Comparison between Sugammadex and Neostigmine after Video-Assisted Thoracoscopic Surgery-Thymectomy in Patients with Myasthenia Gravis: A Single-Center Retrospective Exploratory Analysis.

This single-center retrospective exploratory analysis evaluated the effects of sugammadex compared with neostigmine on postoperative recovery in patients with myasthenia gravis (MG) who underwent video-assisted thoracoscopic surgery (VATS)-thymectomy. This retrospective study included 180 patients with MG, aged >18 years, who received sugammadex (sugammadex group, n = 83) or neostigmine-glycopyrrolate (neostigmine group, n = 88) after VATS-thymectomy between November 2007 and December 2020. Inverse probability of treatment weighting (IPTW) adjustment was performed to balance the baseline characteristics between the two groups. The primary outcome was the length of postoperative hospital stay, and the secondary outcomes were the incidence of postoperative mortality and complications, as well as the postoperative extubation and reintubation rates, in the operating room after VATS-thymectomy; the outcomes were compared between the two groups. After IPTW adjustment, the sugammadex group showed a significantly shorter median postoperative hospital stay than the neostigmine group (4 (2, 4) vs. 5 (3, 6) days, respectively; p = 0.003). There were no significant differences between the two groups in the incidences of postoperative complications (including postoperative myasthenic crisis, nerve palsy, atelectasis, and pleural effusion). Patients with MG following VATS-thymectomy who received sugammadex showed a significantly shorter postoperative hospital stay than those who received neostigmine.

Effect of permissive hypercarbia on lung oxygenation during one-lung ventilation and postoperative pulmonary complications in patients undergoing thoracic surgery: A prospective randomised controlled trial.

BACKGROUND: The effect of hypercarbia on lung oxygenation during thoracic surgery remains unclear. OBJECTIVE: To investigate the effect of hypercarbia on lung oxygenation during one-lung ventilation in patients undergoing thoracic surgery and evaluate the incidence of postoperative pulmonary complications. DESIGN: Prospective randomised controlled trial. SETTING: A tertiary university hospital in the Republic of Korea from November 2019 to December 2020. PATIENTS: Two hundred and ninety-seven patients with American Society of Anaesthesiologists physical status II to III, scheduled to undergo elective lung resection surgery. INTERVENTION: Patients were randomly assigned to Group 40, 50, or 60. An autoflow ventilation mode with a lung protective ventilation strategy was applied to all patients. Respiratory rate was adjusted to maintain a partial pressure of arterial carbon dioxide of 40 ±â€Š5 mmHg in Group 40, 50 ±â€Š5 mmHg in Group 50 and 60 ±â€Š5 mmHg in Group 60 during one-lung ventilation and at the end of surgery. MAIN OUTCOME MEASURES: The primary outcome was the arterial oxygen partial pressure/fractional inspired oxygen ratio after 60 min of one-lung ventilation. RESULTS: Data from 262 patients were analysed. The partial pressure/fractional inspired oxygen ratio was significantly higher in Group 50 and Group 60 than in Group 40 (269.4 vs. 262.9 vs. 214.4; P  < 0.001) but was not significantly different between Group 50 and Group 60. The incidence of postoperative pulmonary complications was comparable among the three groups. CONCLUSION: Permissive hypercarbia improved lung oxygenation during one-lung ventilation without increasing the risk of postoperative pulmonary complications or the length of hospital stay. TRIAL REGISTRATION: NCT04175379.

Impact of obesity on double-lumen endobronchial tube displacement after lateral decubitus positioning.

BACKGROUND: Double-lumen endobronchial tube (DLT) displacement, defined as migration of the DLT > 15 mm from optimal position, may threaten patient safety. Lateral decubitus positioning (LDP) of the patient can induce DLT displacement; however, little is known regarding the predictors for DLT displacement after this maneuver. Obesity may further aggravate DLT displacement by distorting mediastinal anatomy, but no comprehensive data exist concerning the impact of obesity on DLT displacement after LDP. Therefore, we evaluated the predictive value of preoperative risk factors, including obesity, for DLT displacement after LDP in patients who underwent pulmonary resection. METHODS: Data of patients who underwent pulmonary resection between July 2020 and July 2021 were retrospectively reviewed. Age, sex, height, weight, body mass index, left main bronchus diameter, DLT size, lateral decubitus direction, DLT depth, patient height divided by the DLT depths in supine and lateral decubitus positions (H/Dsupine and H/Dlateral, respectively), and extent of DLT dislocation were assessed. Logistic regression analysis identified risk factors, and the optimal cutoff values for continuous variables were determined using receiver operating characteristic curve analysis. RESULTS: Data from 428 patients were analyzed. DLT displacement was observed in 52 patients (12.1%). Obesity and H/Dsupine were independent predictors for DLT displacement after LDP (odds ratio [OR]: 5.69, 95% CI [2.89, 11.23], P < 0.001 and OR: 8.28, 95% CI [2.92, 23.48], P < 0.001, respectively). CONCLUSIONS: Obesity was significantly associated with DLT displacement after LDP. Pre-emptively advancing the DLT from its optimal position before LDP may be advantageous in patients with obesity.

Driving pressure-guided ventilation and postoperative pulmonary complications in thoracic surgery: a multicentre randomised clinical trial.

BACKGROUND: Airway driving pressure, easily measured as plateau pressure minus PEEP, is a surrogate for alveolar stress and strain. However, the effect of its targeted reduction remains unclear. METHODS: In this multicentre trial, patients undergoing lung resection surgery were randomised to either a driving pressure group (n=650) receiving an alveolar recruitment/individualised PEEP to deliver the lowest driving pressure or to a conventional protective ventilation group (n=650) with fixed PEEP of 5 cm H2O. The primary outcome was a composite of pulmonary complications within 7 days postoperatively. RESULTS: The modified intention-to-treat analysis included 1170 patients (mean [standard deviation, sd]; age, 63 [10] yr; 47% female). The mean driving pressure was 7.1 cm H2O in the driving pressure group vs 9.2 cm H2O in the protective ventilation group (mean difference [95% confidence interval, CI]; -2.1 [-2.4 to -1.9] cm H2O; P<0.001). The incidence of pulmonary complications was not different between the two groups: driving pressure group (233/576, 40.5%) vs protective ventilation group (254/594, 42.8%) (risk difference -2.3%; 95% CI, -8.0% to 3.3%; P=0.42). Intraoperatively, lung compliance (mean [sd], 42.7 [12.4] vs 33.5 [11.1] ml cm H2O-1; P<0.001) and Pao2 (median [inter-quartile range], 21.5 [14.5 to 30.4] vs 19.5 [13.5 to 29.1] kPa; P=0.03) were higher and the need for rescue ventilation was less frequent (6.8% vs 10.8%; P=0.02) in the driving pressure group. CONCLUSIONS: In lung resection surgery, a driving pressure-guided ventilation improved pulmonary mechanics intraoperatively, but did not reduce the incidence of postoperative pulmonary complications compared with a conventional protective ventilation. CLINICAL TRIAL REGISTRATION: NCT04260451.

Effects of Iloprost on Arterial Oxygenation and Lung Mechanics during One-Lung Ventilation in Supine-Positioned Patients: A Randomized Controlled Study.

Patients undergoing one-lung ventilation (OLV) in the supine position face an increased risk of intraoperative hypoxia compared with those in the lateral decubitus position. We hypothesized that iloprost (ILO) inhalation improves arterial oxygenation and lung mechanics. Sixty-four patients were enrolled and allocated to either the ILO or control group (n = 32 each), to whom ILO or normal saline was administered. The partial pressure of the arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, dynamic compliance, alveolar dead space, and hemodynamic variables were assessed 20 min after anesthesia induction with both lungs ventilated (T1) and 20 min after drug nebulization in OLV (T2). A linear mixed model adjusted for group and time was used to analyze repeated variables. While the alveolar dead space remained unchanged in the ILO group, it increased at T2 in the control group (n = 30 each) (p = 0.002). No significant differences were observed in the heart rate, mean blood pressure, PaO2/FiO2 ratio, or dynamic compliance in either group. Selective ILO nebulization was inadequate to enhance oxygenation parameters during OLV in the supine position. However, it favorably affected alveolar ventilation during OLV in supine-positioned patients without adverse hemodynamic effects.

Effects of Iloprost on Oxygenation during One-Lung Ventilation in Patients with Low Diffusing Capacity for Carbon Monoxide: A Randomized Controlled Study.

The protective mechanism of hypoxic pulmonary vasoconstriction during one-lung ventilation (OLV) is impaired in patients with a low diffusing capacity for carbon monoxide (DLCO). We hypothesized that iloprost inhalation would improve oxygenation and lung mechanics in patients with low DLCO who underwent pulmonary resection. Forty patients with a DLCO < 75% were enrolled. Patients were allocated into either an iloprost group (ILO group) or a control group (n = 20 each), in which iloprost and saline were inhaled, respectively. The partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, pulmonary shunt fraction, alveolar dead space, dynamic compliance, and hemodynamic parameters were assessed 20 min after the initiation of OLV and 20 min after drug administration. Repeated variables were analyzed using a linear mixed model between the groups. Data from 39 patients were analyzed. After iloprost inhalation, the ILO group exhibited a significant increase in the PaO2/FiO2 ratio and a decrease in alveolar dead space compared with the control group (p = 0.025 and p = 0.042, respectively). Pulmonary shunt, dynamic compliance, hemodynamic parameters, and short-term prognosis were comparable between the two groups. Selective iloprost administration during OLV reduced alveolar dead space and improved oxygenation while minimally affecting hemodynamics and short-term prognosis.

Antitumor activity of a lectibody targeting cancer-associated high-mannose glycans.

Aberrant protein glycosylation is a hallmark of cancer, but few drugs targeting cancer glycobiomarkers are currently available. Here, we showed that a lectibody consisting of the high-mannose glycan-binding lectin Avaren and human immunoglobulin G1 (IgG1) Fc (AvFc) selectively recognizes a range of cell lines derived from lung, breast, colon, and blood cancers at nanomolar concentrations. Binding of AvFc to the non-small cell lung cancer (NSCLC) cell lines A549 and H460 was characterized in detail. Co-immunoprecipitation proteomics analysis revealed that epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) are among the lectibody's common targets in these cells. AvFc blocked the activation of EGFR and IGF1R by their respective ligands in A549 cells and inhibited the migration of A549 and H460 cells upon stimulation with EGF and IGF1. Furthermore, AvFc induced potent Fc-mediated cytotoxic effects and significantly restricted A549 and H460 tumor growth in severe combined immunodeficiency (SCID) mice. Immunohistochemistry analysis of primary lung tissues from NSCLC patients demonstrated that AvFc preferentially binds to tumors over adjacent non-tumor tissues. Our findings provide evidence that increased abundance of high-mannose glycans in the glycocalyx of cancer cells can be a druggable target, and AvFc may provide a new tool to probe and target this tumor-associated glycobiomarker.

Comparison of high flow nasal oxygen and conventional nasal cannula during gastrointestinal endoscopic sedation in the prone position: a randomized trial.

PURPOSE: Deep sedation for endoscopic retrograde cholangiopancreatography (ERCP) can be challenging in elderly patients in the prone position. This study investigated the effect of a high flow nasal oxygen (HFNO) delivery system on oxygenation in this procedure compared with that of conventional nasal cannula oxygen administration. METHODS: A prospective randomized trial was conducted using HFNO and conventional nasal cannula in patients undergoing ERCP in the prone position. For each patient, the lowest oxygen saturation (SpO2), the incidence of hypoxemia defined as an SpO2 below 90%, and interruptions due to airway interventions were recorded during the procedure. RESULTS: The lowest mean (standard deviation) SpO2 recorded during the procedure was higher in the HFNO group than in the conventional control group [99.8 (0.6)% vs 95.1 (7.3)%; mean difference, 4.7%; 95% confidence interval, 2.3% to 7.1%; P Group x Time < 0.001]. While the lowest SpO2 during the procedure was lower than the baseline SpO2 in the control group, the lowest SpO2 during the procedure was higher than the baseline SpO2 in the HFNO group. Hypoxemia occurred only in the control group (n = 7; 19%; P = 0.01). Procedural interruptions, including discontinuation of sedation, patient stimulation, and jaw thrusting, occurred only in the control group (n = 9 [25%], n = 10 [28%], and n = 10 [28%] cases, respectively; P = 0.001 for each). CONCLUSION: In contrast to conventional nasal cannula, high flow nasal oxygen provided adequate oxygenation without causing procedural interruptions during ERCP, suggesting that HFNO may be used as a standard oxygen delivery method during these procedures. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT03872674); registered 11 March 2019.

RéSUMé: OBJECTIF: La sédation profonde pour cholangiopancréatographie rétrograde endoscopique (CPRE) peut être difficile à réaliser chez des patients âgés en position ventrale. Cette étude a exploré l'effet d'un système d'oxygénothérapie nasale à haut débit (ONHD) sur l'oxygénation pendant cette intervention par rapport à l'administration conventionnelle d'oxygène via une lunette nasale. MéTHODE: Une étude randomisée prospective a été réalisée en utilisant une ONHD ou une lunette nasale conventionnelle chez des patients subissant une CPRE en position ventrale. Pour chaque patient, la saturation en oxygène (SpO2) la plus basse, l'incidence d'hypoxémie définie en tant qu'une SpO2 inférieure à 90 %, et les interruptions provoquées par des interventions au niveau des voies aériennes ont été enregistrées au cours de l'intervention. RéSULTATS: La SpO2 moyenne (écart type) la plus basse enregistrée pendant l'intervention était plus élevée dans le groupe ONHD que dans le groupe témoin conventionnel [99,8 (0,6) % vs 95,1 (7,3) %; différence moyenne, 4,7%; intervalle de confiance 95 %, 2,3 % à 7,1 %; P Groupe x Temps < 0,001]. Alors que la SpO2 la plus basse pendant l'intervention était plus basse que la SpO2 de base dans le groupe témoin, la SpO2 la plus basse pendant l'intervention était plus élevée que la SpO2 de base dans le groupe ONHD. L'hypoxémie n'est survenue que dans le groupe témoin (n = 7; 19 %; P = 0,01). Il n'y a eu d'interruptions de l'intervention, y compris la cessation de la sédation, la stimulation du patient et le déplacement de la mâchoire inférieure vers l'avant, que dans le groupe témoin (n = 9 [25 %], n = 10 [28 %], et n = 10 [28 %] cas, respectivement; P = 0,001 pour chaque intervention). CONCLUSION: Comparativement à une lunette nasale conventionnelle, l'oxygénothérapie nasale à haut débit a procuré une oxygénation adéquate sans provoquer d'interruptions de l'intervention pendant une CPRE, suggérant que cette modalité pourrait être utilisée comme méthode standard d'oxygénothérapie pendant de telles interventions. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03872674); enregistrée le 11 mars 2019.

Femoral neuropathy following venoarterial-extracorporeal membrane oxygenation therapy: a case report.

BACKGROUND: Although life-threatening complications of extracorporeal membrane oxygenation (ECMO) are well described, non-life threatening complications are less known. Herein, we report a case of femoral neuropathy (FN) due to nerve compression caused by cannula compression and deep vein thrombosis (DVT) after successful ECMO therapy, which seriously undermined one's quality of life. CASE PRESENTATION: A 70-year old male presented to the emergency department for chest pain. The patient had cardiac arrest before percutaneous coronary intervention (PCI) and was inserted with ECMO. Although he was successfully weaned from ECMO 4 days after PCI, he consistently complained swelling, abnormal sensation, and weakness in his right lower extremity, where the cannulas were inserted. Imaging studies showed deep vein thrombosis (DVT) in his right leg, which was further treated with anticoagulants. Symptoms, however, remained after the regression of DVT. Nerve conduction study revealed femoral neuropathy, which may have been caused by ECMO cannula compression and tissue swelling. CONCLUSION: The current case proposes that non-life threatening complications of ECMO therapy can seriously affect quality of life. Venous drainage distant from the arterial cannula may prevent such complications.

A Randomized Controlled Trial Comparing Novel Triple-Cuffed Double-Lumen Endobronchial Tubes with Conventional Double-Lumen Endobronchial Tubes for Lung Isolation.

Placing a double-lumen endobronchial tube (DLT) in an appropriate position to facilitate lung isolation is essential for thoracic procedures. The novel ANKOR DLT is a DLT developed with three cuffs with a newly added carinal cuff designed to prevent further advancement by being blocked by the carina when the cuff is inflated. In this prospective study, the direction and depth of initial placement of ANKOR DLT were compared with those of conventional DLT. Patients undergoing thoracic surgery (n = 190) with one-lung ventilation (OLV) were randomly allocated into either left-sided conventional DLT group (n = 95) or left-sided ANKOR DLT group (n = 95). The direction and depth of DLT position were compared via fiberoptic bronchoscopy (FOB) after endobronchial intubation between the groups. There was no significant difference in the number of right mainstem endobronchial intubations between the two groups (p = 0.468). The difference between the initial depth of DLT placement and the target depth confirmed by FOB was significantly lower in the ANKOR DLT group than in the conventional DLT group (1.8 ± 1.8 vs. 12.9 ± 9.7 mm; p < 0.001). In conclusion, the ANKOR DLT facilitated its initial positioning at the optimal depth compared to the conventional DLT.

Effects of Inhaled Iloprost on Lung Mechanics and Myocardial Function During One-Lung Ventilation in Chronic Obstructive Pulmonary Disease Patients Combined With Poor Lung Oxygenation.

BACKGROUND: The ventilation/perfusion mismatch in chronic obstructive pulmonary disease (COPD) patients can exacerbate cardiac function as well as pulmonary oxygenation. We hypothesized that inhaled iloprost can ameliorate pulmonary oxygenation with lung mechanics and myocardial function during one-lung ventilation (OLV) in COPD patients combined with poor lung oxygenation. METHODS: A total of 40 patients with moderate to severe COPD, who exhibited the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FIO2) <150 mm Hg 30 minutes after initiating OLV, were enrolled in this study. Patients were randomly allocated into either ILO group (n = 20) or Control group (n = 20), in which iloprost (20 µg) and saline were inhaled, respectively. The PaO2/FIO2 ratio, dead space, dynamic compliance, and tissue Doppler imaging with myocardial performance index (MPI) were assessed 30 minutes after initiating OLV (pre-Tx) and 30 minutes after completion of drug inhalation (post-Tx). Repeated variables were analyzed using a linear mixed-model between the groups. RESULTS: At pre-Tx, no differences were observed in measured parameters between the groups. At post-Tx, PaO2/FIO2 ratio (P < .001) and dynamic compliance (P = .023) were significantly higher and dead space ventilation was significantly lower (P = .001) in iloprost group (ILO group) compared to Control group. Left (P = .003) and right ventricular MPIs (P < .001) significantly decreased in ILO group compared to Control group. CONCLUSIONS: Inhaled iloprost improved pulmonary oxygenation, lung mechanics, and cardiac function simultaneously during OLV in COPD patients with poor lung oxygenation.

Driving pressure guided ventilation.

Protective ventilation is a prevailing ventilatory strategy these days and is comprised of small tidal volume, limited inspiratory pressure, and application of positive end-expiratory pressure (PEEP). However, several retrospective studies recently suggested that tidal volume, inspiratory pressure, and PEEP are not related to patient outcomes, or only related when they influence the driving pressure. Therefore, this review introduces the concept of driving pressure and looks into the possibility of driving pressure-guided ventilation as a new ventilatory strategy, especially in thoracic surgery where postoperative pulmonary complications are common, and thus, lung protection is of utmost importance.

A modified cholera toxin B subunit containing an ER retention motif enhances colon epithelial repair via an unfolded protein response.

Cholera toxin B subunit (CTB) exhibits broad-spectrum biologic activity upon mucosal administration. Here, we found that a recombinant CTB containing an endoplasmic reticulum (ER) retention motif (CTB-KDEL) induces colon epithelial wound healing in colitis via the activation of an unfolded protein response (UPR) in colon epithelial cells. In a Caco2 cell wound healing model, CTB-KDEL, but not CTB or CTB-KDE, facilitated cell migration via interaction with the KDEL receptor, localization in the ER, UPR activation, and subsequent TGF-ß signaling. Inhibition of the inositol-requiring enzyme 1/X-box binding protein 1 arm of UPR abolished the cell migration effect of CTB-KDEL, indicating that the pathway is indispensable for the activity. CTB-KDEL's capacity to induce UPR and epithelial restitution or wound healing was corroborated in a dextran sodium sulfate-induced acute colitis mouse model. Furthermore, CTB-KDEL induced a UPR, up-regulated wound healing pathways, and maintained viable crypts in colon explants from patients with inflammatory bowel disease (IBD). In summary, CTB-KDEL exhibits unique wound healing effects in the colon that are mediated by its localization to the ER and subsequent activation of UPR in epithelial cells. The results provide implications for a novel therapeutic approach for mucosal healing, a significant unmet need in IBD treatment.-Royal, J. M., Oh, Y. J., Grey, M. J., Lencer, W. I., Ronquillo, N., Galandiuk, S., Matoba, N. A modified cholera toxin B subunit containing an ER retention motif enhances colon epithelial repair via an unfolded protein response.

Successful blind lung isolation with the use of a novel double-lumen endobronchial tube in a patient undergoing lung transplantation with massive pulmonary secretion: A case report.

RATIONALE: Precise lung isolation technique with visual confirmation is essential for thoracic surgeries to create a safe and clear surgical field. However, in certain situations, such as when patients have massive pulmonary secretion or when the fiberoptic bronchoscopy (FOB) is not applicable, lung isolation has been performed blindly. PATIENT CONCERN: A 52-year-old woman, whose airway was unable to visualize with FOB due to massive pulmonary secretion, was presented for bilateral sequential lung transplantation. Extracorporeal membranous oxygenation, tracheostomy, and mechanical ventilation were applied to the patient for 39 days preoperatively as a bridge for lung transplantation. DIAGNOSIS: Patient was diagnosed with an idiopathic pulmonary fibrosis and obesity. INTERVENTION: Initially, height-based blind positioning with a conventional double-lumen endobronchial tube (DLT) failed to ventilate the patient properly, and the confirmation of DLT positioning with FOB was impossible due to massive pulmonary secretion. Therefore, a novel DLT (ANKOR DLT) that has one more cuff, located at a point between the distal opening of the tracheal lumen and the starting point of bronchial cuff, than conventional DLT was used for the lung isolation in the patient. OUTCOMES: After the completion of lung graft, FOB finding showed that the ANKOR DLT was optimally positioned at the tracheobronchial tree of the patient, and its depth was 2.5 cm shallower than that of the conventional tube. LESSONS: ANKOR DLT would be a feasible choice to achieve successful blind lung isolation when the use of FOB is impossible to achieve the optimal lung isolation.

Effects of Positive End-Expiratory Pressure on Pulmonary Oxygenation and Biventricular Function during One-Lung Ventilation: A Randomized Crossover Study.

Although the application of positive end-expiratory pressure (PEEP) can alter cardiopulmonary physiology during one-lung ventilation (OLV), these changes have not been clearly elucidated. This study assessed the effects of different levels of PEEP on biventricular function, as well as pulmonary oxygenation during OLV. Thirty-six lung cancer patients received one PEEP combination of six sequences, consisting of 0 (PEEP_0), 5 (PEEP_5), and 10 cmH2O (PEEP_10), using a crossover design during OLV. The ratio of arterial oxygen partial pressure to inspired oxygen fraction (P/F ratio), systolic and diastolic echocardiographic parameters were measured at 20 min after the first, second, and third PEEP. P/F ratio at PEEP_5 was significantly higher compared to PEEP_0 (p = 0.014), whereas the P/F ratio at PEEP_10 did not show significant differences compared to PEEP_0 or PEEP_5. Left ventricular ejection fraction (LV EF) and right ventricular fractional area change (RV FAC) at PEEP_10 (EF, p < 0.001; FAC, p = 0.001) were significantly lower compared to PEEP_0 or PEEP_5. RV E/E' (p = 0.048) and RV myocardial performance index (p < 0.001) at PEEP_10 were significantly higher than those at PEEP_0 or PEEP_5. In conclusion, increasing PEEP to 10 cmH2O decreased biventricular function, especially on RV function, with no further improvement on oxygenation compared to PEEP 5 cmH2O during OLV.

Dexmedetomidine restores autophagy and cardiac dysfunction in rats with streptozotocin-induced diabetes mellitus.

AIMS: Dexmedetomidine (DEX), a highly selective and potent α2-adrenergic receptor agonist, has anti-apoptotic, anti-inflammatory, and anti-oxidative stress effects in diabetes mellitus (DM) rats. The underlying molecular mechanisms and signaling pathways of diabetic cardiomyopathy remain poorly understood. This study aimed to elucidate the effect of DEX on cardiac function in DM rats. METHODS: Eight-week-old male Sprague Dawley rats were divided into three groups: control (n = 5), diabetes (DM, n = 7), and diabetes + DEX (DM + DEX, n = 10). DM was induced via intraperitoneal injection of streptozotocin (70 mg/kg); at 3 days later, DEX (1 µg/kg/h) was administered for 4 weeks. Cardiac function was evaluated using pressure-volume loop analysis and echocardiography. Left ventricular (LV) histological sections were used to analyze the interstitial collagen fraction. Using the LV samples, we performed a western blot analysis to evaluate signaling pathways and autophagic markers. RESULTS: The DM group had lower body weight and higher blood glucose level and heart weight/body weight ratio than the control group. However, metabolic changes did not differ between the DM and DM + DEX groups. Pressure-volume loop analysis and echocardiography showed impaired cardiac function, evidenced by a decrease in systolic and diastolic function, in both DM groups. DEX treatment in DM rats was associated with increased LV end-systolic pressure, LV contractility, cardiac output, and relaxed LV function compared with that in non-treated DM rats. LC3B and autophagy-related gene (ATG) proteins increased in the hearts of DM rats compared with the hearts of control rats. However, DEX reduced the expression of LC3B and ATG proteins in the hearts of DM rats. Increased p-ERK and decreased p-AKT were reduced in the hearts of DEX-treated DM rats. CONCLUSIONS: DEX reduces cardiac dysfunction and impaired autophagy in DM rats. This study reinforces our understanding of the potential anti-autophagic effect of DEX in patients with diabetic cardiomyopathy.

Renoprotective effects of dexmedetomidine against ischemia-reperfusion injury in streptozotocin-induced diabetic rats.

BACKGROUND: Diabetic patients are susceptible to renal ischemia-reperfusion injury, which leads to perioperative complications. Activation of NOD-like receptor protein 3 (NLRP3) inflammasome participates in the development of diabetes, and contributes to renal ischemia-reperfusion injury. Dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist, shows renoprotective effects against ischemia-reperfusion injury. We aimed to elucidate the effects, underlying mechanisms, and optimal timing of DEX treatment in diabetic rats. METHODS: Male Sprague-Dawley rats (n = 12 per group) were randomly divided into normal-sham, diabetes-sham, diabetes-ischemia-reperfusion-control, diabetes-ischemia-reperfusion-DEX-pre-treatment, and diabetes-ischemia-reperfusion-DEX-post-treatment groups. Renal ischemia-reperfusion injury was induced in diabetic rats by occlusion of both renal arteries for 45 min, followed by reperfusion for 24 h. DEX (10 µg/kg) was administered intraperitoneally 1 h before ischemia (pre-treatment) or upon reperfusion (post-treatment). After reperfusion, renal tissue was biochemically and histopathologically evaluated. RESULTS: DEX treatment attenuated ischemia reperfusion-induced increase in NLRP3, caspase-1, IL-1ß, phospho-AKT, and phospho-ERK signaling. Moreover, oxidative stress injury, inflammatory reactions, apoptosis, and renal tubular damage were favorably modulated by DEX treatment. Furthermore, post-reperfusion treatment with DEX was significantly more effective than pre-treatment in modulating NLRP3 inflammasome, AKT and ERK signaling, and oxidative stress. CONCLUSIONS: This study shows that the protective effects of DEX in renal ischemia-reperfusion injury are preserved in diabetic conditions and may potentially provide a basis for the use of DEX in clinical treatment of renal ischemia-reperfusion injury.