Differential role of kinases in brain stem of hypertensive and normotensive rats. (73/582)

Spontaneously hypertensive rats (SHR) are characterized by extreme elevations of blood pressure. The genetic factors underlying this are yet to be identified. Here we demonstrate, in vivo, that in SHR and normotensive Wistar-Kyoto rats (WKY), injection of the mitogen-activated protein kinase inhibitor PD 098,059 bilaterally into the rostral ventrolateral medulla (RVLM) dramatically lowers arterial pressure. PD 098,059 does not alter the responses evoked by microinjection of glutamate into the RVLM or brief apnea. Wortmannin (phosphatidylinositol-3 kinase inhibitor) bilaterally into the RVLM causes a 35+/-4% fall in arterial pressure in SHR but has no effect in WKY. Furthermore, wortmannin reduces the pressor response evoked by microinjection of angiotensin (Ang) II in the RVLM of SHR compared with WKY. The response to Ang II microinjection into the RVLM of WKY was unaffected by wortmannin. Simultaneous bilateral injections of PD 098,059 and wortmannin into the RVLM abolished the response to exogenous Ang II in the RVLM but did not affect the response evoked by glutamate in either SHR or WKY. Thus, it appears that PD 098,059- and/or wortmannin-sensitive mechanisms are not involved in the responses evoked by glutamate in the RVLM and that these kinase inhibitors are not neurotoxic. We conclude that a PD 098,059-sensitive pathway in the RVLM of SHR and WKY tonically regulates arterial pressure and that a wortmannin-sensitive pathway in the RVLM is important in the maintenance of hypertension in SHR. This may be related to a phosphatidylinositol-3 kinase-dependent mechanism involved in the action of Ang II on the Ang II type 1 receptor.  (+info)

Unventilated airway is time-dependently constricted in paralyzed dogs. (74/582)

BACKGROUND: Apnea has been reported to produce bronchoconstriction and to cause hypoxia, hypercapnia, and modulation of vagal afferent nerves, which also change airway tone. In this study, the authors determined the mechanism of apnea-induced bronchoconstriction. METHODS: Twenty-eight dogs anesthetized and paralyzed were assigned to four groups (n = 7 each): apnea after artificial ventilation with 50% and 100% O2 groups (apnea-50% O2 and apnea-100% O2 groups, respectively), an apnea plus vagotomy group (fraction of inspired oxygen [FiO2] = 1.0), and a one-lung ventilation group (FiO2 = 1.0). The trachea was intubated with a single- or double-lumen tube in the three apnea groups or the one-lung ventilation group, respectively. The bronchial cross-sectional area (BCA) was assessed by the authors' bronchoscopic method. In the apnea-100% O2 and apnea plus vagotomy groups, a respirator was turned off for 5 min to produce apnea. In the apnea-50% O2 group, apnea was produced for 3 min. In the one-lung ventilation group, the right lumen was blocked for 5 min, and 15 min later, the left lumen was blocked for 5 min. BCA, arterial oxygen tension (PaO2), and arterial carbon dioxide tension (PaCO2) were assessed every minute. RESULTS: The BCA in intact dogs time-dependently decreased by approximately 20% and 40% at 3 and 5 min after apnea started, respectively, whereas they did not in vagotomized dogs. In the apnea-50% O2 and apnea-100% O2 groups, bronchoconstriction could occur without hypoxemia, although hypercapnia was observed in all dogs. In the one-lung ventilation group, despite the fact that PaCO2 increased by only 2 mmHg without hypoxemia, unventilated BCA time-dependently decreased by 33.6 +/- 10.3%, whereas ventilated BCA did not. CONCLUSION: The current study suggests that the unventilated airway may constrict spontaneously. In addition, the airway constriction could be vagally mediated but not due to hypoxia and hypercapnia.  (+info)

Spontaneous arousal activity in infants during NREM and REM sleep. (75/582)

The infant arousal response involves subcortical and cortical responses occurring as a sequence of stereotyped behaviour regardless of the eliciting stimulus. The spontaneous activity of these responses during sleep, however, is uncertain. We examined the spontaneous arousal pattern in normal infants to determine the sequence of responses, and to examine their periodicity and the effects of sleep state. We performed a nap polysomnographic study on 10 normal infants between 2 and 10 weeks of age. Electroencephalographic and electro-oculographic activity, and respiratory airflow and movements were measured, and video recordings were made throughout each study. Different levels of arousal behaviour were examined. We found that spontaneous arousal activity occurred frequently and the majority of responses occurred as a sequence involving an augmented breath followed by a startle and then cortical arousal. Subcortical arousals as reflected by augmented breaths and startles were more common than cortical arousals. Additionally, augmented breaths followed by apnoea were recorded and were not usually associated with other arousal responses. All of the responses occurred periodically either as bursts of activity or as isolated responses. Each of the responses occurred more frequently during rapid eye movement (REM) sleep than during non-rapid eye movement (NREM) sleep. We conclude that there is an endogenous rhythm of spontaneous activity in infants involving excitatory processes from the brainstem, which may or may not be closely followed by cortical excitation. The spontaneous arousal responses occur periodically but with a high level of irregularity and the level of activity is affected by sleep state.  (+info)

Effects of training on forced submersion responses in harbor seals. (76/582)

In several pinniped species, the heart rates observed during unrestrained dives are frequently higher than the severe bradycardias recorded during forced submersions. To examine other physiological components of the classic 'dive response' during such moderate bradycardias, a training protocol was developed to habituate harbor seals (Phoca vitulina) to short forced submersions. Significant changes were observed between physiological measurements made during naive and trained submersions (3-3.5 min). Differences were found in measurements of heart rate during submersion (naive 18+/-4.3 beats min(-1) versus trained 35+/-3.4 beats min(-1)), muscle blood flow measured using laser-Doppler flowmetry (naive 1.8+/-0.8 ml min(-1) 100 g(-1) versus trained 5.8+/-3.9 ml min(-1) 100 g(-1)), change in venous P(O(2)) (naive -0.44+/-1.25 kPa versus trained -1.48+/-0.76 kPa) and muscle deoxygenation rate (naive -0.67+/-0.27 mvd s(-1) versus trained -0.51+/-0.18 mvd s(-1), a relative measure of muscle oxygenation provided by the Vander Niroscope, where mvd are milli-vander units). In contrast to the naive situation, the post-submersion increase in plasma lactate levels was only rarely significant in trained seals. Resting eupneic (while breathing) heart rate and total oxygen consumption rates (measured in two seals) were not significantly different between the naive and trained states. This training protocol revealed that the higher heart rate and greater muscle blood flow in the trained seals were associated with a lower muscle deoxygenation rate, presumably secondary to greater extraction of blood O(2) during trained submersions. Supplementation of muscle oxygenation by blood O(2) delivery during diving would increase the rate of blood O(2) depletion but could prolong the duration of aerobic muscle metabolism during diving. This alteration of the dive response may increase the metabolic efficiency of diving.  (+info)

Prenatal nicotine exposure increases apnoea and reduces nicotinic potentiation of hypoglossal inspiratory output in mice. (77/582)

We examined the effects of in utero nicotine exposure on postnatal development of breathing pattern and ventilatory responses to hypoxia (7.4 % O2) using whole-body plethysmography in mice at postnatal day 0 (P0), P3, P9, P19 and P42. Nicotine delayed early postnatal changes in breathing pattern. During normoxia, control and nicotine-exposed P0 mice exhibited a high frequency of apnoea (f(A)) which declined by P3 in control animals (from 6.7 +/- 0.7 to 2.2 +/- 0.7 min(-1)) but persisted in P3 nicotine-exposed animals (5.4 +/- 1.3 min(-1)). Hypoxia induced a rapid and sustained reduction in f(A) except in P0 nicotine-exposed animals where it fell initially and then increased throughout the hypoxic period. During recovery, f(A) increased above control levels in both groups at P0. By P3 this increase was reduced in control but persisted in nicotine-exposed animals. To examine the origin of differences in respiratory behaviour, we compared the activity of hypoglossal (XII) nerves and motoneurons in medullary slice preparations. The frequency and variability of the respiratory rhythm and the envelope of inspiratory activity in XII nerves and motoneurons were indistinguishable between control and nicotine-exposed animals. Activation of postsynaptic nicotine receptors caused an inward current in XII motoneurons that potentiated XII nerve burst amplitude by 25 +/- 5 % in control but only 14 +/- 3 % in nicotine-exposed animals. Increased apnoea following nicotine exposure does not appear to reflect changes in basal activity of rhythm or pattern-generating networks, but may result, in part, from reduced nicotinic modulation of XII motoneurons.  (+info)

Apnea at discharge and gastro-esophageal reflux in the preterm infant. (78/582)

OBJECTIVE: To determine the relationship between respiratory patterns and acid gastro-esophageal reflux (g-e reflux) prior to discharge of the formerly preterm infant. STUDY DESIGN: Forty-five infants of <32 weeks' gestation were studied at an average postmenstrual age of 37.2 weeks (SD 3.5). Following informed parental consent, a 12-hour multichannel recording including esophageal pH was obtained. Apneas of greater than 10 seconds were recorded, as well as the occurrence of bradycardia or desaturation. RESULTS: Acid g-e reflux (pH <4.0) occurred at least once in all of the infants; prevalence was between <1% and 41% of the 12-hour record (median 4.6%, interquartile range 0.5% to 9%). The number of reflux episodes ranged from 1 to 143 (median 23). The number of apneas (>10 seconds duration) ranged from 0 to 71, median 6. There was no correlation between apnea frequency or severity and reflux frequency or duration. There was no difference in apnea frequencies between the 5 minutes after the start of a reflux episode and the 5 minutes prior to each episode. CONCLUSION: Acid g-e reflux in the formerly preterm infant at discharge is frequent and may be prolonged; there is no association between reflux and apnea.  (+info)

Extreme value theory applied to postoperative breathing patterns. (79/582)

BACKGROUND: There has been little published work on the statistical features of breath times in postoperative patients. We applied extreme value theory (a statistical method) to the variation in the timing of postoperative breathing. METHODS: We observed 49 patients 3-6 h after a variety of surgical procedures, once they had achieved a stable breathing pattern. The breathing patterns could be one of the three types predicted by the extreme value model. 'Finite' breathing patterns (n=30) have a finite upper limit of duration for any apnoea. Patients that displayed one of the other two patterns ('standard' and 'extended') have, potentially, no limit in duration of apnoea. RESULTS: The type of breathing pattern observed in each patient was not reliably identified by most of the commonly used risk factors (age, type of surgery, opioid type, dose, and route of administration). A finite pattern was observed in 13 of 26 patients receiving epidural (vs 17 of 23 parenteral analgesia: P=0.15), and 15 of 19 receiving morphine (vs 15 of 30 other opioids: P=0.05). The patients with 'finite' patterns were also significantly less drowsy (score 1.04 (0.92) vs 1.62 (0.62), P<0.05). CONCLUSIONS: The breathing pattern was not related to mean breath times, suggesting that the prevalence of apnoeas cannot be reliably predicted by measurement of the respiratory rate alone.  (+info)

Unusual arachnoid cyst of the quadrigeminal cistern in an adult presenting with apneic spells and normal pressure hydrocephalus--case report. (80/582)

A 67-year-old woman was admitted to our clinic with symptoms of normal pressure hydrocephalus, lower cranial nerve pareses, and pyramidal and cerebellar signs associated with respiratory disturbances. Computed tomography (CT) and magnetic resonance imaging revealed a 4.7 x 5.4 cm quadrigeminal arachnoid cyst causing severe compression of the tectum and entire brain stem, aqueduct, and cerebellum, associated with moderate dilation of the third and lateral ventricles. Emergency surgery was undertaken due to sudden loss of consciousness and impaired breathing. The cyst was totally removed by midline suboccipital craniotomy in the prone position. Postoperatively, her symptoms improved except for the ataxia and impaired breathing. She was monitored cautiously for over 15 days. CT at discharge on the 18th postoperative day revealed decreased cyst size to 3.9 x 4.1 cm. Histological examination confirmed the diagnosis of the arachnoid cyst of the quadrigeminal cistern. The patient died of respiratory problems on the 5th day after discharge. Quadrigeminal arachnoid cysts may compress the brain stem and cause severe respiratory disturbances, which can be fatal due to apneic spells. Patients should be monitored continuously in the preoperative and postoperative period until the restoration of autonomous ventilation is achieved.  (+info)