Bupivacaine Research Articles

Human Umbilical Cord Mesenchymal Stem Cells Extricate Bupivacaine-Impaired Skeletal Muscle Function via Mitigating Neutrophil-Mediated Acute Inflammation and Protecting against Fibrosis.

Skeletal muscle injury presents a challenging traumatological dilemma, and current therapeutic options remain mediocre. This study was designed to delineate if engraftment of mesenchymal stem cells derived from umbilical cord Wharton’s jelly (uMSCs) could aid in skeletal muscle healing and persuasive molecular mechanisms. We established a skeletal muscle injury model by injection of myotoxin bupivacaine (BPVC) into quadriceps muscles of C57BL/6 mice. Post BPVC injection, neutrophils, the first host defensive line, rapidly invaded injured muscle and induced acute inflammation. Engrafted uMSCs effectively abolished neutrophil infiltration and activation, and diminished neutrophil chemotaxis, including Complement component 5a (C5a), Keratinocyte chemoattractant (KC), Macrophage inflammatory protein (MIP)-2, LPS-induced CXC chemokine (LIX), Fractalkine, Leukotriene B4 (LTB4), and Interferon-γ, as determined using a Quantibody Mouse Cytokine Array assay. Subsequently, uMSCs noticeably prevented BPVC-accelerated collagen deposition and fibrosis, measured by Masson’s trichrome staining. Remarkably, uMSCs attenuated BPVC-induced Transforming growth factor (TGF)-β1 expression, a master regulator of fibrosis. Engrafted uMSCs attenuated TGF-β1 transmitting through interrupting the canonical Sma- And Mad-Related Protein (Smad)2/3 dependent pathway and noncanonical Smad-independent Transforming growth factor beta-activated kinase (TAK)-1/p38 mitogen-activated protein kinases signaling. The uMSCs abrogated TGF-β1-induced fibrosis by reducing extracellular matrix components including fibronectin-1, collagen (COL) 1A1, and COL10A1. Most importantly, uMSCs modestly extricated BPVC-impaired gait functions, determined using CatWalk™ XT gait analysis. This work provides several innovative insights into and molecular bases for employing uMSCs to execute therapeutic potential through the elimination of neutrophil-mediated acute inflammation toward protecting against fibrosis, thereby rescuing functional impairments post injury.

Role of mitochondrion-dependent apoptosis in reduction of bupivacaine-induced cardiotoxicity by lipid emulsion in rats

Objective To evaluate the role of mitochondrion-dependent apoptosis in reduction of bupivacaine-induced cardiotoxicity by lipid emulsion in rats. Methods Forty-five healthy adult male Sprague-Dawley rats, weighing 300-350 g, were divided into 3 groups by a random number table method: sham operation group (Sham group, n=5), bupivacaine group (B group, n=20), and lipid emulsion group (L group, n=20). Cardiac arrest was induced by intravenously injecting 0.4% bupivacaine 30 mg/kg over 20 s to establish the cardiotoxicity model.Twenty percent lipid emulsion was intravenously injected in a dose of 5 ml/kg during resuscitation in group L, and normal saline was intravenously injected in a loading dose of 5 ml/kg during resuscitation in group B, followed by a 3-min infusion of 1 ml·kg-1·min-1in two groups.The successful resuscitation and survival rate at 120 min of return of spontaneous circulation (ROSC) were recorded.Systolic blood pressure, heart rate, mean arterial pressure, rate-pressure product (RPP) and ratio of RPP at each time point after recovery of spontaneous heart beat to baseline value (RPPh) were recorded every 10 min after ROSC.The time from administration to cardiac arrest (T0), time from beginning of cardiopulmonary resuscitation to appearance of the first spontaneous heart beat (Ts) and time from beginning of cardiopulmonary resuscitation to appearance of ROSC (Tr) were recorded.Rats were sacrificed at 120 min of ROSC, and left ventricular tissues were obtained for determination of the expression of Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3, cytochrome C (Cyt c) in cytoplasm and mitochondria (by Western blot) and expression of Bax and Bcl-2 mRNA (by real-time polymerase chain reaction) and for examination of myocardial ultrastructure. Results Compared with Sham group, the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was significantly down-regulated, and the expression of Bax protein and mRNA, cleaved caspase-9, cleaved caspase-3 and cytoplasmic Cyt c was up-regulated in B group (P 0.05), and the pathological changes of myocardium were significantly attenuated in L group. Conclusion The mechanism by which lipid emulsion reduces bupivacaine-induced cardiotoxicity may be related to inhibiting mitochondrion-dependent apoptosis in rats. Key words: Fat emulsions, intravenous; Bupivacaine; Drug-related side effects and adverse reactions; Mitochondria; Apoptosis

HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: results from the phase 3 EPOCH 2 study

PurposeCurrently available local anesthetics have not demonstrated sufficient analgesia beyond 12–24 h postoperatively. The purpose of the study was to assess the safety and efficacy of HTX-011 (bupivacaine and meloxicam in Biochronomer® polymer technology), a long-acting investigational anesthetic, in reducing both postoperative pain over 72 h and postoperative opioid use compared to bupivacaine hydrochloride (HCl).MethodsA phase 3, randomized, double-blind, active-controlled multi-center study (EPOCH 2; NCT03237481) in subjects undergoing unilateral open inguinal herniorrhaphy with mesh placement was performed. Subjects randomly received a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl, or saline placebo prior to closure.ResultsThe study evaluated 418 subjects, and the primary and all key secondary efficacy endpoints were in favor of HTX-011. HTX-011 reduced mean pain intensity by 23% versus placebo (primary endpoint; p < 0.001) and by 21% versus bupivacaine HCl (p < 0.001) with significant reductions in the number of patients experiencing severe pain. Opioid consumption over 72 h was reduced by 38% versus placebo (p < 0.001) and 25% versus bupivacaine HCl (p = 0.024). Overall, 51% of HTX-011 subjects were opioid-free through 72 h (versus 22% for placebo [p < 0.001] and 40% for bupivacaine HCl [p = 0.049]). HTX-011 was generally well-tolerated with fewer opioid-related adverse events reported compared to the bupivacaine HCl and placebo and no evidence of local anesthetic systemic toxicity.ConclusionsHTX-011 demonstrated significant improvement in postoperative pain control and a clinically meaningful reduction in opioid consumption when compared to the most widely used local anesthetic, bupivacaine HCl.

A randomized double blind study to compare 1% 2-chloroprocaine and 0.5% hyperbaric bupivacaine in spinal anesthesia for infra-umbilical surgeries

Background: Spinal anesthesia is a reliable and safe technique for infra-umbilical surgeries. Preservative-free 2-chloroprocaine has re-emerged for use in spinal anesthesia. We compared onset and duration of sensory block with intrathecal use of 1% 2-chloroprocaine (30 mg) or 0.5% Hyperbaric Bupivacaine (15 mg) as primary objective. Secondary objectives being onset and duration of motor block, duration of analgesia, time to return of voiding function, hemodynamic parameters and side effects.Methodology: 90 patients of age group 18-60 years, either sex, belonging to ASA physical status I/II undergoing infra-umbilical surgeries were randomly divided into two groups, 1% 2-chloroprocaine Group A (n=45) and 0.5% hyperbaric bupivacaine Group B (n=45). Each group received intrathecally either 30 mg of 2-chloroprocaine or 15 mg of hyperbaric bupivacaine 15 mg. For statistical analysis unpaired-t-test and chi-square test were used.Results: Earlier onset and shorter duration of sensory block were observed in Group A as compared to Group B respectively (p &lt; 0.001). Similarly, onset was earlier and duration of motor block, duration of analgesia and time to return of voiding function were shorter in Group A as compared to Group B respectively (p &lt; 0.001). Hemodynamic parameters (HR, MAP) were comparable in both groups.Conclusion: Intrathecal 1% 2-chloroprocaine 30 mg provides spinal anesthesia of adequate duration for infra-umbilical surgeries with the advantage of earlier onset and faster regression of spinal block resulting in earlier voiding with stable hemodynamics as compared to 0.5% hyperbaric bupivacaine 15 mg.Citation: Khare A, Thada B, Yadav D, Mathur V, Singh M. A randomized double blind study to compare 1% 2-chloroprocaine and 0.5% hyperbaric bupivacaine in spinal anesthesia for infra-umbilical surgeries. Anaesth. pain &amp; intensive care 2019;23(2):162-167

COMPARISON OF BUPIVACAINE AND BUPIVACAINE WITH FENTANYL IN LOWER LIMB ORTHOPAEDIC SURGERIES

INTRODUCTION: A commonly used technique for lower limb surgeries is subarachnoid blockade. If there is inadequate control of pain, will affect quality, and functional recovery, also there is chance of postsurgical complications, and the risk of persistent postsurgical pain. Use of epidural analgesic technique for lower limb surgeries should provide better pain relief with minimal side effects, leading to improved outcome. Bupivacaine hydrochloride is a local anaesthetic drug, which was used clinically in 1963. Bupivacaine acts mainly by blockade of voltage-gated Na+ channels in the axonal membrane and possibly has a further effect on presynaptic inhibition of calcium channels. Fentanyl is a powerful synthetic opioid which is similar to morphine but is 50 - 100 times more potent, which is used to treat patients with severe pain, especially after surgeries. &#x0D; MATERIAL AND METHODS: This prospective randomized study was conducted in the department of anaesthesiology at Rajiv Gandhi Institute of Medical Science, Adilabad, to compare single shot epidural 8ml 0.5 % bupivacaine alone verses 8ml 0.5% bupivacaine along with 0.50 mcg Fentanyl. Total of 80 patients with ASA(American society of anaesthesiologists) I and II with age group between 24 to 56 years were included and 40 patients each were randomly placed in bupivacaine alone group (Group 1) and fentanyl in combination with bupivacaine group (Group 2). Written informed consent from all the patients was obtained. &#x0D; RESULTS: Mean (SD) systolic blood pressure was observed to be 128.45(12.47) and 130.25(11.55) in group 1 and group 2 respectively. Mean time for T 10 sensory block was significantly earlier in group 2 12.03(1.12) compared to group 1 18.24(2.54). Onset of motor block was observed to differ significantly, where onset was significantly earlier in group 2 23.17(1.77) in comparison to group 1 28.45(1.49). The first analgesic requirement in Group 1 was earlier at 198.20 + 11.49 min as compared to Group 2 at 279.34 + 18.42 min. &#x0D; CONCLUSION: Bupivacaine with Fentanyl enhances the onset of action and duration of effect for two segment regression. In present study the time to achieve T10 sensory block was early in Group 2 12.03(1.12) compared to group1 18.24(2.54).Onset of group2 23.17(1.77) in comparison to group1 28.45(1.49). Time of first analgesic requirement was found to be earlier at 279.34 + 18.42 minutes in group2 in comparison to group1 198.20 + 11.49 minutes.

Comparison of effects of spinal anesthesia and general anesthesia on early postoperative cognitive function in elderly patients undergoing hip replacement

Objective To compare the effects of spinal anesthesia and general anesthesia on early postoperative cognitive function in elderly patients undergoing hip replacement. Methods One hundred and four elderly patients of both sexes, aged ≥ 60 yr, with body mass index of 18.5-24.0 kg/m2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective unilateral hip replacement, were randomized into 2 groups (n = 52 each) using a random number table method: general anesthesia group (group G) and spinal anesthesia group (group S). Total intravenous general anesthesia was adopted to maintain the bispectral index value at 40-60 during surgery in group G. In group S, spinal anesthesia was applied by injecting 0.5% bupivacaine 1.5-3.0 ml at the L3-4 vertebral interspace, and the level of anesthesia was regulated and maintained at T10.Mini-Mental State Examination scale was used to evaluate the cognitive function on 1 day before surgery (T0) and 7 days after surgery (T1). Difference value method, 1 standard deviation method and Z score method were applied to diagnose postoperative cognitive dysfunction.Patients′ spouses in two groups were recruited as control group (group C) according to the Z-scoring method. Results There were 47 and 49 cases in G and S groups, respectively, and 33 cases in group C. Compared with group C, the memory score was significantly decreased at T1 (P 0.05). The memory score was significantly higher at T1in group S than in group G (P 0.05). Conclusion Spinal anesthesia and general anesthesia exerts no effect on early postoperative cognitive function in elderly patients undergoing hip replacement. Key words: Anesthesia, spinal; Anesthesia, general; Cognition disorders; Aged; Arthroplasty, replacement, hip

The Effect of Bupivacaine on the Efficacy of Antibiotic Coating on Penile Implants in Preventing Infection.

BackgroundIn an effort to reduce dependence on opioids following inflatable penile prosthesis placement, intra-operative soaking of the implant in Bupivacaine (BUP) has been proposed as part of a multimodal approach to pain control. However, no study has shown if the addition of BUP affects the antimicrobial properties of InhibiZone on AMS700 (Boston Scientific, Marlborough, MA) and/or of antibiotic soaked Titan Coloplast (Coloplast Corporation, Minneapolis, MN).AimTo determine if BUP alters the zone of inhibition (ZOI) against Staphylococcus epidermidis (S epidermidis) and Escherichia coli (E coli), common gram-positive and gram-negative bacterial causes of infection, respectively, created by InhibiZone coated AMS and/or by antibiotic-soaked Coloplast implant.MethodsS epidermidis and E coli were spread on agar plates. After a 30-minute incubation, four AMS with InhibiZone strips treated with sterile saline or BUP (1.25 mg/mL) were placed on a plate. 4 Coloplast strips were dipped in varying routinely used concentrations of Rifampin (0–10 mg/mL) plus Gentamicin (0–1 mg/mL; rifampin and gentamicin (R+G)) solution with or without BUP. The ZOI for AMS with InhibiZone and Coloplast dipped in antibiotic solution was measured using ImageJ software. Normalized ZOI was calculated as (ZOI area/plate area) × 100. Unpaired t-test compared the mean ± SD ZOI between BUP and no BUP groups (n = 4/group).OutcomesThe primary outcome of the study was the ZOI against E coli and S epidermidis at 24 and 48 hours.ResultsGrowth of both S epidermidis and E coli at 24 and 48 hours of incubation was inhibited in both implants and the addition of BUP did not alter the ZOI. Coloplast strips dipped in R+G produced a ZOI in a dose-dependent manner. Interestingly, the ZOI against S epidermidis compared to that of E coli was much wider for both implants.Clinical ImplicationsThis suggests that the use of BUP does not affect the protective effects of antibiotic dips and can potentially be used during penile prosthesis surgery pending clinical trials.Strengths and LimitationsThis is the first study to evaluate the effect of BUP on anti-bacterial dips. As with all in vitro analysis, further research must be done to see if these findings hold true in the clinical setting.ConclusionsThe addition of BUP does not impede the in vitro antibacterial activity of InhibiZone-coated AMS or R+G-soaked Coloplast. Whether these in vitro findings translate to surgical outcomes needs to be evaluated in future preclinical trials.Lokeshwar SD, Horodyski L, Lahorewala SS, et al. The Effect of Bupivacaine on the Efficacy of Antibiotic Coating on Penile Implants in Preventing Infection. J Sex Med 2019;7:337−344.

Evaluation of pain scoring and free cortisol levels of postoperative analgesic methods in cardiac surgery: A new perspective.

This study aims to evaluate the most appropriate analgesic method of minimizing postoperative pain to prevent complications in patients scheduled for cardiac surgery. Between January 2016 and June 2016, a total of 60 patients with the American Society of Anesthesiologists Physical Status Class III (27 males, 33 females; mean age 63 years; range, 49 to 77 years) with an ejection fraction of above 50% who underwent elective coronary artery bypass grafting were included. The patients were divided into two groups following admission to the intensive care unit. Group 1 (n=30) was administered intravenous fentanyl citrate with patient-controlled analgesia protocol, while Group 2 (n=30) was administered 0.1% bupivacaine hydrochloride analgesia protocol with catheter placed between the sternum and subcutaneous tissue. In Group 1, pain intensity scores at two h and visual analog scale scores except at 24, 36, and 48 h were higher than Group 2 (p<0.05). The length of intensive care unit stay and urine cortisol levels were higher in Group 1 than Group 2 (78±12 h and 631±505 ?g at 24 h vs. 66±13 h and 401±297 ?g at 24 h, respectively p<0.05). Partial pressure of oxygen levels at 10 and 16 h during the postoperative intensive care unit stay were lower, while partial pressure of carbon dioxide levels at 24 h was higher in Group 1 than Group 2 (p<0.05). The bupivacaine protocol is a relatively more useful analgesic method which produces improved results in blood gas analysis by reducing the effects of pain and shortens the length of intensive care unit stay. Low levels of free cortisol also confirm this finding.

A comparative study of epidural bupivacaine and epidural bupivacaine with magnesium sulphate for perioperative analgesia in patients undergoing lower limb surgery

Aims and objectives: The aim of the study was to compare epidural plain bupivacaine and plain bupivacaine with magnesium sulphate in patients undergoing elective lower abdominal surgery. Methodology: This Randomized parallel group double-blind controlled study was conducted on 60 patients of elective lower limb surgery. Group B received 0.5% bupivacaine +normal saline1ml of 0.9% and Group BM received 0.5% bupivacaine+ magnesium sulphate (1ml) containing 50mg Bupivacaine.Results: Both the drugs provided post-operative analgesia. Time for onset of sensory block in the two groups and there was significant difference between two groups in respect of onset of sensory block. The onset of block was significantly less in group BM compared to group B. The mean onset of sensory block (mean ± SD) was Group B-15.57±2.27 minutes and Group BM-12.93±1.14 minute. The time for onset of motor block, duration of sensory block, duration of motor block and duration of analgesia in the two groups and there was no significant difference. Visual analogue scale (VAS) score, Verbal rating scale (VRS) score and no of rescue analgesia by the patients in the two groups and there was no significant difference.Conclusion: Single dose epidural administration of 0.5% bupivacaine hydrochloride with 50mg magnesium sulphate produces predictable rapid onset sensory block with less side effect than plain 0.5% bupivacaine hydrochloride.

Evaluation of intrathecal neostigmine methylsulphate in different doses added to hyperbaric bupivacaine hydrochloride for postoperative analgesia

Evaluation of intrathecal neostigmine methylsulphate in different doses added to hyperbaric bupivacaine hydrochloride for postoperative analgesia

Évaluation de la rachianesthésie en chirurgie ambulatoire urologique, comparaison entre deux anesthésiques locaux (Chloroprocaïne/Bupivacaïne)

Spinal anesthesia in outpatient urology is controversial (longer hospital stay, risk of urinary retention). The main goal was to evaluate outpatient spinal anesthesia and to compare 2 local anesthetics secondarily. Monocentric retrospective study including all patients undergoing surgery in urological ambulatory surgery under spinal anesthesia between December 2011 and May 2015, split into two groups according to the local anesthetic used: bupivacaine (BP) and chloroprocaine (CP). Quantitative variables were compared by Student's t-test, qualitative variables by χ2 test. Seventy-one (95%) out of the 75 patients included have been discharged the same day. Discharge was impossible in these cases: patient alone at home (1), bladder clot (1), JJ intolerance (1), delayed micturition (1). The mean duration of the procedure was 27±19min, the SSPI's was 55±31min, the stay's was 360±91min. A total of 45 patients (60%) received BP and 30 (40%) received CP. The mean residence time in SSPI was significantly reduced in the CP group (47±24min vs. 61±34min, P=0.04). One patient experienced urination delay in the BP group with no significant difference. No significant difference for the other criteria studied despite the mean age, which is higher in the CP group (P=0.02). Spinal anesthesia is adapted to ambulatory urology, and does not increase the risk of urinary retention, especially with CP that would decrease the length of stay in SSPI compared to BP. 4.

Dilution and microfiltration of particulate corticosteroids for spinal epidural injections: impact on drug concentration and agglomerate formation.

Particulate corticosteroids have been described to lead to greater pain improvement compared with their non-particulate counterparts when used in epidural injections. It is hypothesised that filtering may significantly impact their concentration and long-term efficacy. We investigated if passing particulate suspensions through different commonly-used filters affects drug dosage. Two particulate corticosteroid formulations, triamcinolone acetonide and methylprednisolone acetate, were mixed at different concentrations with either bupivacaine hydrochloride or 0.9% sodium chloride. Solutions were passed through a 5-μm and a 0.2-μm filter. Mass spectroscopy results indicated a complete loss of corticosteroid from the solutions using both filters, and light microscopy imaging demonstrated agglomerate formation, suggesting that filtering interferes with drug dosage. The choice of diluents must also be considered to reduce large agglomerate formation. Clinicians should be aware of the consequences of filtering particulate suspensions and carefully consider the selection of diluent when considering treatment plans.

Effect of ganglioside preconditioning on endoplasmic reticulum stress-dependent apoptosis during spinal cord injury induced by bupivacaine in rats

Objective To evaluate the effect of ganglioside (GM-1) preconditioning on endoplasmic reticulum stress (ERS)-dependent apoptosis during spinal cord injury induced by bupivacaine in rats. Methods One hundred and eight clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 250-300 g, were divided into 3 groups (n=36 each) using a random number table method: control group (group C), bupivacaine group (group B) and GM-1 pretreatment group (group G). In group B, 5% bupivacaine 0.12 μl/g was intrathecally injected at 1.5 h intervals, 3 times intotal.In group G, GM-1 20 μl (30 mg/kg) was intrathecally injected, and 24 h later bupivacaine was intrathecally injected according to the method previously described in group B. Immediately after intrathecal injection and at 1, 3, 5, 7 and 14 days after intrathecal injection, the maximum percentage of anti-nociceptive effects (%MPE) was detected, the hindlimb motor function score (BBB score) was evaluated, and spinal cord tissues were harvested for determination of cell apoptosis (using TUNEL) and expression of caspase-12 and CCAAT/enhancer-binding protein homologous protein(CHOP) protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction). The apoptosis rate was calculated. Results Compared with group C, the %MPE and apoptosis rate were significantly increased, the BBB score was decreased, and the expression of CHOP and caspase-12 protein and mRNA was up-regulated in group B (P<0.05). Compared with group B, the %MPE and apoptosis rate were significantly decreased, the BBB score was increased, and the expression of CHOP and caspase-12 protein and mRNA was down-regulated in group G (P<0.05). Conclusion GM-1 preconditioning reduces bupivacaine-induced spinal cord injury possibly through inhibiting ERS-dependent apoptosis in rats. Key words: Ganglioside; Bupivacaine; Endoplasmic reticulum stress; Apoptosis

HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: phase III results from the randomized EPOCH 1 study

Background and objectivesThere is a need for local anesthetics that provide consistent analgesia through 72 hours after surgery. This study evaluates the use of HTX-011 (bupivacaine and meloxicam in Biochronomerpolymer...

The Use of Intraperitoneal Bupivacaine in Laparoscopic Roux-en-Y Gastric Bypass: a Double-blind, Randomized Controlled Trial.

Several studies have shown a reduction in postoperative pain and length of hospital stay when using intraperitoneal local anesthetics during laparoscopic surgery. In morbidly obese patients, respiratory depression due to opioid use is a serious side effect. Any different type of analgesia is therefore clinically relevant. To assess the effect of intraperitoneal bupivacaine on postoperative pain after laparoscopic Roux-en-Y gastric bypass (LRYGB). Between March and November 2017, 130 patients were included and randomly assigned to receive 20ml or 0ml of 2.5% bupivacaine hydrochloride sprayed onto the diaphragm. Pain scores for abdominal and shoulder pain were conducted using the visual analogue scale (VAS) for pain score at 0, 1, 6, and 24h postoperatively. The length of hospital stay and use of analgesics was recorded in digital patient records. The primary outcome is the pain scores and the secondary outcomes are postoperative use of opioids or antiemetics and length of hospital stay. The study and control group contained respectively 66 and 61 patients. Patient characteristics were equal in both groups (p < 0.05), except for age. No significant reduction of postoperative pain or opioid use was seen with the use of intraperitoneal bupivacaine. There was also no significant reduction in the use of antiemetics and length of hospital stay. The use of intraperitoneal bupivacaine in LRYGB does not show a statistically significant reduction in postoperative pain or postoperative opioid use. Therefore, using intraperitoneal bupivacaine has no clinical relevance and should no longer be used in LRYGB.

Negative Impact of Icing Treatment on Qualitative Recovery of Injured Soleus Muscle in Rats

PURPOSE: Although the RICE (Rest, Ice, Compression, and Elevation) treatment has been recognized as the gold standard of first aid treatment for sports injuries, we and the others previously demonstrated that a transient icing treatment immediately after skeletal muscle injury impaired muscle regeneration. However, the information about the influence of icing treatment following skeletal muscle injury remains limited. This study was, therefore, to investigate the impact of icing as a first-aid treatment on qualitative recovery of damaged muscle in terms of fibrosis and myosin heavy chain (MyHC) profile. METHODS: Male Wistar rats (9-10 weeks of age) were randomly assigned to control (Con), injured, and injured with icing groups (Ice). Bupivacaine (BPVC) was injected into slow soleus muscles bilaterally in order to induce muscle injury in the two injury groups. Application of icing treatment (ice pack, 0°C for 20 min) to the icing group was carried out immediately after the BPVC injection. At 3 days-4 weeks after BPVC injection, soleus muscles were removed and analyzed. RESULTS: Compared with the Con group, a significant increase in fibrotic area was observed after 2 weeks following injury in the injured groups, but after 1 week following injury in the Ice group (P < 0.05). This area was also tended to be higher in Ice than in injured animals during 1-4 weeks of recovery period. In addition, the number of Tcf4-positive nuclei, a fibroblast marker, located in interstitial spaces in both injured groups markedly increased 1 week after BPVC injection. The numbers were tended to be more magnified in the Ice group than in the injured group, then their number in both injured groups gradually degreased thereafter. Injury-related de novo appearance of embryonic, neonatal, IId/x, and IIb MyHC isoforms was noted in both injured groups 1 week after BPVC injection. These MyHC isoforms were significantly decreased toward the undetectable level thereafter. However, the embryonic MyHC isoform was still detectable in icing, but not in injured, animals 4 weeks after BPVC injection. CONCLUSIONS: Our results suggested that icing treatment following skeletal muscle injury will have a negative impact on recovery process (fibrosis and normalization of MyHC profile) of regenerating muscle.

Evaluation of Intraperitoneal and Incisional Bupivacaine or Levobupivacaine for Postoperative Analgesia in Ovariohysterectomized Dogs

Background: Ovariohysterectomy (OHE) is the most commonly performed elective surgical procedure in companion animals. OHE offers benefits of control of population and decreased risk of potentially life-threatening diseases such as mammarian tumours and pyometra. Traditional OHE intervention causes inflammation and pain due to trauma during organ manipulation. The purpose of this study was to compare the effect of intraperitoneal and incisional administration of bupivacaine (BP) or levobupivacaine (LP) on postoperative analgesia in dogs undergoing the OHE procedure.Materials, Methods &amp; Results: A total of 24 mix-breed bitches aged between 1 - 3 years and weighed 19 - 20 kg were used in this study. The animals were divided into three groups as control (n = 8), BP (n = 8) and LP group (n = 8). The animals were kept under surveillance at the hospitalisation unit of the animal hospital for one day before the elective OHE. The dogs were fasted for 12 h before the surgery, with adlib water consumption. Atropine sulphate 0.045 mg/kg was administered subcutaneously approximately 30 min before general anaesthesia. Midazolam (0.3 mg/kg) was intravenously injected into all dogs for pre-anaesthetic medication. After sedation, anaesthesia was induced with propofol (4 mg/kg, IV) and then the dogs were orotracheally intubated using cuffed endotracheal tubes. General anaesthesia was maintained by administration of 2% isoflurane. The ventral abdomen was prepared aseptically for OHE following the general anaesthesia. All animals were operated on by the same surgeon. During surgery, sprayed bupivacaine 0.5% (4.4 mg/kg) with an equal volume of saline in BP group, levobupivacaine 0.5% (4.4 mg/kg) with an equal volume of saline in LP were then applied over the ovaries, uterine broad ligaments and cervix uteri. After removal of the uterine body, either LP or BP was sprayed to left and right, or cranial and caudal parts of the abdominal cavity. Finally, the incision line was sprayed before closing the skin. The control group received only sprayed saline. The pain evaluation was carried out with modified Melbourne pain scoring scale. To determine cortisol concentrations, blood samples were taken before anaesthesia induction (baseline) and postoperative 0, 0.5, 1, 2, 4, 6, 12 and 24 h. Postoperative pain scores were higher in the control group than BP and LP groups following surgery at 30 min, 1st, 4th, and 6th h. In all groups, cortisol levels increased postoperatively, whereas they decreased more rapidly in BP and LP groups. There was a steady increase at postoperative 0 min, 30 min, 1st, 2nd, 4th and 6th h in the control group and at postoperative 0 min, 30 min and 1 h in BP and LP groups (P &lt; 0.05).Discussion: Intraperitoneal and incisional bupivacaine shows significantly superior postoperative pain management benefits after the closure of skin, compared to untreated dogs and it is also superior to lidocaine treatment at 0.5 h following the visual analogy pain assessment system. In the present study, the observation of lower pain scores in BP group at 0.5, 1, 4 and 6 h as compared to the control group was similar to findings of other studies. LP group also showed decreased pain scores at above-mentioned h without any significant difference. However, only in LP group, pain scores at 24 h were lower than postoperative pain scores. In conclusion, it is suggested that sprayed intraperitoneal and incisional BP and LP are very effective for preventing postoperative pain ovariohysterectomized dogs.

Involvement of TREK-1 Channel in Cell Viability of H9c2 Rat Cardiomyoblasts Affected by Bupivacaine and Lipid Emulsion.

Lipid emulsion (LE) therapy has been used to reduce overdose of bupivacaine (BPV)-induced cardiotoxicity. The TWIK-related potassium channel-1 (TREK-1) is inhibited by BPV and activated by polyunsaturated fatty acids, which are the main component in LE. These pharmacological properties inspired us to investigate whether the TREK-1 channel is associated with cell viability of H9c2 cardiomyoblasts affected by BPV and LE. Consistent with previous studies, BPV-induced cell death was reduced by LE treatment. The reduction in the TREK-1 expression level by BPV was alleviated by LE. The BPV cytotoxicity highly decreased in TREK-1 overexpressed cells but was the opposite in TREK-1 knocked-down cells. TREK-1 channel activators and inhibitors increased and decreased cell viability, respectively. BPV-induced depolarization of the plasma and mitochondrial membrane potential and increase in intracellular Ca2+ level were blocked by LE treatment. BPV-induced depolarization of membrane potential was reduced in TREK-1 overexpressed cells, indicating that TREK-1 channels mediate setting the resting membrane potentials as a background K+ channel in H9c2 cells. These results show that TREK-1 activity is involved in the BPV cytotoxicity and the antagonistic effect of LE in H9c2 cells and suggest that TREK-1 could be a target for action of BPV and LE.

Efficacy of submucosal bupivacaine injection for pain relief after endoscopic submucosal dissection: A multicenter, prospective, randomized controlled, and double-blind trial.

Background and aim:Although abdominal pain is a common adverse event related to endoscopic submucosal dissection (ESD), it can be sometimes underestimated by endoscopists. There are some endoscopic interventions available for the prevention of post-ESD pain, but their efficacy has not been established. We investigated whether a submucosal injection of bupivacaine (BP) can reduce procedure-related abdominal pain compared with the standard method.Methods:We performed a multicenter, double-blinded, randomized controlled trial of 86 adult patients referred for ESD as treatment for gastric neoplasms. Patients were randomly assigned to either the BP submucosal or conventional solution group. Questionnaires were collected when the study began (baseline) and immediately after ESD, as well as at 6, 12, and 24 hours post-operatively. The primary outcome was indicated by the visual analog scale (VAS) evaluated at 6 hours after procedure.Results:There were no significant differences in primary outcomes between groups and among all time points (immediately, 12, and 24 hours after ESD). The VAS and short-form McGill pain (SF-MP) scores were higher immediately after ESD than at 6, 12, or 24 hours post-operatively. The incidence of abdominal pain immediately after ESD was 94.0% (78/83) for all patients of both groups, and there was no significant difference between the 2 groups in the rate of abdominal pain immediately after ESD (BP group 37/40 [92.5%] versus non-BP group 41/43 [95.3%], P = .934). In univariable and multivariable analyses, BP did not have protective effect on post-ESD abdominal pain.Conclusions:Submucosal BP injection does not promote pain relief or mitigate the effects of post-ESD abdominal pain.

Tetramethylpyrazine attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells through regulating apoptosis, autophagy and oxidative damage.

Background: Bupivacaine (BUP) acts as a local anesthetic, which is extensively used for clinical patients but could generate neurotoxicity in neurons. Tetramethylpyrazine (TET) exhibits strong neuron protective effects against neurotoxicity. Hence, we investigate the effect of TET on BUP-induced neurotoxicity in SH-SY5Y cells.Methods: CCK-8 assay was used to detect cell proliferation in SH-SY5Y cells. In addition, Western blotting was used to examine Bax, Bcl-2, active caspase 3, LC3II, Beclin 1 and p-62 protein levels in cells. Moreover, ELISA assay was used to detect the levels of total glutathione (GS), superoxide dismutase (SOD) and malondialdehyde (MDA) in cells.Results: In this study, we found that TET attenuated the neurotoxicity of BUP on SH-SY5Y cells. Meanwhile, TET alleviated BUP-induced apoptosis in SH-SY5Y cell via decreasing the expressions of active caspase-3 and Bax and increasing the expression of Bcl-2. In addition, monodansylcadaverine staining assay and Western blotting results confirmed that TET induced autophagy in SH-SY5Y cells via increasing the LC3II/I and Beclin 1 levels. Furthermore, TET attenuated BUP-induced oxidative damage in SH-SY5Y cells via upregulation of the levels of total GS and SOD and downregulation of the level of MDA. Interesting, the protective effects of TET against BUP-induced neurotoxicity in SH-SY5Y cells were reversed by autophagy inhibitor 3-methyladenine (3MA).Conclusion: These data indicated that TET may play a neuroprotective role via inhibiting apoptosis and inducing autophagy in SH-SY5Y cells. Therefore, TET may be a potential agent for the treatment of human neurotoxicity induced by BUP.