The upper airway is a vital part of the respiratory tract. Although the upper airway serves several functions, protection of the airway and preservation of airway patency are the most essential functions subserved by upper airway reflexes. Various types of nerve endings have been identified in and under the epithelium of the upper airway, and afferent nerve endings are the natural starting of all reflex activity. The upper airway reflexes consist of many different types of reflex responses such as sneezing, apnea, swallowing, laryngeal closure, coughing, expiration reflex, and negative pressure reflex. Although the activation of upper airway reflexes does not necessarily occur at one particular site of the respiratory tract, individual reflex response is usually considered to be highly specific for the particular respiratory site which has been affected. The upper airway reflexes are modified by many factors such as sleep, anesthesia, and background chemical ventilatory drive. Both depression and exaggeration of upper airway reflexes cause clinical problems. Depression of upper airway reflexes enhances the chance of pulmonary aspiration and compromises the maintenance of the airway, whereas exaggeration of airway reflexes such as laryngospasm and prolonged paroxysm of cough can be harmful and dangerous. In this review, various aspects of upper airway reflexes are discussed focusing on the functions of upper airway reflexes in humans and some pathophysiological problems related to clinical medicine.

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The activation of peripheral chemoreceptors by hypoxia or electrical stimulation of the carotid sinus nerve elicited a hypoxic respiratory response consisting of both stimulatory and subsequent or simultaneous inhibitory components (hypoxic respiratory stimulation and depression). Both components have different time domains of responses (time-dependent response), providing an integrated respiratory response to hypoxia. This review has focused on the neuroanatomical and neurophysiological correlations responsible for these responses and their neuropharmacological mechanisms. Hypoxic respiratory depression is characterized by the initial activation of respiration followed by a progressive and gradual decline in ventilation during prolonged and/or severe hypoxic exposure (biphasic response). The responsible mechanisms for the depression are located within the central nervous system and may be dependent upon activity from peripheral chemoreceptor. Two underlying mechanisms contributing to the depression have been advocated. (1) Change in synaptic transmission: Within the neuronal network controlling the hypoxic respiratory response, hypoxia might induce the enhancement of inhibitory neurotransmission (modulation), disfacilitation of excitatory neruotransmission or both. (2) Change in the membrane property of respiratory neurons: Hypoxia might suppress the membrane excitability of respiratory neurons composing the hypoxic respiratory response via modulating ion channels, leading to hyperpolarization or depolarization blocking of the neurons. However, the quantitative aspects of Pao₂ (degree and duration of hypoxic exposure) to induce these changes and the susceptibility of both mechanisms to the Pao₂ level have not yet been clearly elucidated.

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The present study has been attempted to establish a modified intravital microscope system for investigating murine lymphatic pumping activity in vivo and evaluate whether or not there is rhythmic pumping activity of murine mesenteric lymphatic vessels in vivo. We designed and constructed a custom organ chamber with a semicircular channel (8 mm in radius, 5 mm in width, 3 mm in depth), being suitable for the superfusing of murine mesentery in vivo. A marked lymphatic pumping activity was observed in the mesenteries of DDY mice. The maximal and minimal diameter and frequency in the pumping activity were 60.9 ± 1.0 μm, 53.7 ± 1.8 μm and 12.8 min⁻¹ (n = 5), respectively. Both NE (norepinephrine, 10⁻⁸–10⁻⁶ M) and TEA (tetraethylammonium, 1–10 mM) caused dose-dependent constriction of the mesenteric lymphatic vessels in the mice. These findings suggest that a modified intravital microscope system with a specially designed and constructed edge-monitoring device enables us to investigate in vivo lymphatic circulation in murine mesenteries.

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To examine whether the high-frequency (HF) component of heart rate variability (HRV) reflects fluctuation or tonic level of vagal outflow, we investigated the effects of vagal efferent nerve stimulation (VS) on the heart rate and HRV in anesthetized open-chest rabbit under artificial respiration at a rate of 52 breaths/min (0.86 Hz). A power spectral analysis was performed at baseline and during VS (stimuli at 2 ms, 1–10 V and 5–25 Hz). VS was applied using two different patterns. The first was constant VS; continuous stimulation at graded frequency or voltage to simulate changes in the level of vagal "tone." The second pattern was intermittent VS; stimulation at 0.5 Hz of on-off cycle to simulate fluctuations in vagal efferent activity. The power spectrum at baseline showed a single narrow component at 0.86 Hz, identical to respiration rate. Both the constant and intermittent VS prolonged RR interval. The amplitude of the component at 0.86 Hz remained unaffected by either the constant or intermittent VS, whereas the latter evoked a distinct narrow component at 0.5 Hz, reflecting the on-off cycle of intermittent VS. Our results suggest that the HF component of the power spectrum of HRV measures the magnitude of fluctuations of vagal input associated with respiratory modulation.

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Effects of 2- or 4-month bedrest in −6° head-down tilt position with or without countermeasures on the histochemical properties of fiber phenotype and cross-sectional area (CSA) were studied in human soleus. The CSAs in slow fibers decreased ~32% during 4-month bedrest. This reduction was normalized after 1-month recovery. Although the reduction of percent slow fibers was not significant statistically, the percent intermediate fibers was significantly elevated 4 months after bedrest. Such shift in fiber type was not normalized following 1-month recovery. Effects of wearing an anti-g Penguin suit which has a modest, but continuous resistance at the knee and ankle (Penguin-1) or with knee resistance without loading on the ankle (Penguin-2) for 10 consecutive hours daily were also investigated during ~2 months of bedrest. The subjects performed knee extension and flexion for the last 15 min of each hour while in a supine position in bed. Bedrest-induced fiber atrophy was prevented in the Penguin-1 group but not the Penguin-2 group. Transformation of fiber type was not prevented in either Penguin suit group. It is suggested that long-term bedrest causes an atrophy and a shift of fiber phenotype toward fast-twitch type in human soleus. Data also indicated that loading on the muscle is an effective countermeasure for prevention of fiber atrophy but not fiber-type transformation.

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Muscle fatigue induced by consecutive twitches or tetani was studied in single skeletal muscle fibers of the frog, Rana japonica. The fatigue by twitch appeared sooner after the start of stimulation at lower temperatures (2–5°C) than at higher ones (15–20°C), while the fatigue by tetanus appeared sooner at higher temperatures. When a twitch-fatigued fiber was bathed in a solution with caffeine (15 mM), the contracture force was much higher than the fatigued force, while in tetanus fatigue, the force by caffeine was not different from the fatigued force. The length-force relation in fatigued fibers was compared with that in pre-fatigue at low and high temperatures. It was noticed that the ascending limb of the length-force curve in fatigued fibers by twitch was lower than that in pre-fatigue at the low temperatures; namely, the fatigue by twitch was more marked in shorter muscle length, while no marked change in the length-force relation was detected in the tetanus fatigue at the low and high temperatures. The maximum shortening velocity, measured by the slack test, decreased in both types of fatigue. These results suggest that the fatigue by twitch may be mainly due to the failure of activation of the contractile system, while in the fatigue by tetanus, the rate of the interaction between actin and myosin may be impaired due to the change in intracellular chemical environment.

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In young individuals, orthostatic intolerance is associated with marked increases in plasma epinephrine (EPI) concentrations and attenuated rises in plasma norepinephrine (NE) concentrations. This study investigated the cardiovascular, EPI and NE responses of healthy elderly males during orthostatic stress. Twelve men (68 ± 1 yr) with a recent history of orthostatic hypotension and who exhibited orthostatic intolerance (HYPO) during 90° head-up tilt (HUT) were compared with 12 men (69 ± 1 yr) without a history of orthostatic hypotension and who remained normotensive (NORMO) throughout 90° HUT. Beat-by-beat recordings of heart rate (HR), mean (MAP), systolic (SBP), diastolic (DBP), and pulse (PP) pressures were made throughout 90° HUT. Blood samples obtained during supine rest and 90° HUT were analyzed for changes in EPI and NE concentrations, hematocrit, hemoglobin and plasma volume. Compared to supine rest, orthostatic intolerance was characterized by significant reductions (p < 0.0001) in MAP, SBP, DBP, and PP. The HR, MAP, SBP, DBP, and PP at the termination of 90° HUT was significantly lower (p < 0.0001) for HYPO than NORMO. The 90° HUT position resulted in significant increases (p < 0.01) in NE for both HYPO and NORMO, with the rise in NE significantly lower (p < 0.05) in HYPO. There were no differences between groups regarding EPI concentrations at the termination of 90° HUT. These results suggest that the magnitude of arterial pressure (AP) reduction does not influence the EPI response during orthostasis in healthy elderly men. However, marked reductions in AP, leading to orthostatic intolerance, are associated with inadequate increases in NE in these individuals.

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Although the importance of mechanical stress on bone metabolism is well known, the intracellular mechanisms involved are not well understood. To evaluate the role of mechanical stress on osteoclastic function, we investigated the effects of membrane stretch induced by osmotic cell swelling on cytosolic Ca²⁺ and bone resorption activity in freshly isolated rat osteoclasts. The intracellular Ca²⁺ concentration ([Ca²⁺]_i) was measured by fura-2 microspectrofluorimetry. Exposure to hypotonic solution (211–151 mOsm) caused cell swelling and reversibly increased [Ca²⁺]_i in the osteoclasts. This [Ca²⁺]_i increase was abolished by the omission of extracellular Ca²⁺, but was not affected by the depletion of intracellular Ca²⁺ stores. Gd³⁺ and La³⁺ inhibited the swelling-induced [Ca²⁺]_i increase, while nifedipine and Bay K 8644 did not. Neither protein kinase A inhibitors (Rp-cAMP, H-89) nor protein kinase C inhibitors (staurosporine, chelerythrine) affected the [Ca²⁺]_i increase. Membrane depolarization was not essential for the [Ca²⁺]_i increase either. To assess the effects of membrane stretch on the bone resorption activity of osteoclasts, we investigated actin ring formation, the intracellular structure responsible for bone resorption in osteoclasts. Hypotonic stimulation acutely disrupted actin ring formation in an extracellular Ca²⁺-dependent manner, and this disruption was prevented by Gd³⁺. Moreover, Ca²⁺ ionophore (ionomycin) also induced disruption of the actin rings. These results indicate that mechanical stress inhibits osteoclastic bone resorption activity, possibly via the elevation of [Ca²⁺]_i through stretch-activated, non-selective cation channels.

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