oxypurinol and Ischemia

In complicated labor, neonatal outcome may depend not only on the extent of fetal asphyxia and acidosis but also on the effects on the fetal cardiovascular system of reactive oxygen species (ROS) generated during the ischemia-reperfusion (I/R) associated with repeated compressions of the umbilical cord. This study tested the hypothesis that maternal treatment with clinical doses of the antioxidant allopurinol in the setting of fetal asphyxia would reduce oxidative stress in the fetal cardiovascular system. The hypothesis was tested in chronically instrumented fetal sheep in late gestation by investigating the effects of maternal treatment with therapeutic doses of allopurinol or vehicle on the fetal cardiovascular system during and after episodes of I/R. The latter were produced by repeated, measured compressions of the umbilical cord. The data show that maternal treatment with allopurinol helped maintain umbilical blood flow and it reduced fetal cardiac oxidative stress after I/R of the type associated with clinically relevant acidemia and repetitive fetal heart rate decelerations. The data support the hypothesis tested and suggest that maternal treatment with allopurinol may offer plausible clinical intervention in the management of perinatal asphyxia in complicated labor.

Topics: Allopurinol; Animals; Blood Pressure; Cardiovascular System; Enzyme Inhibitors; Female; Fetus; Free Radical Scavengers; Ischemia; Oxidative Stress; Oxypurinol; Pregnancy; Reactive Oxygen Species; Reperfusion; Sheep, Domestic

We investigated the effect of a hydroxyl radical scavenger, 1,3-dimethyl-2-thiourea (dimethylthiourea), and two xanthine oxidase inhibitors, oxypurinol and allopurinol, on the threshold shift of the compound action potential (CAP) after transient ischemia of the cochlea. Transient ischemia of 30 min duration was induced in albino guinea pigs via a skull base approach. The animals were treated with perilymphatic perfusion of dimethylthiourea, oxypurinol or allopurinol from 10 min before the onset of ischemia to 4 h after the termination of ischemia. Dimethylthiourea ameliorated the CAP threshold shifts at 4 h after the onset of reperfusion in a dose-dependent manner. However, oxypurinol and allopurinol did not affect the post-ischemic cochlear dysfunction. These results imply that the hydroxyl radical plays an important role in generation of cochlear dysfunction induced by ischemia-reperfusion and that xanthine oxidase may not be the primary source of this radical.

Topics: Action Potentials; Allopurinol; Animals; Cochlea; Enzyme Inhibitors; Free Radical Scavengers; Guinea Pigs; Hydroxyl Radical; Ischemia; Oxypurinol; Reperfusion Injury; Thiourea; Xanthine Oxidase

The relative contribution of xanthine oxidase (XO) and leukocytes to tissue injury after short-term ischemia is unknown. In this study, we subjected three groups of rat spinotrapezius muscles to 30-min ischemia and 1-h reperfusion: 1) ischemia-reperfusion (I/R) + 0.9% saline, 2) I/R + superoxide dismutase, and 3) I/R + oxypurinol. A fourth group served as nonischemic control. We quantified the increase in resistance (%DeltaR) caused by leukocyte-capillary plugging concurrently with myocyte uptake of propidium iodide (PI) [expressed as no. of PI spots per total volume of perfused tissue (N(PI)/V)] and performed assays to quantify XO activity, thiobarbituric acid-reactive substances (TBARS), and myeloperoxidase (MPO). Groups 2 and 3 exhibited significant decreases in N(PI)/V relative to group 1. MPO levels and TBARS were similar among all groups, and mean %DeltaR was significantly reduced in groups 2 and 3 relative to group 1. However, elevated XO was observed in groups 1 and 2 relative to group 3 and nonischemic controls. These data are consistent with the hypothesis that XO, rather than toxic species produced by plugging or venule-adherent leukocytes, is responsible for postischemic damage in this model.

Topics: Animals; Capillaries; Cell Adhesion; Cell Movement; Female; Ischemia; Leukocytes; Lipid Peroxides; Muscle, Skeletal; Oxidants; Oxypurinol; Peroxidase; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sodium Chloride; Superoxide Dismutase; Time Factors; Vascular Resistance; Xanthine Oxidase

Little is known about the nature of biochemical disturbances during reperfusion after retinal ischemia. Previous studies have suggested that adenosine is responsible for regulation of retinal blood flow soon after ischemia has ended. Therefore, in this study we measured concentrations of adenosine and its metabolites in the rat retina/choroid after brief (10 min) or prolonged (60 min) periods of ischemia, and the functional consequences of inhibiting adenosine metabolism.. Ischemia was produced in anesthetized rats by ligation of the central retinal artery. The eyes were frozen in situ and purine nucleoside concentration was determined by high performance liquid chromatography. The functional effects of pre-ischemic inhibition of xanthine dehydrogenase/xanthine oxidase were assessed by measurement of the electroretinogram before, during, and up to 7 days following 60 min ischemia.. Changes in the concentrations of adenosine and its metabolites were significant early in the reperfusion period, and were greater in magnitude and occurred earlier in prolonged, compared to brief, ischemic periods. Concentrations of adenosine, inosine, and hypoxanthine remained elevated for 30 min following the end of 60 min ischemia, and xanthine concentration was significantly elevated until 60 min after the end of either 10 or 60 min of ischemia. The onset of its peak value after ischemia was delayed in comparison to that of adenosine. Ischemia-evoked increases in xanthine concentration were attenuated by inhibition of adenosine deaminase or xanthine oxidase/xanthine dehydrogenase. Pre-ischemic inhibition of xanthine oxidase/xanthine dehydrogenase by oxypurinol (40 or 80 mg/kg intraperitoneally [IP]) resulted in a significant improvement in recovery of the a and b waves of the electroretinogram in comparison to a saline-treated control group.. These results indicate that adenosine is a major component of the biochemical changes that occur after retinal ischemia. Long-lasting increases in xanthine concentration during reperfusion after ischemia could be a source of oxygen free radicals that may contribute to delayed injury of the retina, attempts to decrease xanthine concentration would ideally be initiated within one hour after the end of ischemia.

Topics: Adenosine; Animals; Choroid; Electroretinography; Enzyme Inhibitors; Ischemia; Osmolar Concentration; Oxypurinol; Pentostatin; Purines; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Retina; Retinal Diseases

The dual radiolabeled monoclonal antibody technique was used to 1) define the magnitude and kinetics of P-selectin expression in murine small intestine exposed to ischemia-reperfusion (I/R), and 2) determine the factor(s) responsible for initiating this response. Within 10 min after release of a 20-min arterial occlusion, intestinal P-selectin expression increased two- to threefold compared with control values. Peak (4-fold) expression of P-selectin was noted at 5 h after reperfusion, returning to the control value at 24 h. The early (10-30 min) I/R-induced upregulation of P-selectin appears to reflect mobilization of a performed pool of the adhesion molecule, whereas the later (5 h) rise appears to be transcription dependent. The early increase in P-selectin expression was not inhibited by pretreatment with either oxypurinol (inhibits xanthine oxidase), diphenhydramine (H1-receptor antagonist), or MK-571 (leukotriene C4/D4 antagonist), nor was it blunted in transgenic mice expressing three times the normal level of copper-zinc superoxide dismutase or in mast cell-deficient mice. However, significant inhibition was noted after treatment with either MK-886 (5-lipoxygenase inhibitor) or a nitric oxide (NO) donor (diethylenetriamine/NO). These findings indicate that the early I/R-induced increase in intestinal P-selectin expression is mediated by a 5-lipoxygenase-dependent NO-inhibitable mechanism.

Topics: Animals; Antibodies, Monoclonal; Diphenhydramine; Intestine, Small; Ischemia; Male; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Transgenic; Microcirculation; Oxypurinol; P-Selectin; Propionates; Quinolines; Reperfusion; Splanchnic Circulation; Superoxide Dismutase

Xanthine oxidase (XO) activity and hydroxyl radical (.OH) formation are widely proposed mediators of renal reperfusion injury, potentially altering the severity of, and recovery from, postischemic acute renal failure. The goal of this study was to ascertain whether combination XO inhibitor (oxypurinol) and .OH scavenger (Na benzoate) therapy, given at the time of renal ischemia, alters the extent of: (1) tubular necrosis and filtration failure; (2) DNA fragmentation/apoptosis (assessed in situ by terminal deoxynucleotidyl transferase reactivity); (3) early tubular regenerative responses (proliferating cell nuclear antigen expression; (3H)thymidine incorporation); and (4) the rate and/or degree of functional and morphologic repair. The effects of XO inhibition, .OH scavengers, and "catalytic" iron (FeSO4) on human proximal tubular cell proliferation in vitro were also assessed with a newly established cell line (HK-2). Male Sprague-Dawley rats were subjected to 35 min of bilateral renal arterial occlusion with or without oxypurinol/benzoate therapy. These agents did not alter the extent of tubular necrosis or filtration failure, proliferating cell nuclear antigen expression or thymidine incorporation, or the rate/extent of renal functional/morphologic repair. DNA fragmentation did not precede tubular necrosis, and it was unaffected by antioxidant therapy. By 5 days postischemia, both treatment groups demonstrated regenerating epithelial fronds that protruded into the lumina. These structures contained terminal deoxynucleotidyl transferase-reactive, but morphologically intact, cells, suggesting the presence of apoptosis. Oxypurinol and .OH scavengers (benzoate; dimethylthiourea) suppressed in vitro tubular cell proliferation; conversely, catalytic Fe had a growth-stimulatory effect. These results suggest that: (1) XO inhibition/.OH scavenger therapy has no discernible net effect on postischemic acute renal failure; (2) DNA fragmentation does not precede tubular necrosis, suggesting that it is not a primary mediator of ischemic cell death; and (3) antioxidants can be antiproliferative for human tubular cells, possibly mitigating their potential beneficial effects.

Topics: Acute Kidney Injury; Animals; Antioxidants; Apoptosis; Benzoates; Benzoic Acid; Cell Division; Cells, Cultured; DNA Damage; DNA Nucleotidylexotransferase; Free Radical Scavengers; Humans; Ischemia; Kidney; Kidney Tubular Necrosis, Acute; Male; Nuclear Proteins; Oxypurinol; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley; Regeneration; Reperfusion Injury; Xanthine Oxidase

This study describes a spin trap technique to determine production of oxygen radicals in rabbit kidneys after ischaemia and reperfusion. OXANOH was infused intra-arterially. When exposed to oxygen free radicals OXANOH is oxidized to the stable radical OXANO(.). The concentration of OXANO. in samples of renal venous blood was determined by ESR. Production of oxygen radicals was calculated from the amount of OXANO. in the venous blood and the blood flow which was determined by an ultrasound technique. The radical production at reperfusion after ischaemia was expressed as a per cent of the pre-ischaemic value. A drastic increase in radical production was observed during (60 min) reperfusion after 60 min of ischaemia. Pretreatment with oxypurinol (20 mg kg-1) before ischaemia and before recirculation almost completely abolished the rise in radical production at recirculation. Similar results were obtained when oxypurinol was given before recirculation only.

Topics: Anesthesia; Animals; Electron Spin Resonance Spectroscopy; Free Radicals; Ischemia; Kidney; Kinetics; Muscles; Oxygen Consumption; Oxypurinol; Rabbits; Renal Circulation; Reperfusion

An increased formation of oxygen free radicals in the reperfused rat small intestine is concluded from accumulations of oxidized glutathione, of thiobarbituric acid-reactive substances and of 4-hydroxynonenal. Xanthine oxidase inhibition prevented these biochemical changes. The histological and electronmicroscopic studies of intestinal sucosa showed significant structural deteriorations already at the end of the ischemic period obviously due to disturbances of cellular energy metabolism. The extent of dosage was increased during the reperfusion without qualitative changes of the pattern of structural dosage. The beneficial effects of oxypurinol on biochemical criteria which occurred already in the early phase of reperfusion were not reflected in significant morphological differences within the first hour of reperfusion. Differences of morphological findings between oxypurinol-treated and untreated animals could be observed after longer periods of reperfusion--during the regeneration of the tissue.

Topics: Animals; Free Radicals; Glutathione; Intestinal Mucosa; Ischemia; Jejunum; Male; Microscopy, Electron; Oxypurinol; Rats; Rats, Inbred Strains; Reperfusion Injury

An in vitro canine tibia model was used to assess the effects of 48 h of hypothermic (4 degrees C) ischemia on bone vascular resistance and on responsiveness of intraosseous blood vessels to circulating norepinephrine. Three groups of bones were studied: Group I (n = 11), 48 h hypothermic ischemia; Group II (n = 11), 48 h hypothermic ischemia with pretreatment with allopurinol and oxypurinol; and Group III (n = 10), no ischemia. Resting vascular resistance in both ischemic groups (79 and 74 mmHg/ml/min) was significantly higher (p less than 0.0001) than in the nonischemic group (22 mmHg/ml/min). Effects of norepinephrine on vascular resistance were significantly greater in both ischemic groups (p less than 0.004). In all three groups, acetylcholine infusion attenuated the increases in perfusion pressure caused by norepinephrine. This demonstrates secretion of endothelial-mediated relaxing factors (EDRF) and prostaglandin for up to 48 h of hypothermic ischemia. As no significant differences were detected between the two ischemic groups, this study failed to demonstrate any protective effect of xanthine oxidase inhibitors.

Topics: Acetylcholine; Allopurinol; Animals; Cold Temperature; Disease Models, Animal; Dogs; Drug Hypersensitivity; Ischemia; Nitric Oxide; Norepinephrine; Oxypurinol; Regional Blood Flow; Reperfusion Injury; Tibia; Vascular Resistance; Xanthine Oxidase

Reoxygenation injury that occurs when blood circulation is restored to previously ischemic tissues is currently discussed as a pathophysiological entity distinct from the primary anoxic injury that develops during ischemia per se. To test the hypothesis that reoxygenation injury in hepatocytes is caused by a postischemic burst of reactive oxygen species (ROS), including superoxide radicals, O2-., and hydrogen peroxide, H2O2, we performed a cytochemical study exploiting the peroxidase activity within peroxisomes as a sensitive ultrastructural detector of intracellular H2O2 generation. The osmiophilic polymer formed when tissue peroxidase is incubated with 3,3'-diaminobenzidine (DAB) and H2O2 was used as a marker for endogenous H2O2 in rat liver slices in short-term organ culture subjected to a cycle of 60-min ischemic anoxia and 30-min reoxygenation in the presence of DAB without exogenous H2O2. Peroxisomal reaction product was quantitatively evaluated in transmission electron micrographs of systematically sampled hepatocytes. Mean densities of positive peroxisomes per 1,000 micron2 (+/- SE) in liver slices subjected to various treatments were as follows: continuous anoxia (negative control) 0 +/- 0; normoxia + exogenous H2O2 (positive control) 45 +/- 12; normoxia only 26 +/- 2; ischemia-reoxygenation 13 +/- 6; ischemia-reoxygenation + xanthine oxidase inhibitor, oxypurinol 5 +/- 3; ischemia-reoxygenation + peroxidase inhibitor, aminotriazole 7 +/- 3. Endogenous H2O2 can be detected in hepatocytes by electron microscopic cytochemistry and may in part derive from xanthine oxidase, but it is not substantially increased in the postischemic state. We conclude that hepatocytes do not exhibit a postischemic burst of reactive oxygen species that could cause reoxygenation injury.

Topics: Amitrole; Animals; Histocytochemistry; Hydrogen Peroxide; Ischemia; Liver; Liver Diseases; Male; Microbodies; Microscopy, Electron; Oxygen; Oxypurinol; Rats; Rats, Inbred Strains; Reperfusion Injury

The effect of 60 min of ischaemia on glomerular and tubular functions (osmolar clearance, fractional Na+ excretion, K+ clearance, concentrating ability) after different periods of time was studied in New Zealand White rabbits. Pronounced changes in both glomerular and tubular functions were observed immediately on reperfusion and after 48 h. One week after ischaemia the functions appeared to be normalized. Mannitol is routinely used in clinical kidney transplantation due to its hyperosmolar effects and its ability to scavenge the hydroxyl radical. In the present study the possible additive protective effect against ischaemia-reperfusion damage of a combined pretreatment with mannitol and oxygen free radical scavengers or mannitol and a xanthine oxidase inhibitor was examined. Oxypurinol was chosen as the xanthine oxidase inhibitor due to its direct inhibitory effect. Concerning glomerular function, no protective effect of the combined pretreatment compared with mannitol alone was observed. However, concerning the tubular function tests combined pretreatment with either mannitol-superoxide dismutase-catalase or mannitol-oxypurinol turned out to be superior compared with that of mannitol alone.

Topics: Animals; Catalase; Creatinine; Deamino Arginine Vasopressin; Ischemia; Kidney; Kidney Tubules; Mannitol; Oxypurinol; Potassium; Rabbits; Sodium; Superoxide Dismutase

Allopurinol, a xanthine-oxidase (XO) inhibitor, has been used to improve the resistance to ischemia with disappointing results that have been attributed to administration regimen of the drug. Our aim was to investigate the effect of different administration schedules of allopurinol on the survival in rats undergoing intestinal ischemia testing the blockade of XO. Intestinal ischemia was achieved by 90 min of clamping the superior mesenteric artery (SMA) close to its origin from the aorta. Three groups of animals were evaluated: A-group: only the allopurinol solvent was given; B-group: the full dose of allopurinol (100 mg/k b.w.) was given iv and C-group: the 75% dose was administered orally 24 hr before and the remaining 25% was administered 30 min before. Survival was evaluated at 48 hr and the blockade of XO was assayed by High Efficacy Liquid Chromatography (HELC) in homogenate of intestinal wall. Survival was only improved in the C-group (P = 0.02). Levels of hypoxanthine were significantly increased both in B-group and C-group (P = 0.003) when compared with the A-group. Levels of uric acid in B-group (P = 0.0003) and C-group (P = 0.0009) were significantly decreased with respect to A-group. That means that an effective blockade of XO is achieved whichever the regimen of administration. Allopurinol and oxypurinol levels were significantly increased (P = 0.05 and P = 0.008) in C-group when compared with B-group. We conclude that the protective effect of allopurinol on survival in intestinal ischemia in rats is not related to the blockade of XO but rather to the allopurinol and oxypurinol levels in intestinal wall.

Topics: Allopurinol; Animals; Chromatography, Liquid; Hypoxanthine; Hypoxanthines; Intestines; Ischemia; Oxypurinol; Rats; Rats, Inbred Strains; Uric Acid; Xanthine Oxidase

Skeletal muscle edema secondary to an increase in capillary permeability after reflow is an important cause of the compartment syndrome after acute arterial revascularization. The purpose of this study was to investigate the possible role of oxygen free radicals, generated at reperfusion, in the pathogenesis of the compartment syndrome secondary to acute arterial ischemia/reperfusion. A reproducible model of this syndrome was produced in anesthetized rabbits by femoral artery occlusion after surgical devascularization of collateral branches from the aorta to the popliteal artery. Increasing periods of ischemia from 6 to 12 hours, followed by 2 hours of reperfusion, were associated with corresponding increases in the anterior muscle compartment hydrostatic pressure and inversely proportional decreases in tibialis anterior muscle blood flow within that compartment as assessed by xenon 133 washout (n = 46) (r = -0.62, p less than 0.001). Anterior compartment pressure increased from 5 +/- 1 to 48 +/- 5 mm Hg (n = 46) (p less than 0.001) after 7 hours of total arterial ischemia and 2 hours of reperfusion. Ablation of free radicals generated from xanthine oxidase with either allopurinol (n = 8) or oxypurinol (n = 8), by scavenging the superoxide radical at reperfusion with superoxide dismutase (n = 8), or by blocking secondary hydroxyl radical formation with deferoxamine (n = 8) significantly ameliorated the rise in compartment pressure (p less than 0.05) in each case; it also significantly improved muscle perfusion in the superoxide dismutase-, allopurinol-, and deferoxamine-treated animals (p less than 0.05). These findings indicate that development of the compartment syndrome after acute arterial revascularization may be due, at least in part, to microvascular injury mediated by oxygen-derived free radicals generated from xanthine oxidase at reperfusion.

Topics: Allopurinol; Animals; Blood Pressure; Compartment Syndromes; Deferoxamine; Free Radicals; Ischemia; Oxygen; Oxypurinol; Rabbits; Regional Blood Flow; Reperfusion Injury; Superoxide Dismutase

During the last few years, the scientific field has focused its attention on the pathogenic role of free radicals in the process of ischemia-revascularization. It is a well-known fact that xanthine oxidase is an important source of tissular free radicals. Bearing this in mind, we designed an experimental protocol to analyse the effect of allopurinol (a xanthine oxidase inhibitor) in the survival of rats after the occlusion of the superior mesenteric artery during a period of 90 minutes and its action on the superoxide radical liberation. The concentration of oxipurinol and allopurinol in the ischemic area (intestine), liver and blood were measured. We concluded that the administration of allopurinol increased the survival rate, which is correlated to higher concentrations of allopurinol and oxipurinol in the inner part of the intestinal cells. A correlation between the survival rate and superoxide radicals was not found.

Topics: Acute Disease; Allopurinol; Animals; Female; Free Radicals; Intestines; Ischemia; Male; Oxypurinol; Prognosis; Purines; Rats; Rats, Inbred Strains; Reperfusion Injury; Superoxides; Xanthine Oxidase

To assess the effects of xanthine oxidase (XO) inhibition on ischemic injury, rats were pretreated with oxypurinol (OXY, 5 mg/kg) and subjected to 30 min of bilateral renal artery occlusion. OXY's effect on adenine nucleotide-nucleoside-purine base concentrations was determined at 10 and 30 min of ischemia and during reperfusion (5 and 30 min). To assess whether XO-mediated oxidant stress influences the severity of ischemic acute renal failure (IARF), the effects of 1) OXY pretreatment and 2) hypoxanthine infusion were assessed. During ischemia OXY inhibited XO activity (more than fourfold rise in hypoxanthine-xanthine ratios) and induced quantitatively trivial but significant increases in ATP and total adenine nucleotide concentrations (by 30 min). Increased OXY dosage (15 mg/kg) or allopurinol (40 mg/kg) had no greater effects. At 5 min of reflow, OXY maintained XO inhibition but did not influence adenine nucleotide levels. By 30 min of reflow, 17-20% increments in ATP-total adenine nucleotides resulted. Nevertheless, OXY did not lessen the severity of IARF (assessed by azotemia-histology at 24 h). Hypoxanthine infusion increased end-ischemic hypoxanthine concentrations by 47%, but it did not change the severity of renal damage. Conclusions include 1) OXY-allopurinol induces intrarenal XO inhibition; 2) XO inhibitors slightly increase late ischemic-reperfusion adenine nucleotide concentrations; and 3) neither XO inhibition nor intrarenal hypoxanthine loading alters the severity of IARF, suggesting that XO-mediated oxidant stress is not a critical, consistent mediator of ischemic renal injury.

Topics: Acute Kidney Injury; Adenine Nucleotides; Allopurinol; Animals; Female; Hypoxanthine; Hypoxanthines; Inosine; Ischemia; Kidney; Kinetics; Oxypurinol; Pyrimidines; Rats; Rats, Inbred Strains; Renal Artery; Renal Circulation; Reperfusion; Xanthine Oxidase

The relationship between nucleotide catabolism and generation of activated oxygen species was investigated in liver, hepatocytes and small intestine of rats. In severe hypoxia nucleotide degradation via xanthine oxidase and urate oxidase requires about half of the oxygen consumed. Data on the changes of nucleobase compounds in rat hepatocytes and small intestine during ischemia and reoxygenation and the effects of allopurinol and oxypurinol thereon are presented. From EPR measurements it is concluded that OH. radicals induce reactions of allopurinol yielding long-living products which are able to react with DMPO-OH with loss of its radical properties.

Topics: Allopurinol; Animals; Cell Hypoxia; Intestine, Small; Ischemia; Liver; Male; Oxygen; Oxypurinol; Purine Nucleotides; Purines; Pyrimidines; Rats; Rats, Inbred Strains

The Langendorff isolated rat heart preparation was used to determine the effect of oxypurinol, a xanthine oxidase inhibitor, on myocardial function when administered during reperfusion after 30 min of warm ischemia. Twenty rats were randomly sorted into 2 groups of 10, and an isolated heart preparation made from each rat. The isolated hearts were perfused for 15 min with a modified Krebs-Henseleit solution to permit stabilization of the preparation. Each heart was then subjected to 30 min of total ischemia at 37 degrees C followed by 40 min of reperfusion with either saline-treated perfusate or oxypurinol-treated perfusate (1.3 mM). The maximum power produced and the preload required to produce maximum power were both determined prior to ischemia and every 10 min after ischemia during 40 min of reperfusion. The saline-treated group, but not the oxypurinol-treated group, showed significantly less maximum power output at all testing times during reperfusion compared to the preischemic value (P less than 0.05). There was a significantly greater maximum power output (P less than 0.02) in the oxypurinol-treated group compared to the saline-treated group after 20, 30, and 40 min of reperfusion. There were no differences within either group, or between groups, for the preload required to produce maximum power at any of the testing times. Ultrastructural examination of myocardium after reperfusion showed severe mitochondrial and myofibrillar disruption in the saline-treated group but not in the oxypurinol-treated group. We conclude that oxypurinol administered following 30 min of total ischemia at the onset of reperfusion, can preserve myocardial function during the early reperfusion period in the isolated rat heart.

Topics: Animals; Coronary Circulation; Heart; Ischemia; Male; Myocardium; Oxygen; Oxypurinol; Pyrimidines; Rats; Rats, Inbred Strains; Resuscitation