We evaluated therapeutic and preventive properties of dehydroepiandrosterone (DHEA), a weak androgenic steroid, against isoproterenol-induced cardiomyopathy. The cardiomyopathy was induced by daily i.p. administration of isoproterenol to rats for five days. One group of rats were given with daily s.c. for 5 days during isoproterenol and the other group with daily s.c. DHEA for total 10 days, including 5 days before and during isoproterenol. The animals were killed after each treatment, and cardiac muscle failure was evaluated using histopathologic examination and biochemical indices. DHEA was found to reduce the damaged area and inhibit the elevation in the serum levels of glutamic oxaloacetic transaminase (SGOT), lactate dehydrogenase (LDH), skeletal muscle creatine kinase (CK) and heart creatine kinase (CK-MB) induced by isoproterenol. We also assayed widely used oxidative stress parameters, including thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase and glutathion peroxidase (GPx). DHEA decreased the escalated level of TBARS and enhanced the anti oxidant defense reaction with an increase in Mn-SOD and Cu/Zn-SOD. On the other hand, the treatment with DHEA did not affect catalase and GPx activity. The present study indicates that DHEA has a therapeutic and preventive effect against isoproterenol-induced cardiomyopathy and its effects may depend largely on the increase in SOD activity.
Animals ; Aspartate Aminotransferases ; Cardiomyopathies* ; Catalase ; Creatine Kinase ; Dehydroepiandrosterone* ; Hand ; Heart ; Isoproterenol ; L-Lactate Dehydrogenase ; Muscle, Skeletal ; Myocardium ; Oxidative Stress ; Peroxidase ; Rats* ; Superoxide Dismutase ; Thiobarbituric Acid Reactive Substances

BACKGROUND: Spinal cord injury occurring as the result of surgical repair of thoracic and thoracoabdominal aortic disease remains a devastating complication. Excitatory amino acids have been known to cause neurologic injury after neuronal ischemia. The purpose of this study was to elucidate the effects of intrathecal ketamine or NBQX on neurologic outcome and NMDA receptor gene expression in transient spinal ischemia. METHODS: Sprague-Dawley rats were anesthetized with enflurane, divided by 4 groups: Control (C group), Intrathecal ketamine 0.1 mg (K-1 group), Intrathecal ketamine 0.2 mg (K-2 group), and intrathecal NBQX 1 nM (N group). Spinal ischemia was produced by both induced hypotension and thoracic aortic cross clamping. After spinal ischemia, neurologic scores were assessed after 1, 2, 3 hours. After 3 hours rats were euthenized and spinal cords were removed for the assay of NMDAR and mGlu1 mRNA. RESULTS: The neurol ogic scores of K-2 and N groups were significantly lower than C group and K-1 group. There were no significant difference between K-1 group and C group. The NMDAR and mGlu1 gene expression was increase in C and K-1 group compared to sham operation. In K-2 and N groups, the gene expressions were significantly lesser than C group. CONCLUSIONS: The NMDAR and mGlu1 gene expressions were increased in transient spinal ischemia. Intrathecal ketamine and NBQX were effective in preventing neurologic injury after transient spinal ischemia. The NMDA antagonistic action of ketamine might involve to prevent neurologic injury.
Animals ; Aortic Diseases ; Constriction ; Enflurane ; Excitatory Amino Acids ; Gene Expression ; Glutamic Acid* ; Hypotension ; Ischemia* ; Ketamine* ; N-Methylaspartate ; Neurons ; Rats* ; Rats, Sprague-Dawley ; Receptors, Glutamate* ; RNA, Messenger* ; Spinal Cord Injuries ; Spinal Cord*

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. Amrinone, a specific inhibitor of phosphodiesterase 3, has an antioxidant activity against PMNs. Therefore, we hypothesized that amrinone could attenuate PMNs-induced cardiac dysfunction by suppression of reactive oxygen species (ROS) produced fby PMNs. In the present study, we examined the effects of amrinone on isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Amrinone at 25microM, given to hearts during the first 5 min of reperfusion, significantly improved coronary flow, left ventricular developed pressure (P< 0.001), and the maximal rate of development of left ventricular developed pressure (P< 0.001), compared with ischemic/reperfused hearts perfused with PMNs in the absence of amrinone. In addition, amrinone significantly reduced myeloperoxidase activity by 50.8%, indicating decreased PMNs infiltration (p< 0.001). Superoxide radical and hydrogen peroxide production were also significantly reduced in fMLP- and PMA-stimulated PMNs pretreated with amrinone. Hydroxyl radical was scavenged by amrinone. fMLP-induced elevation of [Ca2+]i was also inhibited by amrinone. These results provide evidence that amrinone can significantly attenuate PMN-induced cardiac contractile dysfunction in the ischemic/ reperfused rat heart via attenuation of PMNs infiltration into the myocardium and suppression of ROS release by PMNs.
Amrinone* ; Animals ; Cyclic Nucleotide Phosphodiesterases, Type 3* ; Heart ; Hydrogen Peroxide ; Hydroxyl Radical ; Ischemia ; Myocardium ; Neutrophils ; Peroxidase ; Rats ; Reactive Oxygen Species ; Reperfusion ; Superoxides

BACKGROUND: The purpose of this study was to compare the onset time, degree and duration of motor block, and the satisfaction of surgeons of given single epidural injections of 1.0% ropivacaine and 0.5% bupivacaine in patients undergoing hip arthroplasty surgery. METHODS: In a double-blind randomized study involving 20 patients, patients randomly received 12 ml of 1.0% ropivacaine or 0.5% bupivacaine at the L2 - 3 or L3 - 4 interspace. Parameters measured were the onset time, duration and degree of motor block, and the satisfaction of the surgeons. RESULTS: Mean onset time of Bromage scale 2 was significantly slower with 1% ropivacaine (14.6 +/- 1.3 min) than with 0.5% bupivacaine (15.7 +/- 2.0 min). However, each frequency of motor blockade (Bromage scale 1, 2 and 3) with 1.0% ropivacaine (10, 8 and 7) was greater than that seen with 0.5% bupivacaine (7, 6 and 1). For scales 1 and 2, 1.0% ropivacaine had a significantly longer duration than 0.5% bupivacaine and the overall duration of motor blockade with 1.0% ropivacaine was longer than 0.5% bupivacaine. Motor block was in 80% achieved satisfactorily of the ropivacaine group and 60% of the bupivacaine group by the surgeons. CONCLUSIONS: In conclusion this study demonstrated that 1.0% ropivacaine provides a more rapid onset time, greater degree and longer duration of motor block without unacceptable side effects than 0.5% bupivacaine for hip arthroplasty surgery. From these results, it may suggest that 1.0% ropivacaine may be useful for lower extremity orthopedic surgery requiring good muscle relaxation.
Anesthesia, Epidural* ; Arthroplasty* ; Bupivacaine* ; Hip* ; Humans ; Injections, Epidural ; Lower Extremity ; Muscle Relaxation ; Orthopedics ; Weights and Measures

BACKGROUND: Delayed neuronal injury after cerebral ischemia came major neurologic complication after stroke or cardiac arrest. Apoptosis formation after ischemia may be one of a mechanism of delayed neuronal injury. This study was conducted to evaluate the effect of moderate hypothermia on apoptosis formation after one hour of middle cerebral artery degrees Cclusion in rats. METHODS: Ten Sprague-Dawley rats (300 g) were freely fed till just before operation. Anesthesia was induced with 4 vol% isoflurane in oxygen and then maintained with 2 vol% isoflurane in oxygen. Middle cerebral artery degrees Cclusion (MCAO) was induced by intraluminal monofilament nylon with blunted tip. All rats were divided randomly into two groups. In group 1 (n=5), rectal temperature was maintained at 38 degrees C. In group 2 (n=5), rectal temperature was maintained at 32 degrees C. Rectal temperature was monitored during experiment. After 60 minutes of MCAO, intraluminal monofilament was removed and all rats were returned to cages. Brain were quickly removed and cerebral hemispheres were separated after 23 hours reperfusion. Apoptosis formation were counted with TUNEL stain. RESULTS: In group 1, after 60 minutes of MCAO and 23 hours reperfusion, 51 3.6% of hipp degrees Campal neurons were TUNEL-positive stained apoptotic cells. In group 2, TUNEL-positve neurons were 26.1 6.5% and significantly less than those of group 1 (p<0.05). CONCLUSIONS: Sixty minutes of MCAO and 23 hours reperfusion induce hipp degrees Campal neuronal apoptosis. Moderate hypothermia of 32 degrees C reduces apoptosis of hipp degrees Campal neurons after 60 minutes of MCAO and 23 hours reperfusion.
Anesthesia ; Animals ; Apoptosis* ; Brain ; Brain Ischemia* ; Cerebrum ; Heart Arrest ; Hypothermia* ; In Situ Nick-End Labeling ; Ischemia ; Isoflurane ; Middle Cerebral Artery ; Neurons ; Nylons ; Oxygen ; Rats* ; Rats, Sprague-Dawley ; Reperfusion ; Stroke

BACKGROUND: Intravenous anesthetics such as propofol and ketamine have been known to have neuroprotective effects. However, the combination of these drug is not known. This study was conducted to determine the neuroprotective effects of propofol, ketamine or both after transient forebrain ischemia. METHODS: Twenty Sprague-Dawley rats (250-300 gm) were used. Anesthesia was induced with 4% isoflurane in oxygen and then maintained with 1 - 2% isoflurane in oxygen. Ischemic injury was induced by 10 minutes of both common carotid artery ligation and hypotension (MAP < 50 mmHg). All rats were randomly divided into four groups: group I; control group; group II; ketamine 10 mg/kg was administered 10 minutes before injury; group III; propofol (1 mg/kg/min) was administered until EEG isoelectricity; and group IV; ketamine 10 mg/kg and propofol 1 mg/kg/min was administered. The Rectal temperature was maintained at 38oC. After forebrain ischemia, neurologic scores were estimated at 1 hr, 2 hrs, 1 day and 2 days after recovery. The brain was removed 3 days after and stained with H-E stain. RESULTS: Neurologic and histologic scores of group II, III, IV were significantly lower than that of group I. However, there were no significant difference between group II, III and IV. CONCLUSIONS: Ketamine and propofol have neuroprotective effects in transient forebrain ischemia in rats. However, the combination of propofol and ketamine did not show any synergistic or additive effects.
Anesthesia ; Anesthetics, Intravenous ; Animals ; Brain ; Carotid Artery, Common ; Electroencephalography ; Hypotension ; Ischemia* ; Isoflurane ; Ketamine* ; Ligation ; Neuroprotective Agents* ; Oxygen ; Propofol* ; Prosencephalon* ; Rats* ; Rats, Sprague-Dawley

BACKGROUND: Tissue injury by surgical manipulation or trauma may cause pain hypersensitivity secondary to central sensitization. The aim of this study was to evaluate the postoperative effect of gabapentin on incisional pain in rat pretreated with pentylenetetrazole. METHODS: Thirty rats were divided into 5 groups, a control group (n = 10), PTZ 10 group (n = 5), PTZ 20 group (n = 5), PTZ 30 group (n = 5), and a PG 30 group (n = 5). To evaluate postoperative mechanical hyperalgesia in injured feet, withdrawal thresholds were measured by calibrated von Frey filaments at 2 hr, 1 day, 2 days, 3 days, 4 days, and 5 days after the incision. RESULTS: The PTZ 10, 20, and 30 groups showed no significant difference in withdrawal thresholds when compared with the control group during 5 days postoperatively. There were no significant differences in withdrawal thresholds among the PTZ 10, 20, and 30 groups. However, the PG 30 group showed a significantly lower withdrawal threshold compared with the control group at postoperative days 3, 4 (p < 0.05), and 5 (p < 0.01). CONCLUSIONS: Intraperitoneal pentylenetetrazole administered before an incision had no effect on postoperative pain in the incisional pain model. However, gabapentin injection after an incision in rats pretreated with pentylenetetrazole caused hyperalgesia during 5 days postoperatively.
Animals ; Central Nervous System Sensitization ; Foot ; Hyperalgesia ; Hypersensitivity ; Pain, Postoperative ; Pentylenetetrazole* ; Rats*

BACKGROUND: The bispectral index (BIS) has been used as an indicator of a sedative state and has been considered to be related to anesthetic agents and noxious stimulus. In this study, we measured the BIS, blood pressure (BP) and heart rate (HR) during induction of anesthesia after premedication with or without midazolam or morphine and evaluated the bispectral index as an indicator of an objective evaluation of midazolam premedication and relation to the cardiovascular response to the anesthetic induction. METHODS: Seventy five patients scheduled to undergo elective surgery under general anesthesia were divided into 3 groups. Each group received midazolam and glycopyrrolate (midazolam group, n = 25), or morphine and glycopyrrolate (morphine group, n = 25), or glycopyrrolate only (control group, n = 25) as premedication (midazolam 0.08 mg/kg IM, morphine 0.05 mg/kg IM, glycopyrrorate 0.2 mg IM). Then, anesthetic induction (propofol 2 mg/kg, succynylcholine 1 mg/kg) was done. The bispectral index, blood pressure, and heart rate were measured at before induction, after propofol injection, and intubation. RESULTS: The Bispectral index was significantly lower in the midazolam group and the morphine group compared with the control group before anesthetic induction. Blood pressure was not significantly different among the three groups. Heart rate was significantly lower in the midazolam group compared with the control group before anesthetic induction. CONCLSIONS: Midazolam or morphine premedicated patients appear to maintain a stable heart rate and have a low BIS at before induction. The Bispectral index could be objectively used in midazolam-premedicated patients when evaluating the degree of sedation and predicting hemodynamic changes, and probably in morphine-premedicated patients also.
Anesthesia ; Anesthesia, General ; Anesthetics ; Blood Pressure ; Glycopyrrolate ; Heart Rate ; Hemodynamics ; Humans ; Intubation ; Midazolam* ; Morphine* ; Premedication* ; Propofol

BACKGROUND: Midazolam is often used as an anxiolytic premedication before surgery, but it is difficult and complex to assess its effect. This study evaluated the bispectral index as an objective indicator of midazolam premedication and the relation of cardiovascular response to anesthetic induction. METHODS: Forty patients (aged 20 to 60 and in ASA class I or II) to undergo simple elective surgery under general anesthesia entered the study. The patients were divided into the midazolam group (n = 20) that received midazolam (0.08 mg/kg IM) and glycopyrrolate (0.2 mg IM) premedication, and the control group (n = 20) that received glycopyrrolate (0.2 mg IM) only. Then, anesthetic induction (fentanyl 1 microgram/kg, propofol 2 mg/kg, succinylcholine 1 mg/kg) was done. The bispectral index of the electroencephalogram, blood pressure, and heart rate were measured under unanesthetized conditions, after fentanyl, propofol injection, and intubation. RESULTS: The bispectral index was significantly lower in the midazolam group as compared with the control group before anesthetic induction, after fentanyl injection, and intubation. Blood pressure was not significantly different in the two groups. Heart rate was significantly lower in the midazolam group compared with the control group before anesthetic induction and after fentanyl injection. CONCLUSIONS: Midazolam-premedicated patients appear to maintain stable hemodynamics during anesthetic induction and intubation. The bispectral index can be objectively used in midazolam-premedicated patients when evaluating the degree of sedation. (Korean J Anesthesiol 2000; 38: 947~953)
Anesthesia, General ; Blood Pressure ; Electroencephalography ; Fentanyl ; Glycopyrrolate ; Heart Rate ; Hemodynamics ; Humans ; Intubation ; Midazolam* ; Premedication* ; Propofol ; Succinylcholine

BACKGROUND: After experimental cryogenic cerebral injury, severe focal brain contusion develops due to blood-brain barrier breakdown and vasogenic cerebral edema formation. This study has been conducted to find out the effects of hypertonic saline against cryogenic brain edema in rats. METHODS: Thirty rats of either sex weighing 250 to 300 g underwent a 60 seconds of cryogenic brain injury. All rats were randomly divided into one of three groups; control group (n = 10), 7.5% saline group (n = 10), and 10% mannitol group (n = 10). The water contents were measured 60 minutes after cryogenic injury by using the dry-weight method. RESULTS: The water contents in the 7.5% saline and 10% mannitol groups were significantly decreased compared with the control group. The levels of edema in the 7.5% saline and 10% mannitol groups were also significantly decreased compared with the control group. Although it appeared as if that 10% mannitol might decrease edema formation more than 7.5% saline, there were no statistical differences between the 7.5% saline and 10% mannitol groups. CONCLUSIONS: Hypertonic saline (7.5%) may be as effective agent to reduce edema formation after brain trauma to the same degree as mannitol.
Animals ; Blood-Brain Barrier ; Brain Edema ; Brain Injuries* ; Brain* ; Edema* ; Mannitol* ; Rats*