Yoko Masaki

Neuroprotective effects of a combination of dexmedetomidine and hypothermia after incomplete cerebral ischemia in rats.

Background: Dexmedetomidine and hypothermia are known to reduce neuronal injury following cerebral ischemia. We examined whether a combination of dexmedetomidine and hypothermia reduces brain injury after transient forebrain ischemia in rats to a greater extent than either treatment alone.

β-adrenoreceptor Antagonists Attenuate Brain Injury After Transient Focal Ischemia in Rats

&bgr;-adrenoreceptor antagonists experimentally reduce cardiac and renal injury after ischemia and are also clinically useful for myocardial infarction and severe burns. In addition, &bgr;-adrenoreceptor antagonists provide neuroprotective effects after focal cerebral ischemia in experimental settings. We conducted the present study to compare the neuroprotective effects of several &bgr;-adrenoreceptor antagonists in rat transient focal cerebral ischemia. Halothane-anesthetized normothermic adult male Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion using the intraluminal suture technique confirmed by laser Doppler flowmetry. Rats received an IV infusion of saline 0.5 mL/h, propranolol 100 &mgr;g · kg−1 · min−1, carvedilol 4 &mgr;g · kg−1 · min−1, esmolol 200 &mgr;g · kg−1 · min−1, or landiolol 50 &mgr;g · kg−1 · min−1 (n = 6 in each group). Infusion was initiated 30 min before middle cerebral artery occlusion and continued for 24 h. Additional rats received esmolol 50 &mgr;g · kg−1 · min−1 or landiolol 10 &mgr;g · kg−1 · min−1 intrathecally (IT) via the cisterna magna (n = 5 in each group), according to the same experimental protocol. The neurological deficit score was evaluated at 22 h after reperfusion, and the brains were removed and stained with triphenyltetrazolium chloride for evaluation of infarct volume. Additional rats that received saline, esmolol, and landiolol IV (n = 6 in each group) were allowed to survive for 7 days followed by measurement of infarct size. Neurological deficit scores were smaller in rats treated with propranolol-IV, carvedilol-IV, esmolol-IV, landiolol-IV, esmolol-IT, and landiolol-IT compared with saline-treated rats (P < 0.05). Cortical and striatum infarct volumes were less in the rats receiving &bgr;-adrenoreceptor antagonists via either IV or IT than in saline-treated rats (P < 0.05). We conclude that &bgr;-adrenoreceptor antagonists improve neurological and histological outcomes after transient focal cerebral ischemia in rats independent of administration route.

Esmolol and Landiolol, Selective β1-Adrenoreceptor Antagonists, Provide Neuroprotection Against Spinal Cord Ischemia and Reperfusion in Rats

BACKGROUND:Paraplegia is a devastating and unpredictable complication occasionally resulting from surgery of the thoracic and thoracoabdominal aorta. Because ultrashort-acting selective &bgr;1-adrenoreceptor antagonists provide neuroprotective effects after brain ischemia, we hypothesized that they would also ameliorate spinal cord injury after transient ischemia and reperfusion in rats. METHODS:Male Sprague-Dawley rats were randomly assigned to one of the following 4 groups: saline (received IV infusion of 0.9% saline at a rate of 0.5 mL/h, n = 8), esmolol (esmolol 200 &mgr;g/kg/min, n = 8), landiolol (landiolol 50 &mgr;g/kg/min), or sham surgical (n = 6). Infusion of saline or drugs was initiated 30 minutes before spinal cord ischemia and continued for the subsequent 24-hour reperfusion. Spinal cord ischemia was induced by intraaortic balloon occlusion combined with proximal arterial hypotension for 10 minutes. The spinal cord was then reperfused for 24 hours. Ischemic injury was assessed in terms of the motor deficit index score of the hindlimb and the number of viable motor nerve cells in the anterior spinal cord at 24 hours after reperfusion. RESULTS:The motor deficit index scores were significantly lower in the esmolol and landiolol groups compared with the saline group (P < 0.05). Histopathologic evaluation of the spinal cord showed less damage in the esmolol and landiolol groups than in the saline group (P < 0.05). CONCLUSIONS:These data show that ultrashort-acting selective &bgr;1-adrenoreceptor antagonists can reduce neurological injury in a rat model of spinal cord ischemia-reperfusion.

The combined neuroprotective effects of lidocaine and dexmedetomidine after transient forebrain ischemia in rats.

Background: We investigated whether coadministration of lidocaine and dexmedetomidine would reduce brain injury following transient forebrain ischemia in rats to a greater extent than either drug alone.

The Effect of Intravenous or Subarachnoid Lidocaine on Glutamate Accumulation During Transient Forebrain Ischemia in Rats

UNLABELLED We studied whether IV or subarachnoid (SA) lidocaine would influence the increase in extracellular glutamate concentration in the hippocampal CA1 and the cerebral cortex during transient forebrain ischemia in rats by using the dialysis electrode method. Fifty-four Sprague-Dawley rats were assigned to one of six treatment groups: IV lidocaine 5 mg/kg, IV lidocaine 10 mg/kg, IV 0.9% saline 0.5 mL/kg, SA lidocaine 5 mg/kg, SA lidocaine 10 mg/kg, and SA 0.9% saline 0.5 mL/kg (n = 9 in each group). Transient forebrain ischemia was induced by hemorrhagic hypotension and carotid artery occlusion, 15 min after administration of lidocaine or saline. The maximal values of glutamate concentration and the areas under glutamate concentration curves in the CA1 were significantly less in the IV lidocaine 10 mg/kg group than the IV saline group, whereas those in the CA1 and the cortex were significantly less in the SA lidocaine 5 and 10 mg/kg groups than the SA saline group. The accumulation of glutamate in the CA1 or the cortex during transient forebrain ischemia was attenuated by IV or SA lidocaine. We conclude that the neuroprotective effect of lidocaine against transient cerebral ischemia involves the suppression of the increase in extracellular glutamate concentration. IMPLICATIONS IV or subarachnoid lidocaine was demonstrated to suppress glutamate accumulation in the hippocampus and the cortex during transient forebrain ischemia in rats by using the dialysis electrode method. Lidocaine can have a neuroprotective effect through the suppression of the increase in extracellular glutamate concentration.

Changes in propofol concentration in a propofol-lidocaine 9:1 volume mixture.

P ropofol (2,6-diisopropylphenol) is widely used for the induction and maintenance of anesthesia as well as for sedation of intensive care patients. However, a 30%–70% incidence of pain associated with IV injection is one important source of patient dissatisfaction (1). Although several methods for alleviating pain have been described (2), the addition of lidocaine is one of the most common methods in clinical practice. The manufacturer of propofol recommends administration of the propofol-lidocaine mixture immediately after preparation, without specifying any safety period. To date, the only published study regarding the compatibility of propofol and lidocaine dealt with changes in the microscopic appearance of emulsion after mixing and in the zeta potential of various combination doses (4). More importantly, the chemical stability of the propofollidocaine mixture has never been addressed. The characteristics of a colorless, liquid, separate layer that appears on the surface of the emulsion after the addition of lidocaine to propofol (5) suggest that it is propofol, per se. Accordingly, the purpose of our study was to test a hypothesis that propofol is dissociated as a immiscible layer after the addition of lidocaine and, as a consequence, propofol concentrations decrease in a time-dependent manner in the propofollidocaine mixture. We made serial determinations of propofol concentrations by gas chromatography (GC) for 24 h after the preparation of a clinically relevant combination dose of propofol and lidocaine.

Intravenous dexmedetomidine decreases lung permeability induced by intracranial hypertension in rats.

BACKGROUND: Intracisternal dexmedetomidine (Dex) attenuates cardiac dysfunction in rats with intracranial hypertension (ICH). However, the effects of IV Dex on cardiac function and lung permeability during ICH have not been evaluated. We tested the hypothesis that IV Dex attenuates hemodynamic changes and decreases lung permeability induced by ICH in rats. METHODS: Halothane-anesthetized and mechanically ventilated rats were divided into four groups. In two groups, a subdural balloon catheter was inflated for 60 s to produce ICH. Arterial blood gas analysis was performed before and 30 min after ICH. Mean arterial blood pressure, heart rate (HR) and intracranial pressure were monitored for 30 min. The Dex group (n = 8) received IV Dex 80 &mgr;g/kg, followed by 6 &mgr;g · kg−1 · min−1 (40 &mgr;g/mL) for 10 min and the control group (n = 8) received IV saline 2 mL/kg, followed by at 0.15 mL · kg−1 · min−1 for 10 min. Surgery was performed without ICH with Dex (Sham-Dex group, n = 5) and without Dex (Sham-control, n = 5). In all groups, pulmonary permeability was measured using a modification of the Evans blue dye extravasation technique. IV Evans blue dye 20 mg/kg was administered 2 h before being killed and Evans blue dye in plasma and lung tissue was quantified by dual-wavelength spectrophotometric analysis. RESULTS: There were no significant differences in basal arterial blood pressure, HR, and Pao2 among groups. In the control group, ICH resulted in transient increases in mean arterial blood pressure and HR, followed by a rapid decline and a plateau. In the Dex group, mean arterial blood pressure showed a transient increase and subsequent, rapid decrease to baseline, whereas HR did not change during ICH. Pao2 was higher in the Dex group than in the control group after ICH [138 (127–169) vs 78 (59–124) mm Hg, median (range), P < 0.01]. The pulmonary permeability index was lower in the Dex group than the control group [430 (182–450) vs 570 (427–1170), P < 0.01]. It was however, higher in the Sham-Dex group than the Sham-Control group [25 (24–35) vs 6 (4–7), P < 0.01]. CONCLUSIONS: Prophylactic IV Dex decreases lung permeability as well as hemodynamic changes induced by ICH in rats.

Neuroprotective effects of selective beta-1 adrenoceptor antagonists, landiolol and esmolol, on transient forebrain ischemia in rats; a dose–response study

Although selective beta-1 adrenoceptor antagonists are known to provide neuroprotective effects after brain ischemia, dose-response relationships of their neuroprotective effects have not been examined. The present study was conducted to evaluate whether the degree of brain protection against transient forebrain ischemia would be influenced by different doses of selective beta-1 adrenoceptor antagonists, esmolol and landiolol, in rats. Adult male S.D. rats received intravenous infusion of saline 0.5 ml/h, esmolol 20, 200, 2,000 μg/kg/min, or landiolol 5, 50, 500 μg/kg/min. Infusion was initiated 30 min prior to ischemia and continued for 24h. Ten-minute forebrain ischemia was induced by hemorrhagic hypotension and occlusion of the bilateral carotid arteries. Neurological and histological examinations were performed. Neurological deficit scores at 1, 4 and 7 days were lower, and the number of intact neurons in CA1 hippocampal region was larger in the rats treated with esmolol and landiolol after ischemia, compared with saline-treated rats (P<0.05), whereas no difference was found among different doses of esmolol and landiolol. These results suggested that selective beta-1 adrenoceptor antagonists improved neurological and histological outcomes following forebrain ischemia in rats, irrespective of their doses.

Neuroprotective effect of mivazerol, an α2‐agonist, after transient forebrain ischemia in rats*

Background:  We examined whether mivazerol, an α2‐agonist, had neuroprotective effects after transient forebrain ischemia in rats.

Long-term effects of post-ischaemic oestrogen on brain injury in a rat transient forebrain ischaemia model.

The current study was conducted to compare the effects of post‐treatment with oestrogen on histological and neurological outcomes after short (7‐day) and long (28‐day) recovery periods in rats subjected to transient forebrain ischaemia.