[Anesthetic management for removal of a giant ovarian tumor using FloTrac x Vigileo monitoring system].

We successfully managed anesthesia in a patient with a giant ovarian tumor weighting 22 kg, using FloTrac x Vigileo monitoring system. A 43-year-old woman (67.2 kg, 154.5 cm and abdominal girth 111.3 cm) was admitted for removal of a giant ovarian tumor. Arterial blood pressure (ABP), heart rate, percutaneous arterial oxygen saturation, cardiac index (CI) and stroke volume variation (SVV) were monitored. General anesthesia was induced, with the patient in the supine position, using 50 mg propofol, 0.25 microgram x kg(-1) x min(-1) remifentanil. 30 mg rocuronium bromide and inhalation of 100% oxygen, and maintained with sevoflurane 1.5% and remifentanil administration between 0.1-0.3 microgram x kg(-1) x min(-1). Following 6 l fluid drainage from the ovarian tumor, ABP and CI decreased, but SVV remained within normal ranges. Therefore, we only decreased the drainage speed without increasing fluid administration rate. When the tumor was lifted up, both CI and SVV increased, but the increase of SVV was 10%, still within normal ranges. Therefore, we did not increase fluid administration rate to avoid excessive hydration. After tracheal extubation, respiratory and hemodynamic states were stable, and the patient had no postoperative complication. We conclude that FloTrac x Vigileo System is useful for monitoring cardiac performance parameters, and helps anesthesiologists adjust drainage speed of the content and infusion rate to maintain the stability of circulatory state, in removal of a giant cyst.

Alleviation of ischemia-induced brain edema by activation of the central histaminergic system in rats.

We have reported that facilitation of central histaminergic activity prevents the development of ischemia-induced brain injury. Since cerebral edema is a major cause of brain damage, we studied effects on brain edema of postischemic administration of L-histidine, a precursor of histamine, and thioperamide, a histamine H(3)-receptor antagonist, both of which enhance central histaminergic activity. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery in rats, and the water content and infarct size were determined 24 h after reperfusion. Changes in the extracellular concentration of histamine were examined in the striatum by a microdialysis procedure, and effects of these compounds were evaluated. Repeated administration of L-histidine (1000 mg/kg x 2, i.p.), immediately and 6 h after reperfusion, reduced the increase in the water contents in ischemic regions. Simultaneous administration of thioperamide (5 mg/kg, s.c.) with L-histidine (1000 mg/kg, i.p.) completely prevented edema formation and alleviated brain infarction, although a single dose of L-histidine, immediately after reperfusion, showed no benefits. The striatal histamine level was gradually increased after reperfusion as well as during ischemia. Simultaneous administration of thioperamide with L-histidine markedly increased the brain histamine concentration, and the value increased up to 230% of that in the saline group 5 - 6 h after reperfusion. L-Histidine alone did not affect the increase in the histamine output after ischemia. These findings suggest that further activation of the central histaminergic system after initiation of cerebral ischemia prevents development of ischemia-induced brain edema.

Bilateral brachial plexus injury after liver transplantation.

We report a case of bilateral brachial plexus injury following living-donor liver transplantation. A 35-year-old man with hepatitis C cirrhosis underwent liver transplantation under general anesthesia, performed in the supine position with 90 degrees arm abduction. The surgery lasted for 14 h, and the anesthesia for 16 h. On postoperative day 1, it was noticed that he had brachial plexus injuries. We investigated the cause of the nerve injuries, in particular, the possible involvement of stretching, compression, or nerve ischemia, which can often result from excessive abduction, the use of shoulder braces, compression by the poles used in the operating theater or compression caused by surgeons leaning on the patient, or serious general status (e.g., hypotension or hypoxemia). Our findings were inconclusive, but we postulated that 90 degrees abduction of the arms per se may have resulted in excessive stretching of the brachial nerves, causing his injuries.

Suppression of ischaemia-induced cytokine release by dimaprit and amelioration of liver injury in rats.

Inflammatory reactions play an important role in ischaemia/reperfusion injury in various organs. Since histamine H(4) action has been shown to prevent the development of ischaemia/reperfusion liver injury, we examined the effects of dimaprit, a histamine H(2)/H(4) receptor agonist, on ischaemia-induced cytokine release and liver damage. Male Wistar rats (300 g) were subjected to warm ischaemia for 30 min. by occlusion of the left portal vein and hepatic artery under halothane anaesthesia. Saline or dimaprit (20 mg/kg, subcutaneously) was injected immediately after reperfusion of blood flow. Transient ischaemia provoked severe liver damage 24 hr after reperfusion, and the plasma concentrations of alanine transaminase and aspartate transaminase were 4600 IU/l and 13,200 IU/l, respectively. The values in the dimaprit group were 55% and 46% of those in control animals, respectively. Dimaprit also reduced the infarct size to 50%. Liver ischaemia markedly increased interleukin-12 levels 2-24 hr after reperfusion. The dimaprit treatment depressed the values to 40-64% of those in the corresponding control group 4-24 hr after reperfusion. Since interleukin-12 facilitates cell-mediated cytotoxicity, the protective effect of dimaprit may be attributed to regulation of cytokine release during reperfusion.

Recovery of brain dopamine metabolism by branched-chain amino acids in rats with acute hepatic failure.

A decrease in the serum ratio of branched-chain amino acids (BCAAs) to aromatic amino acids (Fischer ratio) reflects the severity of hepatic encephalopathy, and clinical improvement by dietary augmentation with BCAAs has been demonstrated. As behavioral alteration results from changes in central neurotransmission, we investigated the role of BCAA administration on changes in the levels of central neurotransmitters in acute liver injury. Male Wistar rats were subjected to liver ischemia by occluding the left portal vein and hepatic artery for 90 minutes. A 4% BCAA solution containing valine, leucine, and isoleucine was intraperitoneally administered 3 times (8 mL/kg, each) at 1 hour, 6 hours, and 24 hours after vascular reperfusion, and changes in the extracellular concentrations of neurotransmitter amino acids, monoamines, and their metabolites were evaluated in the striatum by a microdialysis procedure. Although the extracellular concentration of dopamine was affected by neither liver ischemia nor BCAA injections, the level of 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine, decreased to 34% in the ischemic group 24 hours after reperfusion. The 3,4-dihydroxyphenylacetic acid level was normalized by treatments with BCAAs. The improvement of deranged cerebral dopaminergic activity may be a contributing factor in the improvement of hepatic encephalopathy by BCAAs.

Histaminergic involvement in neuropathic pain produced by partial ligation of the sciatic nerve in rats.

BACKGROUND AND OBJECTIVES: Because the histaminergic system in the brain is involved in regulation of pain, the relationship between central histaminergic activity and neuropathic pain is of interest. METHODS: Neuropathic pain was induced in rats by partial ligation of the left sciatic nerve, and changes in the extracellular concentration of histamine in the right striatum were examined by a microdialysis procedure 2 weeks later. The nociceptive threshold was determined with von Frey tests, and effects of histaminergic ligands were examined. RESULTS: Although the extracellular concentration of histamine did not differ between the sham-operated and ligated groups, histaminergic activity assessed by metoprine-induced accumulation of histamine was facilitated in ligated animals. The metoprine treatment ameliorated neuropathic pain in ligated animals, although the agent did not affect the threshold in sham-operated rats. Either intracerebroventricular (ICV) administration of histamine (30 microg) or intraperitoneal (IP) administration of L-histidine (370 mg/kg) decreased the nociceptive threshold in ligated rats. However, a high dose of histamine (180 microg ICV) increased the nociceptive threshold. Ranitidine (100 microg ICV), an H2 antagonist, increased the threshold, whereas pyrilamine (15 microg ICV), an H1 antagonist, showed no remarkable change. Administration of thioperamide (30 microg ICV), an H3 antagonist, increased the threshold, although systemic administration of the agent (3.6 mg/kg IP) decreased it. CONCLUSIONS: Blockade of supraspinal histamine H2 receptors or stimulation of spinal H3 receptors may contribute to alleviation of neuropathic pain.

Suppression of inflammatory cell recruitment by histamine receptor stimulation in ischemic rat brains.

Inflammation is a crucial factor in the development of ischemia-induced brain injury. Since facilitation of central histaminergic activity ameliorates reperfusion injury, effects of postischemic administration of L-histidine, a precursor of histamine, and thioperamide, a histamine H3 receptor antagonist, on inflammatory cell infiltration were evaluated in a rat model of transient occlusion of the middle cerebral artery. After reperfusion for 12, 24, or 72 h following 2 h of occlusion, brain slices were immunohistochemically stained with antibodies against myeloperoxidase and CD68, which were markers of polymorphonuclear leukocytes and macrophages/microglia, respectively. After reperfusion for 12-24 h, the number of neutrophils on the ischemic side increased markedly, whereas the increase was not observed on the contralateral side. Administration of L-histidine (1000 mg/kg x 2, i.p.), immediately and 6 h after reperfusion, reduced the number of neutrophils to 52%. Simultaneous administration of thioperamide (5 mg/kg, s.c.) further decreased the number of neutrophils to 32%. Likewise, the ischemia induced increase in the number of CD68-positive cells after 24 h was suppressed by L-histidine injections. The L-histidine administration decreased the number of CD4+ T lymphocytes on both ischemic and contralateral sides after 12 h, and concurrent administration of thioperamide prolonged the effect. Although administration of mepyramine (3 nmol, i.c.v.) did not affect suppression of leukocyte infiltration, ranitidine tended to reverse the effect of L-histidine. These data suggest that enhancement of central histaminergic activity suppresses inflammatory cell recruitment after ischemic events through histamine H2 receptors, which may be a mechanism underlying the protective effect of L-histidine.

Fluoroscopically guided epidural block in the thoracic and lumbar regions.

BACKGROUND AND OBJECTIVES: Epidural block in the midthoracic region is difficult, even with fluoroscopically guided methods, because of the inability to view the interlaminar space on radiographs. We have, therefore, proposed fluoroscopically guided epidural block for the midthoracic region, as well as other thoracic and lumbar regions, by use of the pedicle as a landmark to show the height of the interlaminar space. METHODS: Twenty patients scheduled to receive an indwelling epidural catheter at Th6-7, Th9-10, Th12-L1, or L3-4 were studied. The skin insertion site was at the junction of a line parallel to the vertebral column that passed through the middle of the pedicle and the lower border of vertebral body, immediately inferior to the target interlaminar space on an anteroposterior radiograph. The needle was walked up the lamina, and the interlaminar space was sought near the midline of the vertebra at the height of the pedicle. RESULTS: Epidural block was easily performed in all cases. No difference was observed in the angulation of the epidural needle among the groups; the mean inward and upward angulation were 38 degrees and 63 degrees , respectively, although the skin insertion site relative to the spinous process was different among the groups. CONCLUSIONS: This study showed the usefulness of our fluoroscopically guided method for the midthoracic region, and other thoracic and lumbar regions. We propose an alternative method for a blind epidural approach at Th6-7, Th9-10, Th12-L1, or L3-4.

A comparison of protective effects between L-histidine and hypothermia against ischemia-induced neuronal damage in gerbil hippocampus.

An increase in the histamine concentration in the brain has been demonstrated to provide protective effects against ischemia/reperfusion brain injury. Since hypothermia and barbiturates are also regarded to protect ischemic brains, effects of postischemic treatments were compared in gerbils between mild hypothermia and intraperitoneal administration of L-histidine, a precursor of histamine. Furthermore, effects of thioperamide, a histamine H(3) receptor antagonist, were evaluated in histidine-treated gerbils after 60 days. Transient forebrain ischemia for 4 min at 37 degrees C provoked severe neuronal damage in the hippocampal CA1 pyramidal cells after 7 days. Postischemic hypothermia (33 degrees C) for 3 h under pentobarbital anesthesia alleviated neuronal death, and the number of preserved neurons was 77+/-56/mm (mean+/-S.D., n=14). The effect of L-histidine injected three times, immediately, 6 h, and 24 h after reperfusion (1,000 mg/kg, i.p., each), was more prominent than that of hypothermia, and the number of preserved neurons was 142+/-55/mm (n=14). When the histologic outcome was evaluated after 60 days, most neurons were damaged in both the hypothermic and histidine groups. The improvement of the histologic outcome was observed even after 60 days in animals injected with thioperamide, immediately and 6 h after reperfusion (5 mg/kg, s.c., each), with three injections of l-histidine. The number of preserved neurons was 133+/-88/mm (n=10), while that in the hypothermic group was 7+/-15 (n=10). Activation of the central histaminergic system provides beneficial effects against cerebral ischemia.

Suppression of ischemia/reperfusion liver injury by histamine H4 receptor stimulation in rats.

Inflammatory reactions play an important role in ischemia/reperfusion injury in various organs. Since histamine is closely related to inflammatory reactions and immune responses, effects of postischemic administration of histaminergic ligands on ischemia-induced liver injury were examined in rats. Animals were subjected to warm ischemia for 30 min by occlusion of the left portal vein and hepatic artery under halothane anesthesia, and liver damage was evaluated by assessing plasma concentrations of transaminases after 24 h. Warm ischemia for 30 min provoked severe liver damage after 24 h, and the plasma concentrations of alanine transaminase (ALT) and aspartate transaminase (AST) were 8600 I.U./l and 13100 I.U./l, respectively. Subcutaneous injections of histamine twice, immediately and 6 h after reperfusion (20 mg/kg, each), alleviated liver damage. The plasma concentrations of ALT and AST in the histamine group were 35% and 24% of those in the control group, respectively. Neither mepyramine (3 mg/kg x 2), an H1 antagonist, nor cimetidine (15 mg/kg x 2), an H2 antagonist, affected the outcome in histamine-treated rats. However, thioperamide (5 mg/kg x 2), an H3/H4 antagonist, completely abolished the alleviation caused by histamine. Administration of dimaprit (1-10 mg/kg x 2), an H2/H4 agonist, mimicked the protective effect of histamine, and the effect of dimaprit is reversed by thioperamide, whereas neither H1 nor H2 antagonists altered the outcome caused by dimaprit. Clozapine (15 mg/kg x 2), an H4 agonist, also mimicked the protective effect of histamine. These findings indicate that stimulation of histamine H4 receptors after ischemic events prevents development of reperfusion injury in the liver.

Reduction in brain infarction by augmentation of central histaminergic activity in rats.

Inflammation is a factor in the aggravation of reperfusion injury after cerebral ischemia. Since histamine H(2) receptor stimulation suppresses inflammatory reactions, effects of the central histaminergic activation on brain infarction were examined in rats. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery, and the infarct size was determined by 2,3,5-triphenyltetrazolium chloride stain after 24 h. Effects of postischemic administration of thioperamide, an H(3) antagonist, and metoprine, an inhibitor of histamine-N-methyltransferase, were evaluated in rats treated with l-histidine, a precursor of histamine. Furthermore, effects of these agents on changes in the striatal histamine level were examined by a microdialysis procedure. Focal ischemia provoked marked damage in rats treated with l-histidine (1000 mg/kg) alone. Administration of l-histidine (1000 mg/kg) with either thioperamide (5 mg/kg) or metoprine (10 mg/kg) alleviated brain infarction. The size of brain infarction was 27% and 10% of that in animals treated solely with l-histidine, respectively. The combination treatment with thioperamide and metoprine decreased the size of brain infarction in rats given l-histidine (500 mg/kg), although protective effects were not clear without l-histidine. A marked increase in the histamine concentration was observed in the histidine plus metoprine group, the value being 363% of that in the saline-injected group after 2-3 h. The histamine concentrations in the histidine group and histidine plus thioperamide group were 188% and 248%, respectively. These findings indicate that facilitation of central histaminergic activity reduced the brain infarction.

Flumazenil-induced improvement of the central dopaminergic system in rats with acute hepatic failure.

Several reports have demonstrated the alleviation of hepatic encephalopathy by flumazenil, an antagonist of benzodiazepine receptors. As changes in central monoaminergic activity are involved in the mechanisms for hepatic encephalopathy, the effects of flumazenil on central monoaminergic activity were evaluated in acute hepatic failure produced by ischemia-reperfusion injury in rats. Eighteen male Wistar rats were evenly assigned to three groups: sham-operated group given saline, liver-ischemic group given saline, and liver-ischemic group given flumazenil. Flumazenil (1 mg/kg) or saline (10 mL/kg) was intraperitoneally administered three times, at 1, 6, and 24 hours after 90 minutes of liver ischemia produced by occlusion of the left portal vein. The extracellular concentrations of neurotransmitter amino acids, monoamines, and their metabolites were determined in the striatum using a microdialysis procedure. Another set of 12 rats was subjected to liver ischemia, and the effect of flumazenil on spontaneous motor activity was examined after 24 hours. The extracellular concentration of 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine, decreased to 39% of that in sham-operated animals 24 hours after surgery (P < 0.05), although the dopamine level did not change. The treatment with flumazenil completely abolished the decrease in the metabolite (P < 0.05). Although the glutamate level in the injured animals decreased to 42% of that in sham-operated animals (P < 0.05), no remarkable increase in the glutamate level was observed in animals treated with flumazenil. Spontaneous motor activity decreased 24 hours after surgery in animals subjected to liver ischemia. Flumazenil led to improvement of spontaneous motor activity 5 minutes after administration, but this effect was not observed after 30 minutes. The restoration of the central dopaminergic function may be a contributing factor in the improvement of hepatic encephalopathy.

Suppression of energy requirement by lidocaine in the ischemic mouse brain.

Effects of lidocaine on parameters of membrane functional integrity were investigated in the mouse brain. Changes in the direct-current potential shift in the cerebral cortex provoked by decapitation ischemia were compared in animals given lidocaine (0.05, 0.25, or 1.0 micromol, intracerebroventricular) or saline 15 minutes before ischemia. The brain content of adenosine 5'-triphosphate (ATP) was measured in animals subjected to 0, 0.5, 1, and 2 minutes of decapitation ischemia, and the effect of preischemic administration of lidocaine (0.25 micromol, intracerebroventricular) was evaluated. Na+, K+-ATPase, and Ca2+-ATPase activity was evaluated in brains pretreated with lidocaine (0.25 micromol, intracerebroventricular) or saline 15 minutes before decapitation. Changes in the intracellular Ca concentration ([Ca2+]i) were evaluated in hippocampal slices and the effects of lidocaine (50, 100, or 400 microM) were assessed in the hippocampal CA1 field and dentate gyrus at pH 7.4 and pH 6.8 every 60s for a duration of 50 min. The preischemic administration of lidocaine (1.0 and 0.25 micromol) delayed the onset of anoxic depolarization to 49 seconds and 44 seconds, respectively, as compared with that in the saline group at 27 seconds. Lidocaine maintained ATP levels higher than those in corresponding saline groups, values being 165% after 1 minute of ischemia and 212% after 2 minutes, respectively. Lidocaine did not affect Na+, K+-ATPase, and Ca2+-ATPase activity. Lidocaine did not affect changes in the [Ca2+]i in either area at either pH. The findings may suggest that lidocaine maintains the energy level by delaying depolarization in neurons, which may contribute to removal of cytosolic Ca2+ in ischemic states.

Prevention of brain infarction by postischemic administration of histidine in rats.

Focal cerebral ischemia for 2 h by occlusion of the right middle cerebral artery provoked severe brain infarction in the rat brain after 24 h. Intraperitoneal administration of histidine, a precursor of histamine, immediately and 6 h after reperfusion, alleviated brain infarction. The infarct size in the histidine (200 mg/kg, 500 mg/kg, and 1000 mg/kg, each time) groups was 71%, 39%, and 7% of that in the control group, respectively. Although intracerebroventricular administration of mepyramine (3 nmol), an H1 antagonist, did not affect the morphologic outcome in histidine-treated rats, ranitidine (30 nmol), an H2 antagonist, completely abolished the alleviation caused by histidine. These findings indicate that postischemic administration of histidine prevents development of brain infarction by stimulating central histamine H2 receptors.

Facilitation of serotonergic activity and amnesia in rats caused by intravenous anesthetics.

BACKGROUND: Midazolam and propofol often provoke retrograde amnesia after recovery from anesthesia in humans. Because an increase in central serotonergic activity impairs learning and memory, the authors examined the relation between changes in the serotonergic activity caused by intravenous anesthetics and memory. METHODS: Changes in extracellular concentrations of monoamines and their metabolites were investigated in rat striatum by a microdialysis procedure, and the effects of intraperitoneal injections of midazolam (5 mg/kg), propofol (60 mg/kg), and pentobarbital (15 mg/kg) were then examined. To evaluate the behavioral alteration with these agents, the authors used a step-through passive avoidance test. RESULTS: Midazolam and propofol slightly increased the extracellular concentration of 5-hydroxytryptamine in the striatum, although pentobarbital did not produce any changes. Midazolam and propofol increased the extracellular concentration of 5-hydroxyindoleacetic acid, a metabolite of 5-hydroxytryptamine, with the peak values each 138% and 138% of that in saline-injected animals, respectively. However, pentobarbital decreased the 5-hydroxyindoleacetic acid concentration to 61% of that in the saline group. Administration of midazolam or propofol immediately after the completing the passive avoidance learning reduced step-through latencies after 24 h, although pentobarbital-injected animals maintained a consistent performance. The effects of midazolam and propofol on step-through latencies were completely antagonized by intracerebroventricular administration of spiroxatrine (5 microg), a 5-hydroxytryptamine 1A antagonist, 30 min before training. CONCLUSIONS: Midazolam and propofol increased central serotonergic activity and provoked retrograde amnesia. Because amnesia was completely diminished by a 5-hydroxytryptamine antagonist, facilitation of the serotonergic system may be involved in retrograde amnesia caused by these agents.

Acute effects of 17beta-estradiol on oxidative stress in ischemic rat striatum.

Changes in the extracellular concentrations of monoamines, their metabolites, and hydrogen peroxide in the rat striatum during middle cerebral artery (MCA) occlusion and reperfusion were investigated by a microdialysis procedure, and the effects of 17beta-estradiol and tamoxifen (an antagonist of estrogen receptors) on them were evaluated. Male Wistar rats were randomly divided into four groups: saline-treated animals, 17beta-estradiol-treated animals, saline-plus-tamoxifen-treated animals, and 17beta-estradiol-plus-tamoxifen-treated animals. Sixty minutes after an intracerebroventricular injection of saline (20 microL) or 17beta-estradiol (150 microg/20 microL), all animals were subjected to 15-minute MCA occlusion under anesthesia. Tamoxifen (1.5 mg) or vehicle was intravenously administered 30 minutes before the saline or 17beta-estradiol treatment. Microdialysis samples in the striatum were collected every 15 minutes, and concentrations of monoamines, their metabolites, and hydrogen peroxide were determined. Delayed neuronal death in the striatal neurons was observed after 7 days by light microscopy. Administration of 17beta-estradiol reduced neuronal damage caused by focal ischemia. Tamoxifen did not affect the improvement by 17beta-estradiol. Although transient ischemia produced a marked increase in the dopamine level, there were no differences in the peak level among the groups. The level of hydrogen peroxide was increased after reperfusion in the saline group. The level in the 17beta-estradiol group was suppressed before induction of ischemia, and no increase was observed by ischemia. Tamoxifen did not affect the suppression of the increase by 17beta-estradiol. Acute treatment with 17beta-estradiol showed a protective effect against ischemia-reperfusion injury. Antioxidant effects of the agent may be a predominant mechanism underlying the protection.

Enhancement of Na+,K(+)-ATPase and Ca(2+)-ATPase activities in multi-cycle ischemic preconditioning in rabbit hearts.

OBJECTIVE: Ischemic preconditioning (IP) has been shown to attenuate intracellular Na+ accumulation and Ca2+ overload during ischemia and reperfusion, both of which are closely related to the outcome of myocardial damage. We compared the effects of single- and four-cycle IP in Na+,K(+)-activated adenosine 5'-triphosphatase (Na+,K(+)-ATPase) and Ca(2+)-activated adenosine 5'-triphosphatase (Ca(2+)-ATPase) activities in in vivo rabbit hearts, correlating these differences to the quality of protection against subsequent ischemia. METHODS: The morphological outcome was evaluated in in vivo rabbit hearts subjected to 30 min of coronary occlusion and reperfusion for 180 min by assessing the ratio of infarct volume to risk zone volume. The effects of single- and four-cycle preconditioning ischemia were then examined. Another set of in vivo rabbit hearts was subjected to the measurement of ATPase activities at the conclusion of final preconditioning ischemia and at 60 min after reperfusion following 30 min of ischemia. RESULTS: The infarct volume was reduced by single-cycle IP to 38% of that in the control group. The four-cycle IP further reduced the infarct volume, which was 11% of that in the control group. Na+,K(+)-ATPase activity at 60 min after reperfusion in the four-cycle group was increased to 172% of that in the control group (10.8 micromol ADP/h/mg protein), whereas no difference was found in the single-cycle group. On the other hand, Ca(2+)-ATPase activity at the conclusion of IP was increased by single-cycle IP, the value being 255% of that in the control group (4.9 micromol ADP/h/mg protein). The four-cycle IP further increased the activity, and the value was 158% of that in the single-cycle group. CONCLUSIONS: Since increases in Na+,K(+)-ATPase and Ca(2+)-ATPase activities contribute to the decrease in intracellular Ca2+ concentration, the enhancement of these activities by four-cycle IP may be involved in the additional protection.

Alleviation of ischemic neuronal damage by histamine H2 receptor stimulation in the rat striatum.

Transient ischemia was produced for 15 min by occlusion of the middle cerebral artery in halothane-anesthetized rats, and changes in the extracellular concentrations of neurotransmitter monoamines and amino acids were examined in the striatum. The occlusion produced marked increases in the extracellular concentrations of both dopamine and glutamate in the striatum in the saline-injected control group, the peak values being 148 and 5.2 times those before ischemia, respectively. Preischemic administration of histamine (200 nmol, i.c.v.) suppressed the increase in dopamine and glutamate levels during ischemia, the peak values being 38% and 40% of those in the control group, respectively. Neither the dopamine nor glutamate level was affected by 6-[2-(4-imidazolyl)ethylamino]-N-(trifluoromethylphenyl)heptanecarboxamide (HTMT), an H(1) agonist (100 nmol, i.c.v.). However, dimaprit, an H(2) agonist (100 nmol, i.c.v.) suppressed the peak values to 42% and 32%, respectively. Most neurons were degenerated 7 days after ischemia in control animals. Histologic outcome was alleviated by either histamine or dimaprit treatment, whereas HTMT did not affect the outcome. Although postischemic administration of mepyramine, an H(1) antagonist (5 nmol, i.c.v.), did not affect the histologic alleviation caused by preischemic treatment with histamine, ranitidine, an H(2) antagonist (30 nmol, i.c.v.), partly abolished the improvement caused by histamine. These results suggest that suppression of ischemic release of excitatory neurotransmitters by histamine H(2) action is a contributing factor in alleviation of histologic outcome.

Alleviation of ischemic neuronal damage by postischemic loading with histidine in the rat striatum.

Inflammatory reactions play an important role in ischemia-reperfusion injury in the brain. Since histamine H(2) action suppresses inflammatory reactions, effects of postischemic loading with histidine, a precursor of histamine, were examined. Focal cerebral ischemia for 15 min was provoked by transient occlusion of the right middle cerebral artery in rats, and delayed neuronal death were evaluated in striatal neurons after 7 days. Histidine was administered four times, immediately, 6, 24, and 48 h after reperfusion of blood flow (1000 mg/kg, i.p., each time). To examine the role of histaminergic action on changes in histologic outcome, effects of mepyramine (3 nmol, i.c.v.), an H(1) antagonist, and ranitidine (30 nmol, i.c.v.), an H(2) antagonist, were evaluated in histidine-treated rats. Transient ischemia for 15 min provoked severe neuronal damage in the saline-injected control group, and the number of striatal neurons decreased to 21% of that on the contralateral side. Administration of histidine alleviated ischemic neuronal damage, and the number of preserved neurons was 76% of that on the contralateral side. Simultaneous administration of mepyramine with histidine did not affect the histologic outcome. However, administration of ranitidine abolished the alleviation by histidine. These findings indicate that the elevation of histamine H(2) receptor stimulation by massive administration of histidine suppresses reperfusion injury in the brain.