shows the importance of the perfusate calcium concentration in long-term kidney preservation. The specific mechanism by which calcium or chlorpromazine exert their effect is not known, but it is apparent that excessively high or low concentrations of calcium are damaging to the preserved organ, and an optimal calcium concentration combined with metabolic inhibition of calcium-dependent pathways can significantly improve the function of organs preserved for extended time periods.

Animals↗
PubMed1989

Preservation of dog liver, kidney, and pancreas using the Belzer-UW solution with a high-sodium and low-potassium content.

The UW solution developed for cold storage of the liver, pancreas, and kidney was used in a modified form in this study and tested in the orthotopic transplantation of dog livers, kidneys, and pancreases preserved for 48 hr. The modification was the alteration of the concentrations of potassium and sodium. The original UW solution contained 120 mM K+ and 30 mM Na+. In this study the Na+ was 140 mM and the K+ only 9 mM, all other agents were identical to the original UW solution. Six of 11 dogs survived with livers preserved for 48 hr. The five deaths were due to technical complications and unrelated to preservation failure. Postoperative AST and partial thromboplastin time (PTT) values were lower (statistically significant on days 1, 3, and 4) in livers preserved in the high Na+ UW solution than as previously shown in the high-k+ UW solution. Other measures of liver function (bilirubin and fibrinogen) were similar between the high-Na+ and high-K+ groups. Six dogs survived with kidneys preserved for 48 hr in the high-Na+ UW solution. The results were comparable to those obtained with the high K+ solution. Four of six dogs survived for up to 28 days with pancreases preserved for 48 hr. The two deaths were due to technical complications unrelated to preservation failure. Three of the four dogs had normal blood glucose values for one month, and intravenous glucose tolerances test on day 7 and 28 were identical to those obtained in pancreases preserved with the high-K+ UW solution. The high-Na+ version of the UW solution appears equally or slightly more effective for 48-hr organ preservation than the original high-K+ UW solution. The use of a high-Na+ UW solution reduces the problems of hyperkalemic cardiac arrest in in situ flushing of the donor for multiple organ harvesting and in transplantation of the liver. Thus, with this solution livers do not need to be flushed with a low K+-containing solution prior to transplantation.

Animals↗
PubMed1989

Prevention of postoperative intestinal intussusception by prophylactic morphine administration in dogs used for organ transplantation research.

In this report 149 kidney transplants were performed as part of experiments on renal perfusion preservation, and the effect of morphine treatment on the incidence of postoperative intussusception was concurrently evaluated. Intestinal intussusception developed in 17% (14 of 83 dogs transplanted) of untreated dogs after transplantation. Intraoperative intravenous administration of morphine (0.5 mg/kg) resulted in a reduction in the rate of intussusception to 3.3% (2 of 61 dogs transplanted). Postoperative administration of morphine was ineffective in reducing the incidence of intussusception. The results indicate that intraoperative administration of morphine is effective in preventing postoperative intussusception in dogs used for experimental transplantation and may reduce animal losses and research costs in experimental surgical laboratories.

Animals↗
PubMed1988

Comparison of the effects of adenine-ribose with adenosine for maintenance of ATP concentrations in 5-day hypothermically perfused dog kidneys.

The quality of preservation of kidneys is dependent upon a number of factors, one of which may be the concentration of adenine nucleotides in the tissue during long-term perfusion preservation. In this study we have investigated how adenine (5 mM) and ribose (5 mM) in combination affect the concentration of adenine nucleotides in dog kidney cortical tissue after 5 days of continuous hypothermic perfusion preservation. These results were compared to kidneys perfused with adenosine and without any added purine precursors of adenine nucleotide synthesis. Additionally, we investigated how these conditions affected renal tissue slice function after 5 days of preservation and how adenine plus ribose affected renal function after autotransplantation in the dog. Adenosine is nearly completely degraded during 5 days of perfusion but there was little loss of adenine (10%). The adenosine triphosphate concentration in kidney cortical tissue was higher in adenine/ribose-perfused kidneys (1.41 +/- 0.19 mumol/g) than in adenosine-perfused kidneys (0.71 +/- 0.1 mumol/g) after 5 days of preservation. Tissue slices prepared from kidneys preserved in the presence of adenine plus ribose were metabolically more functional (slice volume control and electrolyte pump activity) than slices from adenosine-perfused kidneys. Adenine plus ribose had no detrimental effects on kidneys preserved for 3 days as tested in the autotransplant model but did not yield successful 5-day preservation. Because of some potentially detrimental factors in using adenosine as an adenine nucleotide synthesis precursor, we have now switched to the combination of adenine and ribose for perfusion preservation of kidneys both in the laboratory and in the clinic.

Adenine↗
PubMed1988

Successful 72-hour cold storage of dog kidneys with UW solution.

Effects of three cold-storage solutions on kidney function in dogs were examined with the isolated perfused (IPK) kidney model and the autotransplant model. EuroCollins' (EC) solution, phosphate-buffered sucrose solution, and a new solution developed at the University of Wisconsin (UW) were studied. Kidneys were cold-stored for 48 hr or 72 hr. With the IPK model, cold storage for 48 hr or 72 hr in each of the three solutions caused creatinine clearance to decrease by 80%-90%. More protein was excreted by kidneys stored for 48 hr in PBS solution than by kidneys stored in EC or UW solution; protein excretion after 72 hr of storage was similar for kidneys stored in EC or UW solution. Sodium reabsorption decreased after 48 hr or 72 hr of storage, but was higher in kidneys stored in UW solution (83% and 56%, respectively) than in EC solution (52% and 22%, respectively). With the autotransplant model, 40% of the kidneys were viable after 48-hr storage in PBS solution, but 80% viable when stored in EC solution and 100% were viable when stored in UW solution. All kidneys were viable when stored for 72 hr in UW solution; none were viable when stored for 72 hr in EC solution. These results suggest that UW solution effectively preserves kidneys for 72 hr. We previously reported successful 72-hr pancreas preservation. Recently UW solution was able to preserve canine livers for 30 hr. Thus, this single solution appears to be effective for preserving all intraabdominal organs and may simplify cold storage of organs for transplantation.

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