Biomedical subjects
D S Warner
Publications and source records attributed to D S Warner.
Assessing a tool to measure patient functional ability after outpatient surgery.
UNLABELLED: The "24-Hour Functional Ability Questionnaire" (24hFAQ) was developed to measure final recovery and satisfaction 24 h after surgery. We used structured interviews preoperatively to measure baseline patient concerns, and up to 24 h after discharge, to assess patient function and satisfaction. The primary objective was to assess the validity of the newly developed 24hFAQ in the postoperative outpatient setting. The criteria assessed were 1) CONTENT: comparison with expert opinion and patients' views and response frequency distributions for asymptotes and irrelevance, 2) Construct: contribution of cognitive, physical, and satisfaction domains to postoperative functional ability, 3) Discrimination: comparing mean clinical end points with patient satisfaction, and 4) Criterion (predictive) validity: testing that related constructs are best correlated. CONTENT validity was supported by the appropriate frequency distribution of subject responses, by the lack of floor or ceiling effects, and by <2% of responses indicating irrelevance. Construct validity was supported by moderate-to-strong positive interitem correlations within the cognitive and physical domains as predicted a priori. Discriminant validity support was mixed: key symptoms were associated with adverse patient satisfaction, but operating room and postanesthesia care unit residence times were unrelated. Criterion validity was supported by the finding that preoperative concern with key symptoms was independent of postoperative outcomes. The validity assessment presented was the first assessment of the measurement capability of the 24hFAQ in an outpatient postoperative population. These results provide overall support for the validity of the 24hFAQ for use in outpatient populations. IMPLICATIONS: This study assessed the validity of a novel functional ability questionnaire that measured functional status after recovery from anesthesia and satisfaction 24 h after outpatient surgery. The content, construct, discriminant, and criterion (predictive) validities demonstrated the utility of this assessment instrument in the outpatient setting.
The effects of anesthetics on stress responses to forebrain ischemia and reperfusion in the rat.
UNLABELLED: Rats exposed to forebrain ischemia have reduced injury when anesthetized with isoflurane versus fentanyl + N(2)O. The protection caused by isoflurane is reversed by trimethaphan. We hypothesized that these anesthetic-dependent effects on ischemic outcome can be associated with altered stress responses to ischemia. Rats were randomized to four treatments: isoflurane; fentanyl + N(2)O; isoflurane + trimethaphan; or isoflurane + metyrapone. Severe forebrain ischemia was then induced for 10 min. Plasma and brain corticosterone, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 were assayed. Plasma corticosterone concentrations were similar in the isoflurane and isoflurane + trimethaphan groups, but greater than in the fentanyl + N(2)O and isoflurane + metyrapone groups. Brain corticosterone was similar among all groups except isoflurane + metyrapone, in which values were markedly reduced. The addition of metyrapone to isoflurane also reduced plasma TNF-alpha; however, values among other groups were similar. There were no differences among groups for brain TNF-alpha. Plasma IL-6 concentrations were below the limit of detection. Brain IL-6 concentrations were increased by ischemia; however, there was no difference among groups. In conclusion, there were no differences between the isoflurane and isoflurane + trimethaphan groups for any of the measured stress markers. Further, there was little difference between the isoflurane and fentanyl + N(2)O groups, except for plasma corticosterone concentration. Accordingly, isoflurane neuroprotection and its reversal by trimethaphan appear to be independent of effects on the stress responses measured in this study. IMPLICATIONS: Differential anesthetic effects on ischemic outcome are independent of effects on adrenergic/noradrenergic responses to ischemia. The absence of a consistent differential effect of anesthetics on either corticosterone or cytokine responses to ischemia serves to further refute the hypothesis that isoflurane neuroprotection can be attributed to dampening of adverse stress responses to ischemic insults.
A comparison of remifentanil and fentanyl in patients undergoing surgery for intracranial mass lesions.
UNLABELLED: We compared the effects of remifentanil versus fentanyl during surgery for intracranial space-occupying lesions. Patients were randomly assigned to receive either remifentanil (0.5 microg. kg(-1). min(-1) IV during the induction of anesthesia reduced to 0.25 microg. kg(-1). min(-1) after endotracheal intubation; n = 49) or fentanyl (dose per usual practice of the anesthesiologist; n = 54). Anesthesia maintenance doses of isoflurane, nitrous oxide, and opioid were at the anesthesiologist's discretion for both groups. There were no differences between opioid groups for the frequency of responses (hemodynamic, movement, and tearing) to intubation, pinhead holder placement, skin incision, or closure of the surgical wound. Adverse event frequencies were similar between groups. Times to follow verbal commands (P < 0.001) and tracheal extubation (P = 0. 04) were more rapid for remifentanil. The percentage of patients with a normal recovery score (were alert or arousable to quiet voice, were oriented, were able to follow commands, had motor function unchanged from their preoperative evaluation, were not agitated, and had modified Aldrete Scores of 9-10) at 10 min after surgery was more for remifentanil (45% vs 18%; P = 0.005). By 20 min, no difference between groups existed (P = 0.27). Anesthesiologists used more isoflurane in the fentanyl group (4.22 vs 1.93 minimum alveolar anesthetic concentration hours). Neurosurgeons, blinded to treatment group, favored the use of remifentanil. Similar frequencies of light anesthesia responses and other adverse events suggest that intraoperative depths of anesthesia were similar in the two groups. Under these conditions, emergence was more rapid with remifentanil. This is consistent with the necessity for less isoflurane use in the remifentanil group and the intrinsic rapid clearance of this opioid. IMPLICATIONS: Patients given remifentanil-based anesthesia for craniotomy had faster recovery times from anesthesia than did those given fentanyl-based anesthesia.
A randomized, double-blinded comparison of ondansetron, droperidol, and placebo for prevention of postoperative nausea and vomiting after supratentorial craniotomy.
UNLABELLED: Nausea or vomiting occurs frequently after craniotomy. Because of the need for frequent postoperative neurological assessment, an effective antiemetic with minimal sedative side effects is needed. Therefore, we compared ondansetron to droperidol in a randomized, double-blinded, placebo-controlled study. A total of 60 adults requiring elective supratentorial craniotomy received standardized IV anesthesia with 4 mg of ondansetron, 0.625 mg of droperidol, or placebo at skin closure. The incidence of postoperative nausea, emesis, pain and sedation scores, and rescue antiemetic use were recorded at 0, 0.5, 1, 4, 8, 12, 24, and 48 h. All groups were demographically similar. Differences existed for cumulative 8, 12, and 24 h incidences of nausea (24 h, P = 0.03) and emesis (24 h, P = 0.04). Within 4 h, when maximal effect could be expected from treatment, 20% of the ondansetron group, 25% of the droperidol group and 50% of the placebo group received rescue antiemetic (P = 0.12). No differences in pain (P = 0.82) or sedation (P = 0.74) scores were detected. Both ondansetron and droperidol prevent nausea; however, only droperidol reduces emesis after supratentorial craniotomy. The dose of droperidol used was not more sedating than ondansetron. Sustained reduction in nausea and emesis over 24 h indicates a preemptive benefit of prophylactic antiemetic in this surgical population. IMPLICATIONS: Nausea and vomiting after brain surgery are particularly troubling, because effective treatment may cause sedation, making postoperative neurological assessment difficult. Our study shows that both ondansetron and droperidol are effective in reducing nausea, and that droperidol is particularly effective in reducing vomiting. Neither drug caused more sedation than placebo.
Is there a learning curve associated with the use of remifentanil?
UNLABELLED: This study prospectively determined whether there was a learning curve with the use of remifentanil, as indicated by decreased hemodynamic variability, improved recovery profile, and decreased incidence of opioid-related adverse events with increasing experience. Patients undergoing diverse surgical procedures (outpatient [n = 1340] and inpatient [n = 560]) were enrolled by investigators (n = 190) who had no previous experience with remifentanil use. Each investigator enrolled 10 patients. A standardized protocol for administration of remifentanil was used. Data were analyzed to determine differences between the first three patients and the last three patients enrolled for each anesthesiologist in the study. There were no differences in hemodynamic variables between the first triad and the last triad in either outpatients or inpatients. Requirements for hypnotic drugs and the doses of remifentanil used were also similar between groups. Analgesic medications administered at the end of surgery and in the postanesthesia care unit (PACU) were similar between groups, except that the last triad in the outpatient group received smaller doses of fentanyl compared with the first triad. Times to response to verbal command, tracheal extubation, and operating room discharge did not differ between groups. However, patients in the last triad undergoing outpatient surgery had shorter times to eligibility for PACU discharge, but times to eligibility for discharge home did not differ. The overall incidence of all adverse events (i.e., hypotension, hypertension, muscle rigidity, respiratory depression, apnea, nausea, and vomiting) was less in the last triad as compared with the first triad. When analyzed separately, only the incidence of vomiting (in the outpatient group) was decreased in the last triad as compared with the first triad. This study suggests that there is a learning curve that aids reduction of minor adverse effects associated with the use of analgesic medications administered at the end of surgery in outpatients, which might have reduced the incidence of postoperative vomiting and the duration of PACU stay. IMPLICATIONS: This study demonstrated that anesthesiologists rapidly acquire the ability to use remifentanil with limited experience. However, there is a learning curve that aids reduction of minor adverse effects associated with the use of analgesic medications administered at the end of surgery in outpatients, which might have reduced the incidence of postoperative vomiting and the duration of postanesthesia care unit stay.
Interscalene brachial plexus block with a continuous catheter insertion system and a disposable infusion pump.
Continuous interscalene brachial plexus blockade traditionally requires a hospital stay for local anesthetic infusion, and achieving consistent catheter insertion may be difficult. Incorporating long-acting pain relief from a continuous peripheral nerve block, with a reliable method of catheter insertion, and a self-contained infusion system would be a valuable asset for short-stay care. We compared the efficacy of single injection interscalene brachial plexus blockade to a continuous peripheral nerve block, with an insulated Tuohy system and a disposable infusion pump. Forty adult patients scheduled for open rotator cuff repair were entered in this randomized, double-blinded, placebo-controlled study. Patients received an interscalene brachial plexus blockade and a continuous peripheral nerve catheter as their primary anesthetic and then, were assigned to receive one of two different postoperative infusions: either 0.2% ropivacaine at 10 mL/h via a disposable infusion pump or normal saline at 10 mL/h via a disposable infusion pump (n = 18-20 per group). Visual analog pain scores and postoperative morphine consumption were measured for 24 h. The ropivacaine group showed less pain than the placebo group (P: = 0.0001) between 12 and 24 h after the initial injection of local anesthetic. In addition, initial interscalene blockade was successful in all patients and all redosed catheters were functional after 24 h with the continuous catheter insertion system. We conclude that it is possible to achieve a high rate of successful catheter placement and analgesia by using the continuous catheter insertion system and a disposable infusion pump in the ambulatory setting. This method of analgesia may offer improved pain relief after outpatient rotator cuff repair.
Anesthetic effects on cerebral metabolic rate predict histologic outcome from near-complete forebrain ischemia in the rat.
BACKGROUND: Although reduction of cerebral metabolic rate is thought to contribute to anesthetic neuroprotection, histologic evidence to support this concept has not been provided. In this study, histologic outcome was evaluated in rats subjected to different durations of severe forebrain ischemia while anesthetized with volatile anesthetics that have substantially different effects on cerebral metabolic rate. METHODS: Normothermic rats that underwent fasting were anesthetized with 0.75 minimum alveolar concentration (MAC) isoflurane-60% nitrous oxide (N2O) or 0.75 MAC halothane-60% N2O. Ischemia was induced with use of a combination of bilateral carotid occlusion and controlled hypotension. Rats in the isoflurane group were subjected to 6.5 min or 8.0 min ischemia, whereas the halothane group received 6.5 min ischemia. Histologic damage was assessed 4 days later. RESULTS: With 6.5 min ischemia, mean +/- SD, hippocampal CA1 percent of dead (% dead) neurons was reduced with isoflurane-N2O (45 +/- 18) versus halothane-N2O (60 +/- 23, P = 0. 023). Eight minutes of ischemia increased % dead neurons in the isoflurane-N2O group (60 +/- 17, P = 0.017). There was no difference between the isoflurane 8.0-min and halothane 6.5-min groups (P = 0. 935). A similar pattern was observed in hippocampal CA4 and the neocortex. Striatal damage was not affected by anesthetic or ischemic duration. CONCLUSIONS: At 6.5 min ischemia, isoflurane provided improved outcome versus halothane. Previous research has shown that 0.75 MAC isoflurane-N2O increases the time to onset of ischemic depolarization by 1.5 min and reduces cerebral metabolic rate by 42% versus 0.75 MAC halothane-N2O. In the current study, when the duration of ischemia was increased by 1.5 min in the isoflurane-N2O group, histologic outcome became similar to that in halothane-N2O-anesthetized rats. These results provide evidence that cerebral metabolic rate reduction has an advantageous effect on outcome from severe brain ischemia, but also suggest that such benefit is likely to be small.
Periischemic cerebral blood flow (CBF) does not explain beneficial effects of isoflurane on outcome from near-complete forebrain ischemia in rats.
BACKGROUND: Isoflurane improves outcome from near-complete forebrain ischemia in rats compared with fentanyl-nitrous oxide (N2O). Sympathetic ganglionic blockade with trimethaphan abolishes this beneficial effect. To evaluate whether anesthesia-related differences in cerebral blood flow (CBF) may explain these findings, this study compared regional CBF before, during, and after near-complete forebrain ischemia in rats anesthetized with either isoflurane (with and without trimethaphan) or fentanyl-nitrous oxide. METHODS: Fasted, normothermic isoflurane anesthetized Sprague-Dawley rats were prepared for near-complete forebrain ischemia (10 min of bilateral carotid occlusion and mean arterial pressure = 30 mmHg). After surgery, rats were anesthetized with either 1.4% isoflurane (with or without 2.5 mg of trimethaphan intravenously at onset of ischemia) or fentanyl-nitrous oxide (25 microgram. kg-1. h-1. 70% N2O-1). Regional CBF was determined (14C-iodoantipyrine autoradiography) before ischemia, 8 min after onset of ischemia, and 30 min after onset of reperfusion. RESULTS: Regional CBF did not differ significantly among groups at any measurement interval. Ischemia caused a marked flow reduction to 5% or less of baseline (P < 0.001) in selectively vulnerable regions, such as the cortex, caudoputamen and hippocampus, whereas flow in the brain stem and cerebellum was preserved. Reperfusion at 30 min was associated with partial restoration of flow to 35-50% of baseline values in ischemic structures. CONCLUSIONS: The results indicate that improved histologic-behavioral outcome provided by isoflurane anesthesia cannot be explained by differential vasodilative effects of the anesthetic states before, during, or after severe forebrain ischemia. This study also shows severe postischemic delayed hypoperfusion that was not affected by choice of anesthetic or the presence of trimethaphan. Mechanisms other than effects on periischemic CBF must be responsible for beneficial effects of isoflurane in this model.
Hyperglycemia enhances extracellular glutamate accumulation in rats subjected to forebrain ischemia.
BACKGROUND AND PURPOSE: An increase in serum glucose at the time of acute ischemia has been shown to adversely affect prognosis. The mechanisms for the hyperglycemia-exacerbated damage are not fully understood. The objective of this study was to determine whether hyperglycemia leads to enhanced accumulation of extracellular concentrations of excitatory amino acids and whether such increases correlate with the histopathological outcome. METHODS: Rats fasted overnight were infused with either glucose or saline 45 minutes before the induction of 15 minutes of forebrain ischemia. Extracellular glutamate, glutamine, glycine, taurine, alanine, and serine concentrations were measured before, during, and after ischemia in both the hippocampus and the neocortex in both control and hyperglycemic animals. The histopathological outcome was evaluated by light microscopy. RESULTS: There was a significant increase in extracellular glutamate levels in the hippocampus and cerebral cortex in normoglycemic ischemic animals. The increase in glutamate levels in the cerebral cortex, but not in the hippocampus, was significantly higher in hyperglycemic animals than in controls. Correspondingly, exaggerated neuronal damage was observed in neocortical regions in hyperglycemic animals. CONCLUSIONS: The present results demonstrate that, at least in the neocortex, preischemic hyperglycemia enhances the accumulation of extracellular glutamate during ischemia, providing a tentative explanation for why neuronal damage is exaggerated.
Isoflurane neuroprotection: a passing fantasy, again?
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Effect of intracerebral norepinephrine depletion on outcome from severe forebrain ischemia in the rat.
Manipulations of plasma catecholamine concentrations influence outcome from ischemic brain insults. It has been suggested that these effects are mediated by influences on brain catecholamine concentrations. This study examined whether major changes in brain norepinephrine concentrations can alter outcome from severe forebrain ischemia. Sprague-Dawley rats were administered 50 mg/kg i. p. N-(chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) or were left untreated (control). One week later, these rats were subjected to either 7 or 8 min of normothermic forebrain ischemia (bilateral carotid occlusion and MABP=30 mmHg) and allowed to recover for 4 days. Histologic damage was then evaluated. In other control and DSP-4-treated animals, hippocampal microdialysate norepinephrine concentrations were measured before, during and after 8 min of forebrain ischemia. Norepinephrine concentrations were also determined in brain homogenates from non-ischemic DSP-treated and control rats. A 95% depletion of norepinephrine was observed in brain homogenates from non-ischemic DSP-4-treated rats compared with control. During ischemia, microdialysate norepinephrine concentrations increased in control but not in DSP-4-treated rats (P=0.002). For plasma, intra-ischemic epinephrine concentrations increased 8-10-fold and returned to baseline values post-ischemia with no differences between groups. Plasma norepinephrine values remained unchanged in both groups. Histologic damage resulting from either 7 or 8 min of ischemia in hippocampal structures, caudoputamen, and neocortex was similar between DSP-4-treated and control groups. This study could not identify any effect of major changes in brain norepinephrine concentrations on ischemic brain damage. These data indicate that peripheral catecholamine effects on near-complete forebrain ischemic outcome are unlikely to be mediated by effects on central catecholamine concentrations.
Pre-ischemic depletion of brain norepinephrine decreases infarct size in normothermic rats exposed to transient focal cerebral ischemia.
This study examined the importance of brain norepinephrine concentration on outcome from a focal ischemic insult. Fasted temperature-controlled male Wistar rats pretreated with DSP-4, (N-(chloroethyl)-N-ethyl-2-bromobenzylamine), to selectively deplete brain norepinephrine, were subjected to reversible filament occlusion of the middle cerebral artery for 75 min in the awake state. After 3 days recovery, total infarct volume in DSP-4 treated rats (185 +/- 107 mm3) was reduced vs. untreated control animals (242 +/- 71 mm3, P = 0.04). Subcortical infarct volume was also smaller in the DSP-4 group (93 +/- 44 vs. 121 +/- 28 mm3, P = 0.02). Cortical infarct volume was not statistically different between groups. Neurologic function correlated with infarct-size. These findings suggest that brain norepinephrine affects stroke development either by direct neuronal toxicity and/or through influences on the penumbral circulation. Dampening of the central stress response induced by the onset of stroke may thus be advantageous.
Extracellular superoxide dismutase deficiency worsens outcome from focal cerebral ischemia in the mouse.
The role of endogenous extracellular superoxide dismutase (EC-SOD) was examined in a murine model of transient focal cerebral ischemia. Homozygous EC-SOD deficient (EC-SOD-/-; n = 18) and wild type (EC-SOD+/+; n = 19) littermates were anesthetized with halothane and subjected to 50 min of intraluminal middle cerebral artery occlusion with pericranial temperature maintained at 37.0 degrees C. After 24 h of reperfusion, resultant hemiparesis and cerebral infarct size were measured. Total infarct volume was 81% greater (P = 0.03) and hemiparesis was more severe (P = 0.01) in EC-SOD-/- versus EC-SOD+/+ mice. The worsened ischemic outcome observed in EC-SOD-/- mice is consistent with prior work which found transgenic EC-SOD overexpressing mice to exhibit enhanced tolerance to focal ischemia. The results suggest that endogenous antioxidant activity in the extracellular compartment plays an important role in the histologic/neurologic response to focal cerebral ischemia.
Effects of RSR13, a synthetic allosteric modifier of hemoglobin, alone and in combination with dizocilpine, on outcome from transient focal cerebral ischemia in the rat.
This study examined the effect of a pharmacologically induced rightward shift in the partial pressure of oxygen at which 50% of hemoglobin is saturated (P50) on outcome from transient focal cerebral ischemia in the rat. Halothane anesthetized rats (n=20 per group) were given saline or a single 15-min infusion of 150 mg/kg RSR13 (2-[4-[[3,5-dimethylanilino) carbonyl]methyl]phenoxy]-2-methylproprionic acid) intravenously before or 30 min after onset of 75 min of middle cerebral artery filament occlusion (MCAO). Seven days later, severity of hemiparesis and cerebral infarct size were examined. RSR13 alone did not significantly improve outcome. Conscious normothermic rats (n=12 per group) were also given RSR13 (150 mg/kg) or 0.9% NaCl intravenously and subjected to 75 min of MCAO with 7 days of recovery. Again, RSR13 alone did not significantly reduce infarct size or improve neurologic score. A dose-response curve for dizocilpine (MK-801) was then constructed in conscious normothermic rats subjected to 75 min of MCAO. Dizocilpine (0.5 mg/kg i.v.) caused a 90% reduction in mean infarct size while 0.25 mg/kg reduced infarct size by 48%. Other rats were then subjected to 75 min of MCAO after being given dizocilpine (0.25 mg/kg i.v.; n=18) or RSR13 (150 mg/kg i.v. )+dizocilpine (0.25 mg/kg i.v.; n=15). RSR13+dizocilpine resulted in smaller cortical infarct volume (8+/-14 mm3 vs. 34+/-37 mm3, p<0.02) and total cerebral infarct volume (46+/-28 mm3 vs. 81+/-60 mm3, p<0. 05) compared to dizocilpine alone, respectively. We conclude that a pre-ischemic peak increase in P50 of approximately 25 mmHg alone is insufficient to reduce focal ischemic injury, but may be advantageous when used in conjunction with other neuroprotective agents.
Characterization of a recovery global cerebral ischemia model in the mouse.
Transgenic/knockout murine variants allow roles of specific proteins to be studied in cerebral ischemia. Because of the size of mice, however, study of prolonged recovery from global ischemia has been limited. This project characterized an adaptation of the rat two-vessel occlusion model of global ischemia for use in the mouse. C57B1/6J mice (8 weeks old; 21 +/- 1 g) were overnight fasted, anesthetized with halothane, intubated and mechanically ventilated. The right internal jugular vein and femoral artery were cannulated. Pericranial temperature was held at 37.0 degrees C. The carotid arteries were occluded and mean arterial pressure was reduced to 35 mmHg with 0.3 mg intra-arterial trimethaphan and venous exsanguination. Electroencephalographic isoelectricity was confirmed in cohort mice. Ten minutes later ischemia was reversed. Mice were allowed 1, 3 or 5 days survival followed by histologic analysis. Regional cerebral blood flow (CBF) was determined autoradiographically. Outcome effects of intra-ischemic hyperglycemia (approximately 350 mg/dl) or hypothermia (34 degrees C) were also examined. The mortality rate was less than 10% in all recovery groups. Ischemia caused reduction of CBF to < 2% of sham values in cortex, hippocampus, and caudoputamen. CBF was unchanged in thalamus, brainstem and cerebellum. CA1 damage, greater after 3 days vs. 1 day reperfusion, was not further increased at 5 days. Histologic injury was increased by hyperglycemia although seizures did not occur. Hypothermia reduced CA1 damage. This study demonstrates feasibility of using the two-vessel occlusion + hypotension recovery model in the mouse. Recovery intervals of > or = 3 days are required to account for delayed CA1 neuronal necrosis. Histologic outcome can be modulated by known physiologic determinants of ischemic brain damage.
Mice overexpressing extracellular superoxide dismutase have increased resistance to focal cerebral ischemia.
Transgenic mice, which had been transfected with the human extracellular superoxide dismutase gene, causing an approximate five-fold increase in brain parenchymal extracellular superoxide dismutase activity, were used to investigate the role of extracellular superoxide dismutase in ischemic brain injury. Transgenic (n = 21) and wild-type (n = 19) mice underwent 90 min of intraluminal middle cerebral artery occlusion and 24 h of reperfusion. Severity of resultant hemiparesis and cerebral infarct size were measured. Wild-type mice had larger infarcts (cortex: wild type =37+/-14 mm3, transgenic = 27+/-13 mm3, P=0.03; subcortex: wild type = 33+/-14 mm3, transgenic = 23+/-10 mm3, P = 0.02). Neurological scores, however, were similar (P = 0.29). Other mice underwent autoradiographic determination of intra-ischemic cerebral blood flow. The volume of tissue at risk of infarction (defined as volume of tissue where blood flow was <25 ml/100g/min) was similar between groups (cortex: wild type = 51+/-15 mm3, transgenic = 47+/-9 mm3, P=0.65; subcortex: wild type = 39+/-16 mm3, transgenic= 37+/-17 mm3, P=0.81). These results indicate that antioxidant scavenging of free radicals by extracellular superoxide dismutase plays an important role in the histological response to a focal ischemic brain insult.
The effects of aprotinin on outcome from cerebral ischemia in the rat.
UNLABELLED: The administration of aprotinin has been associated with a reduction in cardiac surgery-related stroke. Intrinsic neuroprotective properties of this drug have not been evaluated in laboratory outcome models of cerebral ischemia. The purpose of this study was to determine whether aprotinin exhibits neuroprotective effects against either global or focal cerebral ischemia in the rat. Fasted rats were administered aprotinin (30,000 or 60,000 KIU/kg) or vehicle (0.9% NaCl) IV before global ischemia (10 min bilateral carotid occlusion with mean arterial pressure 30 mm Hg) or focal ischemia (75 min of transient middle cerebral artery occlusion [MCAO]). Five days after global ischemia, the percentage of dead hippocampal CA1 neurons (mean +/- SD) was similar among the groups (small-dose aprotinin: 49+/-31, n = 15; large-dose aprotinin: 55+/-31, n = 13; vehicle: 47+/-31, n = 16; P = 0.74). After 7 days' recovery from MCAO, no difference among the groups was observed for either neurologic score (P = 0.99) or cerebral infarct volume (small-dose aprotinin: 136+/-80 mm3, n = 23; large-dose aprotinin: 132+/-101 mm3, n = 11; vehicle: 121+/-81 mm3, n = 21; P = 0.87). IMPLICATIONS: Aprotinin offers no neuroprotection against either global or focal cerebral ischemia in the rat when administered as a single preischemic bolus.