effects of hypothermic versus normothermic cardiopulmonary bypass on hepatic blood flow

To explore Trans-esophageal Echo [TEE] as a monitoring device for hepatic blood flow during cardiac1 surgery and to correlate between the hepatic venous blood flow measurements and the liver function tests during normothermic and hypothermic cardiopulmonary bypass. Forty patients scheduled for cardiac surgery were randomly divided into 2 groups: group 1 [Gl] undergoing normothermic cardiopulmonary bypass [CPB] and group 2 [G2] undergoing hypothermic CPB. Serum AST, ALT, billirubin and hyalurinic acid levels were measured before, during and 6 hours after the bypass. During these same phases, TEE was used to measure both cardiac index [Cl] and middle hepatic vein blood flow. During CPB there were no significant differences in demographic data, AST, ALT or billirubin levels between the 2 groups. There was, however, a significant increase [P<0.001], in both groups, in serum hyalurinic acid levels during CBP in relation to the baseline and in Cl 6 hours after bypass in relation to pre and intra bypass phases. The middle hepatic venous blood flow was significantly higher amongst Gl patients six hours following the procedure in relation to the pre and intra bypass phases, whereas G2 patients showed a significant decrease in middle hepatic venous flow during the bypass followed by a significant increase 6 hours after the procedure in relation to the baseline. Hepatic venous blood flow is reduced significantly more during hypothermic bypass than during normothermic bypass. This may cause disturbances in sinusoidal endothelial cell [SEC] function. However, this change may be well tolerated by the healthy liver. Multiplan TEE may be used to monitor hepatic blood flow during CPB

Topiramate associated hypohidrosis and hyperthermia.

Topiramate is a new antiepileptic drug, used for treatment of partial onset seizure and refractory seizures. Although it is well tolerated in children, some adverse effects including hypohidrosis and hyperthermia are reported. We present two children with epilepsy who were treated with topiramate and developed hypohidrosis and hyperthermia.

Influence of epipregnanolone on the modulation of rapid tolerance to ethanol by neurosteroids

OBJECTIVE: The objective of the present study was to investigate the effect of epipregnanolone on the influence of neurosteroids on the development of rapid tolerance to the motor impairing and hypothermic effects of ethanol. METHOD: Experiment 1: on Day 1 groups of mice were pretreated with saline or with epipregnanolone. After 30 min each group was further divided in subgroups that received ethanol or saline. Thirty, 60 and 90 min after the injections the animals were tested on the rota-rod or the body temperature was measured. On Day 2 all groups received ethanol and a similar procedure was followed to evaluate rapid tolerance. Experiment 2 and 3: On Day 1 groups of mice were treated with epipregnanolone and after 15 min each group was divided into three groups in order to receive pregnenolone sulfate, dehydroepiandrosterone sulfate or saline. Thirty minutes later, each group was further divided into two subgroups in order to receive ethanol or saline, respectively, and 30, 60 and 90 min later the animals were tested as in the experiment 1. On Day 2 all groups received ethanol and a similar procedure was followed to evaluate rapid tolerance. RESULTS: Pretreatment with epipregnanolone (0.10-0.30 mg/kg) significantly blocked the development of tolerance to the motor impairing and hypothermic effects induced by ethanol in mice. Considering tolerance to ethanol-induced motor impairment, epipregnanolone (0.15 mg/kg) reversed the stimulatory action of dehydroepiandrosterone sulfate (0.15 mg/kg), but did not affect the actions of pregnenolone sulfate (0.08 mg/kg). Moreover, epipregnanolone prevented the inhibitory action of allotetrahydrodeoxycorticosterone (0.10 mg/kg). In relation to ethanol-induced hypothermia, the results showed that pretreatment with epipregnanolone (0.30 mg/kg) significantly prevented the stimulatory action of dehydroepiandrosterone sulfate and pregnenolone sulfate, as well as the inhibitory action of...

OBJETIVO: O objetivo do presente estudo foi o de investigar o efeito da epipregnanolona sobre a influência de neuroesteróides no desenvolvimento da tolerância rápida aos efeitos de incoordenação motora e hipotermia induzidos pelo etanol. MÉTODO: Experimento 1: no Dia 1, grupos de camundongos foram pré-tratados com salina ou com epipregnanolona. Após 30 min, cada grupo foi subdividido recebendo etanol ou salina. Aos 30, 60 e 90 min após as injeções, os animais foram testados no rota-rod ou a temperatura corporal foi avaliada. No Dia 2, todos os grupos receberam etanol e um procedimento similar foi seguido para avaliar a tolerância rápida. O pré-tratamento com a epipregnanolona (0,10-0,30 mg/kg) bloqueou significantemente o desenvolvimento da tolerância aos efeitos de incoordenação motora e hipotermia induzidos pelo etanol em camundongos. Experimento 2 e 3: no Dia 1, grupos de animais foram tratados com epipregnanolona e, após 15 min, cada grupo foi dividido em três grupos para receber sulfato de pregnanolona, sulfato de dehidroepiandrosterona ou salina. Após 30 min, cada grupo foi dividido em dois subgrupos para receber etanol ou salina, respectivamente, e após 30, 60 e 90 min os animais foram testados como no experimento 1. No Dia 2, todos os grupos receberam etanol e 30 min após foram testados como mencionado no experimento 1. RESULTADOS: Considerando a tolerância ao prejuízo motor induzido pelo etanol, a epipregnanolona (0,15 mg/kg) bloqueou a ação estimulatória do sulfato de dehidroepiandrosterona (0,15 mg/kg), mas não afetou a ação do sulfato de pregnanolona (0,08 mg/kg). Entretanto, a epipregnanolona bloqueou a ação inibitória da alotetrahidrodeoxicorticosterona (0,10 mg/kg). Em relação à hipotermia induzida pelo etanol, os resultados demonstraram que o pré-tratamento com epipregnanolona (0,30 mg/kg) bloqueou significantemente a ação estimulatória do sulfato de dehidroepiandrosterona e do sulfato de pregnanolona, bem como a ação...

The time course of ethanol tolerance: associative learning

The effect of different contextual stimuli on different ethanol-induced internal states was investigated during the time course of both the hypothermic effect of the drug and of drug tolerance. Minimitters were surgically implanted in 16 Wistar rats to assess changes in their body temperature under the effect of ethanol. Rat groups were submitted to ethanol or saline trials every other day. The animals were divided into two groups, one receiving a constant dose (CD) of ethanol injected intraperitoneally, and the other receiving increasing doses (ID) during the 10 training sessions. During the ethanol training sessions, conditioned stimuli A (tone) and B (buzzer) were presented at "state +" (35 min after drug injection) and "state -" (170 min after drug injection), respectively. Conditioned stimuli C (bip) and D (white noise) were presented at moments equivalent to stimuli A and B, respectively, but during the saline training sessions. All stimuli lasted 15 min. The CD group, but not the ID group, developed tolerance to the hypothermic effect of ethanol. Stimulus A (associated with drug "state +") induced hyperthermia with saline injection in the ID group. Stimulus B (associated with drug "state -") reduced ethanol tolerance in the CD group and modulated the hypothermic effect of the drug in the ID group. These results indicate that contextual stimuli acquire modulatory conditioned properties that are associated with the time course of both the action of the drug and the development of drug tolerance.

Preoperative warming combined with intraoperative skin-surface warming does not avoid hypothermia caused by spinal anesthesia in patients with midazolam premedication

CONTEXT AND OBJECTIVE: Inadvertent perioperative hypothermia is common during spinal anesthesia and after midazolam administration. The aim of this study was to evaluate the effects of intraoperative skin-surface warming with and without 45 minutes of preoperative warming in preventing intraoperative and postoperative hypothermia caused by spinal anesthesia in patients with midazolam premedication. DESIGN AND SETTING: Prospective and randomized study at Hospital das Clínicas, Universidade Estadual Paulista, Botucatu. METHODS: Thirty patients presenting American Society of Anesthesiologists (ASA) physical status I and II who were scheduled for elective lower abdominal surgery were utilized. The patients received midazolam premedication (7.5 mg by intramuscular injection) and standard spinal anesthesia. Ten patients (Gcontrol) received preoperative and intraoperative passive thermal insulation. Ten patients (Gpre+intra) underwent preoperative and intraoperative active warming. Ten patients (Gintra) were only warmed intraoperatively. RESULTS: After 45 min of preoperative warming, the patients in Gpre+intra had significantly higher core temperatures than did the patients in the unwarmed groups (Gcontrol and Gintra) before the anesthesia (p < 0.05) but not at the beginning of surgery (p > 0.05). The patients who were warmed intraoperatively had significantly higher core temperatures than did the patients in Gcontrol at the end of surgery (p < 0.05). All the patients were hypothermic at admission to the recovery room (T CORE < 36° C). CONCLUSIONS: Forty-five minutes of preoperative warming combined with intraoperative skin-surface warming does not avoid but minimizes hypothermia caused by spinal anesthesia in patients with midazolam premedication.

CONTEXTO E OBJETIVO: Hipotermia inadvertida no perioperatório é freqüente durante anestesia subaracnóidea e após a administração de midazolam. O objetivo foi avaliar os efeitos do aquecimento da pele no intra-operatório, associado ou não ao aquecimento da pele durante o período de 45 minutos no pré-operatório, na prevenção de hipotermia intra- e pós-operatória determinada pela anestesia subaracnóidea em pacientes com medicação pré-anestésica com midazolam. TIPO DE ETUDO E LOCAL: Estudo prospectivo e aleatório, realizado no Hospital das Clínicas, Universidade Estadual Paulista (Unesp), Botucatu, SP. MÉTODOS: O estudo foi realizado em 30 pacientes com estado físico ASA (da Sociedade Norte-americana de Anestesiologistas) I e II submetidos à cirurgia eletiva do abdômen. Como medicação pré-anestésica, utilizou-se o midazolam, 7,5 mg via intramuscular (IM) e anestesia subaracnóidea padrão. Em 10 pacientes (Gcontrole) utilizou-se isolamento térmico passivo; 10 pacientes (Gpré+intra) foram submetidos a aquecimento ativo no pré- e intra-operatório; e 10 pacientes (Gintra) foram aquecidos ativamente somente no intra-operatório. RESULTADOS: Após 45 minutos de aquecimento no pré-operatório, os pacientes do Gpré+intra apresentaram temperatura central mais elevada em relação aos dos grupos não aquecidos antes da anestesia (p < 0,05) mas não no início da cirurgia (p > 0,05). Os pacientes que receberam aquecimento no intra-operatório apresentaram temperatura central mais elevada no final da cirurgia em relação aos de Gcontrole (p < 0,05). Todos os pacientes estavam hipotérmicos na admissão da sala de recuperação pós-anestésica (temperatura central < 36° C). CONCLUSÕES: 45 minutos de aquecimento no pré-operatório combinado com aquecimento no intra- operatório não evita, mas minimiza a ocorrência de hipotermia determinada pela anestesia subaracnóidea em pacientes que receberam midazolam como medicação pré-anestésica.

Effect of isopregnanolone on rapid tolerance to the anxiolytic effect of ethanol / Influência da isopregnenolona na tolerância rápida ao efeito ansiolítico do etanol

OBJETIVE: It has been shown that neurosteroids can either block or stimulate the development of chronic and rapid tolerance to the incoordination and hypothermia caused by ethanol consumption. The aim of the present study was to investigate the influence of isopregnanolone on the development of rapid tolerance to the anxiolytic effect of ethanol in mice. METHOD: Male Swiss mice were pretreated with isopregnanolone (0.05, 0.10 or 0.20 mg/kg) 30 min before administration of ethanol (1.5 g/kg). Twenty-four hours later, all animals we tested using the plus-maze apparatus. The first experiment defined the doses of ethanol that did or did not induce rapid tolerance to the anxiolytic effect of ethanol. In the second, the influence of pretreatment of mice with isopregnanolone (0.05, 0.10 or 0.20 mg/kg) on rapid tolerance to ethanol (1.5 g/kg) was studied. CONCLUSIONS: The results show that pretreatment with isopregnanolone interfered with the development of rapid tolerance to the anxiolytic effect of ethanol.

OBJETIVO: Estudos prévios têm mostrado que os neuroesteróides podem bloquear ou estimular o desenvolvimento da tolerância rápida e crônica aos efeitos de incoordenação e hipotermia produzidos pelo etanol. O objetivo do presente estudo foi investigar a influência da isopregnenolona sobre o desenvolvimento da tolerância rápida ao efeito ansiolítico do etanol em camundongos. MÉTODO: Camundongos suíços, machos, foram pré-tratados com isopregnenolona (0,05, 0,10 ou 0,20 mg/kg) 30 minutos antes da administração de etanol (1,5 g/kg). Após 24 horas, todos os animais foram testados no labirinto em cruz elevado. O primeiro experimento foi realizado com o intuito de selecionar uma dose de etanol que produzisse tolerância rápida ao efeito ansiolítico do etanol. No segundo experimento, o objetivo foi investigar o efeito da isopregnenolona (ISO; 0,05, 0,10 ou 0,20 mg/kg) sobre a tolerância rápida ao etanol (1,5 g/kg). CONCLUSÕES: Os resultados mostram que o tratamento prévio com isopregnenolona interferiu no desenvolvimento da tolerância rápida ao efeito ansiolítico etanol.

Effect of aspartate and glutamate on nociception, catalepsy and core temperature in rats.

Effects of excitatory aminoacids (EAAs) aspartate (ASP) and glutamate (GLU) in a low (50 ng, i.c.) and high dose (20 micrograms, i.c.), were studied on nociception, catalepsy and rectal temperature in albino rats. Both ASP and GLU altered the tail flick reaction time to thermal stimulation in a dose dependent manner, increasing it with low doses and reduced with high doses. Naloxone (10 micrograms, ic) antagonized the anti-nociceptive effect of EAAs while ketamine (10 micrograms, ic)-a NMDA receptor antagonist antagonized the hyperalgesic effect. These EAAs also antagonized catalepsy induced by haloperidol, chlorpromazine, trifluoperazine and morphine. Both ASP and GLU produced a hyperthermic response in all animals, including those in which hypothermia was induced by reserpine. These EAAs produced a comparable central modulatory effects on nociception, catalepsy and core temperature.

Ethanol-induced hypothermia in rats is antagonized by dexamethasone

The effect of dexamethasone on ethanol-induced hypothermia was investigated in 3.5-month old male Wistar rats (N = 10 animals per group). The animals were pretreated with dexamethasone (2.0 mg/kg, ip; volume of injection = 1 ml/kg) 15 min before ethanol administration (2.0, 3.0 and 4.0 g/kg, ip; 20 per cent w/v) and the colon temperature was monitored with a digital thermometer 30, 60 and 90 min after ethanol administration. Ethanol treatment produced dose-dependent hypothermia throughout the experiment (-1.84 ñ 0.10, -2.79 ñ 0.09 and -3.79 ñ 0.l5 degrees Celsius for 2.0, 3.0 and 4.0 g/kg ethanol, respectively, 30 min after ethanol) but only the effects of 2.0 and 3.0 g/kg ethanol were significantly antagonized (-0.57 ñ 0.09 and - 1.25 ñ 0.10, respectively, 30 min after ethanol) by pretreatment with dexamethasone (ANOVA, P<0.05). These results are in agreement with data from the literature on the rapid antagonism by glucocorticoids of other effects of ethanol. The antagonism was obtained after a short period of time, suggesting that the effect of dexamethasone is different from the classical actions of corticosteroids.

Thermal changes produced by norepinephrine application in the preoptic area of monkeys.

The effect of injection of norepinephrine in the anterior regions of hypothalamus on rectal temperature, skin temperature, heart rate and respiratory rate in rhesus monkeys was studied. The injection of 2 micrograms of norepinephrine in the preoptic area produced a fall in body temperature without any accompanying change in skin temperature, heart rate and respiratory rate. The findings suggest that the suppression of heat production may be responsible for the norepinephrine induced hypothermia in monkeys.

Hypothermia dn alphamethyldopa treatment.

The hypotensive drug alphamethyldopa, an inhibitor of serotonin synthesis, caused significant hypothermia ranging from 33.4 to 34.8 degrees C (t=3.09 at P less than 0.05) in four out of nine hypertensive patients, with evidence of cerebral atherosclerosis. The anti-serotonin effect of alphamethyldopa correlated with statistically significant (t=6.8 at P less than 0.001) fall in the 24 hour urinary 5-hydroxyindoleacetic acid on the third day of the therapy. The possible mode of hypothermic side effect is discussed.