Diabetes impairs the protective effects of sevoflurane postconditioning in the myocardium subjected to ischemia/ reperfusion injury in rats: important role of Drp1.

BACKGROUND: Sevoflurane postconditioning (SevP) effectively relieves myocardial ischemia/reperfusion (I/R) injury but performs poorly in the diabetic myocardium. Previous studies have revealed the important role of increased oxidative stress in diabetic tissues. Notably, mitochondrial fission mediated by dynamin-related protein 1 (Drp1) is an upstream pathway of reactive oxygen production. Whether the ineffectiveness of SevP in the diabetic myocardium is related to Drp1-dependent mitochondrial fission remains unknown. This study aimed to explore the important role of Drp1 in the diabetic myocardium and investigate whether Drp1 inhibition could restore the cardioprotective effect of SevP. METHODS: In the first part of the study, adult male Sprague-Dawley rats were divided into 6 groups. Rats in the diabetic groups were fed with high-fat and high-sugar diets for 8 weeks and injected intraperitoneally with streptozotocin (35 mg/kg). Myocardial I/R was induced by 30 min of occlusion of the left anterior descending branch of the coronary artery followed by 120 min of reperfusion. SevP was applied by continuous inhalation of 2.5 % sevoflurane 1 min before reperfusion, which lasted for 10 min. In the second part of the study, we applied mdivi-1 to investigate whether Drp1 inhibition could restore the cardioprotective effect of SevP in the diabetic myocardium. The myocardial infarct size, mitochondrial ultrastructure, apoptosis index, SOD activity, MDA content, and Drp1 expression were detected. RESULTS: TTC staining and TUNEL results showed that the myocardial infarct size and apoptosis index were increased in the diabetic myocardium. However, SevP significantly alleviated myocardial I/R injury in the normal myocardium but not in the diabetic myocardium. Additionally, we found an elevation in Drp1 expression, accompanied by more severe fission-induced structural damage and oxidative stress in the diabetic myocardium. Interestingly, we discovered that the beneficial effect of SevP was restored by mdivi-1, which significantly suppressed mitochondrial fission and oxidative stress. CONCLUSIONS: Our study demonstrates the crucial role of mitochondrial fission dependent on Drp1 in the diabetic myocardium subjected to I/R, and strongly indicates that Drp1 inhibition may restore the cardioprotective effect of SevP in diabetic rats.

Pain management after ambulatory surgery: a prospective, multicenter, randomized, double-blinded parallel controlled trial comparing nalbuphine and tramadol.

BACKGROUND: Postoperative pain in ambulatory surgery is a multifactorial issue affecting patient satisfaction, time of discharge, and rehospitalization. This study evaluated the efficacy and safety of nalbuphine for the treatment of postoperative pain after ambulatory surgery, relative to tramadol. METHODS: This multi-center, randomized, double blind, and controlled study was conducted at 10 centers. In accordance with the inclusion criteria, 492 ambulatory surgery patients were recruited. These patients had moderate to severe pain after ambulatory surgery, with a visual analogue scale (VAS) score > 3 cm. They were randomly divided into an experimental (n = 248) or control (n = 244) group and treated for analgesia with 0.2 mg/kg of nalbuphine or 2 mg/kg of tramadol, respectively. VAS scores, adverse events, and vital signs of the patients were recorded before administration (baseline; T1); and 30 min (T2), 2 h (T3), 4 h (T4), and 6 h (T5) after administration of analgesia. A decrease in pain intensity of more than 25% compared with the baseline was used as an indicator of analgesic efficacy. The experimental and control groups were compared with regard to this indicator of efficacy at each timepoint. RESULTS: The VAS scores of the experimental and control groups were statistically comparable at timepoints T1-T4. At T5, the VAS scores of the experimental group were significantly lower than that of the control. The pain intensity was significantly higher in the experimental group compared with the control at T2 and T3. Adverse events and vital signs were similar for the two groups at each timepoint. CONCLUSIONS: Nalbuphine can provide effective and safe pain relief in patients after ambulatory surgery. TRIAL REGISTRATION: The registration number is ChiCTR-IOR-16010032 , the date of registration was 2016-11-28.

Both Bupivacaine and Levobupivacaine inhibit colon cancer cell growth but not melanoma cells in vitro.

BACKGROUND: Retrospective studies indicate that the use of regional anaesthesia causes a reduction in cancer recurrence after oncological surgery, which could be due to anaesthetic's negating effect on immunosuppression related to the surgical stress response. Local anaesthetics may also exert direct suppressive effects on malignant cells, an area where further investigation is urgently needed. METHODS: Human colon cancer cells and human melanoma cells were cultured and then treated with 1 mM bupivacaine or levobupivacaine for up to 24 or 48 h. Their migratory ability was measured by scratch assay, proliferation determined with Ki67 immunofluorescence staining, and apoptosis accessed with annexin V and PI staining on flow cytometry. The effects of bupivacaine and levobupivacaine on cellular signaling and molecular response, specifically, on endoplasmic reticulum stress (ERS), were studied with immunostaining and western blot. RESULTS: In colon cancer cells, treatment with bupivacaine and levobupivacaine significantly inhibited cell migration (**p < 0.01, ***p < 0.001; n = 4) and proliferation (**p < 0.01; n = 4), while increasing the expression of CHOP (***p < 0.001; n = 4) and decreased the expression of Grp78 (*p < 0.05; n = 4). These effects were not mirrored by melanoma cells, such that no significant increase in apoptosis was seen in either melanoma cell lines following treatment. CONCLUSION: These in vitro data suggested that both bupivacaine and levobupivacaine suppress colorectal adenocarcinoma cell proliferation and migration, which are concurrent with increased endoplasmic reticulum stress. Conversely, melanoma cells are more resilient to these two commonly used local anaesthetics. Further in vivo studies or clinical trials are needed.

The Effect of CT-Guided Pulsed Radiofrequency Combined with Ozone Injection on Zoster-Associated Pain: A Retrospective Study.

Purpose: Globally, the incidence of herpes zoster (HZ) is increasing, and the resulting zoster-associated pain (ZAP) severely affects the quality of life of patients. Therefore, active treatment of ZAP and prevention of postherpetic neuralgia (PHN) are very important for patients in the early stage of the disease. This retrospective observational study aimed to evaluate the effect of CT-guided pulsed radiofrequency (PRF) combined with ozone injection on zoster-associated pain. Patients and Methods: From 2018 to 2020, 84 patients with AHN (n=28), SHN (n=32), or PHN (n=24) underwent PRF combined with ozone injection treatment after pharmacologic and conservative therapies failed. The visual analogue scale (VAS), the Pittsburgh Sleep Quality Index (PSQI), and pregabalin consumption were recorded at baseline, post-PRF, and at 1, 3, 6, and 12 months after treatment. The number of remediations performed and adverse reactions were recorded, and treatment inefficiency was calculated using a VAS score greater than 3 as the criterion. Results: The pooled results demonstrated statistically significant decreases in VAS scores, PSQI scores and consumption of pregabalin post-PRF and at 1, 3, 6, and 12 months follow-up (P<0.05). Compared with the PHN group, both the AHN and SHN groups showed clinical and statistical improvement in VAS scores and PSQI scores and in consumption of pregabalin (P< 0.05). At 1 year after the operation, the PHN group had a significantly greater number of remediation events and greater treatment inefficiency than the other two groups. No serious adverse events were observed during the procedure or during the follow-up period. Conclusion: CT-guided PRF combined with ozone injection is safe and effective for individuals with ZAP, and its short-term and long-term effects are significant. In a sense, early PRF combined with ozone injection is more effective.

Wavelet and pain rating index for inhalation anesthesia: A randomized controlled trial.

BACKGROUND: Wavelet index (WLi) and pain rating index (PRi) are new parameters for regulating general anesthesia depth based on wavelet analysis. AIM: To investigate the safety and efficacy of using WLi or PRi in sevoflurane anesthesia. METHODS: This randomized controlled trial enrolled 66 patients scheduled for elective posterior lumbar interbody fusion surgery under sevoflurane anesthesia between September 2017 and February 2018. A random number generator was used to assign the eligible patients to three groups: Systolic blood pressure (SBP) monitoring group, WLi monitoring group, and PRi monitoring group. The main anesthesiologist was aware of the patient grouping and intervention used. The primary endpoint was anesthesia recovery time. Secondary endpoints included extubation time, sevoflurane consumption, number of unwanted events/ interventions, number of adverse events and postoperative visual analogue scale for pain. RESULTS: A total of 62 patients were included in the final analysis (SBP group, n = 21; WLi group, n = 21; and PRi group, n = 20). There were no significant differences among the three groups in patient age, gender distribution, body mass index, American Society of Anesthesiologists class, duration of surgery, or duration of anesthesia. Anesthesia recovery time was shorter in the WLi and PRi groups than in the SBP group with no significant difference between the WLi and PRi groups. Extubation time was shorter in the WLi and PRi groups than in the SBP group. Sevoflurane consumption was lower in the WLi and PRi groups than in the SBP group. Nicardipine was more commonly needed to treat hypertension in the WLi and PRi groups than in the SBP group. CONCLUSION: Regulation of sevoflurane anesthesia depth with WLi or PRi reduced anesthesia recovery time, extubation time and sevoflurane consumption without intraoperative unwanted events.