Spontaneous Breathing Group Research Articles

PCO2 values in asphyxiated infants under therapeutic hypothermia after tailored respiratory management: a retrospective cohort study.

Hypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants. This is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO2 ± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system. A total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO2 comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively, p 0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively, p 0.522). Mean pH, pH standard deviation, mean pO2, pO2 standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069-2.117). Infants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants.

Effects of laryngeal mask ventilation on postoperative atelectasis in children undergoing day surgery: a randomized controlled trial

BackgroundTo compare the effects of laryngeal mask mechanical ventilation and preserved spontaneous breathing on postoperative atelectasis in children undergoing day surgery.MethodsChildren aged 3–7 who underwent elective day surgery were randomly divided into a spontaneous breathing group (n = 23) and a mechanical ventilation group (n = 23). All children enrolled in this trial used the same anesthesia induction protocol, the incidence and severity of atelectasis before induction and after operation were collected. In addition, the baseline data, intraoperative vital signs, ventilator parameters and whether there were complications such as reflux and aspiration were also collected. SPSS was used to calculate whether there was a statistical difference between these indicators.ResultsThe incidence of atelectasis in the spontaneous breathing group was 91.30%, and 39.13% in the mechanical ventilation group, and the difference was statistically significant (P = 0.001). There was a statistically significant difference in carbon dioxide (P < 0.05), and the severity of postoperative atelectasis in the mechanical ventilation group was lower than that in the spontaneous breathing group (P < 0.05). In addition, there were no significant differences in the vital signs and baseline data of the patients (P > 0.05).ConclusionLaryngeal mask mechanical ventilation can reduce the incidence and severity of postoperative atelectasis in children undergoing day surgery, and we didn’t encounter any complications such as reflux and aspiration in children during the perioperative period, so mechanical ventilation was recommended to be used for airway management.Trial registrationThe clinical trial was registered retrospectively at the Chinese Clinical Trial Registry. (https://www.chictr.org.cn. Registration number ChiCTR2300071396, Weiwei Cai, 15 May 2023).

Effect and mechanical mechanism of spontaneous breathing on oxygenation and lung injury in mild or moderate animal ARDS

ObjectiveThe present study aimed to determine the effect and mechanical mechanism of spontaneous breathing during mechanical ventilation on oxygenation and lung injury using Beagles dogs mild or moderate acute respiratory distress syndrome (ARDS) model.MethodsAfter inducing mild or moderate ARDS by infusion of oleic acid, Eighteen Beagles dogs were randomly split into Spontaneous breathing group (BIPAPSB, n = 6), and Complete muscle paralysis group (BIPAPPC, n = 6),Six Beagles without ventilator support comprised the control group. Both groups were ventilated for 8 h under BIPAP mode. High-pressure was titrated TV to 6 ml/kg. A multi-pair esophageal balloon electrode catheter was used to measure respiratory mechanics and electromyogram. End-expiratory lung volume (EELV), gas exchange and respiratory variables were recorded in the process of mechanical ventilation. The contents of Interleukin (IL)-6 and IL-8 in lung tissue were measure using qRT-PCR. Besides, lung injury score was calculated in the end of mechanical ventilation.ResultsBased on the comparable setting of ventilator, BIPAPSB group exhibited higher safety peak transpulmonary pressure, abdominal pressure, EELV and P/F(PaO2/FiO2) than BIPAPPC group, whereas mean transpulmonary pressure, the mRNA levels of the IL-6 and IL-8 in the lung tissues and lung injury score in BIPAPSB group were lower than those in BIPAPPC group.ConclusionIn mild to moderate ARDS animal models, during mechanical ventilation, SB may improve respiratory function and reduce ventilator-induced lung injury. The mechanism may be that spontaneous inspiration up-regulates peak transpulmonary pressure and EELV; Spontaneous expiration decreases mean transpulmonary pressure by up-regulating intra-abdominal pressure, thereby reducing stress and strain.

Clinical application of intubation-free anesthesia in radical resection of lung cancer.

In recent years, video-assisted thoracic surgery (VATS) has become increasingly widespread. However, the implementation of VATS requires the assistance with lung isolation techniques. Spontaneous breathing with laryngeal masks is also increasingly used in VATS. However, evidence on the characteristics of intubated anesthesia is insufficient. This study aimed to explore whether intubation-free anesthesia has more advantages than other intubation methods in the clinical setting. Patients with lung tumors who underwent VATS in our hospital between June 2022 and October 2022 were included in the study. Perioperative data of patients, including basic information, intraoperative hemodynamic changes, postoperative inflammatory indicators, and adverse reactions were obtained through the electronic medical record system. According to the protocol of airway management during anesthesia, participants were divided into the following groups: laryngeal mask with spontaneous breathing group (LMSB group), laryngeal mask combined with bronchial blocker group (LM + BB group), double-lumen tube group (DLT group), and tracheal tube combined with bronchial blocker group (TT + BB group). All data were analyzed using SPSS 25.0 software. At baseline, patients in the LMSB and LM + BB groups had a lower body weight (P = 0.024). Systolic blood pressure (SBP), diastolic BP (DBP), and heart rate (HR) were significantly higher in the DLT group than in the non-intubated group during surgery (SBP: T1 P = 0.048, T4 P = 0.021, T5 P ≤ 0.001, T6 P ≤ 0.001, T7 P = 0.004; DBP: T5 P ≤ 0.001, T6 P ≤ 0.001, T7 P ≤ 0.001; HR: T1 P = 0.021, T6 P ≤ 0.001, T7 P = 0.007, T8 P ≤ 0.001). The input fluid (P = 0.009), urine output (P = 0.010), surgery duration (P = 0.035), and procalcitonin levels (P = 0.024) of the DLT group were also significantly higher than those of the other groups. The recovery duration of the LMSB group was significantly longer (P = 0.003) and the incidence of postoperative adverse reactions, mainly atelectasis, was higher (P = 0.012) than those of the other groups. Although the intubation-free anesthesia has less stimulation during operation and less postoperative inflammatory response, it has obvious adverse reactions after operation, which may be not the best anesthesia scheme for radical resection of lung cancer in VATS. https://www.chictr.org.cn/showproj.html?proj=182767, identifier ChiCTR2200066180.

Biphasic positive airway pressure spontaneous breathing attenuates lung injury in an animal model of severe acute respiratory distress syndrome

ObjectiveTo compare the effects of unassisted spontaneous breathing (SB) and complete muscle paralysis (PC) on early severe acute respiratory distress syndrome (ARDS) in an animal model, and to explore the possibility of biphasic positive airway pressure (BIPAP) as lung protective ventilation support for patients in the early stage of severe ARDS.MethodsTwelve healthy beagle dogs between the ages of 10 and 15 months were randomly divided into two groups: the SB group (BIPAPSB) and the PC group (BIPAPPC). Arterial blood samples were drawn before modelling. Arterial blood gas analysis and mechanical tests were conducted. The animal model of severe ARDS was established using a deep intravenous injection of oleic acid, and BIPAP ventilation was performed for 8 hours. Lung tissue and blood were taken to detect lung function, inflammatory reactions and degree of pathological damage.ResultsAt the beginning of the experiment, there was no significant difference in the arterial blood gas analysis between the two groups (p > 0.05). After successful modelling, the oxygenation index and the end-expiratory lung volume in the SB group were significantly higher than those in the PC group 8 hours after MV. Pathologically, the wet-dry ratio and pathological score of the PC group were higher than those of the SB group; the lung injury in the gravity-dependent area in the SB group was less than that in the PC group (p< 0.05).ConclusionsIn the early stage of severe ARDS induced by oleic acid, compared with PC, retention of the BIPAP mode of SB can reduce the risk of lung injury and improve respiratory function.

Role of Mitophagy-based TLR9 Signal Pathway in Neonatal Ventilator-induced Lung Injury

The study focused on the role of mitophagy in neonatal ventilator-induced lung injury (VILI). Immunoassays were used to study the TLR9 signaling pathway of neonatal VILI, expected to provide a feasible solution for neonatal VILI. The mice were randomly divided into four groups, group A: spontaneous breathing group; group B: normal tidal volume (VT) group (VT=9mL/kg); group C: high VT group (VT=39mL/kg); and group D: ODN2088 (400μg/ Only) intervention + high VT group. The four groups were compared for the expression of inflammatory factors. It was found that as the culture time increased, the expression of TLR9, MyD88, and NF-κBp65 in the lung tissue of the large VT group was significantly higher than those in the spontaneous breathing group and normal VT group, and the differences were statistically significant; and TLR9 inhibitors could activate the TLR9-MyD88 signaling pathway to up-regulate the expression of NF-κB, mediating the release of inflammatory factors to cause VILI.

Spontaneous breathing for managing analgesia during balanced anesthesia with remifentanil and desflurane: a prospective, single center randomized controlled trial.

The main goal of anesthesiology is to achieve the best level of analgesia and a fast recovery of consciousness following anesthesia. The preservation of spontaneous breathing during general anesthesia with anesthetic gases is practiced by many anesthetists. However, very few studies have dealt with these positive properties of volatile anesthetics such as sevoflurane or desflurane. Remifentanil is a very short half-life opiate that combines sufficient intra-operative analgesia with a fast post-operative recovery time. We tested the hypothesis that spontaneous breathing can reduce overdosing with remifentanil during desflurane anesthesia. In this prospective, single center, multiple anesthetist study, 30 patients were randomized into two groups (volume-controlled ventilation mode and spontaneous breathing). The spontaneous breathing group showed a significantly lower post-operative pain level than the volume-controlled ventilation mode group. Furthermore, less remifentanil as well as less piritramide was needed in the spontaneous breathing group compared with volume-controlled ventilation mode. It was possible to achieve spontaneous breathing in all patients with 0.6 minimum alveolar concentration desflurane, in order to control the remifentanil rate and prevent an overdose. All spontaneous breathing patients had low intra- and post-operative pain levels and the need for analgesics was equal to or lower than that in the volume-controlled ventilation mode group. By reducing the intra-operative amount of opiates, both the post-operative pain and the amount of post-operative analgesia required can be reduced. A balanced anesthesia with spontaneous intra-operative breathing is needed to determine the required amount of opiates. This study was approved by the Ethic Committee of the Ruhr-University of Bochum (approval No. 2435) in September, 2004.

Low Spontaneous Breathing Effort during Extracorporeal Membrane Oxygenation in a Porcine Model of Severe Acute Respiratory Distress Syndrome.

A lung rest strategy is recommended during extracorporeal membrane oxygenation in severe acute respiratory distress syndrome (ARDS). However, spontaneous breathing modes are frequently used in this context. The impact of this approach may depend on the intensity of breathing efforts. The authors aimed to determine whether a low spontaneous breathing effort strategy increases lung injury, compared to a controlled near-apneic ventilation, in a porcine severe ARDS model assisted by extracorporeal membrane oxygenation. Twelve female pigs were subjected to lung injury by repeated lavages, followed by 2-h injurious ventilation. Thereafter, animals were connected to venovenous extracorporeal membrane oxygenation and during the first 3 h, ventilated with near-apneic ventilation (positive end-expiratory pressure, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5/min). Then, animals were allocated into (1) near-apneic ventilation, which continued with the previous ventilatory settings; and (2) spontaneous breathing: neuromuscular blockers were stopped, sweep gas flow was decreased until regaining spontaneous efforts, and ventilation was switched to pressure support mode (pressure support, 10 cm H2O; positive end-expiratory pressure, 10 cm H2O). In both groups, sweep gas flow was adjusted to keep Paco2 between 30 and 50 mmHg. Respiratory and hemodynamic as well as electric impedance tomography data were collected. After 24 h, animals were euthanized and lungs extracted for histologic tissue analysis. Compared to near-apneic group, the spontaneous breathing group exhibited a higher respiratory rate (52 ± 17 vs. 5 ± 0 breaths/min; mean difference, 47; 95% CI, 34 to 59; P < 0.001), but similar tidal volume (2.3 ± 0.8 vs. 2.8 ± 0.4 ml/kg; mean difference, 0.6; 95% CI, -0.4 to 1.4; P = 0.983). Extracorporeal membrane oxygenation settings and gas exchange were similar between groups. Dorsal ventilation was higher in the spontaneous breathing group. No differences were observed regarding histologic lung injury. In an animal model of severe ARDS supported with extracorporeal membrane oxygenation, spontaneous breathing characterized by low-intensity efforts, high respiratory rates, and very low tidal volumes did not result in increased lung injury compared to controlled near-apneic ventilation.

Effect of mechanical ventilation versus spontaneous breathing on abdominal edema and inflammation in ARDS: an experimental porcine model

BackgroundMechanical ventilation (MV), compared to spontaneous breathing (SB), has been found to increase abdominal edema and inflammation in experimental sepsis. Our hypothesis was that in primary acute respiratory distress syndrome (ARDS) MV would enhance inflammation and edema in the abdomen.MethodsThirteen piglets were randomized into two groups (SB and MV) after the induction of ARDS by lung lavage and 1 h of injurious ventilation.1. SB: continuous positive airway pressure 15 cmH2O, fraction of inspired oxygen (FIO2) 0.5 and respiratory rate (RR) maintained at about 40 cycles min− 1 by titrating remifentanil infusion.2. MV: volume control, tidal volume 6 ml kg− 1, positive end-expiratory pressure 15 cmH2O, RR 40 cycles min− 1, FIO2 0.5.Main outcomes: abdominal edema, assessed by tissues histopathology and wet-dry weight; abdominal inflammation, assessed by cytokine concentration in tissues, blood and ascites, and tissue histopathology.ResultsThe groups did not show significant differences in hemodynamic or respiratory parameters. Moreover, edema and inflammation in the abdominal organs were similar. However, blood IL6 increased in the MV group in all vascular beds (p < 0.001). In addition, TNFα ratio in blood increased through the lungs in MV group (+ 26% ± 3) but decreased in the SB group (− 17% ± 3).ConclusionsThere were no differences between the MV and SB group for abdominal edema or inflammation. However, the systemic increase in IL6 and the TNFα increase through the lungs suggest that MV, in this model, was harmful to the lungs.

WISP1 and TLR4 on Macrophages Contribute to Ventilator-Induced Lung Injury

Injurious mechanical ventilation has been shown to directly affect pulmonary and systemic immune responses. How these responses propagate or attenuate remains unknown. The goal of this study was to further determine whether toll-like receptor (TLR) 4 and WNT1-inducible signaling pathway protein 1 (WISP1) could contribute to injurious mechanical ventilation, especially focusing on the role of macrophages during experimental ventilator-induced lung injury. A prospective, randomized, and controlled animal study was designed, and male, wild-type (WT) C57BL/6 mice, TLR4 knockout (TLR4−/−), and lyzTLR4 knockout (lyzTLR4−/−) mice aging 8~12 weeks were used. Animals were anesthetized and randomized to spontaneous breathing (SB) group or to high tidal volume (VT, 20 ml/kg) mechanical ventilation (HTV) group. Histological evaluation, alveolar–capillary permeability of Evan’s blue albumin (EBA), WISP1 protein levels, macrophage inflammatory protein-2 (MIP-2), and interleukin-6 (IL-6) in plasma and bronchoalveolar lavage fluid (BALF) concentrations were analyzed. HTV group was associated with a significant increase of WISP1 and EBA ratio in C57BL/6 mice, a significant decrease of WISP1 protein levels, and a significant decrease of IL-6, MIP-2 in plasma, and BALF concentrations of pro-inflammatory cytokines in TLR4−/− and lyzTLR4−/− knockout mice. In TLR4−/− mice and lyzTLR4−/− mice, there were also significant differences between SB group and HTV group in terms of H&E score and EBA ratio and level of pro-inflammation cytokines. The entire TLR4-targeted mice could further improve various inflammatory changes and damages when compared with lyzTLR4-targeted mice. What is more, TLR4−/− mice and lyzTLR4−/− mice reacted differently to rWISP1 and/or BMMC treated. TLR4−/− mice had no response to rWISP1, while lyzTLR4−/− mice still showed drastic response to both treatments. TLR4 and WISP1, especially the former one, on macrophages could contribute to releasing of pro-inflammatory cytokines during ventilator-induced lung injury. Injurious mechanical ventilation may result in an immune response which is similar to that of infection.

High amplitude bubble continuous positive airway pressure decreases lung injury in rats with ventilator-induced lung injury.

Bubble continuous positive airway pressure (BCPAP) has been used in neonates with respiratory distress for decades; however, the optimal setting for BCPAP circuits remains unknown. This study compared the gas exchange efficiency and lung protection efficacy between conventional and high-amplitude BCPAP devices. We compared gas exchange, lung volume, and pulmonary inflammation severity among rats with ventilator-induced lung injury (VILI) that were treated with conventional BCPAP (BCPAP with an expiratory limb at 0°), high-amplitude BCPAP (BCPAP with an expiratory limb at 135°), or spontaneous breathing (SB). After mechanical ventilation for 90 minutes, the rats were randomly divided into four groups: a control group (euthanized immediately; n = 3), an SB group (n = 8), and two BCPAP groups that received BCPAP with the expiratory limb at either 0° (n = 8) or 135° (n = 7) for 90 minutes. The high-amplitude BCPAP group exhibited significantly lower alveolar protein, lung volume, and Interleukin-6 (IL-6) levels than did the SB group. The high-amplitude BCPAP group exhibited significantly lower IL-6 levels than did the conventional BCPAP group. The two BCPAP groups demonstrated no difference in gas exchange efficiency. High-amplitude BCPAP reduced lung inflammation and alveolar overdistension in rats with VILI after mechanical ventilation was ceased. Thus high-amplitude BCPAP may offer a superior lung protective effect than conventional BCPAP.

Role and mechanism of Ly6Chigh monocyte in ventilator-induced lung injury in mice

To investigate the role and mechanism of Ly6Chigh monocyte in mice with ventilator-induced lung injury (VILI). Forty-eight healthy male SPF C57BL/6 mice were divided into spontaneous breathing group (n = 8), normal tidal volume (VT) group (VT was 8 mL/kg, n = 8), and high VT group (VT was 20 mL/kg, n = 32). The mice in the high VT group were subdivided into 1, 2, 3 and 4 hours subgroups, with 8 mice in each subgroup. All mice underwent direct tracheal intubation, those in the spontaneous breathing group maintained spontaneous breathing, and those in the normal VT group and high VT group were mechanically ventilated with different VT. After ventilation for 4 hours, bronchoalveolar lavage fluid (BALF) was collected to determine total protein, and the levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by enzyme-linked immune sorbent assay (ELISA). The lung tissues were harvested to determine the wet/dry (W/D) ratio, and lung tissue injury was assessed in terms of lung histopathologic examination after hematoxylin-eosin (HE) staining under the light microscope. The protein expressions of monocyte chemotactic protein-1 (MCP-1) and CC-chemokine receptor 2 (CCR2) in lung tissues were determined by Western Blot. Flow cytometry was used to detect the proportion of Ly6Chigh monocyte in lung tissue. The histopathology of lung tissue structures was normal in the spontaneous breathing group and the normal VT group. Inflammatory reaction began to appear at 2 hours of high VT ventilation, and inflammatory reaction was gradually aggravated with the time extension. Compared with the spontaneous breathing group, the total protein, TNF-α, and IL-1β levels in BALF, the lung W/D ratio and MCP-1 expression were increased from 2 hours of high VT ventilation [total protein in BALF (g/L): 1.05±0.13 vs. 0.58±0.11, TNF-α in BALF (ng/L): 116.86±16.14 vs. 38.27±8.00, IL-1β in BALF (ng/L): 178.98±10.41 vs. 117.56±23.40, lung W/D ratio: 5.76±0.27 vs. 4.98±0.39, MCP-1/GAPDH: 0.87±0.19 vs. 0.29±0.12, all P < 0.05], and CCR2 expression and the proportion of Ly6Chigh monocyte was significantly increased from 3 hours of high VT ventilation [CCR2/GAPDH: 0.84±0.19 vs. 0.24±0.11, Ly6Chigh monocyte proportion: (9.01±2.47)% vs. (1.06±0.35)%, both P < 0.05], and they all showed an increased tendency with the time extension. There was no significant difference in the parameters mentioned above among the spontaneous breathing group, normal VT group and high VT ventilation 1-hour group. Ly6Chigh monocytes are involved in VILI, which aggravate VILI by activating the MCP-1/CCR2 axis.

Efficacy of TEAS for general anesthesia preserving spontaneous breathing in patients undergoing thoracoscopic surgery

Objective To evaluate the efficacy of transcutaneous electrical acupoint stimulation (TEAS) for general anesthesia preserving spontaneous breathing in the patients undergoing thoracoscopic surgery. Methods Forty patients of both sexes, aged 18-67 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with Mallampati physical status Ⅰ or Ⅱ, scheduled for elective thoracoscopic lobectomy, were divided into 2 groups (n=20 each) using a random number table method: general anesthesia preserving spontaneous breathing group (group GS) and TEAS plus general anesthesia preserving spontaneous breathing group (group TE+ GS). Anesthesia was routinely induced and maintained, a laryngeal mask was placed, and patients kept spontaneous breathing in two groups.The bispectral index value was maintained at 45-60.Patient-controlled intravenous analgesia was used after operation, and visual analogue scale score was maintained<4 points.In group TE+ GS, Xinshu and Feishu acupoints ipsilateral to the operated side and bilateral Hegu and Neiguan acupoints were stimulated with a disperse-dense wave, frequency 2/100 Hz and intensity 5-15 mA starting from 30 min before anesthesia induction until the end of surgery.The mean arterial pressure (MAP), heart rate (HR) and respiratory rate (RR) were recorded before induction of anesthesia, immediately after start of operation, during thoracic exploration, immediate after lobectomy , and at 30 min and 1 h after lobectomy.The intraoperative MAP, HR, and RR were recorded when clinically significant events occurred in two groups.Central venous blood samples were simultaneously collected for determination of concentrations of cortisol, norepinephrine, epinephrine, and blood glucose in serum (by enzyme-linked immunosorbent assay). The highest value of PETCO2, the lowest value of SpO2, and consumption of anesthetic drugs were recorded.Duration of post-anesthesia care unit stay, time to first flatus, ambulation time, occurrence of nausea and vomiting, chest tube drainage time, development of surgical complications, length of postoperative hospital stay and hospitalization expenses were recorded. Results MAP, HR and RR all fluctuated within the normal range, and no clinically significant events occurred in two groups.Compared with group GS, the highest value of PETCO2 was significantly decreased, the lowest value of SpO2 was increased, the MAP and HR were decreased, the consumption of propofol and remifentanil was decreased, the cortisol, norepinephrine, epinephrine, and blood glucose concentrations in serum were decreased, the time to first flatus, ambulation time, chest tube drainage time and length of postoperative hospital stay were shortened, and the incidence of nausea and vomiting and hospitalization expenses were decreased in group TE+ GS (P<0.05). Conclusion TEAS can reduce the amount of opioids consumed in the perioperative period, effectively inhibits intraoperative stress responses, and is helpful in improving the early outcomes when used for general anesthesia preserving spontaneous breathing in the patients undergoing thoracoscopic surgery. Key words: Electric stimulation therapy; Anesthesia, general; Thoracoscopy

Matching pursuit based indices for examining physiological differences of meditators and non-meditators: An HRV study

Since meditation has recently been used as a complementary therapy, the study of physiological effects of different kinds of meditation has been augmented over the last decade. In this study, a robust method based on the matching pursuit (MP) algorithm was proposed to examine the heart rate variability (HRV) differences of meditators and non-meditators. The non-meditators were comprised of metronomic breathing (MB) and spontaneous nocturnal breathing (SNB) groups. The meditators were comprised of pre Chinese Chi meditation (pCCM), during CCM (dCCM), pre Kundalini yoga meditation (pKYM), and during KYM (dKYM). Following MP based decomposition of HRV into its sparse parts, eleven indices were extracted for the MP coefficients. The efficiency of the indices was also examined through statistical significance between the groups. It was shown that for almost all indices, significant differences between the classes were observed. Furthermore, a probabilistic neural network (PNN) with a variable sigma (σ) value, was trained to classify the physiological responses of the groups. A maximum accuracy of 99.61% was detected for dKYM using 5-fold cross validation scheme. It was also shown that lower σ values give higher classification rates and upper σ values provide more robust accuracies. In conclusion, the proposed method is a promising technique for showing significant differences between HRV responses of different non-meditator and meditator groups.

Effect of high tidal volume mechanical ventilation on pulmonary autophagy and mitochondrial damage in rats

To investigate the relationship between different tidal volume (VT) mechanical ventilation (MV) and autophagy and mitochondrial damage in rats. A total of 120 clean-grade male Sprague-Dawley (SD) rats were divided into five groups (n = 24) by random number table method, and then given 0 (spontaneous breathing), 10, 20, 30, 40 mL/kg VT for MV. The rats in each group were subdivided into four subgroups of 1, 2, 3, and 4 hours according to ventilation time, with 6 rats in each subgroup. The lung tissue and bronchoalveolar lavage fluid (BALF) were harvested, and alveolar macrophages (AMs) and type II alveolar epithelial cells (AEC II) were cultured in vitro. The mRNA and protein expressions of autophagy-associated protein microtubule-associated protein 1 light chain 3B-II (LC3B-II) and autophagy-related genes Beclin1 and p62 were determined by reverse transcription-polymerase chain reaction (RT-PCR) or Western Blot. Lung autophagosome formation was observed under transmission electron microscope. The levels of adenosine triphosphate (ATP), reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in lung tissue were determined for assessing mitochondrial damage. There were no significant differences in the mRNA and protein expressions of LC3B-II, p62 and Beclin1 at 1 hour after ventilation among the groups. With the prolonged ventilation time, the mRNA and protein expressions of LC3B-II, p62 and Beclin1 in MV groups were increased gradually, peaked at 2-3 hours, and they were increased significantly in 30 mL/kg VT group as compared with those in spontaneous respiration group with statistical significances [ventilation for 2 hours: LC3B-II mRNA (2-ΔΔCt) was 2.44±0.24 vs. 1.12±0.04, LC3B-II/LC3B-I was 1.42±0.16 vs. 0.57±0.03, p62 mRNA (2-ΔΔCt) was 2.96±0.14 vs. 1.14±0.02, Beclin1 mRNA (2-ΔΔCt) was 2.80±0.13 vs. 1.14±0.02; ventilation for 3 hours: p62/β-actin was 1.14±0.15 vs. 0.55±0.04, Beclin1/β-actin was 1.27±0.06 vs. 0.87±0.04, all P < 0.05]. Autophagosomes and autolysosomes were found in AEC II after ventilation for 2 hours at 30 mL/kg VT by transmission electron microscopy, but not in AEC I. Compared with spontaneous breathing group, ATP synthesis in AMs was significantly decreased at 2 hours of ventilation in 30 mL/kg VT group (A value: 0.82±0.05 vs. 1.00±0.00, P < 0.05), ROS accumulate in AMs and AEC II were significantly increased [ROS in AMs: (33.83±4.00)% vs. (6.90±0.62)%, ROS in AEC II: (80.68±0.90)% vs. (2.16±0.19)%, both P < 0.05]. With the increase in VT and the prolongation of ventilation time, ATP and ROS levels in AMs and AEC II were gradually decreased, the ATP (A value) in AMs at 4 hours of ventilation in 40 mL/kg VT group was 0.41±0.05, the ROS in AMs was (12.95±0.88)%, and the ROS in AEC II was (40.43±2.29)%. With the increase in VT and the prolongation of ventilation time, MMP levels were gradually increased, the MMP (green/red fluorescence intensity ratio) in AMs at 2 hours of ventilation in 30 mL/kg VT group was 1.11±0.17, the MMP in AEC II was 0.96±0.04, and the MMP (green/red fluorescence intensity ratio) at 4 hours of ventilation in 40 mL/kg VT group was 0.51±0.07 and 0.49±0.06, respectively. The MV with high VT could induce autophagy activation and mitochondrial damage in lung tissue of rats, and the longer the ventilation time, the more obvious autophagy in the lung.

Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragmatic dysfunction through myogenic regulatory factors

Objective: To explore the protective effect of electrical stimulation of phrenic nerve on diaphragmatic function during mechanical ventilation. Methods: Forty healthy adult SD rats were randomly divided into 5 groups: blank control group (BC), spontaneous breathing group (SB), electrical stimulation group (ES), mechanical ventilation group (MV), and electrical stimulation and mechanical ventilation group (MS). The rats in each group were treated for 18 h except for the BC group. After treatment, the diaphragm muscle tissue was obtained and the diaphragm contractility including peak-to-peak value(Vpp) and maximum rate of contraction(+ dT/dt max) were measured. Expression of MyoD and myogenin were detected. Results: Except for the ES and the MS groups, there was a significant difference for peak-to-peak value (Vpp) between each 2 groups (P<0.05). Expression levels of MyoD in treatment groups were also significantly different (P<0.05). Expressions of MS(Q-PCR 2(-ΔΔCt) value: 11.66±2.80) and MV(Q-PCR 2(-ΔΔCt) value: 40.89±24.71) in the treatment group were significantly different (P<0.05). The expression of myogenin in the MS and the MV groups were significantly different from those of the BC group(P<0.05), however there was no significant difference between the MS(Q-PCR 2(-ΔΔCt) value: 2.58±2.75) and the MV group(Q-PCR 2(-ΔΔCt) value: 1.63±0.71). Conclusions: Electrical stimulation of the phrenic nerve can change the expression level of MyoD and myogenin to offset mechanical ventilation induced diaphragmatic function damage, and therefore plays a protective effect on the diaphragm.

Role and mechanism of mitochondrial DNA mediated Toll-like receptor 9-myeloid differentiation factor 88 signaling pathway activation in rats with ventilator-induced lung injury

To investigate the role and mechanism of mitochondrial DNA (mtDNA) in rats with ventilator-induced lung injury (VILI) via Toll-like receptor 9 (TLR9)-myeloid differentiation factor 88 (MyD88) signaling pathway. Thirty adult male Sprague-Dawley (SD) rats were randomly divided into three groups (each n = 10): spontaneous breathing group, normal tidal volume (VT) group (NVT group, VT = 8 mL/kg), and high VT group (HVT group, VT = 40 mL/kg). Rats in the NVT group and HVT group were ventilated mechanically with a positive end-expiratory pressure (PEEP) of 0 and the fraction of inspired oxygen (FiO2) at 0.50. After 4 hours of ventilation, the blood from the rats' hearts was collected and the rats were sacrificed, the levels of interleukins (IL-6, IL-1β) and tumor necrosis factor-α (TNF-α) in serum were determined with enzyme-linked immune sorbent assay (ELISA). The bronchoalveolar lavage fluid (BALF) was collected for a determination of total protein by using the bicinchoninic acid (BCA) assay. The lung tissues were harvested to determine the wet/dry (W/D) ratio. The changes in pathobiology of lung tissue were observed with hematoxylin and eosin (HE) staining. The protein expression levels of mtDNA-encoded cytochrome C oxidase subunit IV (COX-IV), TLR9, MyD88 and nuclear factor-κB p65 (NF-κB p65) in lung tissues were determined by immunohistochemistry. The histopathology of lung tissues indicated that lungs from animals ventilated with HVT developed marked lung inflammation changes, whereas no major histological change was observed in animals ventilated with NVT or spontaneously breathing. The pathological score in HVT group was significantly higher than that of spontaneous breathing group and NVT group (3.50±0.41 vs. 0.25±0.09, 0.33±0.10, both P < 0.05). Compared with spontaneous breathing group and NVT group, the ratio of W/D in the HVT group was significantly increased (6.42±0.41 vs. 4.14±0.04, 4.28±0.11, both P < 0.05), the contents of total proteins in BALF were significantly increased (g/L: 0.43±0.04 vs. 0.13±0.01, 0.14±0.01, both P < 0.05), and serum IL-6, IL-1β and TNF-α levels were also increased [IL-6 (μg/L): 1.15±0.17 vs. 0.42±0.10, 0.46±0.04; IL-1β (μg/L): 6.73±0.38 vs. 2.08±0.90, 2.19±0.18; TNF-α (μg/L): 4.10±0.11 vs. 1.12±0.10, 1.14±0.04; all P < 0.05]. Immunohistochemistry results demonstrated that the proteins of COX-IV, TLR9, MyD88 and NF-κB p65 in HVT group were shown in brown, which meant strongly expressed. However, these proteins in spontaneous breathing group and NVT group were uncolored or shown in buff, which meant unexpressed or weakly expressed. The results of quantitative analysis indicated that the immunoreactive scores (IRS) of COX-IV, TLR9, MyD88 and NF-κB p65 in HVT group were significantly higher than those in spontaneous breathing group and NVT group (COX-IV IRS: 8.80±2.17 vs. 0.80±0.45, 1.40±0.55; TLR9 IRS: 8.40±2.51 vs. 1.00±0.71, 1.20±0.84; MyD88 IRS: 9.40±1.52 vs. 1.40±0.55, 1.60±0.55; NF-κB p65 IRS: 9.80±2.05 vs. 1.00±0.71, 1.20±0.84; all P < 0.05). There was no significant difference in all of the parameters between spontaneous breathing group and NVT group (all P > 0.05). mtDNA contributes significantly to VILI by activating the TLR9-MyD88 signaling pathway, resulting in subsequent secretion of NF-κB p65 and the proinflammatory cytokines, which induce acute inflammatory injury of lung tissue.

Changes in circulating microparticles in mice with ventilator-induced lung injury

To investigate the changes in serum level of microparticles (EMPs) in mice with ventilator-induced lung injury (VILI), and explore its significance in VILI. Forty-eight grade SPF male C57BL/6J mice were randomly divided into two groups, with 24 mice in each group: the mice in mechanical ventilation (MV) group were given high tidal volume (VT 30 mL/kg) MV for 4 hours after tracheal intubation, and those in spontaneous breathing group were spontaneously breathed for 4 hours. The apical blood of 12 mice in each group were collected, and serum levels of interleukins (IL-1β, IL-6) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA), and serum EMPs levels were determined by flow cytometer. The correlations between EMPs and IL-1β, IL-6, and TNF-α were analyzed by linear regression analysis. The lung tissues of other 12 mice in each group were harvested, and wet/dry weight (W/D) ratio was assessed. After hematoxylin-eosin (HE) staining, the morphological changes in lung tissue were observed under light microscope. After double staining of uranium acetate and lead citrate, the ultrastructural changes in lung tissue were observed with electron microscope. Compared with spontaneous breathing group, the levels of lung W/D ratio in MV group was significantly increased (5.47±0.14 vs. 4.34±0.11), the levels of IL-1β, IL-6, TNF-α and EMPs were also significantly increased [IL-1β (ng/L): 42.4±4.4 vs. 7.7±3.6, IL-6 (ng/L): 1 239.5±66.3 vs. 21.7±4.6, TNF-α (ng/L): 237.6±25.8 vs. 37.1±19.1, EMPs (cells/μL): 28.6±1.8 vs. 5.9±1.8, all P < 0.01]. It was shown by correlation analysis that EMPs were positively related with IL-1β, IL-6, and TNF-α (r value was 0.968, 0.932, 0.945, respectively, all P = 0.000). It was shown by fitting linear regression analysis that when EMPs increased by 1 cell/μL, IL-1β increased by 2.4 ng/L [95% confidence interval (95%CI) = 1.9-2.8, P < 0.001], IL-6 increased by 34.5 ng/L (95%CI = 25.1-44.0, P < 0.001), and TNF-α increased by 13.6 ng/L (95%CI = 10.3-16.9,P < 0.001). It was shown by light microscope that the structure of lung tissue and alveolar of mice in spontaneous breathing group appeared normal, while the shrinks of alveolar and disappearance of alveolar architecture were found in MV group. It was shown by electron microscopy that alveolar wall edema and thickening and broken alveolar septa were found in MV group, by contrast, the structure of alveolar was normal in spontaneous breathing group. 30 mL/kg VT ventilation for 4 hours could induce VILI with increase in EMPs, suggesting EMPs closely related to VILI, and EMPs level may be putative biomarker of VILI.

Study on Rac1/MAPK/ERK pathway mediated mechanism and role in rats with ventilator induced lung injury

To investigate the role of Ras-related C3 botulinum toxin substrate 1/mitogen-activated protein kinase/extracellular signal-regulated kinase (Rac1/MAPK/ERK) signal pathway in rats with ventilator induced lung injury (VILI) and its mechanism. Thirty Sprague-Dawley (SD) rats were randomly divided into spontaneous respiration group, normal tidal volume (VT) group and high VT group with 10 rats in each group. The rats in spontaneous respiration group were kept their spontaneous breathing. The rats in normal VT group and high VT group were performed tracheal intubation after tracheostomy, and underwent mechanical ventilation on bilateral lungs with 6 mL/kg and 40 mL/kg VT respectively with maintenance anesthesia. After 4-hour ventilation, heart blood, bronchoalveolar lavage fluid (BALF) and lung tissues were harvested. The levels of interleukins (IL-1β, IL-6), tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) and macrophage inflammatory protein-2 (MIP-2) in serum and BALF were determined by enzyme linked immunosorbent assay (ELISA). Lung wet/dry radio (W/D) was determined. The lung tissues were stained with hematoxylin and eosin (HE), and pathological changes were observed, and pathological scores were evaluated. The ultra structure changes in type II alveolar epithelial cells (AEC II) were observed with transmission electron microscope. The positive expressions of phosphorylation of extracellular signal-regulated kinase (p-ERK) were determined by immunohistochemistry, and those of Rac1 and F-actin were determined by immunofluorescence. The mRNA expressions of ERK and Rac1 were determined by real-time fluorescent quantitation reverse transcription-polymerase chain reaction (RT-qPCR), and protein expressions of Rac-1, p-ERK and F-actin were determined by Western Blot. (1) Compared with spontaneous breathing group, lung W/D in both mechanical ventilation groups was significantly increased, with more significant increase in the high VT group (6.64±0.88 vs. 1.79±0.36, P < 0.01). (2) There was no obvious pathological changes in the lung tissue and AEC II of the spontaneously breathing group. In the normal VT group, there was slight edema and infiltration of inflammatory cells; AEC II had less lamellar bodies and uniform distribution of the villi of the alveolar epithelium. In the high VT group, the edema of the lung tissue, the widening of the pulmonary septum, the alveolus congestion, the infiltration of inflammatory cells, and alveolar structure disorder were found; and AEC II was irregular, the number of lamellar bodies in the plastids was decreased and was unevenly distributed. The pulmonary histopathological score in the high VT group was significantly higher than that in the spontaneous breathing group and the normal VT group (12.00±2.00 vs. 6.00±1.51, 8.50±0.53, both P < 0.01). (3) Compared with spontaneous breathing group, IL-1β, IL-6, TNF-α, MPO, and MIP-2 in serum and BALF in both mechanical ventilation groups were significantly increased, with more significant increase in the high VT group [serum IL-1β (ng/L): 104.2±15.1 vs. 20.3±8.3, IL-6 (ng/L): 46.6±11.5 vs. 22.7±7.5, TNF-α (ng/L): 39.4±6.5 vs. 5.4±1.9, MPO (ng/L): 0.66±0.24 vs. 0.06±0.03, MIP-2 (ng/L): 109.2±25.8 vs. 22.8±8.4; BALF IL-1β (ng/L): 121.5±25.6 vs. 24.0±7.5, IL-6 (ng/L): 136.7±32.7 vs. 31.4±10.5, TNF-α (ng/L): 98.0±14.8 vs. 10.1±2.6, MPO (ng/L): 0.80±0.31 vs. 0.08±0.04, MIP-2 (ng/L): 144.4±28.9 vs. 41.2±20.7; all P < 0.01]. (4) There were only a few p-ERK, Rac1 and F-actin positive expressions in the spontaneous breathing group. The positive expressions in normal VT group were increased. In high VT group, the positive expression of p-ERK was significantly increased; Rac1 and F-actin were mainly distributed in the cell membrane and cytoplasm respectively, the positive expressions were further enhanced. (5) The gene expressions of ERK and Rac1, and protein expressions of p-ERK, Rac1 and F-actin in the high VT group were significantly higher than those in the spontaneous breathing group and normal VT group [ERK mRNA (2-ΔΔCt): 8.23±2.83 vs. 1, 3.02±1.38, p-ERK protein (gray value): 1.15±0.36 vs. 0.61±0.23, 0.88±0.22; Rac1 mRNA (2-ΔΔCt): 4.45±2.26 vs. 1, 1.22±0.39, Rac1 protein (gray value): 0.91±0.16 vs. 0.48±0.11, 0.55±0.10; F-actin protein (gray value): 0.70±0.09 vs. 0.49±0.08, 0.55±0.04; all P < 0.01]. F-actin expression in lung tissue was up-regulated in rats with VILI, which resulted in reconstruction of AEC II cyto-skeleton, and variation of cell membrane permeability through Rac1/MAPK/ERK signaling pathway during VILI.

Role and mechanism of mitophagy in ventilator-induced lung injury in rats

To explore the role and mechanism of mitophagy in ventilator-induced lung injury (VILI) in rats. Thirty-six adult Sprague-Dawley (SD) rats were randomly divided into three groups (each n = 12): spontaneous breathing group (CON group), normal tidal volume (VT) group (NVT group, VT was 8 mL/kg) and high VT group (HVT group, VT was 40 mL/kg). All rats received endotracheal tube by tracheostomy. The rats in CON group were maintained spontaneous breathing, while those in NVT and HVT groups received mechanical ventilation with corresponding VT. After 4 hours of ventilation, the serum, bronchoalveolar lavage fluid (BALF) and lung tissues were harvested. The lung wet/dry weight (W/D) ratio was assessed, and the histopathology changes were observed by light microscopy, and the ultra structure changes in type II alveolar epithelial cell (AEC II) were observed by electron microscopy. The levels of interleukin (IL-1β and IL-6) and tumor necrosis factor-α (TNF-α) in serum and BALF were determined by enzyme linked immunosorbent assay (ELISA). The total protein in BALF was measured by bicinchoninic acid methods, and the infiltrated cells in BALF were counted. The mRNA expressions and protein levels of microtube associated light chain 3B (LC3B), mitochondrial DNA coded cytochrome C oxidase IV (COX-IV) and nuclear factor-KB p65 (NF-KB p65) in lung tissues were determined by real-time fluorescent quantitation reverse transcription-polymerase chain reaction (RT-qPCR) and Western Blot. The histopathology of lung tissue and the ultra structure of AEC II were normal in CON group and NVT group, and the obvious inflammatory changes and pathological injury were found in HVT group. Compared with CON and NVT groups, the W/D ratio in HVT group was significantly increased (8.53±1.05 vs. 5.12±0.65, 5.57±0.55, both P < 0.05), and total protein, infiltrated cells, and IL-1β, IL-6 and TNF-α in BALF were significantly increased [total protein (g/L): 2.35±0.45 vs. 1.46±0.34, 1.76±0.51; infiltrated cells (×105/mL): 2.05±0.48 vs. 0.40±0.08, 0.60±0.23; IL-1β (ng/L): 119.82±6.56 vs. 76.15±3.32, 79.39±4.44; IL-6 (μg/L): 4.10±0.52 vs. 1.97±0.40, 2.27±0.36; TNF-α (mg/L): 1.49±0.28 vs. 0.43±0.23, 0.61±0.24; all P < 0.05], IL-1β, IL-6 and TNF-α levels in serum were also elevated [IL-1β (ng/L): 127.53±7.10 vs. 79.40±2.80, 82.95±2.25; IL-6 (μg/L): 6.28±0.82 vs. 2.96±0.35, 3.36±0.72; TNF-α (mg/L): 1.59±0.42 vs. 0.53±0.22, 0.78±0.25; all P < 0.05]. The mRNA expressions and protein levels of LC3B, COX-IV and NF-KB p65 in lung tissue of HVT group were significantly higher than those of CON group and NVT group, the mRNA expressions of LC3B-II, COX-IV and NF-KB p65 were (3.52±0.90), (3.76±1.16) and (9.54±2.06) folds of those in CON group, and the protein expressions were (1.76±0.24), (1.65±0.20) and (1.91±0.12) folds of those in CON group, with significantly statistical differences (all P < 0.05). There were no significant differences in the parameters mentioned above between NVT group and CON group. Mitophagy may be associated with VILI resulting from escaped mitochondrial DNA for activation of inflammation.