[Suspected diltiazem intoxication resulting in repeated asystole after the induction of anesthesia].

We present a case of diltiazem intoxication resulting in repeated asystole after the induction of anesthesia. A 39-year-old man was diagnosed as subarachnoid hemorrhage, and cerebral aneurysm clipping was scheduled on the next day. Electrocardiogram revealed normal sinus rhythm with complete right bundle branch block. Continuous intravenous administration of diltiazem, nicardipine and midazolam were started for intractable hypertension and tachycardia. In the operating room, electrocardiogram showed atrioventricular nodal rhythm. Nicardipine and midazolam were stopped and anesthesia was induced with thiamylal, fentanyl and vecuronium, and was maintained with sevoflurane. After tracheal intubation, the patient developed asystole, and cardiopulmonary resuscitation was provided immediately. Diltiazem was stopped. Cardiac rhythm was restored 8 min afterwards; however, asystole recurred six times. Temporary cardiac pacing was effective, and percutaneous cardiopulmonary support (PCPS), intraaortic balloon pumping (IABP), and continuous hemodiafiltration (CHDF) were initiated. The operation was canceled. On the next day, normal sinus rhythm was restored and the temporary pacing, PCPS, IABP, and CHDF were discontinued. Cerebral aneurysm was treated by endovascular coiling and the patient was discharged from the hospital without sequelae. This case illustrates asystole associated with diltiazem intoxication. It is necessary to consider this potential complication when diltiazem is used.

Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat.

The present study re-evaluated an existing notion that serotonin (5-hydroxytryptamine; 5-HT) could not cross the brain to the circulating blood via the blood-brain barrier (BBB). To elevate brain 5-HT alone, 5-hydroxytryptophan (5-HTP; 30-75 mg/kg) was administrated intravenously to anaesthetized rats that had undergone gastrointestinal and kidney resections along with liver inactivation (organs contributing to increasing blood 5-HT after 5-HTP administration). A microdialysis method and HPLC system were used to determine the brain 5-HT levels in samples collected from the frontal cortex. Blood 5-HT levels were determined from whole blood, not platelet-poor plasma, collected from the central vein. We found that blood 5-HT levels showed a significant augmentation whenever brain 5-HT levels were significantly elevated after the administration of 5-HTP in those rats with the abdominal surgical procedures. This elevation was abolished after pretreatment with a selective serotonin reuptake inhibitor (fluoxetine; 10 mg/kg i.v.), although brain 5-HT levels remained augmented. These results indicate that augmented brain 5-HT can cross the BBB through the 5-HT transporter from the brain to the circulating blood.

Swim stress exaggerates the hyperactive mesocortical dopamine system in a rodent model of autism.

Several clinical reports have suggested that there is a hyperactivation of the dopaminergic system in people with autism. Using rats exposed prenatally to valproic acid (VPA) as an animal model of autism, we measured dopamine (DA) levels in samples collected from the frontal cortex (FC) using in vivo microdialysis and HPLC. The basal DA level in FC was significantly higher in VPA-exposed rats relative to controls. Since the mesocortical DA system is known to be sensitive to physical and psychological stressors, we measured DA levels in FC before, during, and after a 60-min forced swim test (FST). There were further gradual increases in FC DA levels during the FST in the VPA-exposed rats, but not in the control rats. Behavioral analysis during the last 10 min of the FST revealed a significant decrease in active, escape-oriented behavior and an increase in immobility, which is thought to reflect the development of depressive behavior that disengages the animal from active forms of coping with stressful stimuli. These results suggest that this rodent model of autism exhibits a hyperactive mesocortical DA system, which is exaggerated by swim stress. This abnormality may be responsible for depressive and withdrawal behavior observed in autism.

Abnormality of circadian rhythm accompanied by an increase in frontal cortex serotonin in animal model of autism.

Several clinical reports have indicated that autistic patients often show disturbance of the circadian rhythm, which may be related to dysfunction of the serotonergic system in the brain. Using rats exposed prenatally to valproic acid (VPA) as an animal model of autism, we examined locomotor activity and feeding under a reversed 12-h light/dark cycle, and found disturbance of the circadian rhythm characterized by frequent arousal during the light/sleep phase. In addition, measurement of brain serotonin (5-HT) level using in vivo microdialysis showed that the brain 5-HT level in VPA-exposed rats was significantly higher than that in control rats. These results suggest that a higher brain 5-HT level might be responsible for the irregular sleep/awake rhythm in autism.