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Systemic 8-OH-DPAT (a 5-HT 1A receptor agonist) challenge evokes hyperventilation independent of peripheral 5-HT 1A receptors. Though the pre-Botzinger Complex (PBC) is critical in generating respiratory rhythm and activation of local 5-HT 1A receptors induces tachypnea via disinhibition of local GABA A neurons, its role in the respiratory response to systemic 8-OH-DPAT challenge is still unclear. In anesthetized rats, 8-OH-DPAT (100 μg/kg, iv) was injected twice to confirm the reproducibility of the evoked responses. The same challenges were performed after bilateral microinjections of (S)-WAY-100135 (a 5-HT 1A receptor antagonist) or gabazine (a GABA A receptor antagonist) into the PBC. Our results showed that: 1) 8-OH-DPAT caused reproducible hyperventilation associated with hypotension and bradycardia; 2) microinjections of (S)-WAY-100135 into the PBC attenuated the hyperventilation by ˜60 % without effect on the evoked hypotension and bradycardia; and 3) the same hyperventilatory attenuation was also observed after microinjections of gabazine into the PBC. Our data suggest that PBC 5-HT 1A receptors play a key role in the respiratory response to systemic 8-OH-DPAT challenge likely via disinhibiting local GABAergic neurons., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We recently demonstrated that peripheral and central administration of nesfatin-1 in fasting and satiety states generate hyperventilation activity by increasing tidal volume (TV), respiratory rate (RR), and respiratory minute ventilation (RVM). The present study aimed to investigate the mediation of central cholinergic receptors effective in respiratory control in the hyperventilation activity of nesfatin-1. Besides this, we intended to determine possible changes in blood gases due to hyperventilation activity caused by nesfatin-1 and investigate the mediation of central cholinergic receptors in these changes. Intracerebroventricular (ICV) administration of nesfatin-1 revealed a hyperventilation response with an increase in TV, RR, RMV, and pO 2 and a decrease in pCO 2 in saturated Sprague Dawley rats. ICV pretreatment with the muscarinic receptor antagonist atropine partially blocked the RR, RMV, pO 2 , and pCO 2 responses produced by nesfatin-1 while completely blocking the TV response. However, central pretreatment with nicotinic receptor antagonist mecamylamine blocked the respiratory and blood gas responses induced by nesfatin-1. The study's conclusion demonstrated that nesfatin-1 had active hyperventilation effects resulting in an increase in pO 2 and a decrease in pCO 2 . The critical finding of the study was that activation of central cholinergic receptors was involved in nesfatin-1-evoked hyperventilation and blood gas responses., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Olanzapine is increasingly used as a sleep aid in hospitalized patients. Although thought to have less extrapyramidal effects, known side effects include oversedation, arrythmias, and hypotension. We present the unusual case of hyperventilation with respiratory alkalosis after the administration of olanzapine for insomnia in an elderly postoperative patient. This led to a second admission to the intensive care unit with invasive interventions including mechanical ventilation and vasopressor support. Caution must be exercised in prescribing antipsychotics for off-label use, especially in a population whose baseline characteristics can affect the pharmacokinetics of second-generation antipsychotics., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Reflex cardiorespiratory alterations elicited after instillation of nociceptive agents intra-arterially (i.a) are termed as 'vasosensory reflex responses'. The present study was designed to evaluate such responses produced after i.a. instillation of histamine (1 mM; 10 mM; 100 mM) and to delineate the pathways i.e. the afferents and efferents mediating these responses. Blood pressure, electrocardiogram and respiratory excursions were recorded before and after injecting saline/histamine, in a local segment of femoral artery in urethane anesthetized rats. Paw edema and latencies of responses were also estimated. Separate groups of experiments were conducted to demonstrate the involvement of somatic nerves in mediating histamine-induced responses after ipsilateral femoral and sciatic nerve sectioning (+NX) and lignocaine pre-treatment (+Ligno). In addition, another set of experiments was performed after bilateral vagotomy (+VagX) and the responses after histamine instillation were studied. Histamine produced concentration-dependent hypotensive, bradycardiac, tachypnoeic and hyperventilatory responses of shorter latencies (2-7 s) favouring the neural mechanisms in eliciting the responses. Instillation of saline (time matched control) in a similar fashion produced no response, excluding the possibilities of ischemic/stretch effects. Paw edema was absent in both hind limbs indicating that the histamine did not reach the paws and did not spill out into the systemic circulation. +NX, +VagX, +Ligno attenuated histamine-induced cardiorespiratory responses significantly. These observations conclude that instillation of 10 mM of histamine produces optimal vasosensory reflex responses originating from the local vascular bed; afferents and efferents of which are mostly located in ipsilateral somatic and vagus nerves respectively., (© 2021. The Author(s).)

Nesfatin-1, which is an anorexiogenic peptide, plays a crucial role as a neurotransmitter and/or neuromodulator in the central nervous system for cardiovascular control and energy balance etc. It is expressed abundantly in multiple brain nuclei including central respiratory control areas such as nucleus tractus solitarius, nucleus ambiguous, dorsal vagal complex, dorsal motor nucleus of the vagus nerve, and hypothalamus. To date, no previous studies have been found to report nesfatin-1-evoked respiratory effects. Therefore, the present study was designed to investigate the possible impacts of centrally and/or peripherally injected nesfatin-1 on respiratory parameters in either 12h-fasted or fed-ad libitum rats. Intracerebroventricular (ICV) administration of nesfatin-1 provoked significant hyperventilation by increasing tidal volume (TV), respiratory rate (RR) and respiratory minute ventilation (RMV) in both the 12h-fasted and the fed-ad libitum Spraque Dawley rats in dose- and time- dependent manner. Moreover, the hyperventilatory effects of centrally injected nesfatin-1 were more potent in the fed-ad libitum rats. Intravenous injection of nesfatin-1 induced a significant rise in RR and RMV, but not in TV, in the fed-ad libitum rats. In conclusion, these findings plainly report that both centrally and/or peripherally injected nesfatin-1 induces significant hyperventilatory effects in the 12h-fasted and the fed-ad libitum rats. These hyperventilatory effects of nesfatin-1 might show a discrepancy according to the food intake of the rats and the delivery method of the peptide., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cough number and/or sound have been used to assess cough sensitivity/intensity and to discriminate cough patterns in clinical settings. However, to date, only manual counting of cough number in an offline manner is applied in animal cough studies, which diminishes the efficiency of cough identification and hinders the diagnostic discrimination of cough patterns, especially in animals with pulmonary diseases. This study aims to validate a novel recording/analysis system by which cough numbers are automatically counted and cough patterns are comprehensively differentiated in real time. The experiment was carried out in conscious guinea pigs exposed to aerosolized citric acid (CA, 150 mM) and prostaglandin E2 (PGE2, 0.43 mM). Animal body posture (video), respiratory flow, and cough acoustics (audio) were simultaneously monitored and recorded. Cough number was counted automatically, and cough sound parameters including waveform, duration, power spectral density, spectrogram, and intensity, were analyzed in real time. Our results showed that CA- and PGE2-evoked coughs had the same cough numbers but completely different patterns [individual coughs vs. bout(s) of coughs]. Compared to CA-evoked coughs, PGE2-evoked coughs possess a longer latency, higher cough rate (coughs/min), shorter cough sound duration, lower cough sound intensity, and distinct cough waveforms and spectrograms. A few mucus- and wheeze-like coughs were noted in response to CA but not to PGE2. In conclusion, our recording/analysis system is capable of automatically counting the cough number and successfully differentiating the cough pattern by using valuable cough sound indexes in real time. Our system enhances the objectivity, accuracy, and efficiency of cough identification and count, improves the intensity evaluation, and offers ability for pattern discrimination compared to traditional types of cough identification. Importantly, this approach is beneficial for assessing the efficacy of putative antitussive drugs in animals without or with pulmonary diseases, particularly in cases without significant change in cough number., Competing Interests: The authors have declared that no competing interests exist.

A 64-year-old woman with no previous mental illness took a single 500 mg tablet of levofloxacin for cystitis. Two hours later, she developed psychosis with involuntary movement and severe hyperventilation with respiratory alkalosis. Cranial magnetic resonance imaging findings were unremarkable, and an electroencephalogram revealed no epileptiform discharge. Her symptoms improved on the third day after levofloxacin was discontinued. Levofloxacin-associated encephalopathy with psychotic features is a rare adverse event. Disturbance of gamma-aminobutyric acid-ergic (GABAergic) interneurons by levofloxacin may lead to hyperventilation via dysfunction of the brainstem respiratory network. Physicians should be aware of hyperventilation as an additional serious symptom of levofloxacin-associated encephalopathy in acute settings.

Objective: Increased breathing rate, apnea, and respiratory failure are associated with sudden unexpected death in epilepsy (SUDEP). We recently demonstrated the progressive nature of epilepsy and mortality in Kcna1 -/- mice, a model of temporal lobe epilepsy and SUDEP. Here we tested the hypothesis that respiratory dysfunction progresses with age in Kcna1 -/- mice, thereby increasing risk of respiratory failure and sudden death (SD)., Methods: Respiratory parameters were determined in conscious mice at baseline and following increasing doses of methacholine (MCh) using noninvasive airway mechanics (NAM) systems. Kcna1 +/+ , Kcna1 +/- , and Kcna1 -/- littermates were assessed during 3 age ranges when up to ~30%, ~55%, and ~90% of Kcna1 -/- mice have succumbed to SUDEP: postnatal day (P) 32-36, P40-46, and P48-56, respectively. Saturated arterial O 2 (SaO 2 ) was determined with pulse oximetry. Lung and brain tissues were isolated and Kcna1 gene and protein expression were evaluated by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blot techniques. Airway smooth muscle responsiveness was assessed in isolated trachea exposed to MCh., Results: Kcna1 -/- mice experienced an increase in basal respiratory drive, chronic oxygen desaturation, frequent apnea-hypopnea (A-H), an atypical breathing sequence of A-H-tachypnea-A-H, increased tidal volume, and hyperventilation induced by MCh. The MCh-provoked hyperventilation was dramatically attenuated with age. Of interest, only Kcna1 -/- mice developed seizures following exposure to MCh. Seizures were provoked by lower concentrations of MCh as Kcna1 -/- mice approached SD. MCh-induced seizures experienced by a subset of younger Kcna1 -/- mice triggered death. Respiratory parameters of these younger Kcna1 -/- mice resembled older near-SD Kcna1 -/- mice. Kcna1 gene and protein were not expressed in Kcna1 +/+ and Kcna1 +/- lungs, and MCh-mediated airway smooth muscle contractions exhibited similar half-maximal effective concentration( EC 50 ) in isolated Kcna1 +/+ and Kcna1 -/- trachea., Significance: The Kcna1 -/- model of SUDEP exhibits progressive respiratory dysfunction, which suggests a potential increased susceptibility for respiratory failure during severe seizures that may result in sudden death., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Background: The optimal ventilated status under total intravenous or inhalation anesthesia in neurosurgical patients with a supratentorial tumor has not been ascertained. The purpose of this study was to intraoperatively compare the effects of moderate hyperventilation on the jugular bulb oxygen saturation (SjO 2 ), cerebral oxygen extraction ratio (O 2 ER), mean arterial blood pressure (MAP), and heart rate (HR) in patients with a supratentorial tumor under different anesthetic regimens., Methods: Twenty adult patients suffered from supratentorial tumors were randomly assigned to receive a propofol infusion followed by isoflurane anesthesia after a 30-min stabilization period or isoflurane followed by propofol. The patients were randomized to one of the following two treatment sequences: hyperventilation followed by normoventilation or normoventilation followed by hyperventilation during isoflurane or propofol anesthesia, respectively. The ventilation and end-tidal CO 2 tension were maintained at a constant level for 20 min. Radial arterial and jugular bulb catheters were inserted for the blood gas sampling. At the end of each study period, we measured the change in the arterial and jugular bulb blood gases., Results: The mean value of the jugular bulb oxygen saturation (SjO 2 ) significantly decreased, and the oxygen extraction ratio (O 2 ER) significantly increased under isoflurane or propofol anesthesia during hyperventilation compared with those during normoventilation (SjO 2 : t = -2.728, P = 0.011 or t = -3.504, P = 0.001; O 2 ER: t = 2.484, P = 0.020 or t = 2.892, P = 0.009). The SjO 2 significantly decreased, and the O 2 ER significantly increased under propofol anesthesia compared with those values under isoflurane anesthesia during moderate hyperventilation (SjO 2 : t = -2.769, P = 0.012; O 2 ER: t = 2.719, P = 0.013). In the study, no significant changes in the SjO 2 and the O 2 ER were observed under propofol compared with those values under isoflurane during normoventilation., Conclusions: Our results suggest that the optimal ventilated status under propofol or isoflurane anesthesia in neurosurgical patients varies. Hyperventilation under propofol anesthesia should be cautiously performed in neurosurgery to maintain an improved balance between the cerebral oxygen supply and demand.

Prenatal nicotine exposure alters breathing and ventilatory responses to stress through stimulation of nicotine acetylcholine receptors (nAChRs). We tested the hypothesis that α4-containing nAChRs are involved in mediating the effects of prenatal nicotine exposure on ventilatory and metabolic responses to intermittent mild asphyxia (MA). Using open-flow plethysmography, we measured ventilation (V̇(E)) and rate of O2 consumption ( V̇(O2)) of wild-type (WT) and α4-knock-out (KO) mice, at postnatal (P) days 1-2 and 7-8, with and without prenatal nicotine exposure (6 mg kg(-1) day(-1) beginning on embryonic day 14). Mice were exposed to seven 2 min cycles of mild asphyxia (10% O2 and 5% CO2), each interspersed with 2 min of air. Compared to WT, α4 KO mice had increased air V̇(E) and V̇(O2) at P7-8, but not P1-2. Irrespective of age, genotype had no effect on the hyperventilatory response (increase in V̇(E)/V̇(O2)) to MA. At P1-2, nicotine suppressed air V̇(E) and V̇(O2) in both genotypes but did not affect the hyperventilatory response to MA. At P7-8 nicotine suppressed air V̇(E) and V̇(O2) of only α4 KO's but also significantly enhanced V̇(E) during MA (nearly double that of WT; p<0.001). This study has revealed complex effects of α4 nAChR deficiency and prenatal nicotine exposure on ventilatory and metabolic interactions and responses to stress., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We examined the ventilatory response of the spiny dogfish, to elevated internal or environmental ammonia. Sharks were injected via arterial catheters with ammonia solutions or their Na salt equivalents sufficient to increase plasma total ammonia concentration [TAmm]a by 3-5 fold from 145±21μM to 447±150μM using NH4HCO3 and a maximum of 766±100μM using (NH4)2SO4. (NH4)2SO4 caused a small increase in ventilation frequency (+14%) and a large increase in amplitude (+69%), while Na2SO4 did not. However, CO2 partial pressure (PaCO2) also increased and arterial pHa and plasma bicarbonate concentration ([HCO3(-)]a) decreased. NH4HCO3 caused a smaller increase in plasma ammonia resulting in a smaller but significant, short lived increases in ventilation frequency (+6%) and amplitude (36%), together with a rise in PaCO2 and [HCO3(-)]a. Injection with NaHCO3 which increased pHa and [HCO3(-)]a did not change ventilation. Plasma ammonia concentration correlated significantly with ventilation amplitude, while ventilation frequency showed a (negative) correlation with pHa. Exposure to high environmental ammonia (1500μM NH4HCO3) did not induce changes in ventilation until plasma [TAmm]a increased and ventilation amplitude (but not frequency) increased in parallel. We conclude that internal ammonia stimulates ventilation in spiny dogfish, especially amplitude or stroke volume, while environmental ammonia only stimulates ventilation after ammonia diffuses into the bloodstream., (Copyright © 2014 Elsevier B.V. All rights reserved.)

CDP-choline is an endogenous metabolite in phosphatidylcholine biosynthesis. Exogenous administration of CDP-choline has been shown to affect brain metabolism and to exhibit cardiovascular, neuroendocrine neuroprotective actions. On the other hand, little is known regarding its respiratory actions and/or central mechanism of its respiratory effect. Therefore the current study was designed to investigate the possible effects of centrally injected CDP-choline on respiratory system and the mediation of the central cholinergic receptors and phospholipase to thromboxane signaling pathway on CDP-choline-induced respiratory effects in anaesthetized rats. Intracerebroventricularly (i.c.v.) administration of CDP-choline induced dose- and time-dependent increased respiratory rates, tidal volume and minute ventilation of male anaesthetized Spraque Dawley rats. İ.c.v. pretreatment with atropine failed to alter the hyperventilation responses to CDP-choline whereas mecamylamine, cholinergic nicotinic receptor antagonist, mepacrine, phospholipase A2 inhibitor, and neomycin phospholipase C inhibitor, blocked completely the hyperventilation induced by CDP-choline. In addition, central pretreatment with furegrelate, thromboxane A2 synthesis inhibitor, also partially blocked CDP-choline-evoked hyperventilation effects. These data show that centrally administered CDP-choline induces hyperventilation which is mediated by activation of central nicotinic receptors and phospholipase to thromboxane signaling pathway., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The aim of this study was to clarify, using in vitro and in vivo approaches in the rat, the site of mediation of the inhibition of H(2)S induced arterial chemoreceptor stimulation, by hyperoxia and methemoglobinemia. We first determined the ventilatory dose-response curves during intravenous injections of H(2)S. A very high dose of NaHS, i.e. 0.4 μmol (concentration: 800 μM), was needed to stimulate breathing within 1s following i.v. injection. Above this level (and up to 2.4 μmol, with a concentration of 4800 μM), a dose-dependent effect of H(2)S injection was observed. NaHS injection into the thoracic aorta produced the same effect, suggesting that within one circulatory time, H(2)S pulmonary exchange does not dramatically reduce H(2)S concentrations in the arterial blood. The ventilatory response to H(2)S was abolished in the presence of MetHb (12.8%) and was significantly depressed in hyperoxia and, surprisingly, in 10% hypoxia. MetHb per se did not affect the ventilatory response to hypoxia or hyperoxia, but dramatically enhanced the oxidation of H(2)S in vitro, with very fast kinetics. These findings suggest that, the decrease/oxidation of exogenous H(2)S in the blood is the primary effect of MetHb in vivo. In contrast, the in vitro oxidative properties of blood for H(2)S were not affected by the level of [Formula: see text] between 23 and >760 mmHg. This suggests that the inhibition of the ventilatory response to H(2)S by hyperoxia during aortic or venous injection originates within the CB and not in the blood. The implications of these results on the role of endogenous H(2)S in the arterial chemoreflex are discussed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Rationale: Functional interaction between upper airway (UA) dilator muscles and the diaphragm is crucial in the maintenance of UA patency. This interaction could be altered by increasing respiratory drive. The aim of our study was to compare the effects of hypercapnic stimulation on diaphragm and genioglossus corticomotor responses to transcranial magnetic stimulation (TMS)., Methods: 10 self-reported healthy men (32 ± 9 yr; body mass index = 24 ± 3 kg/m(-2)) breathed, in random order, room air or 5% and then 7% Fi(CO(2)), both balanced with pure O(2). Assessments included ventilatory variables, isoflow UA resistance (at 300 ml/s), measurement of lower chest wall/diaphragm (LCW/diaphragm), and genioglossus motor threshold (MT) and motor-evoked potential (MEP) characteristics. TMS twitches were applied during early inspiration and end expiration at stimulation intensity 30% above LCW/diaphragm and genioglossus MT., Results: Compared with room air, CO(2) inhalation significantly augmented minute ventilation, maximal inspiratory flow, tidal volume, and tidal volume/respiratory time ratio. UA resistance was unchanged with CO(2) inhalation. During 7% CO(2) breathing, LCW/diaphragm MT decreased by 9.6 ± 10.1% whereas genioglossus MT increased by 7.2 ± 9%. CO(2)-induced ventilatory stimulation led to elevation of LCW/diaphragm MEP amplitudes during inspiration but not during expiration. LCW/diaphragm MEP latencies remained unaltered both during inspiration and expiration. Genioglossus MEP latencies and amplitudes were unchanged with CO(2)., Conclusion: In awake, healthy subjects, CO(2)-induced hyperventilation is associated with heightened LCW/diaphragm corticomotor activation without modulating genioglossus MEP responses. This imbalance may promote UA instability during increased respiratory drive.

Objectives: Quetiapine is an atypical antipsychotic with favorable properties in the treatment of bipolar disorder, but it has recently been associated with respiratory dysfunction., Methods: In this case report, we describe a patient who developed quetiapine-induced hyperventilation and dyspnea after being treated with quetiapine., Results: To our knowledge, this is the first case presented with quetiapine-induced hyperventilation in a patient with bipolar disorder., Conclusions: We recommend a quick reduction of the quetiapine dosage and a change to an alternative antipsychotic for patients treated with quetiapine, who report such respiratory symptoms without a somatic cause for the symptoms.

Background: Traditionally, intraoperative intracranial electroen-cephalography-recordings are limited to the detection of the irritative zone defined by interictal spikes. However, seizure patterns revealing the seizure onset zone are thought to give better localizing information, but are impractical due to the waiting time for spontaneous seizures. Therefore, provocation by seizure precipitants may be used with the precaution that spontaneous and provoked seizures may not be identical., Objective: We present evidence that hyperventilation induced and drug induced focal seizures may arise from different brain regions in the same patient., Methods: Hyperventilation and ultra short acting opioid remifentanil were used separately as intraoperative precipitatants of seizure patterns, while recording from subdural and intraventricular electrodes in a patient with temporal lobe epilepsy. Two different ictal onset zones appeared in response to hyperventilation and remifentanil. Both zones were resected and the patient has remained essentially seizure free for 1 year. Furthermore, this is the first description of hyperventilation used as an intraoperative seizure precipitant in human focal epilepsy.

We present a 19-month-old boy with a history of asthma who presented to the pediatric emergency department with noisy breathing and tachypnea partially responsive to albuterol. He was discharged to routine care at home. His parents brought him back the next day for persistent respiratory distress despite routine home albuterol. A check of electrolytes showed a low bicarbonate level.

We presented the method of treatment of acute poisoning with some substances which is based on izocapnic hyperpnea. It seems that this method may be useful in the treatment of poisoning with various xenobiotics.

Rats are most frequently used to fulfill ICH S7A requirements for respiratory safety pharmacology. We hypothesized that the models used to assess respiratory safety pharmacology present different ventilatory responses to bronchoconstriction, bronchodilation and respiratory depression. Respiratory monitoring was performed with head-out plethysmographs for rats, masks for dogs and bias airflow helmets for monkeys. Respiratory rate (RR), tidal volume (TV) and minute volume (MV) were recorded. Forty rats, 18 dogs and 8 monkeys were acclimated to the respiratory monitoring equipment. Animals received saline (IV), albuterol (inhalation), methacholine (IV) and remifentanil (IV). Albuterol increased TV in all species. Methacholine decreased TV and MV in monkeys. In dogs, methacholine increased TV, RR and MV. In rats, methacholine increased TV and decreased RR. Remifentanil induced central respiratory depression in all species with decreased MV, except in rats. Dogs presented a biphasic response to remifentanil with hypoventilation followed by delayed hyperventilation. The monkeys presented similar responses to humans which may be due to biologic similarities. Dogs and rats presented clinically significant ventilatory alterations following positive control drugs. Although, the response to bronchoconstriction in dogs and rats was different from humans, the two species presented ventilatory changes that highlight the potential adverse effect of test articles.

Candida infections represent a major threat in neonatal intensive care units. This is the first prospective study to obtain caspofungin plasma levels and safety data for neonates and very young infants. Patients of <3 months of age receiving intravenous amphotericin B for documented or highly suspected candidiasis were enrolled in a single-dose (n = 6) or subsequent multiple-dose (n = 12) panel; all received caspofungin at 25 mg/m(2) once daily as a 1-hour infusion. Caspofungin plasma levels were measured by high-performance liquid chromatography and compared to historical data from adults. Patient chronological ages ranged from 1 to 11 weeks, and weights ranged from 0.68 to 3.8 kg. Gestational ages ranged from 24 to 41 weeks. Geometric mean (GM) peak (C(1 h)) and trough (C(24 h)) caspofungin levels were 8.2 and 1.8 microg/ml, respectively, on day 1, and 11.1 and 2.4 microg/ml, respectively, on day 4. GM ratios for C(1 h) and C(24 h) for neonates/infants relative to adults receiving caspofungin at 50 mg/day were 1.07 and 1.36, respectively, on day 1, and 1.18 and 1.21, respectively, on day 4. Clinical and laboratory adverse events occurred in 17 (94%) and 8 (44%) patients, respectively. Five patients (28%) had serious adverse events, none of which were considered drug related. Caspofungin at 25 mg/m(2) once daily was well tolerated in this group of neonates/infants of <3 months of age and appears to provide relatively similar plasma exposure to that obtained in adults receiving 50 mg/day. However, the small number of patients studied precludes any definitive recommendations about caspofungin dosing for this group comprising a broad range of ages and weights.

Ethylene glycol is an alcohol, which is mainly used as antifreeze. Intoxication with ethylene glycol can cause neurological and cardiopulmonary symptoms, metabolic acidosis and acute renal failure. Therapeutic options include reversal of metabolic acidosis, inhibition of alcohol dehydrogenase and early hemodialysis. In survivors of the acute phase, lasting damage is rare. The case of a 49-year-old patient with ethylene glycol intoxication is reported which was characterized by progressive impairment of consciousness, tetraparesis, hyperventilation and metabolic acidosis.

Intra-arterial (i.a.) injection of Indian red scorpion (Mesobuthus tamulus; BT) venom produces cardiorespiratory changes by involving perivascular receptors. The afferents involved in mediating these reflex responses are not known. The present investigation was conducted to examine the afferents mediating the vasosensory reflexes evoked by i.a. injection of BT venom in the peripheral end of femoral artery in urethane anaesthetised rats. Blood pressure (BP), ECG (for heart rate), and respiratory movements (for rate and depth) were recorded for 30min after the i.a. injection of venom. Minute ventilation (MV) was computed by using appropriate calibrations for depth and rate of respiration. After the injection of venom, there was immediate hyperventilatory, intermediate hypertensive and delayed bradycardiac response. Equal volume of saline (0.10ml, i.a.) did not produce any cardiorespiratory changes thus, eliminating the possibility of stretch mediated responses. Sectioning of ipsilateral sciatic and femoral nerves attenuated the hyperventilatory and hypertensive responses produced by venom significantly. After the neurotomy, the latency of bradycardiac response was shortened significantly. Even the time to reach the peak bradycardiac response was also shortened. The data provide evidences for the partial involvement of somatic nerves in mediating the vascular reflexes.

Objective: To report a case of hyperventilation caused by topiramate therapy and propose a pathophysiologic mechanism for this disorder., Case Summary: A 52-year-old woman with refractory seizure disorder was admitted to the burn care unit with burns over 10% of her body. Her seizure medications, unchanged and well tolerated for several months, included carbamazepine 1200 mg, lamotrigine 500 mg, phenobarbital 80 mg, and topiramate 150 mg per day. During hospitalization, despite a relatively normal arterial pH, the woman developed persistent hyperventilation, with respiratory rates up to 50 breaths/min. Alkalinization did not reduce the hyperventilation. Thoracic contrast-enhanced computed tomographic scan ruled out pulmonary embolism and persistent pneumonia. Salicylate and biguanide screening were negative; results of repeated thyroid and liver function tests were normal. Cerebral magnetic resonance imaging excluded a cerebral pathology. After cerebrospinal fluid (CSF) analysis showed acidosis (pH 7.14), topiramate was withdrawn and the patient's general condition rapidly improved. Forty-eight hours later, the CSF pH had increased to 7.26. The woman was discharged from the burn care unit on the 42nd hospital day., Discussion: Hyperchloremic normal anion gap metabolic acidosis, which can lead to hyperventilation, has been reported as an adverse effect of topiramate treatment. However, our patient had respiratory alkalosis. Concurrent etiologies of peripheral hyperventilation were excluded, leaving central neurogenic hyperventilation as the remaining etiology. Such central neurogenic hyperventilation associated with topiramate has previously been reported in intensive care. Our case report demonstrates CSF acidosis. Withdrawing topiramate reduced both CSF acidosis and hyperventilation. The mechanism of topiramate-induced CSF acidosis remains unclear. According to the Naranjo probability scale, the relationship of hyperventilation to administration of topiramate in our patient was probable., Conclusions: Normal doses of topiramate may provoke central neurogenic hyperventilation, as a result of CSF acidosis. The acid-base status of critically ill patients receiving topiramate should be monitored carefully.

In this study 117 panic disorder patients were divided into a respiratory subtype group and a non-respiratory subtype group. The respiratory subtype patients were observed to be more sensitive to the 35% CO(2) inhalation challenge test and the hyperventilation test than the non-respiratory subtype patients.

Inhalation of H2O2 is known to evoke bradypnea followed by tachypnea, which are reflexes resulting from stimulation by reactive oxygen species of vagal lung capsaicin-sensitive and myelinated afferents, respectively. This study investigated the pharmacological receptors and chemical mediators involved in triggering these responses. The ventilatory responses to 0.2% aerosolized H2O2 were studied before and after various pharmacological pretreatments in anesthetized rats. The initial bradypneic response was reduced by a transient receptor potential vanilloid 1 (TRPV1) receptor antagonist [capsazepine; change (Delta) = -53%] or a P2X purinoceptor antagonist [iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (PPADS); Delta = -47%] and was further reduced by capsazepine and iso-PPADS in combination (Delta = -78%). The initial bradypneic response was reduced by a cyclooxygenase inhibitor (indomethacin; Delta = -48%), ATP scavengers (apyrase and adenosine deaminase in combination; Delta = -50%), or capsazepine and indomethacin in combination (Delta = -47%), was further reduced by iso-PPADS and indomethacin in combination (Delta = -75%) or capsazepine and ATP scavengers in combination (Delta = -83%), but was not affected by a lipoxygenase inhibitor (nordihydroguaiaretic acid) or by any of the various vehicles. No pretreatment influenced delayed tachypnea. We concluded that 1) the initial bradypneic response to H2O2 results from activation of both TRPV1 and P2X receptors, possibly located at terminals of vagal lung capsaicin-sensitive afferent fibers; 2) the functioning of the TRPV1 and P2X receptors in triggering the initial bradypnea is, in part, mediated through the actions of cyclooxygenase metabolites and ATP, respectively; and 3) these mechanisms do not contribute to the H2O2-evoked delayed tachypnea.

Airway responses were compared following 6-minute eucapnic voluntary hyperventilation and 6-minute exercise challenges by examining resting and post-challenge impulse oscillometry and spirometry variables. Twenty-two physically active individuals with probable exercise-induced bronchoconstriction took part in this study. Impulse oscillometry and spirometry were performed at baseline and for 20 minutes post-challenge at 5-minute intervals. High correlation was found between the two measures of change in airway function for both methods of challenge. Impulse oscillometry detected a difference in degree of response to the challenges, whereas spirometry indicated no difference, suggesting that impulse oscillometry is a more sensitive measure of change in airway function.

In hypoxia, gray mullet surface to ventilate well-oxygenated water in contact with air, an adaptive response known as aquatic surface respiration (ASR). Reflex control of ASR and its behavioral modulation by perceived threat of aerial predation and turbid water were studied on mullet in a partly sheltered aquarium with free surface access. Injections of sodium cyanide (NaCN) into either the bloodstream (internal) or ventilatory water stream (external) revealed that ASR, hypoxic bradycardia, and branchial hyperventilation were stimulated by chemoreceptors sensitive to both systemic and water O2 levels. Sight of a model avian predator elicited bradycardia and hypoventilation, a fear response that inhibited reflex hyperventilation following external NaCN. The time lag to initiation of ASR following NaCN increased, but response intensity (number of events, time at the surface) was unchanged. Mullet, however, modified their behavior to surface under shelter or near the aquarium edges. Turbid water abolished the fear response and effects of the predator on gill ventilation and timing of ASR following external NaCN, presumably because of reduced visibility. However, in turbidity, mullet consistently performed ASR under shelter or near the aquarium edges. These adaptive modulations of ASR behavior would allow mullet to retain advantages of the chemoreflex when threatened by avian predators or when unable to perceive potential threats in turbidity.

Background: Sulthiame is a central carbonic anhydrase inhibitor found to be effective for both partial and generalized seizures. It has been in use in some European countries and in Israel for over 30 years. The aim of the present study was to evaluate the efficacy and tolerability of sulthiame in childhood epilepsy by conducting a multicenter, retrospective study of patients who received this drug., Methods: The charts of 125 consecutive epilepsy patients treated with sulthiame as monotherapy or add-on therapy were reviewed., Results: Twenty-nine out of 39 patients with benign focal epilepsy of childhood became seizure-free. Total seizure control was also achieved in 17 of 42 patients with symptomatic, non-refractory localization-related epilepsy, and in all 10 cases with juvenile myoclonic epilepsy. Complete normalization of the EEG occurred in 13 of 20 patients with benign partial epilepy of childhood. Side-effects were minimal and caused discontinuation of treatment in only seven children., Conclusion: The high tolerability, efficacy, convenience of use and low cost suggest that sulthiame should become a first line drug in the benign partial epilepsies of childhood and juvenile myoclonic epilepsy. It also has a role as add-on treatment in other partial and myoclonic epilepsies.

The results of vasorespiratory studies in rats anaesthetised with pentobarbital show that (+/-) cannabidiol, a cannabinoid that lacks psychotropic actions and is inactive at cannabinoid (CB) receptors, does not affect respiration or blood pressure when injected (1-2000 microg; 3.2-6360 nmol i.a.). Cannabidiol in doses up to 2 mg (6360 nmol) i.a. or i.v. did not affect the fall in mean blood pressure or the increase in ventilation (respiratory minute volume) caused by capsaicin and high doses of anandamide, responses that are mediated by activation of vanilloid VR1 (TRPV1) receptors in this species. Similar results were obtained with (-) cannabidiol (30-100 microg i.a.; 95-318 nmol). It has previously been shown using human embryonic kidney (HEK) cells over-expressing vanilloid human VR1 (hVR1) receptors that cannabidiol is a full agonist at vanilloid VR1 receptors in vitro. However, in the intact rat cannabidiol lacked vanilloid VR1 receptor agonist effects. We conclude that there are substantial functional differences between human and rat vanilloid VR1 receptors with respect to the actions of cannabidiol as an agonist at vanilloid VR1 receptors. Studies in vivo show that cannabidiol lacks any significant effect on mean blood pressure or respiratory minute volume when injected i.a. or i.v., and that this cannabinoid does not modulate the vanilloid VR1 receptor-mediated cardiovascular and ventilatory changes reflexly evoked by capsaicin or anandamide in rats anaesthetised with pentobarbital., (Copyright 2004 Elsevier B.V.)

The present investigation evaluated anxious and fearful responding to bodily sensations as a function of panic disorder (PD) and smoking status. Participants completed a voluntary hyperventilation procedure that elicits panic-relevant bodily sensations. Psychophysiological data were collected throughout the study procedures. Assessments of anxiety and bodily distress were conducted pre-challenge baseline, post-hyperventilation, and during a recovery period following the challenge. Results indicated that smokers with PD reported greater levels of anxiety and bodily distress than smokers without PD and than nonsmokers with PD at the post-challenge assessment and recovery period. No differences in autonomic responding were evident during the challenge or in the recovery phase. In terms of rate of recovery, the linear decrease in anxiety, but not bodily distress, was significantly more steep for nonsmokers with PD than for smokers with PD. These findings are discussed in relation to better understanding the potential role that smoking may play in terms of anxious and fearful responding to bodily sensations.

Nitrite is a potential problem in aquatic environments. Freshwater fish actively take up nitrite across the gills, leading to high internal concentrations. Seawater fish are less susceptible but do take up nitrite across intestine and gills. Nitrite has multiple physiological effects. Its uptake is at the expense of chloride, leading to chloride depletion. Nitrite also activates efflux of potassium from skeletal muscle and erythrocytes, disturbing intracellular and extracellular K(+) levels. Nitrite transfer across the erythrocytic membrane leads to oxidation of haemoglobin to methaemoglobin (metHb), compromising blood O(2) transport. Other haem proteins are also oxidised. Hyperventilation is observed, and eventually tissue O(2) shortage becomes reflected in elevated lactate concentrations. Heart rate increases rapidly, before any significant elevations in metHb or extracellular potassium occur. This suggests nitrite-induced vasodilation (possibly via nitric oxide generated from nitrite) that is countered by increased cardiac pumping to re-establish blood pressure. Nitrite can form and/or mimic nitric oxide and thereby interfere with processes regulated by this local hormone. Steroid hormone synthesis may be inhibited, while changes in ammonia and urea levels and excretion rates reflect an influence of nitrite on nitrogen metabolism. Detoxification of nitrite occurs via endogenous oxidation to nitrate, and elimination of nitrite takes place both via gills and urine. The susceptibility to nitrite varies between species and in some cases also within species. Rainbow trout fall into two groups with regard to susceptibility and physiological response. These two groups are not related to sex but show significant different nitrite uptake rates.

Purpose: Apnea is known to occur during seizures, but systematic studies of ictal respiratory changes in adults are few. Data regarding respiratory pattern defects during interictal periods also are scarce. Here we sought to generate information with regard to the interictal period in animals with pilocarpine-induced epilepsy., Methods: Twelve rats (six chronically epileptic animals and six controls) were anesthetized, given tracheotomies, and subjected to hyperventilation or hypoventilation conditions. Breathing movements caused changes in thoracic volume and forced air to flow tidally through a pneumotachograph. This flow was measured by using a differential pressure transducer, passed through a polygraph, and from this to a computer with custom software that derived ventilation (VE), tidal volume (VT), inspiratory time (TI), expiratory time (TE), breathing frequency (f), and mean inspiratory flow (VT/TI) on a breath-by-breath basis., Results: The hyperventilation maneuver caused a decrease in spontaneous ventilation in pilocarpine-treated and control rats. Although VE had a similar decrease in both groups, in the epileptic group, the decrease in VE was due to a significant (p < 0.05) increase in TE peak in relation to that of the control animals. The hypoventilation maneuver led to an increase in the arterial Paco2, followed by an increase in VE. In the epileptic group, the increase in VE was mediated by a significant (p < 0.05) decrease in TE peak compared with the control group. Systemic application of KCN, to evaluate the effects of peripheral chemoreception activation on ventilation, led to a similar increase in VE for both groups., Conclusions: The data indicate that pilocarpine-treated animals have an altered ability to react to (or compensate for) blood gas changes with changes in ventilation and suggest that it is centrally determined. We speculate on the possible relation of the current findings on treating different epilepsy-associated conditions.

To elucidate if serotonergic transmission affects respiratory variability, a parameter consistently found increased in patients with panic disorder, we studied the effect of a serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA), on respiratory variability at baseline and during CO2-induced hyperventilation in awake and unrestrained rats. Forty male Wistar rats were given intraperitoneal injections of PCPA (300 mg/kg) or saline 72, 48 and 24 h before registration of respiration in a plethysmograph allowing the animals to move freely. PCPA-treated rats displayed significantly higher tidal volume variability and minute volume variability, both at baseline and during CO2 exposure, compared to controls. The results support the notion that serotonin dysfunction may contribute to the enhanced respiratory variability observed in patients with panic disorder.

We tested the hypothesis that integrated sympathetic and cardiovascular reflexes are modulated by systemic CO2 differently in hypoxia than in hyperoxia (n = 7). Subjects performed a CO2 rebreathe protocol that equilibrates CO2 partial pressures between arterial and venous blood and that elevates end tidal CO2 (PET(CO2)) from approximately 40 to approximately 58 mmHg. This test was repeated under conditions where end tidal oxygen levels were clamped at 50 (hypoxia) or 200 (hyperoxia) mmHg. Heart rate (HR; EKG), stroke volume (SV; Doppler ultrasound), blood pressure (MAP; finger plethysmograph), and muscle sympathetic nerve activity (MSNA) were measured continuously during the two protocols. MAP at 40 mmHg PET(CO2) (i.e., the first minute of the rebreathe) was greater during hypoxia versus hyperoxia (P < 0.05). However, the increase in MAP during the rebreathe (P < 0.05) was similar in hypoxia (16 +/- 3 mmHg) and hyperoxia (17 +/- 2 mmHg PET(CO2)). The increase in cardiac output (Q) at 55 mmHg PET(CO2) was greater in hypoxia (2.61 +/- 0.7 L/min) versus hyperoxia (1.09 +/- 0.44 L/min) (P < 0.05). In both conditions the increase in Q was due to elevations in both HR and SV (P < 0.05). Systemic vascular conductance (SVC) increased to similar absolute levels in both conditions but rose earlier during hypoxia (> 50 mmHg PET(CO2)) than hyperoxia (> 55 mmHg). MSNA increased earlier during hypoxic hypercapnia (> 45 mmHg) compared with hyperoxic hypercapnia (> 55 mmHg). Thus, in these conscious humans, the dose-response effect of PET(CO2) on the integrated cardiovascular responses was shifted to the left during hypoxic hypercapnia. The combined data indicate that peripheral chemoreceptors exert important influence over cardiovascular reflex responses to hypercapnia.

Although olanzapine therapy has been associated with fewer extrapyramidal side effects than the traditional antipsychotic medications, reported side effects include dystonia, tardive dyskinesia, hypotension, diabetes mellitus, seizures and neuroleptic malignant syndrome. There are no previous published reports of hyperventilation associated with olanzapine therapy, but we present the case of a male patient who developed dyspnea and hyperventilation while taking olanzapine.

This study aimed at measuring the functional consequences and the pulmonary cytology changes following a simulation of pulmonary haemorrhage. Pulmonary function tests including lobeline-induced hyperventilation, cytology of tracheo-bronchial wash (TBW) and thoracic radiographs were performed before, as well as 1, 7, 14 and 28 days after, the instillation of 300 ml of blood into the lungs of 4 horses deemed free of exercise-induced pulmonary haemorrhage (Group 1). Control data (Group 2) were obtained by instilling the same volume of saline into the lungs of the same horses in a crossover design (control). The instillation of blood or saline resulted in an increase in the number of neutrophils in the TBW. Thoracic radiographs showed increased opacity in the caudodorsal region of the lungs in 4/4 (Day 1) and 2/4 horses (Day 7), in Group 1, and in 2/4 (Day 1) and 0/4 horses (Day 7) in the control group. These changes were attributed to the instillation procedure rather than the nature of the instilled material. Breathing mechanics and arterial blood gases at rest were not affected in either Groups 1 or 2. However, the maximal expiratory peak flow recorded during lobeline-induced hyperventilation was significantly lower (P<0.05) and the total pulmonary resistance significantly higher (P<0.05) on Day 1 in Group 1, but not Group 2. These observations suggest that expiratory flows might be partly limited in bleeders when breathing at high airflow.

The present investigation utilised simultaneous measurements of chest (Ch) and abdominal (Ab) circumferences and respiratory airflow to test the hypothesis that Ch circumferential expansion contributes proportionally little to tidal volume in the running Thoroughbred. During exercise, there were only small changes in Ch and Ab circumference and no increase with increasing tidal volume. At rest, walk and trot, the flow, Ch and Ab signals were in phase. However, during canter and gallop, the Ch and Ab changes were 180 degrees out of phase with each other and both were out of phase with airflow. In contrast to exercise, increase in ventilation at rest achieved by administration of lobeline resulted in a 4-6-fold increase in tidal volume; large excursions of the chest were always in phase with airflow. Furthermore, 3 horses showed an increase in chest circumference, demonstrating that chest stiffness per se does not preclude chest circumferential expansion. In conclusion, in the absence of significant increases in either Ch or Ab expansion during running, elongation of the thoracoabdominal segment may be the main determinant of tidal volume.

A new combined test, accelerated exercise following mild hyperventilation (HV), was examined to determine whether it is effective at detecting a positive response in patients with pharmacologically-induced coronary vasospasm and near normal coronary arteries. Fifty-eight consecutive patients who underwent both triple non-invasive spasm provocation tests and diagnostic coronary angiography were enrolled. They all had pharmacologically-induced coronary vasospasms and no significant organic stenosis. In these patients, an HV test was performed first, followed by a treadmill exercise test (TET), and finally the new combined test under no medication within 3 days. Of the 58 patients, positive responses were observed in 9 patients to the HV, in 15 to the TET, and in 35 to the newly combined test. The remaining 21 patients had negative responses although the triple sequential tests were perfomed. Thus, the sensitivities of the HV test, TET, and newly combined test were 16% (9/58), 26% (15/58), and 63% (35/56), respectively. Forty-six subjects with near normal coronary arteries and no ACh-provoked spasm served as controls. None of these subjects had positive responses to any of these three tests, and thus their specificity was all 100%. No serious or irreversible complications were seen in this study. We recommend this newly-combined protocol for the induction of coronary artery spasm in patients with vasospastic angina pectoris and without significant stenosis as a diagnostic tool.

In patients with panic disorder or premenstrual dysphoria, anxiety attacks can be triggered by intravenous administration of sodium lactate. Since respiratory symptoms, such as hyperventilation and shortness of breath, are characteristic features of spontaneous as well as lactate-induced panic, an involvement of central or peripheral chemoreceptors in this reaction has been suggested. In the present study, we examined to what extent intravenous infusion of sodium lactate influences respiratory parameters in freely moving male and female Wistar rats. Prompted by clinical reports suggesting that the susceptibility to spontaneous and lactate-induced anxiety may be influenced by the menstrual cycle, we also investigated if the effect of lactate on respiration in female rats is estrus cycle-dependent. Male and ovariectomized female rats exposed to sodium lactate displayed a larger increase in respiratory rate than rats given an infusion of saline. In intact female rats, the response to lactate infusion was significantly more pronounced in the diestrus phase than in the proestrus/estrus phase of the cycle. It is concluded that sodium lactate is a respiratory stimulant in rat, and that this effect is influenced by female sex steroids.

Two children who presented with symptomatic metabolic acidosis after being put on topiramate (TPM) are reported. The first patient was an 11-year-old male with refractory complex partial epilepsy who was put on TPM for 13 months. He developed hyperventilation 1 week after increasing the dose to 300 mg/day. Arterial blood gas revealed hyperchloraemic metabolic acidosis with partial respiratory compensation: pH 7.36, PCO2 27.2 mmHg, bicarbonate 14.9 mEq/L, base excess -8.9 mmol/L. Hyperventilation and acidosis resolved after administration of sodium bicarbonate and reduction of the dose of TPM. The second patient was a female who developed increasing irritability at age 16 months and 21 months, each time associated with introduction of TPM and resolved promptly upon withdrawal of the drug. Venous blood gas taken during the second episode revealed pH 7.34, PCO2 37.4 mmHg, bicarbonate 20.4 mEq/L, base excess -4.2 mmol/L. The predominant mechanism of TPM-induced hyperventilation involves inhibition of carbonic anhydrase at the proximal renal tubule, resulting in impaired proximal bicarbonate reabsorption. The occurrence of hyperpnoea or mental status change in any patient who is on TPM should prompt an urgent blood gas sampling, with correction of the acid-base disturbances accordingly.

We describe a 74-year-old patient with dyspnoea and tachypnoea induced by chlorpromadinone acetate, a synthetic progesterone used to treat prostatic hyperplasia. The dyspnoea, tachypnoea and hypocapnia improved after discontinuing the chlorpromadinone acetate. It is important to recognize that synthetic progesterones can cause dyspnoea and hyperventilation.

The aim of this study was to determine whether respiratory acidosis favors the cerebral distribution of cyanide, and conversely, if respiratory alkalosis limits its distribution. The pharmacokinetics of a nontoxic dose of cyanide were first studied in a group of 7 rats in order to determine the distribution phase. The pharmacokinetics were found to best fit a 3-compartment model with very rapid distribution (whole blood T(1/2)alpha = 21.6 +/- 3.3 s). Then the effects of the modulation of arterial pH on the distribution of a nontoxic dose of intravenously administered cyanide into the brains of rats were studied by means of the determination of the permeability-area product (PA). The modulation of arterial blood pH was performed by variation of arterial carbon dioxide tension (PaCO2) in 3 groups of 8 anesthetized mechanically ventilated rats. The mean arterial pH measured 20 min after the start of mechanical ventilation in the acidotic, physiologic, and alkalotic groups were 7.07 +/- 0.03, 7.41 +/- 0.01, and 7.58 +/- 0.01, respectively. The mean PAs in the acidotic, physiologic, and alkalotic groups, determined 30 s after the intravenous administration of cyanide, were 0.015 +/- 0.002, 0.011 +/- 0.001, and 0.008 +/- 0.001 s(-1), respectively (one-way ANOVA; p < 0.0087). At alkalotic pH the mean permeability-area product was 43% of that measured at acidotic pH. This effect of pH on the rapidity of cyanide distribution does not appear to be limited to specific areas of the brain. We conclude that modulation of arterial pH by altering PaCO2 may induce significant effects on the brain uptake of cyanide.

The effect of acidification on the acid-sensitive species Gammarus fossarum was investigated in the laboratory. The results showed that as mortality increased, mean hemolymph chloride and sodium concentrations decreased rapidly. Concomitantly, organisms hyperventilated during the first 24 h and then started to hypoventilate. These results demonstrated that exposure to acid stress in the acid-sensitive species G. fossarum led to ion-regulatory and respiratory failure as previously reported in fish and crayfish exposed to acid stress.

We previously observed an increase in minute ventilation (V E) with resistive unloading (He-O2 breathing) in healthy elderly subjects with normal pulmonary function. To investigate the effects of resistive unloading in elderly subjects with mild chronic airflow limitation (FEV(1)/FVC: 61 +/- 4%), we studied 10 elderly men and women 70 +/- 3 yr of age. These subjects performed graded cycle ergometry to exhaustion, once breathing room air and once breathing a He-O2 gas mixture (79% He, 21% O2). V E, pulmonary mechanics, and PET(CO2) were measured during each 1-min increment in work rate. Data were analyzed by paired t test at rest, at ventilatory threshold (VTh), and during maximal exercise. V E was significantly (p < 0.05) increased at VTh (3.4 +/- 4.0 L/min or 12 +/- 15% increase) and maximal exercise (15.2 +/- 9.7 L/min or 22 +/- 13% increase) while breathing He-O2. Concomitant to the increase in V E, PET(CO2) was decreased at all levels (p < 0.01), whereas total work of breathing against the lung was not different. We concluded that V E is increased during He-O2 breathing because of resistive unloading of the airways and the maintenance of the relationship between the work of breathing and exercise work rate.