Baseline Minute Ventilation Research Articles

Breathing and Oxygen Carrying Capacity in Ts65Dn and Down Syndrome.

Individuals with Down syndrome (Ds) are at increased risk of respiratory infection, aspiration pneumonia, and apnea. The Ts65Dn mouse is a commonly used model of Ds, but there have been no formal investigations of awake breathing and respiratory muscle function in these mice. We hypothesized that breathing would be impaired in Ts65Dn vs. wild-type (WT), and would be mediated by both neural and muscular inputs. Baseline minute ventilation was not different at 3, 6, or 12 mo of age. However, VT/Ti, a marker of the neural drive to breathe, was lower in Ts65Dn vs. WT and central apneas were more prevalent. The response to breathing hypoxia was not different, but the response to hypercapnia was attenuated, revealing a difference in carbon dioxide sensing, and/or motor output in Ts65Dn. Oxygen desaturations were present in room air, demonstrating that ventilation may not be sufficient to maintain adequate oxygen saturation in Ts65Dn. We observed no differences in arterial PO2 or PCO2, but Ts65Dn had lower hemoglobin and hematocrit. A retrospective medical record review of 52,346 Ds and 52,346 controls confirmed an elevated relative risk of anemia in Ds. We also performed eupneic in-vivo electromyography and in-vitro muscle function and histological fiber typing of the diaphragm, and found no difference between strains. Overall, conscious respiration is impaired in Ts65Dn, is mediated by neural mechanisms, and results in reduced hemoglobin saturation. Oxygen carrying capacity is reduced in Ts65Dn vs. WT, and we demonstrate that individuals with Ds are also at increased risk of anemia.

Comparison of five weaning indices in predicting successful weaning from mechanical ventilation

Introduction: Mechanical ventilation is a life-supporting modality used in patients with respiratory failure. Most patients are extubated early but weaning can be prolonged in some. Aim: Comparison of accuracy of prediction of success of a spontaneous breathing trial (SBT) using CORE, CROP, RSBI, RSBI rate and minute ventilation recovery. Methods: This is a prospective observational study. 62 adult patients admitted to Multidisciplinary Intensive Care Unit during April 2012 - January 2013 were studied. All patients, orotracheally intubated and mechanically ventilated for at least 24 hours and ready for weaning were enrolled. The patients underwent SBT using pressure support ventilation (5 – 8 cm H2O), PEEP of 5 - 8 cm H2O, and 40% oxygen. The weaning indices were measured at 30 min and correlated with weaning success. Results: The mean (± SD) age was 49.7 (± 18.3) years. There were 46 male and 16 female patients. The threshold values were as follows: CORE index: ≥ 6, CROP index: ≥ 13, RSBI < 105 b/min/L, RSBI rate ≤ 20%. The sensitivity (%), specificity (%) and AUC of ROC curve were as follows: CORE (96, 66, 0.74), CROP (95, 33, 0.61), RSBI (89, 46, 0.2), RSBI rate (85, 28, 0.52) and minute ventilation recovery (higher than baseline minute ventilation at 25 min of rest on initial ventilator settings after 30 min of SBT) (n = 26) (92.3, 100, 0.93). Conclusion: CORE and RSBI are moderately accurate while CROP and RSBI rate are inaccurate. Minute ventilation recovery predicted weaning failure accurately.

Acute intermittent hypoxia evokes ventilatory long-term facilitation and active expiration in unanesthetized rats

Acute intermittent hypoxia (AIH) modifies the functioning of the respiratory network, causing respiratory motor facilitation in anesthetized animals and a compensatory increase in pulmonary ventilation in freely behaving animals. However, it is still unclear whether the ventilatory facilitation induced by AIH in unanesthetized animals is associated with changes in the respiratory pattern. We found that Holtzman male rats (80–150 g) exposed to AIH (10 × 6% O2 for 30–40 s every 5 min, n = 9) exhibited a prolonged (30 min) increase in baseline minute ventilation (P < 0.05) compared to control animals (n = 13), combined with the occurrence of late expiratory peak flow events, suggesting the presence of active expiration. The increase in ventilation after AIH was also accompanied by reductions in arterial CO2 and body temperature (n = 5–6, P < 0.05). The systemic treatment with ketanserin (a 5-HT2 receptor antagonist) before AIH prevented the changes in ventilation and active expiration (n = 11) but potentiated the hypothermic response (n = 5, P < 0.05) when compared to appropriate control rats (n = 13). Our findings indicate that the ventilatory long-term facilitation elicited by AIH exposure in unanesthetized rats is linked to the generation of active expiration by mechanisms that may depend on the activation of serotonin receptors. In contrast, the decrease in body temperature induced by AIH may not require 5-HT2 receptor activation.

Leptin Receptor Blockade Abolished Hypertension and Decreased Hypoxic Ventilatory Response in a Model of Obesity‐Related Hypertension

INTRODUCTIONObesity causes hypertension and exacerbates sleep disordered breathing. Leptin is an adipocyte produced hormone which is implicated in regulation of metabolic rate, food intake, control of breathing and blood pressure. Obese individuals are resistant to metabolic and respiratory effects of leptin, but appeared to be sensitive to hypertensive effects of the hormone. We hypothesized that New Zealand obese mice (NZO), which are resistant to metabolic effects of leptin, remain susceptible to cardiovascular, but not respiratory, effects of this hormone.METHODSMale NZO mice of 12–13 weeks‐old were treated with leptin receptor blockers Allo‐aca (n=5) or control peptide Gly11 (n=3) for 9 consecutive days. Doses of 0.2mg/kg were administered 2x/day, at 10AM and 6PM subcutaneously. Blood pressure was measured by telemetry. Ventilation was assessed by whole‐body barometric plethysmography and control of breathing was examined by assessing the hypoxic ventilatory response (HVR). Sleep studies were conducted by full‐polysomnography.RESULTSSystemic leptin receptor blocker Allo‐aca did not affect body weight and food intake in NZO mice. In contrast, it induced a decrease in the mean arterial blood pressure from 132.9±5.9 mmHg to 121.2±11.3 mmHg during the light phase (P&lt;0.001). Allo‐aca did not affect baseline minute ventilation in awake mice, but decreased HVR (P&lt;0.05). There was a trend for systemic blockade of leptin receptors with Allo‐aca to suppress minute ventilation during NREM and REM sleep, whereas the control peptide Gly11 had no effect.CONCLUSIONSNZO mice were resistant to metabolic effects of leptin, but they were sensitive to the hypertensive and respiratory effects of the hormone. Thus, leptin receptor blockers can be used for pharmacotherapy for obesity‐associated hypertension, but sleep‐related hypoventilation should be considered as a potential side effect.Support or Funding InformationNIH R01s HL128970 and HL133100 to Dr. Vsevolod Y. Polotsky. Dr. Tufik and Dr. Andersen are CNPq fellowship (Brazil) recipients. Dr. Lenise Jihe Kim was supported by Associação Fundo de Incentivo à Pesquisa (AFIP, Brazil).

The effects of sleeping position, maternal smoking and substance misuse on the ventilatory response to hypoxia in the newborn period

Maternal smoking, substance misuse in pregnancy and prone sleeping increase the risk of sudden infant death syndrome (SIDS). We examined the effect of maternal smoking, substance misuse and sleeping position on the newborn response to hypoxia. Infants born between 36 and 42 weeks of gestational age underwent respiratory monitoring in the prone and supine sleeping position before and during a hypoxic challenge. Minute ventilation (MV) and end-tidal carbon dioxide (ETCO2) levels were assessed. Sixty-three infants were studied: 22 controls, 23 whose mothers smoked and 18 whose mothers substance-misused and smoked. In the supine position, baseline MV was higher and ETCO2 levels were lower in infants of substance-misusing mothers compared to controls (p = 0.015, p = 0.017, respectively). Infants of substance-misusing mothers had a lower baseline MV and higher ETCO2 levels in the prone position (p = 0.005, p = 0.004, respectively). When prone, the rate of decline in minute ventilation in response to hypoxia was greater in infants whose mothers substance-misused and smoked compared to controls (p = 0.002) and infants of smoking mothers (p = 0.016). The altered response to hypoxia in the prone position of infants whose mothers substance-misused and smoked in pregnancy may explain their increased vulnerability to SIDS.

Short-Term Sustained Hypoxia Elevates Basal and Hypoxia-Induced Ventilation but Not the Carotid Body Chemoreceptor Activity in Rats.

Exposure to chronic sustained hypoxia (SH), as experienced in high altitudes, elicits an increase in ventilation, named ventilatory acclimatization to hypoxia (VAH). We previously showed that rats exposed to short-term (24 h) SH exhibit enhanced abdominal expiratory motor activity at rest, accompanied by augmented baseline sympathetic vasoconstrictor activity. In the present study, we investigated whether the respiratory and sympathetic changes elicited by short-term SH are accompanied by carotid body chemoreceptor sensitization. Juvenile male Holtzman rats (60–80 g) were exposed to SH (10% O2 for 24 h) or normoxia (control) to examine basal and hypoxic-induced ventilatory parameters in unanesthetized conditions, as well as the sensory response of carotid body chemoreceptors in artificially perfused in situ preparations. Under resting conditions (normoxia/normocapnia), SH rats (n = 12) exhibited higher baseline respiratory frequency, tidal volume, and minute ventilation compared to controls (n = 11, P < 0.05). SH group also showed greater hypoxia ventilatory response than control group (P < 0.05). The in situ preparations of SH rats (n = 8) exhibited augmented baseline expiratory and sympathetic activities under normocapnia, with additional bursts in abdominal and thoracic sympathetic nerves during late expiratory phase that were not seen in controls (n = 8, P < 0.05). Interestingly, basal and potassium cyanide-induced afferent activity of carotid sinus nerve (CSN) was similar between SH and control rats. Our findings indicate that the maintenance of elevated resting ventilation, baseline sympathetic overactivity, and enhanced ventilatory responses to hypoxia in rats exposed to 24 h of SH are not dependent on increased basal and sensorial activity of carotid body chemoreceptors.

Abstract WP106: Acetazolamide Stabilizes Stroke Induced Respiratory Dysfunction and Improves Longterm Cognitive Outcome

Background: Respiratory dysfunction is a common complication of stroke, with an incidence more than 60% in first time stroke patients, leading to poorer recovery and increased mortality. We developed a mouse model of stroke induced respiratory dysfunction (SIRD) characterized by hypoventilation and apnea. Mice that had the highest incidence of post-stroke apneas developed progressive cognitive decline. Acetazolamide (Act), a carbonic anhydrase inhibitor, promotes metabolic acidosis increasing respiratory activity. Hypothesis: Acetazolamide will stimulate basal respiratory activity, eliminating apneas and hypoxic events, and will enhance post stroke cognitive outcomes. Methods: Whole body plethysmography was performed on WT C57/B6 young (2-3 month) male mice to establish baseline breathing frequency, tidal volume, minute ventilation and number of apneas. Mice were subjected to 60 MCAO or sham surgery. Plethysmography was performed on day 3, 7 and weekly thereafter. Act (40mg/kg) continuous administration via SQ implanted Alzet pump or vehicle (n=11/group) was initiated on day 14. Cognitive tests were conducted over six weeks. Results: Act treatment improved respiratory frequency (152.6±6.49 vs. 318.4±61.9, p&lt;0.05) and decreased the number of apneas (5.4±0.7 vs. 1±0.5, p&lt;0.001) in stroke mice (Fig. 1). Spatial learning/memory assessed on day 42 with Barnes Maze found Act-treated mice had a shorter escape time than vehicle (median escape time 160.48 vs. 14.16s, survival curve for time to escape p=0.0001, Mantel-Cox test). Summary: Apnea and hypoxia are seen in a murine model of SIRD, the severity of which correlated with post-stroke cognitive decline. These deficits were reversed with chronic Acetazolamide treatment. Research supported by the NCATS Award Number TL1TR000369.

Evaluation of a method for isocapnic hyperventilation: a clinical pilot trial.

Isocapnic hyperventilation (IHV) is a method that shortens time to extubation after inhalation anaesthesia using hyperventilation (HV) without lowering airway CO2 . In a clinical trial on patients undergoing long-duration sevoflurane anaesthesia for major ear-nose-throat (ENT) surgery, we evaluated the utility of a technique for CO2 delivery (DCO2 ) to the inspiratory limb of a closed breathing circuit, during HV, to achieve isocapnia. Fifteen adult ASA 1-3 patients were included. After end of surgery, mechanical HV was started by doubling baseline minute ventilation. Simultaneously, CO2 was delivered and dosed using a nomogram developed in a previous experimental study. Time to extubation and eye opening was recorded. Inspired (FICO2 ) and expired (FETCO2 ) CO2 and arterial CO2 levels were monitored during IHV. Cognition was tested pre-operatively and at 20, 40 and 60 min after surgery. A DCO2 of 285 ± 45 ml/min provided stable isocapnia during HV (13.5 ± 4.1 l/min). The corresponding FICO2 level was 3.0 ± 0.3%. Time from turning off the vaporizer (1.3 ± 0.1 MACage) to extubation (0.2 ± 0.1 MACage) was 11.3 ± 1.8 min after 342 ± 131 min of anaesthesia. PaCO2 and FETCO2 remained at normal levels during and after IHV. In 85% of the patients, post-operative cognition returned to pre-operative values within 60 min. In this cohort of patients, a DCO2 nomogram for IHV was validated. The patients were safely extubated shortly after discontinuing long-term sevoflurane anaesthesia. Perioperatively, there were no adverse effects on arterial blood gases or post-operative cognition. This technique for IHV can potentially be used to decrease emergence time from inhalation anaesthesia.

Respiratory Control in a Rat Model of Alzheimer's Disease (TgF344‐AD)

Synaptic defects seen in tauopathies such as Alzheimer's disease (AD) are known to result in the impaired function of major brain networks. It is plausible to consider that such changes can directly or indirectly affect central respiratory networks within the brainstem with consequences for respiratory homeostasis. Alzheimer's patients display indicative signs of oro‐pharyngeal complications and sleep‐disordered breathing. Upper airway dysfunction has also been shown to develop and persist in animal models of AD. The aim of this study was to characterise respiratory control at an early stage of disease progression in a novel rat model of AD.We utilised a transgenic (Tg) rat model of AD (TgF344‐AD), which expresses the mutant human transgenes: amyloid precursor protein (APPsw) and presenilin 1 (PS1ΔE9). Tg (male n=9; female n=12) and non‐transgenic wild type (non‐Tg; male n=8; female n=7) animals (34–49 weeks) were studied using whole‐body plethysmography to determine ventilation and metabolism. Cardiorespiratory reflex responses to chemostimulation were subsequently determined in a subset of animals under urethane anaesthesia (1.5g/kg). Data were statistically compared by 2‐way ANOVA (genotype × sex) with Bonferroni post hoc tests.Transgenic mutation did not significantly alter baseline minute ventilation (VE; p&gt;0.05) however, sex‐specific differences in breathing were evident. Exposure to 10 minutes of hypoxia (FiO2 =0.1) manifested a greater VE response in females compared with males (p&lt;0.01); however, the ventilatory response to hypoxia was equivalent in Tg animals compared with non‐Tg animals. Similarly, baseline data recorded under anaesthesia revealed that VE was equivalent in Tg and non‐Tg animals (p&gt;0.05) and consistent with data derived from plethysmography, sex differences in breathing were evident. No genotype or sex difference was observed in diaphragm integrated EMG activity for peak amplitude, area under the curve and maximum slope analysis (p&gt;0.05). Baseline mean arterial pressure (MAP) was equivalent in Tg and non‐Tg animals (p&gt;0.05), although females had a significantly increased MAP compared with males (p&lt;0.01).In conclusion, expression of human transgenes in this AD animal model did not significantly alter respiratory behaviour. Further analysis of respiratory stability and respiratory EMG responses to chemostimulation and airway obstruction will be carried out.Support or Funding InformationDepartment of Physiology, University College Cork, Cork, Ireland

Influence of Ethanol on Oxycodone-induced Respiratory Depression: A Dose-escalating Study in Young and Elderly Individuals.

Respiratory depression is a potentially fatal complication of opioid use, which may be exacerbated by simultaneous ethanol intake. In this three-way sequential crossover dose-escalating study, the influence of coadministration of oral oxycodone and intravenous ethanol was assessed on resting ventilation, apneic events and the hypercapnic ventilatory response in healthy young and older volunteers. Twelve young (21 to 28 yr) and 12 elderly (66 to 77 yr) opioid-naive participants ingested one 20 mg oxycodone tablet combined with an intravenous infusion of 0, 0.5, or 1 g/l ethanol. Resting respiratory variables and the primary outcome, minute ventilation at isohypercapnia (end-tidal partial pressure of carbon dioxide of 55 mmHg or VE55), were obtained at regular intervals during treatment. Oxycodone reduced baseline minute ventilation by 28% (P < 0.001 vs. control). Ethanol caused a further decrease of oxycodone-induced respiratory depression by another 19% at 1 g/l ethanol plus oxycodone (P < 0.01 vs. oxycodone). Ethanol combined with oxycodone caused a significant increase in the number of apneic events measured in a 6-min window with a median (range) increase from 1 (0 to 3) at 0 g/l ethanol to 1 (0 to 11) at 1 g/l ethanol (P < 0.01). Mean (95% CI) VE55 decreased from 33.4 (27.9 to 39.0) l/min (control) to 18.6 (15.6 to 21.6) l/min (oxycodone, P < 0.01 vs. control) and to 15.7 (12.7 to 18.6) l/min (oxycodone combined with ethanol, 1 g/l; P < 0.01 vs. oxycodone). Ethanol together with oxycodone causes greater ventilatory depression than either alone, the magnitude of which is clinically relevant. Elderly participants were more affected than younger volunteers.

Abstract TP91: Stroke Induced Respiratory Dysfunction: Age, Apnea and Cognitive Decline

Respiratory dysfunction is a common complication of stroke, with an incidence more than 60%, leading to prolonged recovery and increased mortality. Despite the high prevalence of stroke induced respiratory dysfunction (SIRD) little is known regarding how SIRD influences recovery and cognitive outcomes after ischemic stroke. Studies in non-stroke populations have shown that individuals with respiratory dysfunction are drastically more likely to develop cognitive impairment. We propose stroke will induce chronic respiratory dysfunction, instability, and apnea in mice, which are linked to higher mortality and greater post-stroke cognitive deficits. Respiratory dysfunction will be related to progressive cognitive decline following middle cerebral artery occlusion (MCAo) that is worse in aged mice. Whole body plethysmography was performed on C57/B6 young (2-3 month)/aged (20 month) male mice to establish baseline frequency (BPM), tidal volume, minute ventilation and apnea frequency. Animals were exposed to a variety of gas conditions to assess the contribution of peripheral and central chemoreceptors. Mice were subjected to 60 MCAO, producing chronic respiratory dysfunction, instability and apnea, or sham surgery. Days 3, 7 and weekly thereafter plethysmography and a variety of cognitive tests were performed to track respiratory dysfunction and progressive cognitive decline. Young and aged mice displayed hypoventilation (young stroke 181.4±22 vs. sham 264±35 bpm p&lt;.05 and aged stroke 233.7±46.6 bpm vs. sham 369.4±25.9 p&lt;.05) and increased apneas (young stroke 6.8±1.2 vs. 0.8±.8 apnea/min p&lt;.01; aged stroke 16±1 vs. 12±1.5 apneas/min) at day 3 post-stroke. Six weeks later mice were stratified based on # apneas/min into minor (&lt;5 apneas/min N=8) and moderate/severe (&gt;5 apneas/min N=3). Mice with minor apneas perform better in a variety of cognitive tests. Fear conditioning (freezing behavior minor 1.47±.24s/event vs. mod .74±.07s/event, p=.02), Barnes maze: Escape time minor 158.5±35.2 sec vs. 217.9±82. NORT: ratio time novel/familiar object minor 2.2±.6 vs. 1.1±.3. Suggesting incidence of apneas as an indicator of cognitive decline. Therefore, the treatment of respiratory instability is a viable prospect to improve cognitive outcomes.

Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers.

IntroductionA previous study has suggested that the Human Leukocyte Antigen (HLA) allele DQB1*06:02 affects hypoxic ventilatory response (HVR) but not hypercapnic ventilatory response (HCVR) in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR.MethodsA re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians). HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5) were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST.ResultsHVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2) compared to 0.429±0.266 (liter/minute/%SpO2) in men, p<0.001 (55.4% higher HVR in men). Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, p<0.001), higher SpO2 (98.0±1.3% vs. 96.6±1.7%, p<0.001), and lower EtCO2 (4.65±0.68% vs. 4.82±1.02%, p = 0.025). One hundred and two (18.5%) of the participants had HLA-DQB1*06:02. No association was seen between HLA-DQB1*06:02 and HVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866) and HCVR.ConclusionsThis is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response.

Risk of postoperative complications in chronic obstructive lung diseases patients considered fit for lung cancer surgery: beyond oxygen consumption.

Patients with poor lung function usually undergo cardiopulmonary exercise testing (CPET) and those with a predicted postoperative maximal oxygen consumption (VO2 max) of >10 ml/kg/min undergo lung resection surgery and still some complications are observed. We aimed to determine other parameters beyond VO2 able to predict postoperative complications in patients undergoing lung resection surgery. This is an observational study with longitudinal follow-up. Patients with forced expiratory volume in 1 second (FEV1) or diffusing capacity for carbon monoxide of <40% underwent CPET and those with VO2 max of >10 ml/kg/min were considered fit for surgery. Patients were followed up prospectively for 12 months and postoperative complications and survival were recorded. Physiological parameters obtained during CPET and pulmonary function tests were analysed. Eighty-three chronic obstructive pulmonary disease (COPD) patients were evaluated for surgery between 2010 and 2015. Twenty-four patients were considered unfit for surgery and received an alternative therapy. Fifty-five patients had a VO2 max of >10 ml/kg/min and underwent lung surgery. Among them, 4% died and 41% developed complications postoperatively. Baseline minute ventilation to carbon dioxide output (VE/VCO2) slope was significantly higher among those who developed postoperative complications or died (P = 0.047). Furthermore, VE/VCO2 slope of >35 (at maximal exercise) was the single parameter most strongly associated with the probability of mortality and postoperative complications (hazard ratio 5.14) with a survival probability of 40% after 1 year of follow-up. In a multivariable model, VO2, VE/VCO2 slope of >35 and work load were independently associated with the probability of having an event. VO2 is not the unique parameter to consider when CPET is performed to evaluate the postoperative risk of lung cancer surgery in COPD patients. The signs of ventilatory inefficiency such as VE/VCO2 slope predict complications better than VO2 does.

Airseal During Laparoscopic Radical Prostatectomy and Regional Extended Lymphadenectomy: Intraoperative Advantage

Aim: We retrospectively compared two different carbon dioxide insufflators: Thermoflator (standard gas flow rate) and Airseal IFS (continuos bidirectional gas flow, lower flow rate), during laparoscopic radical prostatectomy and extended pelvic lymphadenectomy (t-LRP) in order to detect any differences in the anesthetic respiratory management. Materials and methods: 77 consecutive patients underwent t-LRP. The last 38 patients treated using Thermoflator (group A) have been compared with the first 39 patients treated using Airseal (group B). Mean intrabdominal pressure was mantained at 12 mmHg in all patients. Baseline tidal, minute ventilation and positive end expiratory pressure (PEEP) were set at 8 ml/Kg, 10 breaths/minute and 5 cm H 2 0 respectively in both groups. End-tidal CO 2 and arterial blood gas analysis were monitored during surgery. Changes of the baseline mechanical ventilator parameters have been made in the case of et CO 2 greater than 40 mmHg. Results: Mean introperative et CO 2 was 38.21 mmHg in group A and 39.28 mmHg in group B. Baseline mechanical ventilator paramethers had to be modified in 21/38 group A patients and in 5/39 group B patients (p<0.01). These changes allowed to maintain the et CO2 within 40 mmHg in all patients of both groups. Discussion Laparoscopic urological interventions were always demanding procedures. It was true in most particular way during learning curve. Duration of anaesthesiology time should be taken in account for planning. AirSeal insufflator could be an useful device in order to reduce anesthesiologic implication. Conclusion: In our experience the Airseal system simplified the anesthetic respiratory management and potentially limited the pulmonary damage.

Lack of functional information explains the poor performance of ‘clot load scores’ at predicting outcome in acute pulmonary embolism

Clot load scores have previously been developed with the goal of improving prognosis in acute pulmonary embolism (PE). These scores provide a simple estimate of pulmonary vascular bed obstruction, however they have not been adopted clinically as they have poor correlation with mortality and right ventricular (RV) dysfunction. This study performed a quantitative analysis of blood flow and gas exchange in 12 patient-specific models of PE, to understand the limitations of current clot load scores and how their prognostic value could be improved. Prediction of hypoxemia in the models when using estimated baseline (non-occluded) minute ventilation and cardiac output correlated closely with clinical metrics for RV dysfunction, whereas the clot load score had only a weak correlation. The model predicts that large central clots have a greater impact on function than smaller distributed clots with the same total clot load, and that the partial occlusion of a vessel only has a significant impact on pulmonary function when the vessel is close to completely occluded. The effect of clot distribution on the redistribution of blood from its normal pattern – and hence the magnitude of the potential effect on gas exchange – is represented in the model but is not included in current clot load scores. Improved scoring systems need to account for the expected normal distribution of blood in the lung, and the impact of clot on redistributing the blood flow.

Rett Syndrome mutation MeCP2 T158A affects hypoxic ventilatory response in mice

Rett syndrome (RTT), whose phenotype includes respiratory disorders, is caused by loss‐of‐function mutations in methyl‐CpG‐binding protein 2 (MeCP2). Mouse models of the syndrome that have been generated by deletion of Mecp2 have an altered ventilatory response to acute hypoxia (HVR) characterized by a minute ventilation (VE) that exceeds wild type (WT) and that persists in the early recovery period. Such large deletions, however, account for only ~10% of cases. Here we determine if mice with a common single point mutation retain this respiratory pattern. Knockin mice that carry a RTT‐associated threonine to alanine mutation at residue 158 (T158A) show RTT‐like behavioral phenotypes similar to Mecp2‐null mice (Nature Neuroscience 15:274,2011). Experiments were performed in heterozygous T158A female mice at 9 months of age. Baseline respiratory frequency, tidal volume and minute ventilation in T158A animals was similar to WT. Compared to WT littermates relative VE of T158A at 1 min of 8% O2 was twice as large. WT mice showed the expected post‐hypoxia frequency decline (224±9.5 to 203±12 bpm) while T158A had a sustained tachypnea (203±10 to 219±14.5). HVR in mice with a T158A mutation is similar to that with a null mutation of MeCP2.Support: IRSF, RSRT, NewLife Foundation (JMB); NIH, IRSF (ZZ)

Chemosensory control by purinergic signaling within the retrotrapezoid nucleus (RTN) in conscious rats

The RTN contains a population of CO2/H+‐sensitive neurons that send excitatory projections to respiratory centers to regulate breathing (i.e., chemoreceptors). Evidence also suggests that ATP, possibly released by astrocytes, is an important mediator of RTN chemoreceptor activity. However, this possibility has yet to be tested in conscious animals. The goal of this study is to determine if purinergic signaling in the RTN contributes to breathing under resting conditions and during central chemoreflex activation in unrestrained awake rats. Male Wistar rats (280–300 g) with bilateral stainless steel cannulas implanted into the RTN were used. Bilateral RTN injections of PPADS (P2‐receptor antagonist: 5 mM ‐ 50 nl) did not change baseline minute ventilation (VE), mean arterial pressure (MAP), or heart rate (HR). However, PPADS treated animals exhibited reduced tidal volume (VT) (6.6 ± 0.14 vs. saline: 9.1 ± 1.4 ml/kg) and VE (748 ± 2.5 vs. saline: 1257 ± 239 ml/kg/min) responses to hypercapnia (7% CO2). CO2‐induced changes in respiratory frequency, MAP and HR were not affected by PPADS. These results suggest that CO2‐evoked ATP release in the RTN contributes to control of breathing in conscious animals

Muscle afferent activation causes ventilatory and cardiovascular responses during concurrent hypercapnia in humans

Respiratory and cardiovascular responses to muscle mechanoreflex (passive calf stretch) and metaboreflex activation (local circulatory occlusion) were examined during inhalation of a hypercapnic gas mixture in four trials. These controlled for the effects of central command, metabolite sensitization of muscle afferents and hypercapnia-induced elevation of central respiratory drive. In an isokinetic dynamometer, with circulation through the right leg occluded by inflation of a thigh cuff, 13 participants either rested (control trial; CON) or plantarflexed their ankle at 50% maximal force for 1.5 min (voluntary exercise trial; EX). Thereafter, circulatory occlusion was maintained and the calf passively stretched before return to the resting position. Both trials were performed while breathing air, as well as while breathing a normoxic, hypercapnic (5% CO(2)) gas mixture (CO(2) trial and CO(2)+EX trial). Hypercapnic gas inhalation increased baseline minute ventilation (V), heart rate and mean arterial pressure (+27.67 ± 1.74 l min(-1), +7 ± 0.85 beats min(-1) and +13 ± 3.41 mmHg, respectively; means ± SEM) above control values (9.78 ± 0.86 l min(-1), 62 ± 2.3 beats min(-1) and 88 ± 2.6 mmHg, respectively). Voluntary exercise further increased these variables from baseline during both trials (P < 0.05). During the continued circulatory occlusion after voluntary exercise, mean arterial pressure remained significantly elevated (P < 0.05). Minute ventilation returned to baseline during circulatory occlusion following exercise in the EX trial, but in the CO(2)+EX trial the V remained elevated at end-exercise levels during this period (+7.12 ± 1.13 l min(-1)). Passive stretch caused further increases in V during CO(2)+EX and CO(2) trials but not in CON and EX. These results indicate that in the absence of central command, either muscle metaboreflex and/or mechanoreflex activation stimulates ventilation during concurrent hypercapnia.

Ovariectomy at 3 or 10 weeks of age does not affect the ventilatory response to hypoxia in adult rats

Although an ovariectomy is the routine approach used to study the role of ovarian hormones on respiratory control, the results have often been contradictory. We tested the hypothesis that the ventilatory response to hypoxia is modified by the age at which the ovariectomy is performed. Female rats were ovariectomized either atan early (3 weeks old, i.e., prepubertal) or late (10 weeks old, i.e., adult) stage, and ventilation was then assessed at 12 weeks of age using whole-body plethysmography. The control group included sham-operated rats that had undergone the same surgical procedure but were not ovariectomized. Independent of the age at which surgery was performed, ovariectomy significantly decreased circulating progesterone and 17-b-estradiol levels without re-ducing them below their detection threshold. Despite that decrease, there was no difference in baseline minute ventilation or in the ventilatory response to hypoxia (FiO2 = 12%, 20 min; expressed as the percentage of increase from baseline) between ovariectomized and shamoperated rats. These results suggest that ovariectomy at either a young or at an adult age is insufficient to completely suppress circulating hormones and disrupt the regulation of ventilation.

Selecting representative ages for developmental changes of respiratory irregularities and hypoxic ventilatory response in rats

Apnea frequency and the weak ventilatory response to hypoxia are a major clinical correlates of the immaturity of respiratory control system in preterm neonates. Rats are frequently used as model to study the respiratory control during development. However, little is known about the postnatal ages that best represent these respiratory irregularities and the hypoxic ventilatory response. Using plethysmography, we assessed baseline minute ventilation, ventilatory response to moderate hypoxia (FiO2 = 12%, 20 min) and apnea frequency in awake and non-anesthetized rats at the postnatal ages of 1, 4, 7, 12, 21 and 90 days old (P1, P4, P7, P12, P21, and P90, respectively). Baseline minute ventilation slightly increased in P4 (~25% vs P1) then gradually decreased with age (age effect: p < 0.05). The lowest level of ventilation was observed in P90 (p < 0.01 vs all ages). Minute ventilation (% from baseline) in response to hypoxia showed the well-known biphasic pattern in all rats at 12 days old or less. Minute ventilation at the initial phase of the hypoxic response was not significantly different between P1, P4, between P7, P12 and between P21, P90. The late phase of the hypoxic response was similar between P1, P4, and between P21, P90, but was significantly different between P7 and P12 (p < 0.05). Under baseline or hypoxic condition, the higher number of apnea frequency (spontaneous and post- sigh) was observed in P1, it then decreased progressively with age (age effect: p < 0.01 for baseline; p < 0.001 for hypoxia). These results suggest that when P4, P7 and P12 are selected to represent the age-dependent changes of the hypoxic ventilatory response in rats, the P1 rats should be included to better describe the age-dependence of apnea frequency.