Changes In Ventilatory Parameters Research Articles

The ventilatory depressant actions but not the antinociceptive effects of morphine are blunted in rats receiving intravenous infusion of L-cysteine ethyl ester

This study demonstrates that intravenous infusion of the cell-penetrant thiol ester, L-cysteine ethyl ester (L-CYSee), to adult male Sprague-Dawley rats elicited (a) minor alterations in frequency of breathing, expiratory time, tidal volume, minute ventilation, or expiratory drive but pronounced changes in inspiratory time, end-inspiratory and expiratory pauses, peak inspiratory and expiratory flows, EF50, relaxation time, apneic pause, inspiratory drive and non-eupneic breathing index, (b) minimal changes in arterial blood-gas (ABG) chemistry (pH, pCO2, pO2, SO2) and Alveolar-arterial (A-a) gradient (index of alveolar gas exchange), and (c) minimal changes in antinociception (tail-flick latency). Subsequent injection of morphine (10 mg/kg, IV) elicited markedly smaller effects on the above parameters, ABG chemistry, and A-a gradient in rats receiving L-CYSee, whereas morphine antinociception was not impaired. Infusions of L-cysteine or L-serine ethyl ester (oxygen rather than sulfur moiety), did not affect morphine actions on ABG chemistry or A-a gradient. L-CYSee (250 μmol/kg, IV) injection elicited dramatic changes in ventilatory parameters given 15 min after injection of morphine in rats receiving L-CYSee. Our findings suggest that (a) L-CYSee acts in neurons that drive ventilation, (b) L-CYSee reversal of the adverse actions of morphine on ventilation, ABG chemistry and A-a gradient may be via modulation of intracellular signaling pathways activated by morphine rather than by direct antagonism of opioid receptors since morphine antinociception was not diminished by L-CYSee, and (c) the thiol moiety of L-CYSee is vital to efficacy, (d) intracellular conversion of L-CYSee to an S-nitrosylated form may be part of its mechanism of action.

L-cysteine methyl ester overcomes the deleterious effects of morphine on ventilatory parameters and arterial blood-gas chemistry in unanesthetized rats.

We are developing a series of thiolesters that produce an immediate and sustained reversal of the deleterious effects of opioids, such as morphine and fentanyl, on ventilation without diminishing the antinociceptive effects of these opioids. We report here the effects of systemic injections of L-cysteine methyl ester (L-CYSme) on morphine-induced changes in ventilatory parameters, arterial-blood gas (ABG) chemistry (pH, pCO2, pO2, sO2), Alveolar-arterial (A-a) gradient (i.e., the index of alveolar gas-exchange within the lungs), and antinociception in unanesthetized Sprague Dawley rats. The administration of morphine (10 mg/kg, IV) produced a series of deleterious effects on ventilatory parameters, including sustained decreases in tidal volume, minute ventilation, inspiratory drive and peak inspiratory flow that were accompanied by a sustained increase in end inspiratory pause. A single injection of L-CYSme (500 μmol/kg, IV) produced a rapid and long-lasting reversal of the deleterious effects of morphine on ventilatory parameters, and a second injection of L-CYSme (500 μmol/kg, IV) elicited pronounced increases in ventilatory parameters, such as minute ventilation, to values well above pre-morphine levels. L-CYSme (250 or 500 μmol/kg, IV) also produced an immediate and sustained reversal of the deleterious effects of morphine (10 mg/kg, IV) on arterial blood pH, pCO2, pO2, sO2 and A-a gradient, whereas L-cysteine (500 μmol/kg, IV) itself was inactive. L-CYSme (500 μmol/kg, IV) did not appear to modulate the sedative effects of morphine as measured by righting reflex times, but did diminish the duration, however, not the magnitude of the antinociceptive actions of morphine (5 or 10 mg/kg, IV) as determined in tail-flick latency and hindpaw-withdrawal latency assays. These findings provide evidence that L-CYSme can powerfully overcome the deleterious effects of morphine on breathing and gas-exchange in Sprague Dawley rats while not affecting the sedative or early stage antinociceptive effects of the opioid. The mechanisms by which L-CYSme interferes with the OR-induced signaling pathways that mediate the deleterious effects of morphine on ventilatory performance, and by which L-CYSme diminishes the late stage antinociceptive action of morphine remain to be determined.

D-Cysteine Ethyl Ester Reverses the Deleterious Effects of Morphine on Breathing and Arterial Blood-Gas Chemistry in Freely-Moving Rats.

Cell-penetrant thiol esters including the disulfides, D-cystine diethyl ester and D-cystine dimethyl ester, and the monosulfide, L-glutathione ethyl ester, prevent and/or reverse the deleterious effects of opioids, such as morphine and fentanyl, on breathing and gas exchange within the lungs of unanesthetized/unrestrained rats without diminishing the antinociceptive or sedative effects of opioids. We describe here the effects of the monosulfide thiol ester, D-cysteine ethyl ester (D-CYSee), on intravenous morphine-induced changes in ventilatory parameters, arterial blood–gas chemistry, alveolar–arterial (A-a) gradient (i.e., index of gas exchange in the lungs), and sedation and antinociception in freely-moving rats. The bolus injection of morphine (10 mg/kg, IV) elicited deleterious effects on breathing, including depression of tidal volume, minute ventilation, peak inspiratory flow, and inspiratory drive. Subsequent injections of D-CYSee (2 × 500 μmol/kg, IV, given 15 min apart) elicited an immediate and sustained reversal of these effects of morphine. Morphine (10 mg/kg, IV) also A-a gradient, which caused a mismatch in ventilation perfusion within the lungs, and elicited pronounced changes in arterial blood–gas chemistry, including pronounced decreases in arterial blood pH, pO2 and sO2, and equally pronounced increases in pCO2 (all responses indicative of decreased ventilatory drive). These deleterious effects of morphine were immediately reversed by the injection of a single dose of D-CYSee (500 μmol/kg, IV). Importantly, the sedation and antinociception elicited by morphine (10 mg/kg, IV) were minimally affected by D-CYSee (500 μmol/kg, IV). In contrast, none of the effects of morphine were affected by administration of the parent thiol, D-cysteine (1 or 2 doses of 500 μmol/kg, IV). Taken together, these data suggest that D-CYSee may exert its beneficial effects via entry into cells that mediate the deleterious effects of opioids on breathing and gas exchange. Whether D-CYSee acts as a respiratory stimulant or counteracts the inhibitory actions of µ-opioid receptor activation remains to be determined. In conclusion, D-CYSee and related thiol esters may have clinical potential for the reversal of the adverse effects of opioids on breathing and gas exchange, while largely sparing antinociception and sedation.

Corticosteroid response predicts bronchopulmonary dysplasia status at 36 weeks in preterm infants treated with dexamethasone: A pilot study.

A major barrier to therapeutic development in neonates is a lack of standardized drug response measures that can be used as clinical trial endpoints. The ability to quantify treatment response in a way that aligns with relevant downstream outcomes may be useful as a surrogate marker for new therapies, such as those for bronchopulmonary dysplasia (BPD). To construct a measure of clinical response to dexamethasone that was well aligned with the incidence of severe BPD or death at 36 weeks' postmenstrual age. Retrospective cohort study. Level IV Neonatal Intensive Care Unit. Infants treated with dexamethasone for developing BPD between 2010 and 2020. Two models were built based on demographics, changes in ventilatory support, andpartial pressure of carbon dioxide (pCO2 ) after dexamethasone administration. An ordinal logistic regression and regularized binary logistic model for the composite outcome were used to associate response level to BPD outcomes defined by both the 2017 BPD Collaborative and 2018 Neonatal Research Network definitions. Ninety-fiveinfants were treated with dexamethasone before 36 weeks. Compared to the baseline support and demographic data at the time of treatment, changes in ventilatory support improved ordinal model sensitivity and specificity. For the binary classification, BPD incidence was well aligned with risk levels, increasing from 16% to 59%. Incorporation of response variables as measured by changes in ventilatory parameters and pCO2 following dexamethasone administration were associated with downstream outcomes. Incorporating drug response phenotype into a BPD model may enable more rapid development of future therapeutics.

Unusual cause of airway obstruction after nasal intubation with a preformed endotracheal tube.

Unusual cause of airway obstruction after nasal intubation with a preformed endotracheal tube.

Regulatory respiratory data refinement with reduced animal usage

IntroductionAssessment of effects of potential drug candidates on the respiratory system is part of the regulatory preclinical safety assessment conducted prior to first in human trials (FTIH). Commonly, this is carried out utilizing head out plethysmography (HOP) or whole body plethysmography (WBP) which record only ventilatory parameters. When dosing via the inhaled route a more thorough respiratory assessment, including a direct measure of airway mechanics, is desirable. The aim of the present work was to improve the strategy for respiratory safety testing by a) evaluating a telemetered pleural pressure – HOP (PP-HOP) model and b) evaluating a crossover study design protocol in the WBP model to reduce variability and animal usage. MethodsFor the PP- HOP model, rats were surgically implanted with a telemetry device for measurement of pleural pressure. Animals were placed in HOP tubes and respiratory function assessed when exposed to methacholine at doses of 0 (saline only), 0.42, 1.6 and 3.8 mg/kg. WBP assessment was performed in rats in a crossover study design when treated with theophylline at doses of 0 (saline only), 3, 10 and 30 mg/kg. ResultsData from the PP-HOP study confirmed the expected changes in ventilatory parameters and airway mechanics in response to inhaled methacholine, including an increase in pulmonary resistance and decrease in tidal volume.Data from the WBP crossover study demonstrated similar sensitivity and statistical power to detect changes in respiratory rate and tidal volume to a standard parallel group design. ConclusionMeasurement of PP-HOP in a stand-alone safety pharmacology study in conjunction with HOP assessment conducted as part of a toxicology study, represents an improved respiratory testing strategy for inhaled drugs. For compounds administered by other routes, we conclude that use of WBP using a crossover dosing design is a suitable alternative to parallel dosing groups, with a significant reduction in animal numbers and no loss of statistical power.

Ventilatory and Carotid Body Chemosensory Responses In Rats Exposed To Short‐Term Sustained Hypoxia

Previous studies performed in in situ rat preparations reported that the exposure to short‐term (24 h) sustained hypoxia (SH) generates active expiration at rest, increases baseline sympathetic activity during expiration and enhances sympathetic responses to peripheral chemoreceptor stimulation. In the present study, we evaluated basal and hypoxic‐induced changes in ventilatory parameters of unanesthetized juvenile male Holtzman rats (80–90 g) previously exposed to SH (10% O2, 24 hs). In addition, we examined the chemosensory response of carotid body chemoreceptors of decerebrated, artificially‐perfused in situ preparations of juvenile rats (60–80 g) submitted to SH. At resting conditions, SH rats (n=12) exhibited augmented (P<0.05) respiratory frequency (109±2 vs 97±1 cpm), tidal volume (14±1 vs 10±1 ml/kg) and minute ventilation (1550±137 vs 979±114 ml/kg.min) compared to control rats (n=12). SH rats also showed greater tachypneic and hyperventilatory responses (P<0.05) to a new hypoxia episode (7% O2, 20 min) in comparison to control rats. The magnitude of increase in tidal volume was similar between groups. The in situ preparations of SH rats (n=8), but not controls (n=8), exhibited additional bursts in baseline abdominal motor activity, indicating the presence of active expiration at rest. Interestingly, basal afferent activity of carotid sinus nerve (CSN) was similar (0.67±0.18 vs 0.65±0.18 μV) between SH and control rats. Moreover, the CSN excitatory response to stimulation of peripheral chemoreceptors with potassium cyanide was not different between groups (ΔCSN: 1235±372 vs 922±278 %), although the in situ preparations of SH rats showed greater sympathoexcitatory reflex responses (P<0.05). Our findings indicate that augmented basal ventilation and enhanced ventilatory and sympathetic responses to hypoxia in rats exposed to SH are not dependent on increased basal and sensorial activity of carotid body chemoreceptors, but may rely on central mechanisms.Support or Funding InformationFAPESP (2013/17.251‐6) and CNPq

The Easytube for airway management: a systematic review of clinical and simulation studies

Study objectiveEndotracheal intubation is considered the criterion-standard technique for securing the airway. Supraglottic airway devices (SADs) represent a major advance in airway management and are recommended by the guidelines in difficult situations such as Advanced Life Support and “cannot ventilate–cannot intubate” scenarios. The Easytube (EzT) is an SAD introduced a decade ago but not included yet in the above guidelines. DesignSystematic review of MEDLINE and EMBASE according to PRISMA guidelines available up to January 12, 2016. SettingWe collected experimental and clinical evidence regarding EzT positioning performed by medial students, anesthesiologists, paramedics, or nurses. PatientsManikins, cadavers, or patients. InterventionsEzT positioning in both clinical and simulation studies, both under standard and under difficult scenarios. MeasurementsTime to insertion and time to ventilation, success rate and operator’s assessment of the device, change in ventilatory parameters, and major complications. Main resultsFifteen manuscripts were found: 6 prospective clinical studies and 9 conducted under experimental conditions (7 with a simulator and 2 on cadavers). The EzT inserted by both inexperienced and experienced personnel in most studies had high success rate, and it showed excellent results also during simulated cardiopulmonary resuscitation and in difficult airway scenarios. The EzT had better ventilatory parameters as compared with the Combitube and showed great airway sealing capacity, comparable to the Combitube and to the laryngeal mask airway and superior to other SADs. EzT allowed the insertion of large nasogastric tubes and has only mild adverse effects like other SADs. No major complications were described. ConclusionThe EzT appears to be a safe and a good alternative to established SADs. It may be considered among SADs by future guidelines on Advanced Life Support and “cannot ventilate–cannot intubate” scenarios.

The Effects of Experimental Sleep Apnea on Cardiac and Respiratory Functions in 6 and 18 Month Old Dystrophic (mdx) Mice.

Duchenne muscular dystrophy (DMD) is a fatal disease where over 90% of patients succumb to respiratory or cardiac failure. Sleep apnea and sleep disordered breathing (SDB) are noted in a plurality of DMD patients, and the resulting nocturnal episodic hypoxia (EH) cannot be ruled out as a contributing factor to cardiac and respiratory dysfunction. In this study, we investigated the impact of long-term episodic hypoxia, which mimics the cyclic hypoxia seen in sleep apnea, on cardiac and respiratory function in a murine model of DMD (mdx mice). Since the severity and prevalence of sleep apnea in DMD increases with age, we studied the impact of EH on young (6-month) and on older (18-month) mdx mice. Mice were either exposed for 12 weeks to EH (8 hours/day, 5 days/week) or to room air. We noted a significant increase in left ventricular (LV) dilatation (transthoracic echocardiography) on EH exposure in both age groups, but reduced LV contractility was seen only in 6-month old mice. With EH exposure, an increased fibrosis (hydroxyproline) was noted in both cardiac and diaphragm muscle in 18-month but not 6-month old mice. No significant change in relative diaphragm strength (in-vitro) was noted on EH exposure in 18-month old mice. In contrast, EH exposed 6-month old mice showed a significant increase in relative diaphragm strength. EH exposure did not result in any significant change in ventilatory parameters (barometric plethysmography) in awake 6-month old mdx mice. In contrast, 18-month old mdx mice showed considerable ventilatory dysfunction, consistent with reduced ventilatory reserve. Our findings highlight that sleep apnea impacts respiratory and cardiac function in muscular dystrophy, and that EH can have divergent effects on both systems. To our knowledge, this is the first comprehensive study to investigate the impact of EH on cardiac and respiratory function in mdx mice.

Long-term toxicity of naturally occurring asbestos in male Fischer 344 rats

ABSTRACTNaturally occurring asbestos (NOA) fibers are found in geologic deposits that may be disturbed by mining, earthworks, or natural processes, resulting in adverse health risks to exposed individuals. The toxicities of Libby amphibole and NOA samples including Sumas Mountain chrysotile (SM), El Dorado tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON) were compared in male Fischer 344 (F344) rats 15 mo after exposure. Rat-respirable fractions of LA and SM displayed greater mean lengths and aspect ratios than ED and ON. After a single intratracheal (IT) instillation (0.5 or 1.5 mg/rat), persistent changes in ventilatory parameters and a significant increase in lung resistance at baseline and after methacholine aerosol dosing were found only in rats exposed to 1.5 mg SM. High-dose ED significantly elevated bronchoalveolar lavage lactate dehydrogenase (LDH) activity and protein levels, while high-dose SM increased γ-glutamyl transferase and LDH activities. A moderate degree of lung interstitial fibrosis after exposure to 1.5 mg SM persisted 15 mo after exposure, unchanged from previous findings at 3 mo. LA induced mild fibrosis, while ED and ON produced minimal and no apparent fibrosis, respectively. Bronchioloalveolar carcinoma was observed 15 mo after exposure to LA or ED. Data demonstrated that SM, given by bolus IT dosing on an equivalent mass basis, induced greater pulmonary function deficits, airway hyperresponsiveness, and interstitial fibrosis than other NOA, although unlike LA and ED, no apparent evidence for carcinogenicity was found. All NOA samples except ON cleavage fragments produced some degree of long-term toxicity.

Incorporation of capillary microsampling into whole body plethysmography and modified Irwin safety pharmacology studies in rats

Limited toxicokinetic data is generated during modified Irwin screen and whole body plethysmography safety pharmacology studies, due to disturbance of primary endpoints by standard blood sampling methods. We evaluated if incorporation of microsampling would impact on data quality, as providing toxicokinetic data from main test animals could reduce the need for satellite animals. MethodsA modified Irwin screen was performed, testing oral clonidine (0, 0.03, 0.1, or 0.3 mg/kg). One cohort of rats per dose level underwent standard blood sampling (post-4 h Irwin assessment), and another cohort underwent microsampling after the 0.5, 1, 2, 4 and 24 h Irwin assessments. The respiratory effects of oral theophylline (0 or 10 mg/kg) and oral baclofen (0 or 5 mg/kg), were tested using whole body plethysmography. Groups of animals underwent standard blood sampling (at end of recording at 4 h post-dose) or microsampling at either 0.5 h or 1 h intervals (4 or 8 microsamples, respectively). ResultsMicrosampling did not impact on the quality of the data generated. The expected effects of clonidine on behavioural parameters, and of theophylline and baclofen on changes in ventilatory parameters were observed at a similar magnitude and duration independent of sampling method. DiscussionThe incorporation of multiple capillary microsamples into the modified Irwin or respiratory study did not adversely affect the primary endpoints. The capillary microsampling method is a refinement in blood sampling technique which can easily be adapted into safety pharmacology studies to generate pharmacokinetic profiles within the same animal as the primary data, thus enhancing scientific robustness and reducing the satellite animals required.

The effects of high intensity exercise during pulmonary rehabilitation on ventilatory parameters in people with moderate to severe stable COPD: a systematic review.

ObjectiveThe objective of this systematic review was to determine whether people with moderate to severe COPD who are participating in pulmonary rehabilitation and exercising at high intensity demonstrate the changes in ventilatory parameters that are associated with decreased dyspnea.Data sourcesThe authors searched EMBASE, The Cochrane Library, and CINAHL databases up to December 2013 for relevant randomized control trials, systematic reviews, and observational studies. References of identified studies were also screened.Study selectionStudies conducted in a pulmonary rehabilitation setting that included education and exercise were included. Symptom-limited, graded exercise testing that measured tidal volume, respiratory rate, minute ventilation, and inspiratory capacity was required. The studies that contained these keywords in the title or the abstract were selected for further evaluation of the text. Disagreements between reviewers were resolved by consensus. Four studies met these inclusion criteria.Data extractionQuality assessment and data extraction were performed independently by two reviewers. Risk of bias and quality was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions.Data synthesisParticipants in three studies trained at high intensity (70%–80% maximum workload), demonstrating statistically significant changes in tidal volume and respiratory rate. One study did not demonstrate positive ventilatory benefits; however, participants may not have met the desired training intensity. Two studies reported improvement in dyspnea at submaximal exercise intensities. One study noted an increased maximum workload with no significant change in dyspnea at peak exercise.ConclusionPeople with moderate to severe, stable COPD were able to perform high intensity exercise, which was associated with positive changes in ventilatory parameters and dyspnea. A number of factors limit the generalizability of these results to people participating in pulmonary rehabilitation.

Effect of chronic ethanol exposure on rat ventilatory responses to hypoxia and hypercapnia

OBJECTIVE:The effect of chronic ethanol exposure on chemoreflexes has not been extensively studied in experimental animals. Therefore, this study tested the hypothesis that known ethanol-induced autonomic, neuroendocrine and cardiovascular changes coincide with increased chemoreflex sensitivity, as indicated by increased ventilatory responses to hypoxia and hypercapnia.METHODS:Male Wistar rats were subjected to increasing ethanol concentrations in their drinking water (first week: 5% v/v, second week: 10% v/v, third and fourth weeks: 20% v/v). At the end of each week of ethanol exposure, ventilatory parameters were measured under basal conditions and in response to hypoxia (evaluation of peripheral chemoreflex sensitivity) and hypercapnia (evaluation of central chemoreflex sensitivity).RESULTS:Decreased respiratory frequency was observed in rats exposed to ethanol from the first until the fourth week, whereas minute ventilation remained unchanged. Moreover, we observed an increased tidal volume in the second through the fourth week of exposure. The minute ventilation responses to hypoxia were attenuated in the first through the third week but remained unchanged during the last week. The respiratory frequency responses to hypoxia in ethanol-exposed rats were attenuated in the second through the third week but remained unchanged in the first and fourth weeks. There was no significant change in tidal volume responses to hypoxia. With regard to hypercapnic responses, no significant changes in ventilatory parameters were observed.CONCLUSIONS:Our data are consistent with the notion that chronic ethanol exposure does not increase peripheral or central chemoreflex sensitivity.

High-flow nasal cannula oxygen for bronchiolitis in a pediatric ward: a pilot study

High-flow nasal cannula (HFNC) is a widely used ventilatory support in children with bronchiolitis in the intensive care setting. No data is available on HFNC use in the general pediatric ward. The aim of this study was to evaluate the feasibility of HFNC oxygen therapy in infants hospitalized in a pediatric ward for moderate–severe bronchiolitis and to assess the changes in ventilatory parameters before and after starting HFNC support. This prospective observational pilot study was carried out during the bronchiolitis season 2011–2012 in a pediatric tertiary care academic center in Italy. Interruptions of HFNC therapy and possible side effects or escalation to other forms of respiratory support were recorded. Oxygen saturation (SpO2), end-tidal carbon dioxide (ETCO2), and respiratory rate (RR), measured for a baseline period of 1 h before and at specific time intervals in 48 h after the start of HFNC were recorded. Twenty-seven infants were included (median age 1.3 months; absolute range 0.3–8.5). No adverse events, no premature HFNC therapy termination, and no escalation to other forms of respiratory support were recorded. Median SpO2 significantly increased by 1–2 points after changing from standard oxygen to HFNC (p <0.001). Median ETCO2 and RR rapidly decreased by 6–8 mmHg and 13–20 breaths per minute, respectively, in the first 3 h of HFNC therapy (p <0.001) and remained steady thereafter. Conclusions: Use of HFNC for oxygen administration is feasible for infants with moderate–severe bronchiolitis in a general pediatric ward. In these children, HFNC therapy improves oxygen saturation levels and seems to be associated with a decrease in both ETCO2 and RR.

A hybrid approach for continuous detection of sleep‐wakefulness fluctuations: validation in patients with Cheyne–Stokes respiration

Fluctuations in sleep/wake state have been proposed as an important mechanism contributing to the development of oscillatory breathing patterns, including Cheyne-Stokes respiration in patients with heart failure. In order to properly assess the interactions between changes in state and changes in ventilatory parameters, a methodology capable of continuously and reliably detecting state transitions is needed. Traditional fixed-epoch analysis of polysomnographic recordings is not suitable for this purpose. Moreover, visual identification of changes in the dominant electroencephalogram activity at the transition from wakefulness to sleep and vice versa is often very subjective. We have therefore developed a hybrid approach--including both visual scoring and computer-based procedures--for continuous analysis of state transitions from polysomnographic recordings, specifically tailored for fluctuations between wakefulness and non-rapid eye movement-1 and -2 sleep. The overall analysis process comprises three major phases: (1) manual identification of relevant electroencephalogram/electrooculogram features and events, including a sample of unequivocal alpha and theta-delta activity; (2) automatic statistical discrimination of dominant electroencephalogram activity; and (3) state classification (wakefulness, non-rapid eye movement-1 and -2). The latter is carried out by merging information from visual scoring with the output of the discriminator. Validation has been carried out in 16 patients with heart failure during daytime Cheyne-Stokes respiration, using a training and testing set of electroencephalogram polysomnograms. The statistical discriminator correctly classified 99.1 ± 1.4% and 99.2 ± 1.1% of unequivocal alpha and theta-delta activity. This approach has therefore the potential to be used to reliably measure the incidence and location of sleep-wake transitions during abnormal breathing patterns, as well as their temporal relationship with major ventilatory events.

Influence of menstrual phase on ventilatory response to submaximal exercise

Objectives. To determine whether an increase in respiratory drive, due to elevated progesterone and oestrogen concentration during various menstrual phases, persists throughout prolonged submaximal exercise and potentially contributes to fatigue. Furthermore, to determine whether the difference in the ventilatory response to exercise from one menstrual phase to another is correlated to the ovarian hormone concentrations. Design. We compared the change in ventilatory parameters during 90 min exercise at 60%VO2max between the early follicular (EF) and mid-luteal (ML) phase (N = 9) and between the EF and late follicular (LF) phase (N = 5) in eumenorrhoeic women. Main outcome measures. Menstrual phase comparisons and correlations between the change in ventilatory parameters (minute ventilation (VE), respiratory rate (RR), tidal volume) from the EF to ML or from the EF to LF phase and ovarian hormone concentration. Results. The difference in RR between EF and ML phases correlated to progesterone concentration in the ML phase (r = 0.7, p = 0.04). In addition, RR was higher during exercise in the ML compared with EF phase for the full duration of exercise by on average 2.3 ± 2.1 breaths/min (p &lt; 0.05). However, no difference in submaximal VO2 between menstrual phases was evident. No significant difference in exercising-VE was observed between menstrual phases, but the change in VE from EF to ML correlated to oestrogen (r = 0.8, p = 0.02) and progesterone (r = 0.7, p = 0.04) concentration in the ML phase. South African Journal of Sports Medicine Vol. 18 (2) 2006: pp. 31-37

The effect of low dose rocuronium on globe position, muscle relaxation and ventilation in dogs: a clinical study

The purpose of this study was to evaluate globe position, muscle relaxation and changes in ventilatory parameters after intravenous administration of 0.1 mg/kg rocuronium. Prospective clinical study. Sixteen dogs of different breeds, with a body weight of 22.1 +/- 13 kg and age of 5.6 +/- 2.8 years (mean +/- SD), were anesthetized for a short ophthalmic examination requiring central position of the globe. All dogs were premedicated with 0.005 mg/kg medetomidine and 0.1 mg/kg methadone IV. Anesthesia was induced with propofol to effect and maintained with 10 mg/kg/h propofol by continuous rate infusion. Following endotracheal intubation all dogs breathed 100% oxygen via an anesthetic circle system. Neuromuscular function was assessed with an acceleromyograph (TOF-Guard, Organon Teknika NV, Turnhout, Belgium) and by stimulation of the nervus peroneus superficialis. The ventilation parameters were measured using spirometry and capnography. After baseline measurements 0.1 mg/kg rocuronium was administered IV. Minute volume (MV), tidal volume (Vt), respiratory rate (RR), end expiratory carbon dioxide concentration (PE'CO(2)) and maximal depression of the response of the first twitch (T1) of train-of-four (TOF) stimulation and train-of-four ratio (TOFR) was measured. The change in the position of the globe was recorded. T1 decreased to 61 +/- 18% and the TOF ratio to 45 +/- 21% of baseline values. Both parameters returned to baseline after 9 min. There was no significant reduction in MV, TV and RR and no increase in PE'CO(2). The globe rotated to a central position of 45 +/- 7.7 s after administration of rocuronium and remained there for 23 +/- 10.8 min in all dogs. Rocuronium administered intravenously at a dose of 0.1 mg/kg to dogs causes a central position of the globe but minimal impairment of ventilation parameters.

Influence of menstrual phase on ventilatory response to submaximal exercise

Objectives. To determine whether an increase in respiratory drive, due to elevated progesterone and oestrogen concentration during various menstrual phases, persists throughout prolonged submaximal exercise and potentially contributes to fatigue. Furthermore, to determine whether the difference in the ventilatory response to exercise from one menstrual phase to another is correlated to the ovarian hormone concentrations. Design. We compared the change in ventilatory parameters during 90 min exercise at 60%VO2max between the early follicular (EF) and mid-luteal (ML) phase (N = 9) and between the EF and late follicular (LF) phase (N = 5) in eumenorrhoeic women. Main outcome measures. Menstrual phase comparisons and correlations between the change in ventilatory parameters (minute ventilation (VE), respiratory rate (RR), tidal volume) from the EF to ML or from the EF to LF phase and ovarian hormone concentration. Results. The difference in RR between EF and ML phases correlated to progesterone concentration in the ML phase (r = 0.7, p = 0.04). In addition, RR was higher during exercise in the ML compared with EF phase for the full duration of exercise by on average 2.3 ± 2.1 breaths/min (p &lt; 0.05). However, no difference in submaximal VO2 between menstrual phases was evident. No significant difference in exercising-VE was observed between menstrual phases, but the change in VE from EF to ML correlated to oestrogen (r = 0.8, p = 0.02) and progesterone (r = 0.7, p = 0.04) concentration in the ML phase. South African Journal of Sports Medicine Vol. 18 (2) 2006: pp. 31-37

VENTILATORY AND HEMODYNAMIC CHANGES DURING RETROPERITONEAL AND TRANSPERITONEAL LAPAROSCOPIC NEPHRECTOMY: A PROSPECTIVE REAL-TIME COMPARISON

Nephrectomies are currently performed via the transperitoneal or retroperitoneal laparoscopic approach. We compared the ventilatory and hemodynamic effects of these approaches. After institutional ethics committee approval was obtained patients requiring nephrectomy in a 9-month period were prospectively allocated to the retroperitoneal (24) or transperitoneal (15) approach. All were initially ventilated in the volume controlled mode (10 ml kg tidal volume). Intraoperative fingertip, pulse derived arterial oxygen saturation less than 97%, end tidal CO2 partial pressure greater than 40 mm Hg and peak inspiratory pressure greater than 36 cm H2O necessitated changes in ventilatory parameters, as deemed necessary by the anesthetist. If tidal volume decreased greater than 25% of baseline, pressure controlled ventilation was begun instead. Peak inspiratory and plateau pressures increased for the transperitoneal approach by approximately 30% more than in the retroperitoneal group (p <0.05). Volume controlled ventilation was changed to pressure controlled ventilation in 8 transperitoneal vs zero retroperitoneal cases (p <0.05). Heart rate, and systolic and diastolic blood pressure increased by approximately 13% more in the transperitoneal than in the retroperitoneal group (p <0.05). Nephrectomy via the retroperitoneal laparoscopic approach interferes with ventilatory and hemodynamic functions less than nephrectomy via the transperitoneal approach.

Effects of Sildenafil on the Human Response to Acute Hypoxia and Exercise

We examined the effects of the 5-phosphodiesterase (5-PDE) inhibitor sildenafil on pulmonary arterial pressure and some oxygen transport and cardiopulmonary parameters in humans during exposure to hypobaric hypoxia at rest and after exercise. In a double-blind study, 100 mg sildenafil or placebo was administered orally to 14 healthy volunteers 45 min before exposure to 5,000 m of simulated altitude. Arterial oxygen saturation (SaO2), heart rate (HR), tidal volume (VT), respiratory rate (RR), left ventricular ejection fraction (EF), and pulmonary arterial pressure (PAP) were measured first at rest in normoxia, at rest and immediately after exercise during hypoxia, and after exercise in normoxia. The increase in systolic PAP produced by hypoxia was significantly decreased by sildenafil at rest from 40.9 +/- 2.6 to 34.9 +/- 3.0 mmHg (-14.8%; p = 0.0046); after exercise, from 49.0 +/- 3.9 to 42.9 +/- 2.6 mmHg (-12.6%; p = 0.003). No significant changes were found in normoxia either at rest or after exercise. Measurements of the effect of sildenafil on exercise capacity during hypoxia did not provide conclusive data: a slight increase in SaO2 was observed with exercise during hypoxia, and sildenafil did not cause significant changes in ventilatory parameters under any condition. Sildenafil diminishes the pulmonary hypertension induced by acute exposure to hypobaric hypoxia at rest and after exercise. Further studies are needed to determine the benefit from this treatment and to further understand the effects of sildenafil on exercise capacity at altitude.