Biomedical subjects

J L Horn

Publications and source records attributed to J L Horn.

At least 19 recordsLinked to original sources

PubMed1999

Lack of effect of flurothyl, a non-anesthetic fluorinated ether, on rat brain synaptic plasma membrane calcium-ATPase.

Plasma membrane Ca2+-ATPase (PMCA), a regulator of intracellular calcium, is inhibited by volatile anesthetics and by xenon and nitrous oxide. Response of a cellular system to anesthetics, particularly to volatile agents, raises the question of non-specific, even toxic, side effects unrelated to anesthetic action. Compounds with chemical and physical properties similar to halogenated anesthetics, but which lack anesthetic effect, have been used to address this question. We have compared the effects of halothane and flurothyl, a non-anesthetic fluorinated ether, on PMCA Ca2+ transport across isolated brain synaptic plasma membranes (SPM). Flurothyl, at concentrations predicted by the Meyer-Overton curve to range from 0.4 to 2.6 MAC (minimum alveolar concentration), had no significant on PMCA activity. In contrast halothane, 1.3 MAC, reduced Ca2+ transport 30 to 40%. These findings provide further evidence for a specific effect of inhalation anesthetics on neuronal plasma membrane Ca2+-ATPase.

Anesthetics, Inhalation↗

PubMed1998

Anesthetic-induced alteration of Ca2+ homeostasis in neural cells: a temperature-sensitive process that is enhanced by blockade of plasma membrane Ca2+-ATPase isoforms.

BACKGROUND: Many inhalation anesthetics at clinically relevant concentrations inhibit plasma membrane Ca2+-adenosine triphosphatase (PMCA) ion pumping in brain synaptic membranes and in cultured cells of neural origin. In this study, the authors investigated the effect of inhalation anesthetics on cytosolic calcium homeostasis in cortical neurons maintained at physiologic and room temperatures and on cortical neurons and pheochromocytoma cells with antisense blockade of specific PMCA isoforms. METHODS: Using Ca2+-specific confocal microfluorimetry, the anesthetic effects on Ca2+ dynamics were examined in mouse embryonic cortical neurons in association with ligand-stimulated Ca2+ influx. Studies were done at 21 degrees C and 37 degrees C. Mouse embryonic cortical neurons with oligodeoxyribonucleotide blockade of PMCA2 expression and transfected rat pheochromocytoma cells with blocked expression of PMCA1 were also examined. RESULTS: Baseline and poststimulation peak cytosolic calcium concentrations ([Ca2+]i) were increased, and Ca2+ clearance was delayed in cells exposed at 37 degrees C, but not at 21 degrees C, to concentrations < or = 1 minimum alveolar concentration (MAC)-equivalent of halothane, isoflurane, and sevoflurane. Neurons exposed to xenon solutions < or = 0.4, 0.6, and 0.8 MAC showed dose-related perturbations of cytosolic Ca2+. Calcium dynamics were altered in neural cells with blocked PMCA isoform production, but at much lower halothane concentrations: 0.5 MAC for cortical neurons and 0.1 MAC for pheochromocytoma cells. CONCLUSIONS: By extruding Ca2+ through the plasma membrane, PMCA maintains resting neuronal [Ca2+]i at low levels and clears physiologic loads of Ca2+ after influx through calcium channels. Inhalation anesthetics perturb this process and thus may interfere with neurotransmitter release, altering interneuronal signaling.

Anesthetics, Inhalation↗

PubMed1996

Halothane alters electrical activity and calcium dynamics in cultured mouse cortical, spinal cord, and dorsal root ganglion neurons.

Halothane inhibits neural plasma membrane Ca(2+)-ATPase, a pump that ejects Ca2+ from the cell after influx through voltage- or ligand-activated channels. Intracellular microelectrode recordings in mouse embryonic cortical and spinal cord neurons showed that halothane and eosin, a pump inhibitor, prolonged repolarization associated with spontaneous bursts of depolarization. These agents also prolonged the repolarization phases of electrically induced action potentials and of capsaicin-mediated Ca(2+)-dependent depolarization in mouse adult dorsal root ganglion neurons. In keeping with these findings, confocal microfluorimetry showed that halothane delayed clearance of intracellular Ca2+ accumulated by N-methyl-D-aspartate stimulation of single neurons.

Anesthetics, Inhalation↗

PubMed1996

Intrathecal ketorolac tromethamine produces analgesia after chronic constriction injury of sciatic nerve in rat.

PURPOSE: The study compared analgesic efficacy of intrathecally administered ketorolac tromethamine (K) and morphine hydrochloride (M) (in equimolar doses) in the chronic neuropathic pain model, induced by chronic constriction injury (CCI) of the sciatic nerve in rat. METHODS: Male Sprague-Dawley rats (n = 30) were anaesthetized with halothane and an intrathecal catheter was inserted to the mid-lumbar level of the spinal cord. On the 5th post-operative day, rats were anaesthetized with halothane and four ligatures were loosely applied around the right sciatic nerve. Seven days later, those animals were randomly divided into three groups and were injected with either saline, M (20 nmoles) or K (20 nmoles). Two pain responses (foot-withdrawal delay and hind paw elevation time) were measured on both sides using the radiant heat method. Further, thermal ("cold") allodynia was assessed by measuring of the total time of hind paw elevation in animals placed on the cold metal plate. RESULTS: Twenty nmoles of M and K injected intrathecally produced decrease of differential pain score calculated for both measured responses (hind paw withdrawal and hind paw elevation), compared with saline injected animals (P < 0.05). The reduction in pain response produced by K was less (P < 0.05). than the reduction in pain response observed in the animals receiving intrathecal M. Measurement of cold allodynia revealed that the animals in M and K injected groups demonstrated decreases in the total hind paw elevation time, when compared with saline-injected animals (P < 0.05). CONCLUSION: M and K produced hypoalgesia after intrathecal administration in rats with CCI, with M being more potent than K at an equimolar dose range. The analgesic effect of K was equal to equimolar doses of M for alleviation of cold allodynia.

Analgesics↗

PubMed1996

Reduced anesthetic requirements in aged rats: association with altered brain synaptic plasma membrane Ca(2+)-ATPase pump and phospholipid methyltransferase I activities.

Aging is associated with a decrease in anesthetic requirements. Animal models of aging manifest alteration of brain Ca2+ homeostasis and increased methyltransferase I (PLMTI) activity. In this study we evaluated concurrently anesthetic requirements and brain plasma membrane Ca(2+)-ATPase (PMCA) and PLMTI activities in young and aged rats. Halothane, desflurane, isoflurane and xenon MEDs (lowest partial pressures that suppress a pain response) were measured in 2 and 25 month old, male Fisher-344 rats. Halothane MED was also measured in 2 and 30 month old F344/BNF1 rats, a strain that undergoes aging with less debilitation. PMCA pumping and PLMTI activities were measured in synaptic plasma membranes (SPM) prepared from the cortex and diencephalon-mesencephalon (DM). For aged Fisher-344 rats, MEDs for halothane, desflurane, isoflurane and xenon were reduced to 81%, 82%, 67% and 86%, respectively, of young controls; PMCA activity was diminished to 91% in cortical SPM and 82% in DM SPM; and cortical and DM PLMTI activities were increased to 131% and 114% of young control. For F344/BNF1 rats, MED for halothane was reduced to 87%, PMCA activity was diminished to 90% in cortical SPM and 72% DM SPM, and PLMTI activity was increased to 133% in cortical SPM and 112% in DM SPM. The strong association between age and reduced anesthetic requirements for inhalational agents on the one hand and altered PMCA and PLMTI activity on the other lends support to the underlying hypothesis that PMCA and PLMTI may be involved in the production of the anesthetic state.

Aging↗

PubMed1996

Increased anesthetic requirements for isoflurane, halothane, enflurane and desflurane in obese Zucker rats are associated with insulin-induced stimulation of plasma membrane Ca(2+)-ATPase.

A wide spectrum of structurally disparate inhalational anesthetics reduce brain synaptic plasma membrane Ca(2+)-ATPase (PMCA) activity, whereas phospholipid methyltransferase I (PLMTI) is enhanced by anesthetics. Several rat models with incidental or disease-induced reduction of PMCA and enhancement of PLMTI activities manifest increased sensitivity to inhalational anesthetics. Because insulin is known to stimulate PMCA, anesthetic requirements in hyperinsulinemic obese Zucker rats (fa/fa) and in normoinsulinemic lean Zucker heterozygotes (fa/+) were examined, and brain synaptic PMCA and PLMTI activities were determined in both genotypes. Significantly higher partial pressures of halothane, enflurane, isoflurane, and desflurane were required to inhibit the pain response in obese rats compared to lean Zucker rats. Dose dependent stimulation of PMCA pumping was observed in synaptic membranes from both types, but insulin concentrations in extracts of diencephalon-mesencephalon, cerebellum, and medulla (but not cortex) were higher in obese than in lean Zucker rats. Microdialysis of three subcortical regions showed marked increases in insulin levels with halothane exposure in obese rats, compared to lean controls. These observations in an anesthetic resistant rat model lend further support to the hypothesis that the calcium pump plays a functional role in production of the anesthetic state.

Anesthetics, Inhalation↗

PubMed1996

Demonstration of halothane-induced hepatic lipid peroxidation in rats by quantification of F2-isoprostanes.

BACKGROUND: Halothane can be reductively metabolized to free radical intermediates that may initiate lipid peroxidation. Hypoxia and phenobarbital pretreatment in Sprague-Dawley rats increases reductive metabolism of halothane. F(2)-isoprostanes, a novel measure of lipid peroxidation in vivo, were used to quantify halothane-induced lipid peroxidation in rats. METHODS: Rats were exposed to 1% halothane or 14% O(2) for 2 h. Pretreatments included phenobarbital, isoniazid, or vehicle. Rats also were exposed to halothane, enflurane, and desflurane at 21% O(2). Lipid peroxidation was assessed by mass spectrometric quantification of F(2)-isoprostanes. RESULTS: Exposure of phenobarbital-pretreated rats to 1% halothane at 21% O(2) for 2 h caused liver and plasma F(2)-isoprostane concentrations to increase fivefold compared to nonhalothane control rats. This halothane-induced increase was enhanced by 14% O(2), but hypoxia alone had no significant effect. Alanine aminotransferase activity at 24 h was significantly increased only in the 1% halothane/14% O(2) group. The effect of cytochrome P450 enzyme induction on halothane-induced F(2)-isoprostane production and liver injury was determined by comparing the effects of isoniazid and phenobarbital pretreatment with no pretreatment under hypoxic conditions. Halothane caused 4- and 11-fold increases in plasma and liver F(2)-isoprostanes, respectively, in non-pretreated rats, whereas isoniazid pretreatment had no effect. Phenobarbital pretreatment potentiated halothane-induced lipid peroxidation with 9- and 20-fold increases in plasma and liver F(2)-isoprostanes, respectively. Alanine aminotransferase activity was increased only in this group. At ambient oxygen concentrations, halothane but not enflurane or desflurane, caused F(2)-isoprostanes to increase. CONCLUSIONS: Specific halothane-induced lipid peroxidation was demonstrated in Sprague-Dawley rats using quantification of F(2)-isoprostanes and was increased by hypoxia and phenobarbital pretreatment, but not isoniazid pretreatment.

Anesthetics, Inhalation↗

PubMed1995

Failure of short-term luminal IGF-I to protect against atrophy in a model of fetal esophageal atresia.

Short-term luminal infusion in utero (3 days) of insulin-like growth factor I (IGF-I) failed to protect the fetal small intestine against atrophy induced by ablation of swallowing. Human recombinant IGF-1 (or vehicle) was infused into the duodenum of fetal sheep at 125 days' gestation for 3 days (day 1, 0.025 mg; day 2, 0.25 mg: day 3, 2.5 mg). Fetal swallowing was prevented by esophageal ligation, and a carotid catheter was implanted for blood sampling. There were no changes in body growth of in major organ growth. Small intestinal (SI) weight (corrected for body weight) was significantly lower for IGF-I treated fetuses. Villus height decreased significantly in proximal regions. Villus enterocyte cellularity was reduced significantly in the proximal regions. The percentage of crypt cells labeled with a 4-hour pulse of tritiated thymidine (as assessed by autoradiography) decreased significantly in the proximal SI only, from 16.14% (1.06% SEM) to 13.28% (1.05% SEM) (P < .05). Plasma levels of IGF-1 increased in the treated fetuses by an average of 76%. IGF-1 immunoreactivity was detected in the apical endocytic complex of enterocytes from proximal SI. This study shows that wasting of fetal intestinal tissues in the absence of enteral input cannot be prevented by IGF-1 delivered luminally.

Animals↗

PubMed1995

Inhibition of plasma membrane Ca(2+)-ATPase pump activity in cultured C6 glioma cells by halothane and xenon.

We have compared the effect of two inhalational anesthetics, halothane and xenon, on Ca(2+)-ATPase (PMCA) pumping activity in plasma membrane vesicles prepared from cultured rat C6 glioma cells. Halothane, at concentrations ranging from 0.5 to 1.75 vol% (equivalent to 0.5 to 1.6 MAC), significantly inhibited Ca2+ uptake (transport) by plasma membrane vesicles in a dose-related fashion. Xenon, at partial pressures ranging from 0.5 to 1.5 atm (equivalent to 0.5 to 1.6 MAC), similarly inhibited PMCA pumping activity. Additive effects on suppression of PMCA pump activity were observed when C6 cell plasma membrane vesicles were exposed to increasing partial pressures of xenon in the presence of halothane (1 vol%). Halothane also inhibited PMCA pumping in cells from two other lines of neural origin, B104 (rat neuroblastoma) and PC12 (rat pheochromocytoma). Studies described in this report support the thesis that PMCA in cells of neural origin is inhibited by quite different inhalational anesthetics at clinically relevant concentrations.

Animals↗

PubMed1995

Reduced anesthetic requirements, diminished brain plasma membrane Ca(2+)-ATPase pumping, and enhanced brain synaptic plasma membrane phospholipid methylation in diabetic rats: effects of insulin.

We have recently reported that streptozocin (STZ)-induced diabetes in rats was associated with i) reduced Ca2+ pumping by rat brain synaptic plasma membrane Ca(2+)-ATPase (PMCA) and ii) a substantial reduction in the partial pressures of halothane and xenon required to prevent movement in response to stimulation (minimum effective dose or MED). MED for both agents correlated well with the degree of hemoglobin glycation and with PMCA activity. We now report that MEDs for isoflurane, enflurane, and desflurane were also substantially reduced in STZ-diabetic rats, compared with placebo-injected controls. In addition, we examined the effect of insulin treatment, begun 2 weeks after induction of diabetes and continued for 3 more weeks, on isoflurane MED and on brain synaptic PMCA and phospholipid-N-methyltransferase I (PLMT I), another enzyme altered by inhalation anesthetics (IA). Partial treatment of diabetes, as indicated by decreased glycated hemoglobin (GHb) compared to untreated diabetic rats, was associated with an isoflurane MED of 1.05 vol%, intermediate between a control mean of 1.57 vol% and an untreated diabetic mean of 0.82 vol% (p < 0.01), with a trend toward normalization of both PMCA and PLMT I activity. We also examined isoflurane MED and PMCA activity in the cerebrum and diencephalon-mesencephalon (D-M) of control and diabetic rats 2 and 12 weeks after induction of diabetes. Isoflurane MED was substantially reduced in diabetic rats from both treatment periods. Cerebral and D-M PMCA activities were each reduced to about 90% of control values 2 weeks after STZ induction. At 12 weeks, cerebral PMCA pumping in SPM from diabetic rats did not differ from control values, but PMCA pumping in SPM from the D-M was reduced to about 85% of control levels. Good correlation (r = 0.89, p < 0.01) was found between isoflurane MED and GHb in all treatment groups. These findings provide further evidence for an important role for PMCA in IA action. They also suggest that anesthetic effects on the calcium pump at specific anatomic sites may be of major importance in producing anesthesia.

Anesthetics, Inhalation↗

PubMed1995

Diminished brain synaptic plasma membrane Ca(2+)-ATPase activity in spontaneously hypertensive rats: association with reduced anesthetic requirements.

We have recently reported that plasma membrane Ca(2+)-ATPase (PMCA) pumping activity in rat brain synaptic plasma membranes (SPM) was reduced by in vitro or prior in vivo exposure to inhalation anesthetics (IA). In addition, rats with streptozocin-induced diabetes were found to have diminished brain synaptic PMCA pumping and a decrease in the partial pressures of several IA required to prevent movement in response to stimulation, defined as the minimum effective dose or MED. Diminished PMCA activity in erythrocytes of spontaneously hypertensive rats (SHR) has been noted. Because PMCA is ubiquitous, it seemed possible that PMCA pumping might be decreased in the brain of SHR and perhaps associated with decreased IA requirement. Eighteen SHR and 18 control, normotensive Wistar-Kyoto rats (WKY) were studied. PMCA activity was assessed by measurement of Ca2+ uptake into synaptic plasma membrane vesicles prepared from cerebrum and diencephalon-mesencephalon (D-M) in WKY and SHR. Ca2+ pumping was significantly less in SHR than in WKY, 85% of control in the cerebrum and 90% in the D-M (p < 0.01). The MEDs for halothane, isoflurane and desflurane were also lower in SHR than in WKY, 91%, 90% and 89%, respectively, of control (p < 0.05). Thus, an animal model of primary hypertension (SHR) manifested diminished brain synaptic PMCA activity and reduced MED for several volatile anesthetics. These findings provide further evidence for a role for PMCA in anesthetic action.

Anesthetics, Inhalation↗

PubMed1995

Nitrous oxide and xenon enhance phospholipid-N-methylation in rat brain synaptic plasma membranes.

Halothane and isoflurane increase the rate of phospholipid methylation (PLM) in rat brain synaptosomal membranes, a process linked to the coupling of neuronal excitation to neurotransmitter release. In contrast, synaptic plasma membrane (SPM) Ca2+ ATPase (PMCA) pumping is reduced by exposure to halothane, isoflurane, xenon and nitrous oxide (N2O). To examine further the relationship between PLM, PMCA and anesthetic action, we investigated the effect of clinically relevant concentrations of two less potent anesthetic gases, N2O and xenon, on PLM in SPM. Biochemical assays were performed on SPM exposed to 1.3 MAC of N2O (2 atm), 1.3 MAC of xenon (1.23 atm) or an equivalent pressure of helium for control. N2O or xenon exposure increased PLM to 115% or 113%, respectively, of helium control (p < 0.02). Similar exposures to N2O or xenon depressed PMCA activity to 78% and 85% of control (p < 0.05). Observations that PLM and PMCA are both altered by a wide variety of inhalation anesthetic agents at clinically relevant partial pressures lend support to a possible involvement and interaction of these processes in anesthetic action.

Animals↗

PubMed1995

Halothane, isoflurane, xenon, and nitrous oxide inhibit calcium ATPase pump activity in rat brain synaptic plasma membranes.

BACKGROUND: Perturbation of neuronal calcium homeostasis may alter neurotransmission in the brain, a phenomenon postulated to characterize the anesthetic state. Because of the central role of plasma membrane Ca(2+)-ATPase (PMCA) in maintaining Ca2+ homeostasis, the authors examined the effect of several inhalational anesthetics on PMCA function in synaptic plasma membranes (SPM) prepared from rat brain. METHODS: Ca(2+)-ATPase pumping activity was assessed by measurement of ATP-dependent uptake of Ca2+ by SPM vesicles. ATPase hydrolytic activity was assessed by spectrophotometric measurement of inorganic phosphate (Pi) released from ATP. For studies of anesthetic effects on PMCA activity, Ca2+ uptake or Pi release was measured in SPM exposed to halothane, isoflurane, xenon, and nitrous oxide at partial pressures ranging from 0 to 1.6 MAC equivalents. Halothane and isoflurane exposures were carried out under a gassing hood. For xenon and nitrous oxide exposures, samples were incubated in a pressure chamber at total pressures sufficient to provide anesthetizing partial pressures for each agent. RESULTS: Dose-related inhibition of Ca(2+)-ATPase pumping activity was observed in SPM exposed to increasing concentrations of halothane and isoflurane, confirmed by ANOVA and multiple comparison testing (P < 0.05). Concentrations of halothane and isoflurane equivalent to one minimum effective dose (MED) depressed PMCA pumping approximately 30%. Xenon and nitrous oxide also inhibited Ca2+ uptake by SPM vesicles. At partial pressures of these two gases equivalent to 1.3 MAC, PMCA was inhibited approximately 20%. Hydrolysis of ATP by SPM fractions was also inhibited in a dose-related fashion. An additive effect occurred when 1 vol% of halothane was added to xenon or nitrous oxide at partial pressures equivalent to 0-1.6 MAC for the latter two agents. CONCLUSIONS: Plasma membranes Ca(2+)-ATPase is significantly inhibited, in a dose-related manner, by clinically relevant partial pressures of halothane, isoflurane, xenon, and nitrous oxide. Furthermore, these anesthetics inhibit PMCA activity in accordance with their known potencies, and an additive effect was observed. How inhalational anesthetics inhibit the PMCA pump is not known at this time. It is noteworthy that the only shared characteristic of this group of agents of widely different structure is anesthetic action. The relevance of this dual commonality, anesthetic action and PMCA inhibition, to actual production of the anesthetic state remains to be determined.

Animals↗

PubMed1995

Stable inhibition of brain synaptic plasma membrane calcium ATPase in rats anesthetized with halothane.

BACKGROUND: The authors recently showed that plasma membrane Ca(2+)-ATPase (PMCA) activity in cerebral synaptic plasma membrane (SPM) is diminished in a dose-related fashion during exposure in vitro to halothane, isoflurane, xenon, and nitrous oxide at clinically relevant partial pressures. They have now extended their work to in vivo studies, examining PMCA pumping in SPM obtained from control rats decapitated without anesthetic exposure, from rats decapitated during halothane anesthesia, and from rats decapitated after recovery from halothane anesthesia. METHODS: Three treatment groups were studied: 1) C, control rats that were decapitated without anesthetic exposure, 2) A, anesthetized rats exposed to 1 minimum effective dose (MED) for 20 min and then decapitated, and 3) R, rats exposed to 1 MED for 20 min and then decapitated after recovery from anesthesia, defined as beginning to groom. Plasma membrane Ca(2+)-ATPase pumping and Ca(2+)-dependent ATPase hydrolytic activity, as well as sodium-calcium exchanger activity and Na+-K+-ATPase hydrolytic activity, were assessed in cerebral SPM. In addition, halothane effect on smooth endoplasmic reticulum Ca(2+)-ATPase (SERCA) was examined. RESULTS: Plasma membrane Ca(2+)-ATPase transport of Ca2+ into SPM vesicles from anesthetized rats was reduced to 71% of control (P < 0.01) compared with 113% of control for the recovered group (NS). No depression by halothane of SERCA activity, sodium-calcium exchanger, or Na+-K+-ATPase activity was noted among the CAR treatment groups. CONCLUSIONS: Plasma membrane Ca(2+)-ATPase is selectively and stably inhibited in cerebral SPM from rats killed while anesthetized with halothane, compared with rats killed without anesthesia or after recovery from anesthesia. The studies described in this report, in conjunction with previously reported inhibition of PMCA activity in vitro by a wide range of anesthetic agents, indicate a relationship between inhibition of PMCA and action of inhalational anesthetics.

Animals↗

PubMed1995

Distribution and retention of nicotine and its metabolite, cotinine, in the rat as a function of time.

Nicotine is oxidized to its major metabolite, cotinine, which has a long biological half-life (19-24 h). The plasma concentration of cotinine has been used as an index of tobacco smoke exposure. Cotinine possibly increases the turnover rate of platelet-activating factor (PAF) because it is a potent activator of PAF hydrolase, and it may play a significant role in tobacco-induced arterial thrombosis. Therefore, we studied the distribution and retention of nicotine as it was metabolized to cotinine in the rat. Nicotine (1 mg/kg, 5 microCi/kg) was administered into the femoral vein of male Sprague-Dawley rats under nembutal anesthesia. At different times (5-60 min) after nicotine administration, nicotine and its metabolite, cotinine, were determined by HPLC in plasma, liver, kidney, heart and brain. Within 5-10 min after administration, nicotine concentrations reached peak values in plasma (2,160 pmol/ml) and the organs analyzed. The plasma level of nicotine decreased by 50% within 20 min (half-time) after its intravenous administration. The half-time of nicotine in the brain was about 50 min. The half-times of nicotine for the other organs were about 20-25 min. The major metabolite, cotinine, accumulated in plasma, and by about 30 min the concentrations of nicotine and cotinine in plasma were about equal (890-1,000 pmol/ml). While cotinine accumulated in plasma, nicotine was eliminated by the kidney. While the nicotine concentrations decreased with time in all organs, cotinine concentrations remained constant. These observations indicate that nicotine is renally eliminated or metabolized to cotinine while cotinine exhibits a long retention time and accumulates in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Diminished brain synaptic plasma membrane Ca(2+)-ATPase activity in rats with streptozocin-induced diabetes: association with reduced anesthetic requirements.

Recent evidence suggests that chronic hyperglycemia may inhibit plasma membrane Ca(2+)-ATPase (PMCA) in cells from several tissues. Inhalational anesthetics (IA) can inhibit brain synaptic PMCA activity. We proposed that diabetic rats may manifest chronic inhibition of brain synaptic PMCA and thus provide a model for testing the hypothesis that synaptic PMCA plays a key role in IA pharmacodynamics. Ca2+ pumping activity of PMCA was measured in cerebral synaptic plasma membrane (SPM) vesicles prepared from rats with streptozocin (STZ)-induced diabetes and from control, normoglycemic rats. Dose requirements for halothane and xenon were estimated in treated and untreated rats. Brain PMCA activity in hyperglycemic rats was depressed by about 8.4%, compared to controls. In vitro glycation also caused a significant decrease in PMCA pumping activity. Halothane requirement for STZ-hyperglycemic rats was dramatically reduced to about 65% of control. Xenon requirement was also significantly reduced, to 88% of control. Correlation of IA dose with percent glycated hemoglobin for each rat revealed a strong association between reduced requirements for halothane or xenon and increased protein glycation. These results indicate that inhibition of brain synaptic PMCA in chronically hyperglycemic rats is associated with a significant reduction in IA requirement.

Anesthetics, Inhalation↗

PubMed1992

Nimodipine reduces the toxicity of intravenous bupivacaine in rats.

We examined nimodipine modification of bupivacaine toxicity in anesthetized male rats. Three minutes after pretreatment, group 1 (n = 11), group 3 (n = 10), and their respective control groups (n = 11 and n = 9) received intravenous bupivacaine LD50 (median lethal dose). After pretreatment, group 2 (n = 10), group 4 (n = 8), and their respective control groups (n = 10 and n = 8) received intravenous bupivacaine LD90 (90% lethal dose). Pretreatment was 200 micrograms/kg intravenous nimodipine in groups 1 and 2 and 500 micrograms/kg in groups 3 and 4. Control animals were pretreated with intravenous saline solution. Data were analyzed by chi 2-analysis and analysis of variance. Survival increased after 200 micrograms/kg nimodipine (P less than 0.05). In group 1, 9 (81%) of 11 survived compared with control animals (4 [36%] of 11). In group 2, 8 (80%) of 10 survived compared with control animals (2 [20%] of 10). Survival was not increased after 500-micrograms/kg nimodipine pretreatment. In group 3, 2 (22%) of 9 survived compared with control animals (4 [40%] of 10). In group 4, 4 (50%) of 8 survived compared with control animals (2 [25%] of 8). We conclude that nimodipine pretreatment with 200 micrograms/kg protects against fatal toxicity from LD50 and LD90 bupivacaine, but 500 micrograms/kg does not.

Animals↗

PubMed1992

Polyuria during Guillain-Barré syndrome.

Severe Guillain-Barré syndrome (GBS) usually results in life-threatening autonomic disturbances requiring a close monitoring of the patient in an Intensive Care Unit. Besides dangerous cardiac manifestations, neuroendocrine changes are also reported and could induce electrolytes and fluid balance impairments. Polyuria has been observed in a severe case of GBS occurring in a 16-year-old boy. Consecutive blood samples were obtained for renin, aldosterone, antidiuretic hormone and atrial natriuretic factor measurements. Polyuria in GBS is multifactorial and would be partly due to a dysregulation of osmoreceptors.

Adolescent↗