Biomedical subjects

S G Simonson

Publications and source records attributed to S G Simonson.

18 recordsLinked to original sources

PubMed2003

Pharmacokinetics and pharmacodynamics of rosuvastatin in subjects with hepatic impairment.

OBJECTIVE: To assess the effect of chronic hepatic impairment on rosuvastatin disposition, pharmacodynamic activity and tolerability. METHODS: This was an open-label, non-randomised, parallel-group trial. Six subjects were enrolled in each of three hepatic-function strata: Child-Pugh class A (CP-A, mild impairment), Child-Pugh class B (CP-B, moderate impairment) and normal hepatic function; the latter two strata were age, weight, race, sex and smoking history matched. All subjects were given rosuvastatin 10 mg for 14 days. RESULTS: In subjects with CP-A, and in four of six subjects with CP-B, rosuvastatin steady-state AUC(0-24) and C(max) were similar to subjects with normal hepatic function (geometric mean values 60.7 ng h/ml and 6.02 ng/ml, respectively). Two of six subjects with CP-B who had the highest CP scores (i.e. the highest degrees of hepatic impairment) had the highest AUC(0-24) (128 ng h/ml and 242 ng h/ml) and C(max) (23.4 ng/ml and 96.7 ng/ml) values. Low-density lipoprotein cholesterol (LDL-C) was decreased in all strata, but the response was more variable in the CP-B group. Rosuvastatin was well tolerated, and the safety profile was similar in subjects with hepatic impairment and normal hepatic function. CONCLUSION: In most subjects with mild-to-moderate hepatic impairment, the steady-state pharmacokinetics of rosuvastatin were similar to subjects with normal hepatic function (more extensive hepatic impairment may increase systemic exposure to rosuvastatin), and most had LDL-C reductions similar to subjects with normal hepatic function.

Adult↗

PubMed2001

Antibody to intercellular adhesion molecule 1 (CD54) decreases survival and not lung injury in baboons with sepsis.

Neutrophil influx into the lung is an important event in the pathogenesis of acute lung injury in gram-negative sepsis. We hypothesized that administration of a monoclonal antibody to intercellular adhesion molecule 1 (ICAM-1, CD54), a molecule mediating neutrophil adhesion to endothelial cells, would decrease neutrophil sequestration and transmigration in the lung and attenuate lung injury in Escherichia coli sepsis. Sepsis was induced in 12 baboons primed with heat-killed E. coli (1 x 10(9) CFU/kg) 12 h before infusion of live bacteria (1 x 10(10) CFU/kg). Six animals received monoclonal antibody to CD54 (1 mg/kg) intravenously at the time of live E. coli infusion. After 48 h or when blood pressure could not be maintained, tissues were harvested and bronchoalveolar lavage (BAL) samples were obtained. Median survival time was decreased in anti-CD54-treated animals. This group also had decreased mean arterial pressure, increased metabolic acidosis, and decreased urine output. Measures of lung injury including gas exchange, lung lavage protein and lactate dehydrogenase (LDH), lung thiobarbituric acid-reactive species, and lung histology, including alveolar neutrophil volumes, were unaffected by treatment. The effect of anti-CD54 on neutrophil influx into tissues as measured by myeloperoxidase was organ specific. These data show that monoclonal antibody to CD54 does not ameliorate acute lung injury in E. coli sepsis, and septic primates given anti-CD54 have worsened metabolic parameters and decreased survival.

Animals↗

PubMed1999

An evaluation of zafirlukast in the treatment of asthma with exploratory subset analyses.

BACKGROUND: Consensus asthma guidelines recommend antileukotriene agents as alternative therapy to existing anti-inflammatory medications; however, the full therapeutic potential of these medications has not yet been determined. OBJECTIVE: The purpose of this study was to assess the efficacy and safety of the oral leukotriene receptor antagonist zafirlukast (20 mg twice daily) in subgroups of patients who have asthma with the use of integrated data from four 13-week trials. METHODS: The trials had comparable designs, entry criteria, and clinical assessments. Patient subgroups were characterized by demographic and baseline asthma characteristics. Analysis of covariance models were tested for overall treatment effect and for interactions between treatment and subgroup characteristics. RESULTS: Patients with mild-to-moderate asthma (12 to 76 years old) who were treated with albuterol alone were randomized (nZ = 879; nP = 605) and included in subset analyses. Significant overall treatment effects, favoring zafirlukast, were noted for measures of daytime and nighttime symptoms, beta2 -agonist use, and pulmonary function (P <.05). A significant, quantitative, treatment-by-age interaction was noted for beta2 -agonist use (P <. 03), suggesting greater reductions in rescue medication use with increasing patient age. Compared with placebo, similar size and/or direction of response was noted with zafirlukast in the various subgroups, indicating a benefit with zafirlukast regardless of subgroup. Significant treatment-by-strata interactions (P <.05), favoring zafirlukast, were noted for various outcome measures in subgroups with the greatest amount of baseline beta2 -agonist use (>8 puffs/day) and with greater baseline peak flow variability (>/=20%) and baseline airflow obstruction (FEV1 /forced vital capacity ratio, <0.70). The overall treatment failure rate was significantly lower in the zafirlukast group compared with the placebo group (P <.003). No associations were observed between any adverse events and subgroups defined by demographic characteristics. CONCLUSIONS: Exploratory subset analyses showed that zafirlukast is similarly efficacious in patients with asthma who have differing demographic characteristics and degrees of subjective symptoms. Additionally, zafirlukast appears to be incrementally beneficial in patients with more moderate disease, defined by a greater requirement for as-needed rescue medication and more abnormal pulmonary function at baseline. Over 13 weeks, zafirlukast was well tolerated and demonstrated a safety profile clinically indistinguishable from placebo.

Adolescent↗

PubMed1998

A single dose of zafirlukast reduces LTD4-induced bronchoconstriction in patients on maintenance inhaled corticosteroid therapy.

BACKGROUND: Previous studies demonstrated that leukotriene receptor antagonists (LTRAs) are effective in reducing asthma symptoms and the airway response to inhaled leukotriene D4 (LTD4) in asthmatic patients receiving inhaled beta2-agonists alone. OBJECTIVE: To investigate the efficacy of a single 20-mg dose of the oral LTRA zafirlukast in reducing the airway response to inhaled LTD4 in mild-to-moderate asthmatic patients receiving inhaled beta2-agonists and inhaled corticosteroids (ICS). METHODS: In this double-blind, crossover trial, six patients on maintenance ICS (median dose 800 microg/day; range 336 to 1600 microg/day), who had a 20% decrease in FEV1 following inhalation of a maximal concentration of 50 microg/mL LTD4, received either zafirlukast or placebo on each of two study days. Two hours after dosing, patients underwent bronchoprovocation challenges with increasing concentrations of LTD4 (0.1 to 1000 microg/mL) at 10-minute intervals until either the patient's FEV1 decreased by 20% or the maximum concentration of LTD4 was given. Spirometric tests were done just before (baseline) and throughout the challenge phase until the patient's FEV1 returned to within 5% of baseline. Blood samples were collected two hours after dosing to determine plasma concentrations of zafirlukast. RESULTS: Compared with placebo, zafirlukast produced a 1.82-unit increase in logPC20FEV1 and a 1.88-unit increase in logPD20FEV1, representing a 66-fold higher concentration and a 76-fold higher dose of LTD4, respectively, to produce a 20% decrease in FEV1 (P < .001). Mean time to recovery after challenge was 36.7 versus 51.7 minutes when patients received zafirlukast and placebo, respectively. No correlation between clinical effects and plasma drug levels was observed. CONCLUSIONS: This trial demonstrated that asthmatic patients on maintenance ICS can respond to exogenously administered LTD4 and that zafirlukast reduced the airway response to LTD4 in these patients.

Administration, Inhalation↗

PubMed1998

Antibody to E- and L-selectin does not prevent lung injury or mortality in septic baboons.

Recruitment of polymorphonuclear leukocytes (PMN) through upregulation of cellular adhesion molecules is a proposed mechanism of injury in sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that pretreatment of baboons with a monoclonal antibody to human E- and L-selectin (EL-246) during sepsis would decrease PMN influx into tissues and result in less organ injury during gram-negative sepsis. We studied 14 anesthetized, ventilated adult baboons; six animals received 1 mg/kg of EL-246 before infusion of an LD100 of live Escherichia coli and six received the E. coli infusion without antibody therapy. Two other animals received 1 mg/kg of EL-246 intravenously without an infusion of bacteria. Intermittent measurements were made of circulatory pressures, cardiac output, urine output, arterial blood gases, ventilation:perfusion ratio (VA/Q), and hematologic status. The experiments were ended at 48 h or at the time of death. Tissues were harvested for pathology and biochemical measurements. The E. coli infusions were associated with a hyperdynamic state, pulmonary hypertension, systemic hypotension, decreased urine output (UOP), and metabolic acidosis. The antibody partly blocked PMN migration, but there were few significant physiologic or biochemical differences between the EL-246-treated and untreated animals. In the antibody-treated animals, UOP was decreased, metabolic acidosis was worsened, and median survival time was decreased significantly. We conclude that treatment with an antibody to E- and L-selectin in gram-negative sepsis does not improve gas exchange or protect against lung injury, and is associated with decreased survival time in primates.

Acidosis↗

PubMed1998

Bacterial priming increases lung injury in gram-negative sepsis.

Sepsis syndrome is a leading cause of acute respiratory distress syndrome (ARDS), but the development of acute lung injury is highly variable for reasons that are poorly understood. We hypothesized that nonlethal systemic exposure to gram-negative bacteria, with its consequent activation of inflammatory processes, would increase functional and structural lung injury on a second exposure to live organisms, as compared with exposure of naive animals. Sixteen adult baboons received 1 to 2 x 10(10) colony-forming-units (cfu)/kg Escherichia coli by intravenous infusion. Eight animals received live bacteria as a single infusion, whereas the other eight received 10% of the total dose as heat-killed organisms (priming dose) 12 h before the live infusion. Pulmonary gas exchange and hemodynamics were monitored for 48 h or until blood pressure could not be maintained. The animals were killed and one lung was processed for electron microscopy and morphometry. Group data were compared through analysis of variance (ANOVA). The systemic circulatory responses to the bacterial challenge were similar, although less severe shock occurred in primed animals. In contrast, primed animals had increased structural damage involving lung epithelium and endothelium, and showed increased cellularity of the interstitium. The morphologic evidence of increased lung injury in septic animals with prior exposure to heat-killed bacteria suggests that prior activation of systemic inflammatory responses is a contributing factor in the pathogenesis of ARDS.

Animals↗

PubMed1997

Changes in the lung after prolonged positive pressure ventilation in normal baboons.

PURPOSE: The effects of prolonged positive pressure ventilation on lung ultrastructure are not well defined in primates. This study was designed to measure cardiopulmonary and morphological responses to 4 days of positive pressure ventilation in normal baboons. MATERIALS AND METHODS: Six adult male baboons were mechanically ventilated on air for 96 hours with 2.5 cm positive end-expiratory ventilation and a tidal volume of 12 to 15 mL/kg. Physiological measurements were obtained every 12 hours and serial measurements of ventilation-perfusion (VA/Q) were performed using the multiple inert gas elimination technique. Quantitative morphotometry, lung dry-to-wet ratio, and surfactant analysis were performed at the end of the experiment. RESULTS: Cardiovascular variables, except for a small increase in mean pulmonary artery pressure at 84 and 96 hours, were not significantly affected by positive pressure ventilation. Arterial Po2 decreased, and shunt fraction increased from 0.7% of cardiac output to 5.4% (P < .01). Dispersion of perfusion increased threefold (P < .01), and dispersion of ventilation doubled (P < .01) indicating increased VA/Q mismatch mismatch. Respiratory system compliance decreased by 30% (P < .01). There was no lung edema or change in surfactant composition. Lung morphometry showed increases in polymorphonuclear cells and type II cell volume. Vacuolated endothelial cells and bare basement membrane were observed consistently. CONCLUSION: Four days of positive pressure ventilation decreases lung compliance and worsens gas exchange by increasing shunt and VA/Q mismatch in healthy baboons. These effects are accompanied by only minor ultrastructural changes and mild inflammatory responses in the lung.

Animals↗

PubMed1997

Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. I. Physiology and biochemistry.

Prolonged hyperoxia causes lung injury and respiratory failure secondary to oxidative tissue damage mediated, in part, by the superoxide anion. We hypothesized that aerosol treatment with recombinant human manganese superoxide dismutase (rhMnSOD) would attenuate hyperoxic lung damage in primates. Adult baboons were anesthetized and ventilated with 100% oxygen for 96 h or until death. Six animals were treated with aerosolized rhMnSOD (3 mg . kg-1 . day-1 in divided doses), and six control animals did not receive enzyme therapy. Physiological variables were recorded every 12 h, and ventilation-perfusion ratio relationships were evaluated by using the multiple inert-gas elimination technique. After the experiments, surfactant composition and lung edema were measured. We found that rhMnSOD significantly decreased pulmonary shunt fraction (P < 0.01) and preserved arterial oxygenation (P < 0.01) during hyperoxia. The rhMnSOD increased lung phospholipids, phosphatidylcholine and disaturated phosphatidylcholine, and decreased lung edema in this model. Testing of higher and lower doses of MnSOD (1 and 10 mg . kg-1 . day-1) in two other groups of baboons produced variable physiological protection, suggesting a "window" of effective dosage. We conclude that aerosolized MnSOD (3 mg . kg-1 . day-1) affords significant preservation of pulmonary gas exchange during hyperoxic lung injury.

Aerosols↗

PubMed1997

Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. II. Morphometric analysis.

Hyperoxia damages lung parenchyma via increased cellular production of reactive oxygen species that exceeds antioxidant defenses. We hypothesized that aerosolized human recombinant manganese superoxide dismutase (rhMnSOD) would augment extracellular antioxidant defenses and attenuate epithelial injury in the lung during hyperoxia in primates. Twenty-four adult male baboons were anesthetized and mechanically ventilated with 100% oxygen for 96 h. The baboons were divided equally into four groups. Oxygen alone and oxygen plus rhMnSOD given at 3 mg . kg-1 . day-1 were compared to assess efficacy of the drug. Subsequently, aerosolized rhMnSOD was given at 1 or 10 mg . kg-1 . day-1 to study dose effects and toxicity. Quantitative morphometry showed protection of alveolar epithelium from hyperoxia by 3 mg . kg-1 . day-1 rhMnSOD (P < 0.05). In addition, interstitial fibroblast volumes were increased in the treatment group (P = 0.06). This effect appeared greater at the two higher doses of the rhMnSOD. The aerosolized drug was localized to the surface of airways and air spaces and macrophages by immunolabeling studies, suggesting efficacy via physicochemical properties that localize it to cell surfaces or by effects on alveolar macrophage function.

Animals↗

PubMed1996

VA/Q abnormalities during gram negative sepsis.

Hypoxemia in bacterial sepsis develops by mechanisms which are incompletely understood. In this study, we measured pulmonary gas exchange in eight baboons to determine the causes of hypoxemia after infusion of live Escherichia coli (1 x 10(10) CFU/kg) followed by resuscitation with intravenous fluid. VA/Q distributions were measured periodically using the multiple inert gas elimination technique until death or for a maximum of 42 h. After E. coli infusion, dispersion of perfusion (logSDq) increased rapidly and a transient rise in dead space was observed at 6 h coinciding with systemic hypotension and acidosis. The intrapulmonary shunt developed later and reached 27 +/- 6% at 24 h. PaO2 began to decrease at 12 h and correlated with increases in intrapulmonary shunt and logSDq. There was no evidence of diffusion limitation. Lung edema was mild despite aggressive fluid resuscitation. Morphometric analysis of postmortem lungs revealed dramatic intravascular accumulation of granulocytes. There were increases in arithmetic mean thicknesses of epithelium and interstitium. These data indicate that gram negative sepsis with fluid resuscitation causes progressive hypoxemia, primarily due to the development of intrapulmonary shunt and very low VA/Q regions in the lung. The VA/Q abnormalities occur early and likely reflect ongoing cellular responses in pulmonary vasculature and smaller airways in sepsis.

Animals↗

PubMed1996

Near-infrared spectroscopy. Clinical applications.

NIRS is an attractive monitoring technology because it is a noninvasive, real-time, repeatable method that allows for regional assessment of the adequacy of tissue oxygenation. It is able to evaluate the oxygenation state of hemoglobin in tissue and redox state of cyt a1,a3, which reflects the overall activity of oxidative metabolism in the cells. The primary technical limitation of current technology is the inability to measure accurately the optical pathlength online, limiting the ability to quantify precisely concentrations of oxygen-dependent chromophores. Even with this limitation, NIRS can provide unique and valuable in vivo metabolic information without invasive intervention.

Algorithms↗

PubMed1996

Ultrastructural changes in skeletal muscle mitochondria in gram-negative sepsis.

Energy metabolism during sepsis is incompletely understood, but alterations in mitochondrial structure and function appear important. We measured time-dependent changes in mitochondrial structure during sepsis using serial skeletal muscle biopsies in anesthetized baboons injected with 10(10) CFU/kg of live Escherichia coli (LD(100)). Skeletal muscle biopsies were taken before bacterial challenge (0 h controls) and at 12 h, 24 h, and death. By qualitative electron microscopy, the organelles became enlarged with distorted cristae and developed electron lucent areas within the matrix. With advanced injury the inner membrane became fragmented. Quantitative morphometric analysis showed a 50% increase in mean cristal membrane surface density by 24 h (p < .05) accompanied by a 100% increase in intermembrane space (p < .01). Matrix volume density decreased progressively (p < .01). These changes in mitochondrial ultrastructure occur within 12 h after the onset of the bacterial insult. This damage, including destruction or reorganization of both membrane and matrix proteins, is severe enough to compromise oxidative metabolism in muscle in Gram-negative sepsis.

Animals↗

PubMed1996

Composition of lung lavage in pulmonary alveolar microlithiasis.

A case of pulmonary alveolar microlithiasis (PAM) is reported wherein total lung lavage was performed for relief of dyspnea. Characterization of the lavage material and examination of the microliths isolated from the lavage fluid confirmed previous reports of their spherical-ovoid shape and a 2:1 calcium to phosphate composition. The microliths contained considerable amounts of ionizable iron and generated oxidants in an in vitro system. A detailed biochemical analysis of the lavage fluid reflected elevations in total protein, phosphatidylserine, phosphatidylglycerol and the ratio of phosphatidylglycerol to phosphatidylinositol. Surfactant apoprotein-A levels approximated that of normal patients. The potential roles of oxidant generation and alterations in surfactant metabolism are discussed in the context of the pathogenesis of PAM.

Adult↗

PubMed1996

Use of near-infrared spectroscopy to monitor tissue oxygenation.

Near-infrared spectroscopy (NIRS) is a relatively new tool that allows continuous noninvasive monitoring of in vivo oxygenation in selected tissues such as muscle and brain. Since hemoglobin, myoglobin, and cytochrome c oxidase are the only biological compounds to exhibit variable absorption of near-infrared (NIR) light in response to changes in oxygen availability, NIRS can determine changes in tissue oxygenation. NIRS can measure regional blood volume, local oxyhemoglobin and deoxyhemoglobin contents, and reduction-oxidation state of cellular mitochondrial cytochrome a, a3. As a comprehensive monitor of regional oxygen metabolism, NIRS has been applied in certain clinical and research settings. Despite technical limitations and the lack of definite "gold standards" to allow validation of results, NIRS remains a promising technology with applications in both the critical care environment and the research laboratory studying mechanisms of oxygen metabolism.

Blood Volume↗

PubMed1996

Central nervous system oxygen toxicity during hyperbaric treatment of patients with carbon monoxide poisoning.

Hyperbaric oxygen (HBO2) is associated with a recognized risk for clinical central nervous system (CNS) toxicity. The risk for oxygen convulsions during routine hyperbaric treatment of most routine conditions is extremely low. Previous observations have suggested that the incidence of CNS toxicity during HBO2 treatment for carbon monoxide (CO) poisoning may be increased, both because of CNS injury caused by the poisoning and because higher treatment pressures are often utilized for this condition. This study reviews data from 900 CO-poisoned patients treated with HBO2 at Virginia Mason and Duke University Medical Centers from 1987 to 1996. One-third of the patient population was treated at each of the three HBO2 treatment pressures most commonly utilized for CO intoxication in North American multiplace chambers. Patient characteristics were similar in all groups. Among the 300 consecutive patients treated at each pressure, there was one seizure at 2.45 atm abs (0.3%), nine seizures at 2.80 atm abs (2.0%), and six seizures at 3.00 atm abs. This difference is statistically significant (P = 0.032; Fisher's Exact Test). The potential difference in seizure risk should be considered when selecting the HBO2 treatment pressure for CO poisoning.

Adult↗

PubMed1995

Artificial surfactant attenuates hyperoxic lung injury in primates. I. Physiology and biochemistry.

Prolonged exposure to O2 causes diffuse alveolar damage and surfactant dysfunction that contribute to the pathophysiology of hyperoxic lung injury. We hypothesized that exogenous surfactant would improve lung function during O2 exposure in primates. Sixteen healthy male baboons (10-15 kg) were anesthetized and mechanically ventilated for 96 h. The animals received either 100% O2 (n = 6) or 100% O2 plus aerosolized artificial surfactant (Exosurf; n = 5). A third group of animals (n = 5) was ventilated with an inspired fraction of O2 of 0.21 to control for the effects of sedation and mechanical ventilation. Hemodynamic parameters were obtained every 12 h, and ventilation-perfusion distribution (VA/Q) was measured daily using a multiple inert-gas elimination technique. Positive end-expiratory pressure was kept at 2.5 cmH2O and was intermittently raised to 10 cmH2O for 30 min to obtain additional measurements of VA/Q. After the experiments, lungs were obtained for biochemical and histological assessment of injury. O2 exposures altered hemodynamics, progressively worsened VA/Q, altered lung phospholipid composition, and produced severe lung edema. Artificial surfactant therapy significantly increased disaturated phosphatidylcholine in lavage fluid and improved intrapulmonary shunt, arterial PO2, and lung edema. Surfactant also enhanced the shunt-reducing effect of positive end-expiratory pressure. We conclude that an aerosolized protein-free surfactant decreased the progression of pulmonary O2 toxicity in baboons.

Animals↗

PubMed1994

Altered mitochondrial redox responses in gram negative septic shock in primates.

Gram negative sepsis causes changes in oxygen supply-demand relationships. We have used a primate model of hyperdynamic gram negative sepsis produced by intravenous infusion of Escherichia coli (E. coli) to evaluate sepsis-induced alterations in mitochondrial oxidation-reduction (redox) state in muscle in vivo. The redox state of cytochrome a,a3, the terminal member of the intramitochondrial respiratory chain, was assessed in the intact forearm by near-infrared (NIR) spectroscopy. The muscle NIR data were compared to routine measures of oxygen delivery (DO2) and oxygen consumption (VO2). After E. coli infusion and fluid resuscitation, DO2 and VO2 showed minimal changes through 24 hr of sepsis. In contrast, changes in cytochrome a,a3 redox state evaluated by NIR occurred within a few hours and were progressive. Mitochondrial functional responses were correlated with structural changes observed on serial muscle biopsies. Gross morphological changes in muscle mitochondria were present in some animals as early as 12 hr, and, in most animals, by 24 hr. The morphologic changes were consistent with decreases in oxidative capacity as suggested by NIR spectroscopy. The NIR data also suggest that two mechanisms are operating to explain abnormalities in oxygen metabolism and mitochondrial function in lethal sepsis. These mechanisms include an early defect in oxygen provision to mitochondria that is followed by a progressive loss in functional cytochrome a,a3 in the muscle.

Animals↗

PubMed1993

Hydrogen peroxide production by monoamine oxidase during ischemia-reperfusion in the rat brain.

Monoamine oxidase (MAO) as a source of hydrogen peroxide (H2O2) was evaluated during ischemia-reperfusion in vivo in the rat brain. H2O2 production was assessed with and without inhibition of MAO during and after 15 min of ischemia. Metabolism of H2O2 by catalase during ischemia and reperfusion was measured in forebrain homogenates using aminotriazole (ATZ), an irreversible H2O2-dependent inhibitor of catalase. Catecholamine and glutathione concentrations in forebrain were measured with and without MAO inhibitors. During ischemia, forebrain blood flow was reduced to 8% of baseline and H2O2 production decreased as measured at the microperoxisome. During reperfusion, a rapid increase in H2O2 generation occurred within 5 min as measured by a threefold increase in oxidized glutathione (GSSG). The H2O2-dependent rates of ATZ inactivation of catalase between control and ischemia-reperfusion were similar, indicating that H2O2 was more available to glutathione peroxidase than to catalase in this model. MAO inhibitors eliminated the biochemical indications of increased H2O2 production and increased the catecholamine concentrations. Mortality was 67% at 48 h after ischemia-reperfusion, and there was no improvement in survival after inhibition of MAO. We conclude that MAO is an important source of H2O2 generation early in brain reperfusion, but inhibition of the enzyme does not improve survival in this model despite ablating H2O2 production.

Amitrole↗