Biphasic action of aldosterone on Akt signaling in cardiomyocytes.

Both aldosterone and Akt signaling play pivotal roles in the pathogenesis of heart failure. However, little is known about the correlation between them. We herein investigated whether aldosterone interacts with Akt signaling in a coordinated manner in cardiomyocytes. Neonatal rat cardiomyocytes were stimulated with aldosterone for either a short (10-min) or long (24-h) time. The phosphorylation of Akt and its downstream effector, GSK3ß, were transiently increased after short-term stimulation, which was blocked by either PI3K or Na(+)/H(+) exchanger inhibitors, but not by the mineralocorticoid receptor antagonist, eplerenone. Long-term stimulation also significantly increased Akt-GSK3ß phosphorylation and this effect was reduced by eplerenone. Thus, these results suggest that aldosterone activates Akt signaling via a biphasic reaction that occurs through different cascades. To understand the significance of the rapid action of aldosterone, cardiomyocytes were exposed to hydrogen peroxide for from 10 to 60 min. A short-term aldosterone stimulation (for up to 30 min) significantly protected cardiomyocytes from oxidative stress-induced cellular damage. Eplerenone did not abrogate this beneficial effect, while a PI3K inhibitor did. Therefore, during the early phase, aldosterone has favorable effects on cardiomyocytes, partly by acute activation of a mineralocorticoid receptor-independent cascade through the Na(+)/H(+) exchanger, PI3K, and Akt. In contrast, its persistent activity produces pathological effects partly by chronic Akt activation in a mineralocorticoid receptor-dependent manner.

Cerebral ischaemia during cardiac surgery in children detected by combined monitoring of BIS and near-infrared spectroscopy.

BACKGROUND: Children frequently suffer transient cerebral ischaemia during cardiac surgery. We measured cerebral ischaemia in children during cardiac surgery by combining two methods of monitoring. METHODS: We studied 65 children aged between 5 months and 17 yr having surgery to correct non-cyanotic heart disease using hypothermic cardiopulmonary bypass (CPB). During surgery, we measured the Bispectral Index (BIS) and regional cerebral haemoglobin oxygen saturation (SrO2) with near-infrared spectroscopy (NIRS). Cerebral ischaemia was diagnosed if both SrO2 and BIS decreased abruptly when acute hypotension occurred. In each patient, the relationship between SrO2 and arterial blood pressure (AP) was indicated by a plot of mean SrO2 against simultaneous mean AP. RESULTS: We noted 72 episodes of cerebral ischaemia in 38 patients. Sixty-three ischaemic events were during CPB. Cerebral ischaemia was less frequent in older patients. Cerebral ischaemia was more common and more frequent in children under 4 yr old. Haematocrit during CPB was lower and SrO2 was more dependent on AP in children under 4 yr. CONCLUSIONS: Children less than 4 yr of age are more likely to have cerebral ischaemia caused by hypotension during cardiac surgery. Ineffective cerebral autoregulation and haemodilution during CPB may be responsible.

[Diagnosis and assessment of pain].

Good management of pain depends on accurate assessment. We describe some approaches to the measurement of pain or suffering, including visual analogue scale, the MacGill Pain Questionnaire and behavioral observation scale. Patient's self-reporting provides the most valid information, because pain is a personal and subjective. Behavioral approaches to pain measurement, such as behavioral observation scale are useful for pain assessment for infants, children without language skills. Intravenous barbiturate, phentolamine(alpha-adrenergic antagonist), lidocaine(Na channel blocker), morphine(opioid), or ketamine(NMDA antagonist) may contribute to pain assessment as diagnostic tools for the investigation of the etiology of pain, especially neuropathic pain.

[Evaluation of estimated blood concentration of propofol on wake-up using "ConGrase", a software to control the syringe pump for propofol infusion].

We developed a software to control a Graseby 3500 syringe pump for propofol infusion through the serial port of Apple Macintosh/Power-Macintosh computer. This software, "ConGrase", was developed with Metrowerks CodeWarrior Professional (CWP 1) and PowerPlant framework using C++. ConGrase communicates with the syringe pump at least every three seconds, and calculates the estimated blood concentration (EBC) of propofol based on the amount of propofol actually infused by applying either the Euler or Runge-Kutta method using the three-compartment pharmacokinetic model. The parameter sets reported by Gepts et al. are used. ConGrase was released at the 44 th Annual Meeting of the Japan Society of Anesthesiology, and is distributed freely. The mean and S.D. of the emergence EBC calculated by ConGrase were 1.22 micrograms.ml-1 and 0.16 microgram.ml-1, respectively. These values are almost the same as values already reported outside Japan. The necessary wake-up time can be calculated with this estimated concentration. With this system, anesthetists can control the EBC at the required level and avoid long delays before the patients wake up after anesthesia.

Intravenous midazolam suppresses noxiously evoked activity of spinal wide dynamic range neurons in cats.

The effects of intravenously (i.v.) administered midazolam on noxiously evoked activity of spinal wide dynamic range (WDR) neurons were investigated in decerebrate, spinal-cord-transected cats. Extracellular, single-unit recordings were measured during stimulation by pinching the receptive field on the hind paw and the effect of midazolam at doses of 0.25, 0.5, 1, 2, and 4 mg/kg were measured. Two series of experiments were performed to characterize the analgesic effects of midazolam. In the first, dose-response experiments (n = 59) demonstrated a dose-dependent suppression of the noxiously evoked activity of spinal WDR neurons after midazolam administration. This effect of midazolam was maximal at a dose of 1 mg/kg i.v.. The second series of experiments (n = 14) demonstrated that a benzodiazepine antagonist, flumazenil (n = 8), promptly reversed the effect of midazolam, while an opioid antagonist, naloxone (n = 6), had no effect on the effect of midazolam. The present study demonstrates that i.v. administered midazolam suppresses noxiously evoked activity of spinal WDR neurons that is reversible by a benzodiazepine antagonist. This is consistent with an analgesic action of midazolam.