CO2 activates orexin-containing neurons in mice.

Accumulating evidence shows possible participation of orexin, a hypothalamic neuropeptide also known as hypocretin, in regulation of breathing. In this study we examined whether hypercapnic stimulation in vivo activates orexin-containing neurons in the hypothalamus. A hypercapnic gas mixture of 10% CO(2), 21% O(2), and residual N(2) or room air was inhaled to awake and freely moving mice for 3h. Their brains were examined by double immunohistochemical staining for orexin and c-Fos. We found that inhalation of CO(2) significantly increased c-Fos expression in the orexin-containing cells that were located in the perifornical region and the dorsomedial hypothalamus (15.8+/-1.6% for room air vs. 28.4+/-2.7% for CO(2), p=0.011) but not in the lateral hypothalamic area (12.3+/-1.2% for room air vs. 12.4+/-3.0% for CO(2)). Although current methodology cannot differentiate between direct effect of CO(2) on the orexin-containing neurons and indirect one through other neurons, this is the first report showing that inhalation of CO(2) did activate the orexin-containing neurons in vivo.

Emotional and state-dependent modification of cardiorespiratory function: role of orexinergic neurons.

Our daily life not only involves calm, resting states but is filled with perturbations that induce active conditions, such as movements, eating, and communicating. During such active periods, cardiorespiratory regulation must be adjusted for bodily demands, which differ from those during resting states, by modulating or resetting baseline levels. To explore neural mechanisms of state-dependent adjustments of central autonomic regulation, we recently focused on the following two states: 1), stress-induced defense (fight-or-flight) responses, because stressors induce both cognitive, emotional, and behavioral changes and autonomic alterations, and 2), sleep/wake differences. Basal respiration and respiratory reflex regulation significantly differ during waking and sleep states. In this review, we will summarize our recent findings with orexin knockout and orexin neuron-ablated mice to determine possible contributions of orexin, a hypothalamic neuropeptide, to state-dependent adjustments of central autonomic regulation. The diversity of synaptic control of cardiovascular and respiratory neurons appears to be necessary for animals to adapt to ever-changing life circumstances and behavioral states. The orexin system likely functions as one essential modulator for coordinating circuits controlling autonomic functions and behaviors.

Contribution of orexin in hypercapnic chemoreflex: evidence from genetic and pharmacological disruption and supplementation studies in mice.

We have previously shown that hypercapnic chemoreflex in prepro-orexin knockout mice (ORX-KO) is attenuated during wake but not sleep periods. In that study, however, hypercapnic stimulation had been chronically applied for 6 h because of technical difficulty in changing the composition of the inspired gas mixture without distorting the animal's vigilance states. In the present study we examined possible involvement of orexin in acute respiratory chemoreflex during wake periods. Ventilation was recorded together with electroencephalography and electromyography before and after intracerebroventricular administration of orexin or an orexin receptor antagonist, SB-334867. A hypercapnic (5 or 10% CO(2)) or hypoxic (15 or 10% O(2)) gas mixture was introduced into the recording chamber for 5 min. Respiratory parameters were analyzed only for quiet wakefulness. When mice breathed normal room air, orexin-A and orexin-B but not vehicle or SB-334867 increased minute ventilation in both ORX-KO and wild-type (WT) mice. As expected, hypercapnic chemoreflex in vehicle-treated ORX- KO mice (0.22 +/- 0.03 mlxmin(-1)xg(-1)x% CO(2)(-1)) was significantly blunted compared with that in WT mice (0.51 +/- 0.05 mlxmin(-1)xg(-1)x% CO(2)(-1)). Supplementation of orexin-A or -B (3 nmol) partially restored the hypercapnic chemoreflex in ORX-KO mice (0.28 +/- 0.03 mlxmin(-1).g(-1)x% CO(2)(-1) for orexin-A and 0.32 +/- 0.04 mlxmin(-1)xg(-1)x% CO(2)(-1) for orexin-B). In addition, injection of SB-334867 (30 nmol) in WT mice decreased the hypercapnic chemoreflex (0.39 +/- 0.04 mlxmin(-1)xg(-1)x% CO(2)(-1)). On the other hand, hypoxic chemoreflex in vehicle-treated ORX-KO and SB-334867-treated WT mice was not different from that in corresponding controls. Our findings suggest that orexin plays a crucial role in CO(2) sensitivity at least during wake periods in mice.

General anesthesia for patients with automatic implantable cardioverter defibrillator in place--a case report.

Automatic implantable cardioverter defibrillator (AICD) was commercially available for use in patients with malignant ventricular tachycardia and ventricular fibrillation since its meeting with FDA approval in 1985. The number of AICD implantation has increased year by year worldwide. It was allowed to be used in clinical setting in Taiwan by the Department of Health in April 1997. Physicians may come across patients with an implanted AICD undergoing surgery unrelated to cardiac issues more frequently. It is also a new challenge to anesthesiologists who must make pre-operative evaluation, maintenance during operative period and post-operative re-evaluation of the AICD function. We bring forward here for discussion a 72-year-old male patient who underwent non-cardiac surgery with AICD implantation under general anesthesia. The anesthetic precautions of patients with the device are also touched.