Allopurinol
External pacing does not potentiate allopurinol protection of the heart from liver ischemia-reperfusion -- a study in an isolated perfused liver-heart rat model.

Weinbroum AA, Dembo G, Hochhauser E, Rudick V, Vidne BA.

The Post-Anesthesia Care Unit, Tel Aviv Sourasky Medical Center, Israel. draviw tasmc.health.gov.il

BACKGROUND: We recently demonstrated that isolated paced hearts perfused with modified Krebs-Henseleit solution containing high dose allopurinol (1 mM) were protected from liver ischemia-reperfusion (IR)-induced reperfusion injury. The objective was to study the effects of low dose allopurinol together with external pacing in attenuating myocardial reperfusion dysfunction following liver IR in the same double organ model. MATERIAL AND METHODS: Isolated rat livers were perfused with modified Krebs-Henseleit solution (groups 1 and 2, n=8/all groups) or underwent global ischemia (groups 3-6) for 120 minutes. Following a 15-minute conjoint reperfusion of earlier separately isolated liver+heart, the hearts were recirculated alone for additional 45 minutes. The organs of three-group donating animals (groups 2, 4, and 6) were treated with allopurinol 18 hours and 1 hour before the experiment (50 mg x kg(-1) intraperitoneally) and it was also added during perfusion (0.1 mM in Krebs). The hearts in groups 5 and 6 were paced (300 x min(-1)). RESULTS: The hearts perfused with IR Krebs (group 3) experienced decreased myocardial left ventricular-developed pressure (LVP), heart rate (in the unpaced hearts) and later coronary flow (by 68%, 21% and 32%, respectively); LVP and coronary flow also decreased correspondingly in the IR-paced hearts (group 4). Xanthine oxidase (XO) was high in groups 3 and 4 compared to group 1. IR allopurinol-treated hearts, both unpaced and paced (groups 5 and 6) had normal, similar myocardial performance, while their circulating XO was as low as in group 2 (allopurinol-treated controls). CONCLUSIONS: External pacing in the double organ, isolated-perfused liver-heart did not ameliorate XO-mediated dysfunction compared to low dose allopurinol. The unexpected delayed coronary insufficiency in myocardial reperfusion injury is discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11687722&dopt=Abstract allopurinol Zyloprim



Allopurinol
Spinal cord metabolism during thoracic aortic cross-clamping in pigs with special reference to the effect of allopurinol.

Backstrom T, Saether OD, Norgren L, Aadahl P, Myhre HO, Ungerstedt U.

Department of Surgery, University Hospital of Trondheim, Trondheim, Norway.

OBJECTIVE: investigate the metabolic response of the spinal cord and the effect of allopurinol following cross clamping of the descending thoracic aorta in a porcine model. DESIGN: experimental animal study. MATERIALS: twelve domestic swine. Six pigs were pre-treated with allopurinol, while six pigs served as controls. METHODS: measurement of extracellular concentrations of glucose, pyruvate, lactate, glycerol and glutamate using microdialysis in the lumbar spinal cord. Measurement of lumbar spinal blood flow using laser Doppler technique. RESULTS: for all animals there was a significant decrease in concentrations of glucose and pyruvate together with a significant increase in the lactate-pyruvate ratio during aortic cross clamping. There was also a significant increase in glycerol concentrations 60 min after cross clamping, and a significant decrease in glutamate concentrations after 50 min. No differences in concentrations of glucose, pyruvate, lactate and glutamate or the glutamate-pyruvate ratio were observed between animals used as controls and those treated with allopurinol. The laser Doppler flux decreased to 40% of pre cross-clamp level, returning to normal values at declamping. CONCLUSION: the changes in energy-related metabolites reflect a considerable ischaemia in the spinal cord tissue but there was no convincing effect of allopurinol on the lumbar spinal cord metabolism during thoracic aortic cross clamping in this model. Copyright 2001 Harcourt Publishers Limited.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11735178&dopt=Abstract allopurinol Zyloprim



Allopurinol
In vivo assessment of free radical activity during shock wave lithotripsy using a microdialysis system: the renoprotective action of allopurinol.

Munver R, Delvecchio FC, Kuo RL, Brown SA, Zhong P, Preminger GM.

Comprehensive Kidney Stone Center, Division of Urology, Department of Surgery, Duke University Medical Center, Room 305 Baker House, Durham, NC 27710, USA.

PURPOSE: Shock wave lithotripsy is believed to cause renal damage directly through cellular injury from high energy shock waves and indirectly through vascular injury and resultant ischemia, which gives rise to oxygen free radical compounds. The transient and volatile nature of free radicals and derived products makes their detection difficult. Moreover, certain medications may provide a protective effect against shock wave lithotripsy induced renal parenchymal injury. We introduced an innovative microdialysis system for in vivo sampling of interstitial fluids that can be analyzed for free radical mediated lipid peroxidation products after shock wave lithotripsy treatment in the swine model. In addition, this system was used to test the antioxidant or renoprotective action of allopurinol. MATERIALS AND METHODS: Ten juvenile swine were assigned to a nonmedicated control group that underwent shock wave lithotripsy or to a group that was premedicated with allopurinol before shock wave lithotripsy. Each group of animals underwent shock wave lithotripsy to the lower pole of the right kidney and received a total of 10,000 shock waves. Dialysate fluid was collected at 1,000-shock wave increments via probes surgically implanted into the lower pole of the right and left kidneys before lithotripsy. Samples were immediately preserved in liquid nitrogen and subsequently analyzed for the presence and concentration of conjugated diene levels, a measure of lipid peroxidation. Five additional juvenile swine were assigned to a sham treated group that did not undergo shock wave lithotripsy. Dialysate fluid was collected from the lower pole of the right and left kidneys to establish baseline or pre-lithotripsy levels of conjugated dienes. RESULTS: After shock wave lithotripsy conjugated diene levels increased almost 100-fold over that in the right kidneys of the nonmedicated control group. The difference was statistically significant compared to levels in the contralateral untreated kidneys (p <0.01). Right kidneys in the group premedicated with allopurinol did not demonstrate an increase in conjugated diene levels during shock wave lithotripsy. CONCLUSIONS: The results of this study confirm shock wave lithotripsy induced free radical activity as well the antioxidant and protective nature of allopurinol. The newly described microdialysis system enables real-time sampling of interstitial fluids during shock wave lithotripsy. It represents a unique method for assessing free radical formation and evaluating the protective effects of additional antioxidant medications.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11743351&dopt=Abstract allopurinol Zyloprim



Allopurinol
Long-term efficacy of hyperuricaemia treatment in renal transplant patients.

Perez-Ruiz F, Gomez-Ullate P, Amenabar JJ, Zarraga S, Calabozo M, Herrero-Beites AM, Nolla JM.

Hospital de Cruces, Rheumatology Section and Nephrology Division, Baracaldo, Pais Vasco, Spain. fperez hcru.osakidetza.net

BACKGROUND: Although hyperuricaemia and gout are frequently found in renal transplant recipients, little has been published on the efficacy of urate-lowering therapy (ULT) in this patient population. We therefore examine the effects of allopurinol and benziodarone therapy in a cohort of renal transplant patients. METHODS: We reviewed files from a cohort of 1328 patients that received renal transplantation. The selection criteria included: functioning allograft, hyperuricaemia for >12 months or gout, ULT lasting at least 1 year and at least two control measurements after the onset of ULT. Patients on azathioprine were treated with benziodarone to avoid azathioprine-allopurinol interactions. RESULTS: Two-hundred and seventy-nine patients fulfilled the criteria for review. They were treated with 289 courses of ULT: 100 with allopurinol (mean dose: 376 mg/day/dl/min of creatinine clearance) and 189 with benziodarone (mean dose: 73 mg/day). The mean follow-up was 38 months. Both drugs were effective for the control of hyperuricaemia, but benziodarone caused greater reductions in serum uric acid levels, especially when used at mean doses of >75 mg/day. Severe side effects were uncommon, in both the allopurinol and benziodarone groups. CONCLUSIONS: Both allopurinol and benziodarone were effective for the control of hyperuricaemia in renal transplantation. Benziodarone at doses >75 mg/day was more effective than allopurinol in reducing serum uric acid levels and also reduced the risk of azathioprine-allopurinol interactions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12584286&dopt=Abstract allopurinol Zyloprim



Allopurinol
Effect of allopurinol on venous endothelial dysfunction after resuscitated hemorrhagic shock.

Flynn WJ Jr, Pilati D, Hoover EL.

Department of Surgery, Erie County Medical Center State University of New York at Buffalo, 14215, USA.

BACKGROUND: Blood flow deficits contribute to organ dysfunction in patients resuscitated from hemorrhage. AIM: To determine the contribution of xanthine oxidase mediated reperfusion injury to venous endothelial function after resuscitated hemorrhagic shock. METHODS: Rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 60 min. Treatment animals received a 50mg/kg bolus and a 25mg/kg/h infusion of the xanthine oxidase inhibitor allopurinol (allo) after shock but before resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group (Std) and a non-hemorrhage group (No HS) served as control. Endothelial function was quantified at baseline, 30 min (R30) and 90 min (R90) post resuscitation as a change in mesenteric vessel diameter after topical application of acetylcholine (Ach), an endothelial dependent vasodilator. RESULTS: Resuscitation restored cardiac output and blood pressure in both hemorrhage groups. First order venules (V1) demonstrated a 39% and a 36% reduction in ability to dilate to Ach at R30 and R90 after resuscitation with shed blood and Ringer's lactate (Std). Second order venules (V2) demonstrated a 20% and a 25% reduction in ability to dilate to Ach at R30 and R90 after resuscitation with shed blood and Ringer's lactate (Std). Addition of allopurinol to standard resuscitation attenuated this response resulting in the preservation of endothelial dependent venous vasodilation. CONCLUSIONS: These data suggest that xanthine oxidase mediated ischemia-reperfusion injury contributes to venous endothelial dysfunction in the mesenteric microcirculation after resuscitated hemorrhagic shock. Endothelial function can be preserved by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation lending support for its inclusion as an adjunct to resuscitation after hemorrhagic shock.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11817331&dopt=Abstract allopurinol Zyloprim



Allopurinol
Protective effect of allopurinol in the renal ischemia--reperfusion in uninephrectomized rats.

Rhoden E, Teloken C, Lucas M, Rhoden C, Mauri M, Zettler C, Bello-Klein A, Barros E.

Department of Urology, Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre (FFFCMPA), Rua Jaragua, 370/302, Bairro Bela Vista, RS 90450-140, Porto Alegre, Brazil. ernanirh terra.com.br

The effect of allopurinol (an inhibitor of xanthine oxidase) on oxidative stress, renal dysfunction, and histologic alterations was evaluated during the renal ischemia--reperfusion in uninephrectomized rats. Renal malondialdehyde and serum creatinine levels significantly increased after renal ischemia--reperfusion. However, the pretreatment with allopurinol demonstrated a protector effect in these parameters. Renal ischemia--reperfusion provoked a significant renal damage in the operated group. Tubular atrophy and interstitial fibrosis were attenuated by allopurinol when given prior to the surgery. In our study, allopurinol had a strong tendency to exert a beneficial effect during renal ischemia--reperfusion in uninephrectomized rats.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11827725&dopt=Abstract allopurinol Zyloprim