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Pulmonary exposure to peat smoke extracts in rats decreases expiratory time and increases left heart end systolic volume.

ABSTRACT: Exposure to wildland fire-related particulate matter (PM) causes adverse health outcomes. However, the impacts of specific biomass sources remain unclear. The purpose of this study was to investigate cardiopulmonary responses in rats following exposure to PM extracts collected from peat fire smoke. We hypothesized that peat smoke PM would dose-dependently alter cardiopulmonary function. Male Sprague-Dawley rats (n?=?8/group) were exposed to 35?µg (Lo PM) or 350?µg (Hi PM) of peat smoke PM extracts suspended in saline, or saline alone (Vehicle) via oropharyngeal aspiration (OA). Ventilatory expiration times, measured in whole-body plethysmographs immediately after OA, were the lowest in Hi PM exposed subjects at 6?min into recovery (p?=?.01 vs. Lo PM, p?=?.08 vs. Vehicle) and resolved shortly afterwards. The next day, we evaluated cardiovascular function in the same subjects via cardiac ultrasound under isoflurane anesthesia. Compared to Vehicle, Hi PM had 45% higher end systolic volume (p?=?.03) and 17% higher pulmonary artery blood flow acceleration/ejection time ratios, and both endpoints expressed significant increasing linear trends by dose (p?=?.01 and .02, respectively). In addition, linear trend analyses across doses detected an increase for end diastolic volume and decreases for ejection fraction and fractional shortening. These data suggest that exposure to peat smoke constituents modulates regulation of ventricular ejection and filling volumes, which could be related to altered blood flow in the pulmonary circulation. Moreover, early pulmonary responses to peat smoke PM point to irritant/autonomic mechanisms as potential drivers of later cardiovascular responses.

SUBMITTER: Thompson LC

PROVIDER: S-EPMC7319252 | biostudies-literature | 2018 Sep - Oct

REPOSITORIES: biostudies-literature

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Pulmonary exposure to peat smoke extracts in rats decreases expiratory time and increases left heart end systolic volume.

Thompson Leslie C LC Kim Yong Ho YH Martin Brandi L BL Ledbetter Allen D AD Dye Janice A JA Hazari Mehdi S MS Gilmour M Ian MI Farraj Aimen K AK

Inhalation toxicology 20180901 11-12

Exposure to wildland fire-related particulate matter (PM) causes adverse health outcomes. However, the impacts of specific biomass sources remain unclear. The purpose of this study was to investigate cardiopulmonary responses in rats following exposure to PM extracts collected from peat fire smoke. We hypothesized that peat smoke PM would dose-dependently alter cardiopulmonary function. Male Sprague-Dawley rats (n = 8/group) were exposed to 35 µg (Lo PM) or 350 µg (Hi PM) of peat smoke PM extrac ...[more]

PMID: 30642191

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Project description:ImportanceVolumetric measurements by transthoracic echocardiogram may better reflect left ventricular (LV) remodeling than conventional linear LV dimensions. However, the association of LV volumes with mortality in patients with chronic hemodynamically significant aortic regurgitation (AR) is unknown.ObjectiveTo assess whether LV volumes and volume-derived LV ejection fraction (Vol-LVEF) are determinants of mortality in AR.Design, setting, and participantsThis cohort study included consecutive asymptomatic patients with chronic moderately severe to severe AR from a tertiary referral center (January 2004 through April 2019).ExposuresClinical and echocardiographic data were analyzed retrospectively. Aortic regurgitation severity was graded by comprehensive integrated approach. De novo disk-summation method was used to derive LV volumes and Vol-LVEF.Main outcome and measuresAssociations between all-cause mortality under medical surveillance and the following LV indexes: linear LV end-systolic dimension index (LVESDi), linear LVEF, LV end-systolic volume index (LVESVi), and Vol-LVEF.ResultsOf 492 asymptomatic patients (mean [SD] age, 60 [17] years; 425 men [86%]), ischemic heart disease prevalence was low (41 [9%]), and 453 (92.1%) had preserved linear LVEF (≥50%) with mean (SD) LVESVi of 41 (15) mL/m2. At a median (interquartile range) of 5.4 (2.5-10.1) years, 66 patients (13.4%) died under medical surveillance; overall survival was not different than the age- and sex-matched general population (P = .55). Separate multivariate models, adjusted for age, sex, Charlson Comorbidity Index, and AR severity, demonstrated that in addition to linear LVEF and LVESDi, LVESVi and Vol-LVEF were independently associated with mortality under surveillance (all P < .046) with similar C statistics (range, 0.83-0.84). Spline curves showed that continuous risks of death started to rise for both linear LVEF and Vol-LVEF less than 60%, LVESVi more than 40 to 45 mL/m2, and LVESDi above 21 to 22 mm/m2. As dichotomized variables, patients with LVESVi more than 45 mL/m2 exhibited increased relative death risk (hazard ratio, 1.93; 95% CI, 1.10-3.38; P = .02) while LVESDi more than 20 mm/m2 did not (P = .32). LVESVi more than 45 mL/m2 showed a decreased survival trend compared with expected population survival.Conclusions and relevanceIn this large asymptomatic cohort of patients with hemodynamically significant AR, LVESVi and Vol-LVEF worked equally as well as LVESDi and linear LVEF in risk discriminating patients with excess mortality. A LVESVi threshold of 45 mL/m2 or greater was significantly associated with an increased mortality risk.

Project description:BackgroundIncreasing functional residual capacity (FRC) or tidal volume (VT) reduces airway resistance and attenuates the response to bronchoconstrictor stimuli in animals and humans. What is unknown is which one of the above mechanisms is more effective in modulating airway caliber and whether their combination yields additive or synergistic effects. To address this question, we investigated the effects of increased FRC and increased VT in attenuating the bronchoconstriction induced by inhaled methacholine (MCh) in healthy humans.MethodsNineteen healthy volunteers were challenged with a single-dose of MCh and forced oscillation was used to measure inspiratory resistance at 5 and 19 Hz (R5 and R19), their difference (R5-19), and reactance at 5 Hz (X5) during spontaneous breathing and during imposed breathing patterns with increased FRC, or VT, or both. Importantly, in our experimental design we held the product of VT and breathing frequency (BF), i.e, minute ventilation (VE) fixed so as to better isolate the effects of changes in VT alone.ResultsTripling VT from baseline FRC significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Doubling VT while halving BF had insignificant effects. Increasing FRC by either one or two VT significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Increasing both VT and FRC had additive effects on R5, R19, R5-19 and X5, but the effect of increasing FRC was more consistent than increasing VT thus suggesting larger bronchodilation. When compared at iso-volume, there were no differences among breathing patterns with the exception of when VT was three times larger than during spontaneous breathing.ConclusionsThese data show that increasing FRC and VT can attenuate induced bronchoconstriction in healthy humans by additive effects that are mainly related to an increase of mean operational lung volume. We suggest that static stretching as with increasing FRC is more effective than tidal stretching at constant VE, possibly through a combination of effects on airway geometry and airway smooth muscle dynamics.

Project description:BackgroundIn acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients' individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient's individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial).MethodsIPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28-30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment.DiscussionThe IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS.Trial registrationClinicalTrials.gov NCT04012073 . Registered 9 July 2019.

Project description:The left ventricular (LV) end-systolic (ES) pressure volume relationship (ESPVR) is the cornerstone of systolic LV function analysis. We describe a 2D real-time (RT) MRI-based method (RTPVR) with separate software tools for 1) semi-automatic level set-based shape prior method (LSSPM) of the LV, 2) generation of synchronized pressure area loops and 3) calculation of the ESPVR. We used the RTPVR method to measure ventricular geometry, ES pressure area relationship (ESPAR) and ESPVR during vena cava occlusion (VCO) in normal sheep. 14 adult sheep were anesthetized and underwent measurement of LV systolic function. Ten of the 14 sheep underwent RTMRI and eight of the 14 underwent measurement with conductance catheter; 4 had both RTMRI and conductance measurements. 2D cross sectional RTMRI were performed at apex, mid-ventricle and base levels during separate VCOs. The Dice similarity coefficient was used to compare LSSPM and manual image segmentation and thus determine LSSPM accuracy. LV cross-sectional area, major and minor axis length, axis ratio, major axis orientation angle and ESPAR were measured at each LV level. ESPVR was calculated with a trapezoidal rule. The Dice similarity coefficient between LSSPM and manual segmentation by two readers was 87.31±2.51% and 88.13±3.43%. All cross sections became more elliptical during VCO. The major axis orientation shifted during VCO but remained in the septo-lateral direction. LV chamber obliteration at the apical level occurred during VCO in 7 of 10 sheep that underwent RTMRI. ESPAR was non-linear at all levels. Finally, ESPVR was non-linear because of apical collapse. ESPVR measured by conductance catheter (EES,Index = 2.23±0.66 mmHg/ml/m2) and RT (EES,Index = 2.31±0.31 mmHg/ml/m2) was not significantly different. LSSPM segmentation of 2D RT MRI images is accurate and allows calculation of LV geometry, ESPAR and ESPVR during VCO. In the future, RTPVR will facilitate determination of regional systolic material parameters underlying ESPVR.

Project description:End expiratory lung volume (EELV) measurement in the clinical setting is routinely performed using the helium dilution technique. A ventilator that implements a simplified version of the nitrogen washout/washin technique is now available. We compared the EELV measured by spiral computed tomography (CT) taken as gold standard with the lung volume measured with the modified nitrogen washout/washin and with the helium dilution technique.Patients admitted to the general intensive care unit of Ospedale Maggiore Policlinico Mangiagalli Regina Elena requiring ventilatory support and, for clinical reasons, thoracic CT scanning were enrolled in this study. We performed two EELV measurements with the modified nitrogen washout/washin technique (increasing and decreasing inspired oxygen fraction (FiO2) by 10%), one EELV measurement with the helium dilution technique and a CT scan. All measurements were taken at 5 cmH2O airway pressure. Each CT scan slice was manually delineated and gas volume was computed with custom-made software.Thirty patients were enrolled (age = 66 +/- 10 years, body mass index = 26 +/- 18 Kg/m2, male/female ratio = 21/9, partial arterial pressure of carbon dioxide (PaO2)/FiO2 = 190 +/- 71). The EELV measured with the modified nitrogen washout/washin technique showed a very good correlation (r2 = 0.89) with the data computed from the CT with a bias of 94 +/- 143 ml (15 +/- 18%, p = 0.001), within the limits of accuracy declared by the manufacturer (20%). The bias was shown to be highly reproducible, either decreasing or increasing the FiO2 being 117+/-170 and 70+/-160 ml (p = 0.27), respectively. The EELV measured with the helium dilution method showed a good correlation with the CT scan data (r2 = 0.91) with a negative bias of 136 +/- 133 ml, and appeared to be more correct at low lung volumes.The EELV measurement with the helium dilution technique (at low volumes) and modified nitrogen washout/washin technique (at all lung volumes) correlates well with CT scanning and may be easily used in clinical practice.Current Controlled Trials NCT00405002.

Project description:IntroductionOne potential mechanism of ventilator-induced lung injury (VILI) is due to shear stresses associated with alveolar instability (recruitment/derecruitment). It has been postulated that the optimal combination of tidal volume (Vt) and positive end-expiratory pressure (PEEP) stabilizes alveoli, thus diminishing recruitment/derecruitment and reducing VILI. In this study we directly visualized the effect of Vt and PEEP on alveolar mechanics and correlated alveolar stability with lung injury.MethodsIn vivo microscopy was utilized in a surfactant deactivation porcine ARDS model to observe the effects of Vt and PEEP on alveolar mechanics. In phase I (n = 3), nine combinations of Vt and PEEP were evaluated to determine which combination resulted in the most and least alveolar instability. In phase II (n = 6), data from phase I were utilized to separate animals into two groups based on the combination of Vt and PEEP that caused the most alveolar stability (high Vt [15 cc/kg] plus low PEEP [5 cmH2O]) and least alveolar stability (low Vt [6 cc/kg] and plus PEEP [20 cmH2O]). The animals were ventilated for three hours following lung injury, with in vivo alveolar stability measured and VILI assessed by lung function, blood gases, morphometrically, and by changes in inflammatory mediators.ResultsHigh Vt/low PEEP resulted in the most alveolar instability and lung injury, as indicated by lung function and morphometric analysis of lung tissue. Low Vt/high PEEP stabilized alveoli, improved oxygenation, and reduced lung injury. There were no significant differences between groups in plasma or bronchoalveolar lavage cytokines or proteases.ConclusionA ventilatory strategy employing high Vt and low PEEP causes alveolar instability, and to our knowledge this is the first study to confirm this finding by direct visualization. These studies demonstrate that low Vt and high PEEP work synergistically to stabilize alveoli, although increased PEEP is more effective at stabilizing alveoli than reduced Vt. In this animal model of ARDS, alveolar instability results in lung injury (VILI) with minimal changes in plasma and bronchoalveolar lavage cytokines and proteases. This suggests that the mechanism of lung injury in the high Vt/low PEEP group was mechanical, not inflammatory in nature.

Dataset Information

Pulmonary exposure to peat smoke extracts in rats decreases expiratory time and increases left heart end systolic volume.

Publications

Pulmonary exposure to peat smoke extracts in rats decreases expiratory time and increases left heart end systolic volume.

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