Desflurane and isoflurane improve neurological outcome after incomplete cerebral ischaemia in rats

Abstract

We have investigated the effects of isoflurane and desflurane on neurological outcome in a rat model of incomplete cerebral ischaemia. We studied 40 non-fasted male Sprague-Dawley rats, anaesthetized, intubated and ventilated mechanically with isoflurane and nitrous oxide in oxygen (FlO2 0.3). Arterial and venous catheters were inserted for measurement of arterial pressure, drug administration and blood sampling. A biparietal electroencephalogram (EEG) was recorded continuously using subdermal platinum electrodes. At completion of surgery, administration of isoflurane was discontinued (with the exception of those animals receiving isoflurane as treatment) and rats were allowed an equilibration period of 30 min according to the following procedure: group 1 (n = 10), 66% nitrous oxide in oxygen and fentanyl (bolus 10 micrograms kg-1 i.v. followed by infusion at a rate of 25 micrograms kg-1 h-1); group 2 (n = 10), 1.0 MAC of isoflurane in oxygen (FlO2 0.3) and air; groups 3 and 4 (n = 10 per group), 1.0 MAC or 1.5 MAC of desflurane in oxygen (FlO2 0.3) and air, respectively. Ischaemia was produced by combined unilateral common carotid artery ligation and haemorrhagic hypotension to 35 mm Hg for 30 min. Functional neurological deficit was evaluated for 3 days after cerebral ischaemia. At baseline, brain electrical activity was higher with fentanyl-nitrous oxide, 1.0 MAC of isoflurane and 1.0 MAC of desflurane (groups 1-3) compared with 1.5 MAC of desflurane (group 4). Neurological outcome was improved in isoflurane and desflurane anaesthetized animals (groups 2-4), regardless of the concentration used compared with fentanyl-nitrous oxide anaesthesia (group 1). The increase in plasma epinephrine and norepinephrine concentrations during ischaemia was significantly higher in fentanyl-nitrous oxide anaesthetized animals (group 1) compared with animals who received volatile anaesthetics (groups 2-4). These data suggest that cerebral protection produced by isoflurane and desflurane appears to be related to reduction in sympathetic activity rather than suppression of cerebral metabolic rate.

Neuroanesthesia and Intensive Care Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine A1 receptor antagonists

“…9 The concentration of 1.5% isoflurane equals 1.0 minimum alveolar anesthetic concentration. 15,16 To exclude the possible influence of hypotension, hypothermia, or respiratory depression on the beneficial effects of isoflurane, we measured the physiological variables during isoflurane pretreatment. The results showed no obvious changes in physiological variables during isoflurane preconditioning.…”

Inhalational Anesthetics as Neuroprotectants or Chemical Preconditioning Agents in Ischemic Brain

“…k or no effect Not determined Koorn et al (1993); Toner et al (2002) k k or no effect Engelhard et al (1999), Mackensen et al (1999), Halothane No effect Not determined Koorn et al (1993); Toner et al (2002) Sevoflurane k or inconsistent effect…”

Anesthetic drugs and sustained neuroprotection in acute cerebral ischemia: can we alter clinical outcomes?

“…Dans nombre d'études, la neuroprotection anesthésique a été confirmée chez le rat soumis à une ischémie hémisphérique focale ou complète; dans ces études, l'administration d'isoflurane, de sévoflurane, de desflurane et de xénon, ainsi que de barbituriques et de propofol, a réduit la taille de l'infarctus et amélioré les fonctions motrice et cognitive lorsqu'elle avait lieu avant l'exposition à l'ischémie. [5][6][7][8][9] Il a été montré que la réduction de la lésion neuronale ischémique était le plus importante dans des modèles d'étude comparant l'état « anesthésié » à des états éveillé ou sous sédation et Nous ne savons pas si les effets des agents anesthésiques observés dans ces différents modèles d'ischémie sont permanents. Les études menées sur des rats soumis à une ischémie cérébrale focale ou globale incomplète ont montré que la mort cellulaire était considérablement réduite dans la période suivant immédiatement l'ischémie; toutefois, aucune différence n'a été observée dans les lésions corticales et sous-corticales dans les semaines ou mois suivants.…”

“…In numerous studies, anesthetic neuroprotection has been confirmed in rodents subjected to focal or incomplete hemispheric ischemia where isoflurane, sevoflurane, desflurane, and xenon, as well as barbiturates and propofol, decreased infarct size and improved motor and cognitive function when given prior to the ischemic challenge. [5][6][7][8][9] The reduction in ischemic neuronal injury has been shown to be most prominent in study designs comparing ''anesthesia'' with awake or sedated states and less pronounced when different anesthetics were compared with each other. Neurologic outcome is reproducible only with brief episodes of cerebral ischemia, while longer durations of low-flow states or permanent focal ischemia are resistant to anesthetic neuroprotection.…”