Ropivacaine Administration Suppressed A549 Lung Adenocarcinoma Cell Proliferation and Migration via ACE2 Upregulation and Inhibition of the Wnt1 Pathway.

BACKGROUND: Previous studies have suggested that perioperative anesthesia could have direct impacts on cancer cell biology. The present study investigated the effects of ropivacaine administration on lung adenocarcinoma cells. METHODS: Ropivacaine was administered to A549 cells at concentrations of 0.1, 1, and 6 mM for 2 h. Angiotensin-converting enzyme 2 (ACE2) small interfering RNA (siRNA) transfection was performed 6 h prior to ropivacaine administration. Cell proliferation and migration were assessed with cell counting kit 8 (CCK-8) and a wound healing assay at 0 and 24 h after anesthesia exposure. PCR arrays were performed, followed by PCR validation. RESULTS: Ropivacaine administration inhibited A549 cell proliferation and migration in a concentration-dependent manner, with ACE2 upregulation and HIF1α (hypoxia-inducible factor 1α) downregulation. The anticancer effect of ropivacaine was canceled out via ACE2 siRNA transfection. PCR arrays showed specific gene change patterns in the ropivacaine and respective ACE2-knockdown groups. EGFR (epidermal growth factor receptor), BAX (Bcl-2-associated X protein) and BCL2 (B-cell/CLL lymphoma 2) were suppressed with ropivacaine administration; these effects were reversed via ACE2 siRNA induction. CONCLUSION: Ropivacaine administration inhibited A549 cell biology in conjunction with ACE2 upregulation via the inhibition of the Wnt1 (wingless/Integrated 1) pathway.

Self-Healing Hydrogel Resulting from the Noncovalent Interaction between Ropivacaine and Low-Molecular-Weight Gelator Sodium Deoxycholate Achieves Stable and Endurable Local Analgesia in Vivo.

Regional analgesia based on the local anesthetic ropivacaine plays a crucial role in postoperative pain management and recovery; however, the short duration of analgesia limits its clinical potential. Various drug delivery systems such as microparticles and lipid carriers have been used to prolong the analgesic effect, yet most of them are prone to abrupt release from the site of administration or have poor analgesic effects of less than 48 h, which fail to meet the needs of postoperative analgesia. In this study, a low-molecular-weight gelator sodium deoxycholate-based hydrogel loaded with ropivacaine (DC-ROP gel) was designed for long-acting analgesia. The noncovalent interaction between ropivacaine and sodium deoxycholate helps to improve the stability and sustained release performance of the gel. This internal drug-binding hydrogel also avoids experiencing the burst release effect commonly seen in polymer hydrogels previously reported for the slow release of local anesthetics. DC-ROP gel exhibited the dual advantages of self-healing after compression and long-term controlled release. In mice with inflammatory pain, DC-ROP gel achieved peripheral nerve block for more than 1 week after a single injection. Histological and blood biochemical analyses confirmed that the DC-ROP gel did not produce systemic toxicity, and cytotoxicity experiments demonstrated that the DC-ROP gel resulted in low irritation. These results suggest that DC-ROP gel provides a promising strategy for local anesthetics in long-term postoperative pain management, broadening the potential of bile salt-based low-molecular-weight hydrogels for drug delivery.

Effect of dexmedetomidine constant rate infusion on the analgesic duration of peripheral nerve blocks in dogs: a randomized clinical study.

The aim of this study was to evaluate whether a constant rate infusion of dexmedetomidine could prolong the analgesic effect of peripheral nerve blocks. Twenty client-owned dogs were enrolled and randomly divided into 2 groups. The DEX group received dexmedetomidine infusion at 1 mcg kg-1 h-1, and the NaCl group received an equivalent volume infusion of saline. Infusions were started after securing vascular access and continued for 10 min, after which intravenous (IV) methadone at 0.2 mg kg-1 and propofol to effect were administered. All animals were maintained with isoflurane in 70% oxygen. Sciatic, saphenous and obturator nerve blocks were performed using 0.1 mL kg-1 0.5% ropivacaine/block. Intraoperative fentanyl was administered if the heart rate and/or mean arterial pressure (MAP) increased > 15% from the previous measurement, and vasopressors were administered if MAP was ≤ 70 mmHg. Postoperative pain was assessed every hour using the Glasgow Composite Pain Scale (GCPS) until the first rescue analgesia administration. Postoperative rescue analgesia (methadone (0.2 mg kg-1 IV) and carprofen (2 mg kg-1 IV)) was administered if the pain score was higher than 6/24 or 5/20. Duration of analgesia was defined as the time between the nerve block procedure and initial postoperative rescue analgesia. Ambulation, proprioception, and skin sensitivity were evaluated to assess the duration of the motor and sensory block. A Student T and chi-square test were used to compare groups for duration of postoperative analgesia and intraoperative fentanyl and vasopressor use, respectively (p values ≤ 0.5 considered significant). A greater number of dogs in the NaCl group required fentanyl (5/10 p = 0.03) and vasopressors (8/10, p = 0.02) than did those in the DEX group (0/10 and 2/10, respectively). The duration of postoperative analgesia was significantly longer (604 ± 130 min) in the DEX group than in the NaCl group (400 ± 81 min, p = 0.0005).Dexmedetomidine infusion at 1 mcg kg-1 h-1 delays the time to first administration of rescue analgesia and reduces intraoperative analgesic and vasopressor requirements during Tibial Tuberosity Advancement surgery.

Ropivacaine prompts ferroptosis to enhance the cisplatin-sensitivity of human colorectal cancer through SIRT1/Nrf2 signaling pathway.

The ineffectiveness of cisplatin therapy in treating colorectal cancer (CRC) is attributed to an increase of resistance. It's necessary to investigate adjunctive agents capable of enhancing drug efficacy. Previous studies have shown that ropivacaine inhibit the growth of various cancer cells, but its impact on cisplatin resistance in tumors is not well understood. This study was to illustrate the impact and mechanism of ropivacaine enhanced cisplatin-sensitivity of CRC. Cisplatin alone treatment resulted in the elevation of reactive oxygen species (ROS) and intracellular Fe2+ levels, as well as a reduction in mitochondrial membrane potential (MMP) in cisplatin-sensitive LOVO cells, while these effects were mitigated in the cisplatin-resistant LOVO/DDP cells. The co-administration of ropivacaine with cisplatin inhibited cell viability and cell migration, decreased MMP, and promoted ROS accumulation and apoptosis in both LOVO cells and LOVO/DDP cells. And they upregulated the levels of ferroptosis makers and downregulated the expression of anti-ferroptosis proteins. However, this effect was reversed by ferroptosis inhibitor ferrostatin-1 or liproxstatin-1. Furthermore, we o demonstrated that the co-administration of ropivacaine and cisplatin resulted in a decrease in SIRT1 expression, and SIRT1 knockdown in LOVO/DDP cells enhanced the ferroptosis and the anti-tumor properties of ropivacaine, while also inhibiting the activation of the Nrf2/Keap1 pathway. The above results suggested that ropivacaine increased the sensitivity of CRC cells to cisplatin by promoting ferroptosis through the inhibition of SIRT1 expression, which proposes a therapeutic approach for overcoming cisplatin resistance in CRC.

Clinical effects of perineural dexmedetomidine or magnesium sulphate as adjuvants to ropivacaine in dogs undergoing tibial plateau leveling osteotomy.

The study aimed to compare the quality of perioperative analgesia, the motor block duration, and the effects on main cardiovascular parameters of dexmedetomidine (1 µg/kg/nerve block) or magnesium sulphate (2 mg/kg/nerve block) as adjuvants to 0.3% ropivacaine for sciatic and saphenous nerves block in dogs undergoing tibial plateau leveling osteotomy (TPLO). Dogs randomly received perineural dexmedetomidine-ropivacaine (D group), magnesium sulphate-ropivacaine (M group), or ropivacaine (C group). Fentanyl was administered in case of intraoperative nociception. Postoperative pain was assessed using the Short Form-Glasgow Composite Measure Pain Scale (SF-GCMPS) and VAS scale. The duration of motor blockade and intra- and postoperative cardiovascular parameters were also recorded. Group M required significantly more fentanyl than D group (p = 0.04). Group M had a significantly higher SF-GCMPS score than group C at 4 (p = 0.002) and 5 h after extubation (p = 0.01), and a significantly higher VAS score than group D at 3 h after extubation (p = 0.03), and at 4 h if compared to group C (p = 0.009). No significant differences regarding the duration of motor blockade were detected between groups (p = 0.07). The heart rate was significantly lower in group D than in M and C groups intraoperatively and during the first 1.5 h post extubation. The addition of dexmedetomidine or magnesium sulphate as adjuvants to perineural ropivacaine did not improve the quality of perioperative analgesia and did not prolong the motor blockade in dogs undergoing sciatic and saphenous nerves block for TPLO surgery.

Effects of dexmedetomidine, fentanyl and magnesium sulfate added to ropivacaine on sensory and motor blocks in lower abdominal surgery: a randomized clinical trial.

This study aimed to compare the effects of intrathecal dexmedetomidine, fentanyl and magnesium sulfate added to ropivacaine on the onset and duration of sensory and motor blocks in lower abdominal surgery. This double-blind randomized clinical trial included 90 patients scheduled for lower abdominal surgery at Vali-Asr Hospital in Arak, Iran. The enrolled patients were randomly divided into three equal groups and then underwent spinal anesthesia. The first group received 10 µg of dexmedetomidine, the second group received 50 µg of fentanyl, and the third group received 200 mg of 20% magnesium sulfate intrathecally in addition to 15 mg of 0.5% ropivacaine. In the dexmedetomidine group, the mean arterial blood pressure was lower than the other two groups (P = 0.001). Moreover, the time to onset of sensory block (P = 0.001) and the mean duration of sensory block (P = 0.001) were shorter and longer, respectively, in the dexmedetomidine group than in the other two groups. In the dexmedetomidine group, the mean time to onset of motor block (P = 0.001) and the mean duration of motor block (P = 0.001) were lower and higher than in the other two groups, respectively. There was no significant difference in visual analog scale score, heart rate, administered opioid, and drug side effects among the three groups. Dexmedetomidine caused early sensory and motor blocks while prolonging the duration of sensory and motor blocks compared with the other two groups. In addition, dexmedetomidine reduced mean arterial blood pressure in patients. Based on the findings of this study, it is recommended that dexmedetomidine can be used in order to enhance the quality of sensory and motor block in patients.

Efficacy of Ropivacaine for Sub-Arachnoid Block in Patients with Recent History of Scorpion Sting: A case series.

Failure of sub-arachnoid block (SAB), due to resistance to bupivacaine after a recent scorpion sting can lead to multiple block attempts and subsequent conversion to general anaesthesia. We report this case series of 10 patients with successful SAB with newly launched 0.75% hyperbaric ropivacaine, in patients with recent scorpion sting. Thus, intrathecal hyperbaric ropivacaine may be considered as the local anaesthetic agent of choice in patients with scorpion sting to prevent failure of SAB.

Effects of Dexmedetomidine Added to Ropivacaine in Ultrasound-Guided Continuous Pericapsular Nerve Group Block Among Elderly Patients Undergoing Total Hip Arthroplasty.

Total hip arthroplasty (THA) is a highly effective intervention for addressing hip joint issues, yet managing perioperative pain remains a significant challenge. In this study, we aimed to investigate the impact of supplementing ropivacaine with dexmedetomidine in ultrasound-guided continuous pericapsular nerve group block (PENGB) among elderly patients undergoing THA. We conducted a retrospective analysis involving 112 elderly patients who underwent THA. These patients were divided into two groups: the Control group, receiving ropivacaine alone, and the DEX group, receiving ropivacaine combined with dexmedetomidine. We evaluated various parameters including hemodynamic data, postoperative pain levels assessed using the Visual Analog Scale, cognitive status measured with the Montreal Cognitive Assessment, and serum markers (S100ß and GFAP). Our findings revealed that the DEX group exhibited improved stability in blood pressure and oxygen saturation following surgery. Moreover, patients in the DEX group reported significantly lower levels of pain at 6 and 12 hours postsurgery, with a prolonged duration of pain relief. Furthermore, dexmedetomidine administration was associated with preserved cognitive function during the early postoperative period. Analysis of serum markers suggested potential cognitive protection conferred by the addition of dexmedetomidine. Overall, our study underscores the multifaceted benefits of incorporating dexmedetomidine into ropivacaine-based PENGB for elderly THA patients.

Efficacy of transversus abdominis plane block on postoperative nausea and vomiting: a meta-analysis of randomized controlled trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common postoperative complication, and Transversus abdominis plane (TAP) block can provide effective analgesia for surgical operation. However, but there is not enough evidence to prove its advantage for nausea and vomiting. The objective of this meta-analysis was to evaluate the efficacy of TAP block on PONV. METHODS: Two independent researchers conducted searches for randomized controlled trials (RCTs) in PubMed, Embase, and Cochrane Central Register of Controlled Trials. We used Review Manager software for meta-analysis. RESULTS: In this meta-analysis, twenty-six trials with 1981 patients were examined. The results showed that TAP block reduced postoperative nausea (Risk Difference (RD) = -0.10, 95% confidence interval (CI): -0.15 to -0.05) compared with no TAP block. TAP block reduced the dose of fentanyl (Standardized Mean Difference (SMD) = -1.17, 95% CI: -2.07 to -0.26) and morphine (SMD = -1.12, 95% CI: -2.10 to -0.13) compared with no TAP block, when the timing of administration was before surgery (RD = -0.13, 95% CI: -0.19 to -0.07). TAP block reduced postoperative nausea when the ropivacaine dosage is ≤ 100 mg (RD = -0.13, 95% CI: -0.21 to -0.06), bupivacaine dosage ≥ 100 mg ( RD = -0.08, 95% CI: -0.13 to -0.03), and when the ropivacaine concentration was ≤ 0.375% (RD = -0.11, 95% CI: -0.18 to -0.04). TAP block significantly reduced the incidence of nausea when the types of opioid drugs in PCA is tramadol (RD = -0.13, 95% CI: -0.24 to -0.03). TAP block could reduce the VAS (SMD= -0.99, 95% CI: -1.29 to -0.70) and reduce the time of extubation (SMD = -0.71, 95% CI: -1.34 to -0.08). CONCLUSION: The meta-analysis conducted in this study revealed that TAP block could reduce the incidence of PONV, and the efficacy of TAP block may be influenced by factors such as administration time, local anesthetic dosage and concentration, types of opioid drugs in PCA.

Ropivacaine as a novel AKT1 specific inhibitor regulates the stemness of breast cancer.

BACKGROUND: Ropivacaine, a local anesthetic, exhibits anti-tumor effects in various cancer types. However, its specific functions and the molecular mechanisms involved in breast cancer cell stemness remain elusive. METHODS: The effects of ropivacaine on breast cancer stemness were investigated by in vitro and in vivo assays (i.e., FACs, MTT assay, mammosphere formation assay, transwell assays, western blot, and xenograft model). RNA-seq, bioinformatics analysis, Western blot, Luciferase reporter assay, and CHIP assay were used to explore the mechanistic roles of ropivacaine subsequently. RESULTS: Our study showed that ropivacaine remarkably suppressed stem cells-like properties of breast cancer cells both in vitro and in vivo. RNA-seq analysis identified GGT1 as the downstream target gene responding to ropivacaine. High GGT1 levels are positively associated with a poor prognosis in breast cancer. Ropivacaine inhibited GGT1 expression by interacting with the catalytic domain of AKT1 directly to impair its kinase activity with resultant inactivation of NF-κB. Interestingly, NF-κB can bind to the promoter region of GGT1. KEGG and GSEA analysis indicated silence of GGT1 inhibited activation of NF-κB signaling pathway. Depletion of GGT1 diminished stem phenotypes of breast cancer cells, indicating the formation of NF-κB /AKT1/GGT1/NF-κB positive feedback loop in the regulation of ropivacaine-repressed stemness in breast cancer cells. CONCLUSION: Our finding revealed that local anesthetic ropivacaine attenuated breast cancer stemness through AKT1/GGT1/NF-κB signaling pathway, suggesting the potential clinical value of ropivacaine in breast cancer treatment.

Ropivacaine combined with sorafenib attenuates hepatocellular carcinoma cell proliferation and metastasis by inhibiting the miR-224/HOXD10 axis.

OBJECTIVE: The development of drug resistance in hepatocellular carcinoma (HCC) cells limits the effectiveness of sorafenib (Sor). However, the regulatory mechanisms underlying the effects of the combination Sor and ropivacaine (Rop) on HCC cells remain unclear. METHODS: miR-224 and HOXD10 mRNA expression in HCC cells was analyzed using qRT-PCR. CCK-8, Transwell assays and tumor formation experiments in nude mice were used to assess HCC cell proliferation, migration, and invasion. Migration of HCC cells was also analyzed using a cell scratch assay. Hematoxylin and eosin staining was used to detect tumor area. RESULTS: miR-224 expression profoundly increased in HepG2 and Huh7 cells. Treatment with Rop and/or Sor blocked miR-244 expression, especially the combination treatment. Transfection of miR-224 mimic increased HCC cell proliferation and tumor size in nude mice, and migration and invasion in vitro in the presence of Rop and Sor compared to the negative control mimic. Dual-luciferase reporter assays showed that HOXD10 was targeted by miR-224. HOXD10 protein expression and was markedly reduced in HepG2 and Huh7 cells. Rop and/or Sor treatment increased HOXD10 protein expression, particularly the combination treatment. miR-224 negatively regulated HOXD10 expression in HCC cells treated with Rop and Sor. Transfection-mediated silencing of HOXD10 increased HCC cell proliferation, migration, and invasion in the presence of Rop and Sor compared with negative control transfection. CONCLUSION: The combination of Rop and Sor attenuates HCC cell proliferation and metastasis via the miR-224/HOXD10 axis.

Effect of ultrasound-guided stellate ganglion block on inflammatory cytokines and postoperative recovery after partial hepatectomy: a randomised clinical trial.

BACKGROUND: Stellate ganglion block (SGB) has been shown to reduce perioperative complications in various surgeries. Because laparoscopic techniques and instruments have advanced during the past two decades, laparoscopic liver resection is being increasingly adopted worldwide. Lesser blood loss, fewer postoperative complications, and shorter postoperative hospital stays are the advantages of laparoscopic liver resection, as compared to conventional open surgery. There is an urgent need for an effective intervention to reduce perioperative complications and accelerate postoperative recovery. This study investigated the effect of ultrasound-guided SGB on enhanced recovery after laparoscopic partial hepatectomy. METHODS: We compared patients who received SGB with 0.5% ropivacaine (group S) with those who received SGB with 0.9% saline (group N). A total of 58 patients with partial hepatectomy were enrolled (30 S) and (28 N). Before induction of anesthesia, SGB was performed with 0.5% ropivacaine in group S and 0.9% saline in group N. MAIN OUTCOME: Comparison of serum inflammatory cytokines concentration at each time point. RESULTS: Main outcome: When comparing IL-6 and IL-10 concentrations among groups, group S showed less variation over time compared to group N. For comparison between groups, the serum IL-6 concentration in group S was lower than that in group N at 6 and 24 h after operation (P < 0.01), and there was a significant linear relationship between serum IL-6 concentration at 24 h after operation and hospitalization situation. CONCLUSIONS: Ultrasound-guided SGB can stabilize perioperative inflammatory cytokines plays a positive role in the enhanced recovery of patients after laparoscopic partial hepatectomy. The serum IL-6 level within 24 h after surgery may be used as a predictor of hospitalization. TRIAL REGISTRATION: The study was registered at the ClinicalTrials.gov (Registration date: 13/09/2021; Trial ID: NCT05042583).

The impact of biological sex in peripheral nerve blockade: A prospective pharmacodynamic, pharmacokinetic and morphometric study in volunteers.

STUDY OBJECTIVE: The impact of biological sex in peripheral regional anaesthesia is largely unknown. We therefore designed a prospective study in volunteers to investigate the impact of biological sex on pharmacodynamic, pharmacokinetic and morphometric characteristics for peripheral nerve blockade. METHODS: The initial study plan was powered to include 90 volunteers to find a difference of 35 min in duration of sensory block (primary outcome variable) with 80% power and alpha error at 5%. After discussions in ethical review, a pilot study of 2 x 12 volunteers from each sex were studied. Female and male volunteers received ultrasound guided nerve blockade with 3.0 mL ropivacaine 7.5 mg mL-1. Sensory duration of blockade, as the primary outcome, was evaluated by pinprick testing. Secondary outcomes were sensory onset time of blockade, pharmacokinetic characteristics and the visibility of ulnar nerves using ultrasound. Analyses included Mann-Whitney U-statistics with P<0.05 (two-sided) as significant. RESULTS: After 24 participants, the median (IQR) duration of sensory blockade was 450 (420; 503) min in women and 480 (450; 510) min in men (P = 0.49). Sensory onset time of blockade, and ultrasound visibility of nerves were also similar between the study groups. The total drug exposure across time (AUC0-infinity) was significantly higher in women (P = 0.017). After a the planned power re-analysis after these 24 study paticipants, which suggested that > 400 subjects would be required with 80% power and alpha error of 5% to find significance for the primary outcome parameter for marginal differences, we terminated the study at this point. CONCLUSIONS: We did not detect significant differences between female and male study participants in terms of pharmacodynamic and morphometric characteristics after ultrasound guided ulnar nerve blocks. Women did show significantly greater pharmacokinetic ropivacaine exposures. The results of this study indicate that peripheral regional block pharmacodynamic characteristics are independent of the biological sex, whereas pharmacokinetic parameters are sex-dependent.

Ropivacaine inhibits the proliferation and metastasis of gastric cancer cells via the SNX10/SRC/STAT3 pathway.

Gastric cancer currently has no effective treatment due to its high metastasis and heterogeneity. It has been reported that ropivacaine (Rop) can inhibit the growth, migration, and invasion of gastric cancer. However, the therapeutic mechanism of Rop still needs to be further explored to provide insights for its clinical application. This study aimed to explore the effects of Rop on the growth, migration, and invasion of gastric cancer cells and the underlying mechanisms. The expression levels of SNX10 were assessed in gastric cancer tissues and cell line AGS by qRT-PCR. Cell Counting Kit-8 (CCK8) assay, wound-healing assay, and transwell assay were then used to examine the effects of Rop on the AGS cell viability, migration, invasion, and proliferation, respectively. Additionally, colony formation assay was used to measure cell proliferation ability, and flow cytometry was used to detect apoptosis level. Protein levels of SNX10, SRC, and STAT3 were detected by western blot. According to the experimental results, the decreased SNX10 mRNA expression was observed in gastric cancer tissue and cell line AGS. Rop inhibited the proliferation, migration, and invasion of AGS cells, but promoted apoptosis and upregulated SNX10 expression. Moreover, Rop inhibited the expression of MMP-2 and MMP-9, phosphorylation of SRC and STAT3. SNX10 knockdown could reverse Rop-induced anticancer effects. Collectively, Rop showed a potential role in preventing proliferation and metastasis of gastric cancer. The action mechanism of Rop may be related to the upregulation of SNX10 expression and further inhibition of SRC/STAT3 signaling pathway. Our findings provide new insights into the anticancer properties of Rop.

Effect of transversus abdominis plane block with or without buprenorphine after inguinal hernia surgery on postoperative pain.

INTRODUCTION: Transversus abdominis plane (TAP) has been mentioned as having bene-ficial effects on chronic pain after hernioplasty. This study assessed the effects of TAP block on acute and persistent postoperative pain after inguinal hernia surgery, with or without buprenorphine. MATERIAL AND METHODS: 64 patients were allocated to group R ( n = 32) and received 20 mL of 0.25% ropivacaine for TAP block; group RB ( n = 32) received 20 mL of 0.25% ropivacaine containing 300 µg of buprenorphine for TAP block. The primary outcome was the analgesic and antihyperalgesic effect of buprenorphine. The duration of analgesia, analgesic consumption, postoperative pain scores at rest and sitting up to 48 hours, and the effect on wound hyperalgesia were evaluated. Secondary outcomes included the incidence of side effects and complications. RESULTS: The median (IQR) duration of analgesia in group R was 386.5 (37.25) minutes vs. 868 (41.3) minutes in the RB group. Median pain scores on sitting were found to be significantly better in group RB than in group R at 6, 12, and 24 hours ( P < 0.001). The wound hyperalgesia index showed a significant difference between groups ( P < 0.001). The incidence of persistent postoperative pain was 6.25% in the R group, as compared to 0% in the RB group. Otherwise, the patients did not have any further complications associated with the block. CONCLUSIONS: The results demonstrated that TAP block with buprenorphine reduced acute postoperative pain severity, but we did not find a difference between groups in persistent pain.

The effect of warming ropivacaine on ultrasound-guided subgluteal sciatic nerve block: a randomized controlled trial.

BACKGROUND: There is a long latent period for the sciatic nerve block before a satisfactory block is attained. Changes in the temperature of local anesthetics may influence the characters of the peripheral nerve block. This study was designed to evaluate the effect of warming ropivacaine on the ultrasound-guided subgluteal sciatic nerve block. METHODS: Fifty-four patients for distal lower limbs surgery were randomly allocated into warming group (group W, n = 27) or room tempeture group (group R, n = 27) with the ultrasound-guided subgluteal sciatic nerve block. The group W received 30 ml of ropivacaine 0.5% at 30℃ and the group R received 30 ml of ropivacaine 0.5% at 23℃. The sensory and motor blockade were assessed every 2 min for 30 min after injection. The primary outcome was the onset time of limb sensory blockade. RESULTS: The onset time of sensory blockade was shorter in group W than in group R (16 (16,18) min vs 22 (20,23) min, p < 0.001), and the onset time of motor blockade was also shorter in group W than in group R (22 (20,24) min vs 26 (24,28) min, p < 0.001). The onset time of sensory blockade for each nerve was shorter in group W than in group R (p < 0.001). No obvious differences for the duration of sensory and motor blockade and the patient satisfaction were discovered between both groups. No complications associated with nerve block were observed 2 days after surgery. CONCLUSIONS: Warming ropivacaine 0.5% to 30℃ accelerates the onset time of sensory and motor blockade in the ultrasound-guided subgluteal sciatic nerve block and it has no influence on the duration of sensory and motor blockade. TRIAL REGISTRATION: The trial was registered on October 3, 2022 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/bin/project/edit?pid=181104 ), registration number ChiCTR2200064350 (03/10/2022).

Ropivacaine inhibits the malignant behavior of lung cancer cells by regulating retinoblastoma-binding protein 4.

Background: Ropivacaine is a local anesthetic commonly used in regional nerve blocks to manage perioperative pain during lung cancer surgery. Recently, the antitumor potential of ropivacaine has received considerable attention. Our previous study showed that ropivacaine treatment inhibits the malignant behavior of lung cancer cells in vitro. However, the potential targets of ropivacaine in lung cancer cells have not yet been fully identified. This study aimed to explore the antitumor effects and mechanisms of action of ropivacaine in lung cancer. Methods: Lung cancer A549 cells were treated with or without 1 mM ropivacaine for 48 h. Quantitative proteomics was performed to identify the differentially expressed proteins (DEPs) triggered by ropivacaine treatment. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and analyze the most significant hub genes. Overexpression plasmids and small interfering RNA were used to modulate the expression of key DEPs in A549 and H1299 cells. MTS, transwell assays, and flow cytometry were performed to determine whether the key DEPs were closely related to the anticancer effect of ropivacaine on the malignant behavior of A549 and H1299 cells. Results: Quantitative proteomic analysis identified 327 DEPs (185 upregulated and 142 downregulated proteins) following ropivacaine treatment. Retinoblastoma-binding protein 4 (RBBP4) was one of the downregulated DEPs and was selected as the hub protein. TCGA database showed that RBBP4 was significantly upregulated in lung cancer and was associated with poor patient prognosis. Inhibition of RBBP4 by siRNA resulted in a significant decrease in the proliferation and invasive capacity of lung cancer cells and the induction of cell cycle arrest. Additionally, the results indicated RBBP4 knockdown enhanced antitumor effect of ropivacaine on A549 and H1299 cells. Conversely, the overexpression of RBBP4 using plasmids reversed the inhibitory effects of ropivacaine. Conclusion: Our data suggest that ropivacaine suppresses lung cancer cell malignancy by downregulating RBBP4 protein expression, which may help clarify the mechanisms underlying the antitumor effects of ropivacaine.

Nanocrystals Slow-Releasing Ropivacaine and Doxorubicin to Synergistically Suppress Tumor Recurrence and Relieve Postoperative Pain.

Although surgical resection provides a straightforward and effective treatment for most malignant solid tumors, tumor recurrence and acute postoperative pain continue to be two big problems associated with this treatment. To resolve these problems, a nanocrystal composite slow-releasing ropivacaine and doxorubicin was fabricated in this study. Briefly, a self-assembling peptide was used to form nanoparticle complexes with the two drugs, based on which homogeneous nanocrystals were obtained by adjusting the pH. In cultured human melanoma cells, the nanocrystals exhibited improved antitumor activity due to a synergistic effect and enhanced cellular uptake of the two drugs. On the other hand, the nanocrystals could slowly release ropivacaine in vitro and in vivo, generating long-acting analgesia on the rat sciatic nerve block model and incisional pain model. On a nude mouse tumor resection model, the nanocrystals simultaneously suppressed the recurrence of solid tumor and relieved postoperative pain, indicating a potential postoperative treatment for tumor resection patients. This nanocrystal system also suggested a promising and facile strategy for developing multifunctional formulations combining different drugs, which could achieve better therapeutic outcomes in a synergistic and sustained manner.

Topical ropivacaine hydrochloride 0.5% and lidocaine hydrochloride 2% significantly reduce corneal sensitivity without short-term negative side effects in horses.

OBJECTIVE: To evaluate corneal sensitivity and acute side effects following application of ropivacaine hydrochloride 0.5% and lidocaine hydrochloride 2% on the healthy equine cornea. ANIMALS STUDIED: Eight healthy adult horses. PROCEDURE: A randomized, masked, crossover study design was utilized. Baseline Semiquantitative Preclinical Ocular Toxicology (SPOT) scores and corneal touch thresholds (CTT) using a Cochet-Bonnet esthesiometer were recorded and measured, respectively, for eight healthy adult horses before medication application. Commercially available eyewash was used as a negative control. Ropivacaine hydrochloride 0.5% or lidocaine hydrochloride 2% solution was sprayed on a randomly selected eye, and the contralateral eye received eyewash. CTT was measured in both eyes at 1, 5, 15, 25, 35, 45, 55, 65, and 75 min post-application. Post-application SPOT scores were recorded immediately following the trial. Linear mixed model statistical analyses (mean ± standard error) were performed (p < .05). RESULTS: Mean eyewash CTT (3.41 cm ± 0.464) was significantly different from ropivacaine-treated (1.44 cm ± 0.562) (p = .008) and lidocaine-treated eyes (1.75 cm ± 0.562) (p = .024); CTT was not significantly different between drug groups (p = .88). Time to maximum anesthesia was not significantly different between ropivacaine (13.25 min ± 3.353) and lidocaine (16.25 min ± 3.353) (p = .40). No side effects were appreciated as confirmed by SPOT. CONCLUSIONS: Ropivacaine and lidocaine similarly decreased corneal sensitivity when applied topically without clinically evident short-term ocular side effects. Lidocaine may be preferable in clinical settings due to its large, multi-use vials and similar effects to ropivacaine.

Comprehensive Analysis of Local Anesthetics Affecting Adipose Stem Cells In Vitro.

BACKGROUND: Adipose stem cells (ASCs) hold a great regenerative capacity because of their differentiation capability and their secretory activity. Thus, ASC survival is of great significance during perioperative harvesting. Various local anesthetics are commonly applied during fat grafting procedures. These substances are known to impair cellular viability, which would affect graft survival and final outcomes, but the exact extent of their impact on ASC biology is unknown. METHODS: The authors analyzed the short- and long-term effects of lidocaine, mepivacaine, ropivacaine, and bupivacaine at increasing concentrations (0.1 to 10 mM) on primary human ASC proliferation and metabolic activity. Trilinear differentiation was assessed by oil red O stain (adipogenesis), safranin O (chondrogenesis), and cresolphthalein (osteogenesis) labeling. In supernatants, cytokine [interleukin (IL)-6/IL-8, vascular endothelial growth factor, hepatocyte growth factor] secretion was analyzed by enzyme-linked immunosorbent assay. RESULTS: Bupivacaine at greater than 100 µM demonstrated the strongest anti proliferative effects, whereas lidocaine and ropivacaine did not affect cell numbers. Mepivacaine evoked reciprocal results regarding cell count at greater than 1 mM. Each compound impaired trilinear differentiation. Secretion of hepatocyte growth factor and IL-8 was reduced significantly by local anesthetic exposure; levels were restored after substances were washed out. CONCLUSIONS: In vitro data show that lidocaine, mepivacaine, and ropivacaine could be applied at concentrations of 1 to 10 mM without affecting ASC survival. In contrast, bupivacaine at concentrations greater than 100 µM should be administered with great caution. The differentiation of ASCs and the ASC's secretome might already be decreased by each local anesthetic at 1 mM. CLINICAL RELEVANCE STATEMENT: The authors' experimental data can be of great significance to the clinical practice, as local anesthetics are routinely administered during liposuction as a tumescent anesthesia adjunct. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.