Dexmedetomidine postconditioning attenuates myocardial ischemia/reperfusion injury by activating the Nrf2/Sirt3/SOD2 signaling pathway in the rats.

OBJECTIVES: To observe the protective effects of dexmedetomidine (Dex) postconditioning on myocardial ischemia/reperfusion injury (IRI) and to explore its potential molecular mechanisms. METHODS: One-hundred forty-seven male Sprague-Dawley rats were randomly divided into five groups receiving the different treatments: Sham, ischemia/reperfusion (I/R), Dex, Brusatol, Dex + Brusatol. By the in vivo rat model of myocardial IRI, cardioprotective effects of Dex postconditioning were evaluated by assessing serum CK-MB and cTnI levels, myocardial HE and Tunel staining and infarct size. Furthermore, the oxidative stress-related markers including intracellular ROS level, myocardial tissue MDA level, SOD and GSH-PX activities were determined. RESULTS: Dex postconditioning significantly alleviated myocardial IRI, decreased intracellular ROS and myocardial tissue MDA level, increased SOD and GSH-PX activities. Dex postconditioning significantly up-regulated myocardial expression of Bcl-2, down-regulated Bax and cleaved caspase-3 and decreased cardiomyocyte apoptosis rate. furthermores, Dex postconditioning promoted Nrf2 nuclear translocation, increased myocardial expression of Sirt3 and SOD2 and decreased Ac-SOD2. However, brusatol reversed cardioprotective benefits of Dex postconditioning, significantly decreased Dex-induced Nrf2 nuclear translocation and reduced myocardial expression of Sirt3 and SOD2. CONCLUSIONS: Dex postconditioning can alleviate myocardial IRI by suppressing oxidative stress and apoptosis, and these beneficial effects are at least partly mediated by activating the Nrf2/Sirt3/SOD2 signaling pathway.

Impact of pulmonary hypertension on arteriovenous fistula failure of hemodialysis patients: A 10 years follow-up cohort study.

BACKGROUND: Pulmonary hypertension (PH) is common in patients with end-stage renal disease (ESRD). Arteriovenous fistulas (AVF) creation may involve in the pathogenesis of PH. The aim of this study was to explore the impact of PH after AVF creation on the AVF failure rate in maintenance hemodialysis (MHD) patients. METHODS: From January 1, 2009, to January 1, 2019, we retrospectively collected data of 578 MHD patients in Guangdong Provincial People's Hospital Blood Purification Center, China. Patients were followed-up until AVF failure or death or May 25, 2020. According to the systolic pulmonary artery pressure (SPAP) within 1 year after the establishment of AVF, the MHD patients were divided into three groups: SPAP ⩽ 35 mmHg, 35 < SPAP < 45 mmHg, SPAP ⩾ 45 mmHg. The primary outcome was AVF failure defined as AVF cannot complete hemodialysis. The secondary outcomes were all-cause mortality. RESULTS: A total of 578 patients were analyzed. The average age was 60.66 ± 15.34 years (58.1% men). Of these, 26.1% of patients were reported PH. The SPAP exhibited a left-skewed nonparametric distribution and the overall SPAP after the creation of AVF was 39.00 (29.00-52.00) mmHg. The median follow-up was 5.8 (5.5-6.3) years. Overall, 12.8% (74/578) patients were reported AVF failure events. There was no significant difference in AVF failure rate among three groups (p = 0.070). A total of 111 (19.2%) died during the follow-up period. Compared with the SPAP ⩽35 mmHg group, only the all-cause death rate significantly increased in MHD patients with PH (p < 0.001). CONCLUSIONS: The secondary pulmonary hypertension after AVF creation did not increase the risk of AVF failure in MHD patients, but significantly increased the risk of mortality for this portion of the patients. Future larger sample sizes, multi-center, and prospective trials are needed to make sure which type of access will benefit on their survival for MHD patients with SPAP ⩾35 mmHg.

Direct arterial puncture for hemodialysis, a neglected but simple and valuable vascular access.

INTRODUCTION: The purpose of this study is to present the prevalence and effects of direct arterial puncture (DAP) for hemodialysis patients, and to introduce optimal option for the vascular access (VA) in certain hemodialysis patients with poor condition of vascular or cardiac function in a compelling situation. METHODS: This was a cross-sectional study. Demographic characteristics and laboratory data were extracted from the health care system. Relevant DAP information was collected by a questionnaire. Case-control matching was performed to compare the hemodialysis adequacy between DAP and other VAs. RESULTS: A total of 526 patients were selected for analysis by convenience sampling, of which 38 patients relied https://www.baidu.com/link?url=eaDh8Hn-yZGJyDB0_h4zBenKd7qY1yX-KNxO-qU49gktQOGTJJg3slTjIbG095st4hRfprQIHRjfhfeGOZyH73y8tvSUCwMmvWbUhyix2ZK on DAP for hemodialysis. The main reasons using DAP for hemodialysis included the cost of arteriovenous access creation or maintenance in 19(50%) patients and the poor condition of vascular or cardiac function in 14 (39.5%) patients. Some complications of DAP occurred, such as aneurysm or pseudoaneurysm in 16(42.1%) patients, infiltration in 12 (31.6%) patients. Differences in hemodialysis adequacy were not statistically significant between DAP and other types of VA. CONCLUSION: In conclusion, DAP can meet the need of prescription hemodialysis, yet it has several limitations. Although the patients in our study were long-term dependent on DAP for hemodialysis with various reasons, we do not recommend DAP as a long-term vascular access if better options are available. However, DAP should not be overlooked to be a supplemental VA for hemodialysis with adequate blood flow and availability for individuals with poor condition of vascular or cardiac function in a compelling situation.

Long-term high-risk drinking does not change effective doses of propofol for successful insertion of gastroscope in Chinese male patients.

BACKGROUND: Available literature indicates that long-term drinkers demand a higher dose of propofol for induction of anesthesia than non-drinkers. However, there is no study having assessed the influence of long-term high-risk drinking (LTHRD) on the effective doses of propofol for successful insertion of gastroscope with sedation. This study was designed to compare the effective doses of propofol for successful insertion of gastroscope between LTHRD and non-drinking (ND) Chinese male patients. METHODS: Thirty-one LTHRD patients and 29 ND male patients undergoing elective gastroscopy with propofol sedation were enrolled. The modified Dixon's up-and-down method was applied to determine the calculated median effective dose (ED50) of propofol for successful insertion of gastroscope. Furthermore, the isotonic regression analysis was used to establish the dose-response curve of propofol and assess the effective doses of propofol where 50% (ED50) and 95% (ED95) of gastroscope insertions were successful. RESULTS: The calculated ED50 of propofol for successful insertion of gastroscope was 1.55 ± 0.10 mg/kg and 1.44 ± 0.11 mg/kg in the LTHRD and ND patients. The isotonic regression analysis further showed that ED50 and ED95 of propofol for successful insertion of gastroscope was 1.50 mg/kg (95%CI, 1.40-1.63) and 1.80 mg/kg (95%CI, 1.74-1.90) in the LTHRD patients, respectively; 1.40 mg/kg (95% CI, 1.27-1.57) and 1.60 mg/kg (95%CI, 1.56-1.65) in the ND patients. The ED50 of propofol for successful insertion of gastroscope was not significantly different between LTHRD and ND patients. CONCLUSIONS: This study demonstrates that the difference in the estimated ED50 of propofol for successful insertion of gastroscope between LTHRD and ND Chinese male patients was not statistically significant. TRIAL REGISTRATION: The study was registered on November 28, 2020 ( ChiCTR2000040382 ) in the Chinese Clinical Trial Registry.

The Protective Effect of Sevoflurane Conditionings Against Myocardial Ischemia/Reperfusion Injury: A Systematic Review and Meta-Analysis of Preclinical Trials in in-vivo Models.

Objective: Myocardial ischemia/reperfusion injury (IRI) is a common and serious complication in clinical practice. Sevoflurane conditionings have been identified to provide a protection against myocardial IRI in animal experiments, but their true clinical benefits remain controversial. Here, we aimed to analyze the preclinical evidences obtained in animal models of myocardial IRI and explore the possible reasons for controversial clinical benefits. Methods: Our primary outcome was the difference in mean infarct size between the sevoflurane and control groups in animal models of myocardial IRI. After searching the databases of PubMed, Embase, Web of Science, and the Cochrane Library, a systematic review retrieved 37 eligible studies, from which 28 studies controlled comparisons of sevoflurane preconditioning (SPreC) and 40 studies controlled comparisons of sevoflurane postconditioning (SPostC) that were made in a pooled random-effects meta-analysis. In total, this analysis included data from 313 control animals and 536 animals subject to sevoflurane conditionings. Results: Pooled estimates for primary outcome demonstrated that sevoflurane could significantly reduce the infarct size after myocardial IRI whether preconditioning [weighted mean difference (WMD): -18.56, 95% CI: -23.27 to -13.85, P < 0.01; I 2 = 94.1%, P < 0.01] or postconditioning (WMD: -18.35, 95% CI: -20.88 to -15.83, P < 0.01; I 2 = 90.5%, P < 0.01) was performed. Interestingly, there was significant heterogeneity in effect size that could not be explained by any of the prespecified variables by meta-regression and stratified analysis. However, sensitivity analysis still identified the cardioprotective benefits of sevoflurane conditionings with robust results. Conclusion: Sevoflurane conditionings can significantly reduce infarct size in in-vivo models of myocardial IRI. Given the fact that there is a lack of consistency in the quality and design of included studies, more well-performed in-vivo studies with the detailed characterization of sevoflurane protocols, especially studies in larger animals regarding cardioprotection effects of sevoflurane, are still required.

How to Reduce the Risk of Arteriovenous Fistula Dysfunction by Observing Prepump Arterial Pressure during Hemodialysis: A Multicenter Retrospective Study.

OBJECTIVE: Prepump arterial (Pa) pressure indicates the ease or difficulty with which the blood pump can draw blood from the vascular access (VA) during hemodialysis. Some studies have suggested that the absolute value of the Pa pressure to the extracorporeal blood pump flow (Qb) ratio set on the machine (|Pa/Qb|) can reflect the dysfunction of VA. This study was conducted to explore the impact of arteriovenous fistula (AVF) dysfunction and to explore the clinical reference value of |Pa/Qb|. METHODS: We retrospectively identified adults who underwent hemodialysis at 3 hospitals. Data were acquired from electronic health records. We evaluated the pattern of the association between |Pa/Qb| and AVF dysfunction during 1 year using a Cox proportional hazards regression model with restricted cubic splines. Then, the patients were grouped based on the results, and hazard ratios were compared for different intervals of |Pa/Qb|. RESULTS: A total of 490 patients were analyzed, with an average age of 55 (44, 66) years. There were a total of 85 cases of AVF dysfunction, of which 50 cases were stenosis and 35 cases were thrombosis. There was a U-shaped association between |Pa/Qb| and the risk of AVF dysfunction (p for nonlinearity <0.001). |Pa/Qb| values <0.30 and >0.52 increased the risk of AVF dysfunction. Compared with the group with a |Pa/Qb| value between 0.30 and 0.52, the groups with |Pa/Qb| <0.30 and |Pa/Qb| >0.52 had a 4.04-fold (p = 0.002) and 3.41-fold (p < 0.001) greater risk of AVF dysfunction, respectively. CONCLUSIONS: The appropriate range of |Pa/Qb| is between 0.30 and 0.52. When |Pa/Qb| is <0.30 or >0.52, the patient's AVF function or Qb setting should be reevaluated to prevent subsequent failure.

How to carry out monthly blood flow surveillance of fistula in large-scale hemodialysis units: A cross-sectional study.

BACKGROUND: The important effect of regular blood flow surveillance on arteriovenous fistula maintenance is emphasized. The ultrasonic dilution technique for blood flow surveillance can be performed during hemodialysis, but there are some limitations. Blood flow is traditionally measured by duplex Doppler ultrasound during the nondialysis period. However, the surveillance workload for arteriovenous fistula has increased with the rapid increase in the hemodialysis population size. Efficient methods for blood flow surveillance during hemodialysis are needed. METHODS: Eighty-four hemodialysis patients with a forearm radiocephalic arteriovenous fistula were enrolled in this cross-sectional study. Each received blood flow measurements using ultrasonic dilution technique and duplex Doppler ultrasound during hemodialysis. Duplex Doppler ultrasound measurements included the blood flow of the brachial artery and radial artery. The correlations between these variables were analyzed. RESULTS: The correlation coefficients (r) between flow measured by ultrasonic dilution technique and brachial artery flow measured by duplex Doppler ultrasound, between flow measured by ultrasonic dilution technique and radial artery flow measured by duplex Doppler ultrasound, and between brachial artery flow and radial artery flow measured by duplex Doppler ultrasound were 0.724, 0.784, and 0.749, respectively (all p < 0.001). CONCLUSION: Blood flow measured by ultrasonic dilution technique was positively correlated with blood flow measured by duplex Doppler ultrasound during hemodialysis, suggesting that duplex Doppler ultrasound can be used to monitor the trends in the blood flow of the brachial artery and radial artery for timely intervention to improve patency during hemodialysis.

It is time to implement prepump arterial pressure monitoring during hemodialysis: A retrospective multicenter study.

INTRODUCTION: Prepump arterial pressure (Pa) indicates the ease or difficulty with which the blood pump can draw blood from vascular access (inflow) during hemodialysis. The absolute prepump arterial pressure to blood pump speed (Qb) ratio (|Pa/Qb|) may reflect the dysfunction of other vascular accesses. There is no consensus on the impact of |Pa/Qb| on arteriovenous fistula dysfunction. This study aimed to demonstrate the impact of |Pa/Qb| on arteriovenous fistula dysfunction. METHODS: In this retrospective analysis, 490 hemodialysis patients with arteriovenous fistula from three hospitals were enrolled. Data were extracted from the I-Diapro database and hospital case systems. The absolute values for |Pa/Qb| and other data collected in the first month of enrollment were used to predict arteriovenous fistula dysfunction and determine the |Pa/Qb| cutoff value. Based on this value, patients were grouped, and 1-year arteriovenous fistula function was analyzed. Patients were followed until arteriovenous fistula dysfunction, until access type replacement, or for 12 months. RESULTS: The area under the receiver operating characteristic curve for fistula dysfunction over 1 year was 0.65, with an optimal |Pa/Qb| value, sensitivity, and specificity of 0.499, 60.7%, and 72.6%, respectively. |Pa/Qb| > 0.499 was associated with earlier intervention (317.37 ± 7.68 vs 345.96 ± 3.64 days), lower survival (p < 0.001), and a 3.26-fold greater risk of arteriovenous fistula dysfunction (p < 0.001) than |Pa/Qb| ⩽ 0.499. CONCLUSIONS: |Pa/Qb| was an independent risk factor for arteriovenous fistula dysfunction. Nurses should emphasize |Pa/Qb| monitoring and properly set blood pump speed according to this ratio to protect arteriovenous fistula function. |Pa/Qb| > 0.499 might be a predictive measure of arteriovenous fistula dysfunction.

Can the fistula arm be used to lift heavy items? Six-pound dumbbells versus handgrip exercise in a 6-month follow-up secondary analysis of a randomized controlled trial.

INTRODUCTION: Patients with arteriovenous fistulas are advised to avoid carrying heavy objects draped over the fistula arm. Awareness gradually leads to overprotection and a reduction in the use of the fistula arm. However, restricting motion in the fistula arm leads to decreased quality of life and diminished muscle strength. The current safety recommendations regarding lifting heavy items with the fistula arm are primarily based on experience. Few studies have provided evidence clarifying the scope of safe activity and the influence of load bearing on the continued patency of arteriovenous fistulas. METHODS: This prospective observation was based on a long-term follow-up study in which 86 hemodialysis recipients with arteriovenous fistulas were randomized into either a dumbbell group or a handgrip group. The dumbbell group exercised with 6-lb dumbbells, while the handgrip group squeezed rubber balls. Postintervention primary patency and adverse events at the 6-month follow-up were analyzed. RESULTS: No significant difference in postintervention primary patency was observed between the dumbbell group and the handgrip group at 6 months (97.4% vs 95.0%). There were two participants with high-flow fistulas in the dumbbell group and three in the handgrip group, with no significant difference between the two groups (5.3% vs 7.5%). In both groups, there were no other adverse events reported regarding cardiac failure, aneurysm, puncture site hematoma, or hemorrhage. CONCLUSION: Hemodialysis patients can safely use their fistula arm to lift objects weighing less than 6 lb, which encourages increased motion and helps preserve the functionality of the fistula arm.