Effects of subconjunctival ropivacaine, liposomal bupivacaine, and mepivacaine on corneal sensitivity in healthy horses.

OBJECTIVE: To evaluate corneal sensitivity and adverse events following subconjunctival administration of three local anesthetics in horses. STUDY DESIGN: Randomized, masked, crossover study. ANIMALS: Twelve healthy adult mares. METHODS: The subconjunctival space of the treated eye was injected with 0.2 mL of liposomal bupivacaine (1.3%), ropivacaine (0.5%), or mepivacaine (2%). All horses received each medication once and the contralateral eye received saline (control). Corneal touch threshold (CTT) was measured using a Cochet-Bonnet esthesiometer before sedation, after sedation, and at specified intervals until it returned to baseline. Ocular examinations were performed at 24-, 72, and 168 h post-injection to monitor for adverse effects. RESULTS: The mean total time of anesthesia (TTA) was 168.3 min for ropivacaine, 169.2 min for liposomal bupivacaine, 103.3 min for mepivacaine and 30.7 min for the control. TTA for liposomal bupivacaine (p < .001) and ropivacaine (p = .001) was longer than the control. TTA for mepivacaine was not different from the control (p = .138), liposomal bupivacaine (p = .075) or ropivacaine (p = .150). Injection site hemorrhage reduced TTA regardless of treatments (p = .047). No adverse effects attributed to injections were noted. CONCLUSION: All three medications were well tolerated. Subconjunctival administration of ropivacaine and liposomal bupivacaine resulted in longer TTAs compared to the control; however, their TTAs were not different from that of mepivacaine. CLINICAL SIGNIFICANCE: Subconjunctivally administered liposomal bupivacaine and ropivacaine are viable options to provide prolonged corneal analgesia in horses. Future studies are needed to assess the efficacy in diseased eyes.

MicroRNA-27a Suppresses the Toxic Action of Mepivacaine on Breast Cancer Cells via Inositol-Requiring Enzyme 1-TNF Receptor-Associated Factor 2.

Objective: To investigate the toxic effects of microRNA-27a on breast cancer cells through inositol-acquiring enzyme 1-TNF receptor-associated factor 2 inhibition by mepivacaine. Methods: The elevation of miR-27a in MCF-7 of BCC lines was measured, and groups were set up as control, mepivacaine, and elevated groups. Cells from each group were examined for inflammatory progression. Results: Elevated miR-27a in MCF-7 cells was able to distinctly augment the cell advancement (P < 0.01) and decline cell progression (P < 0.01). Meanwhile, miR-27a reduced the content of intracellular inflammatory factors IL-1ß (P < 0.01) and IL-6 (P < 0.01), elevated the content of IL-10 (P < 0.01), suppressed levels of cleaved-caspase-3 and p-signal transducer and activator of transcription-3 (STAT3) (P < 0.01), and increased Bcl-2/Bax (P < 0.01). Conclusion: Elevated miR-27a in MCF-7 of BCC lineage was effective in reducing the toxic effects of mepivacaine on cells and enhancing cell progression. This mechanism is thought to be related to the activation of the IRE1-TRAF2 signaling pathway in BCC. The findings may provide a theoretical basis for targeted treatment of BC in clinical practice.

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.

Comparison of 2% mepivacaine and a solution of 2% lidocaine/epinephrine administered for median and ulnar nerve blocks in horses with naturally occurring forelimb lameness.

OBJECTIVE: To compare a 2% lidocaine solution containing 5 µg/ml (1:200 000) epinephrine with 2% mepivacaine for reducing lameness in horses after use in proximal nerve blocks. STUDY DESIGN: Experimental randomized crossover. ANIMALS: Six adult horses with naturally occurring forelimb lameness. METHODS: Horses were evaluated using an inertial gait sensor system. Lameness was measured as a vector sum (VS). Following baseline lameness examination, median and ulnar nerve blocks were performed with lidocaine/epinephrine (0.5 mg epinephrine added to 50 ml of 2% lidocaine immediately prior to administration) or an equal volume of 2% mepivacaine. Horses were trotted at 5 min and then at 30 min intervals for 150 min. After 24 h, nerve blocks were repeated using the other local anesthetic. Data were evaluated using linear models. RESULTS: The reduction in the VS did not differ after nerve blocks with lidocaine/epinephrine or mepivacaine (P = .791). Mean time to VS <8.5 mm (n = 5) was 5 and 9.6 min for lidocaine/epinephrine and mepivacaine, respectively. For one horse, VS was not reduced to <8.5 mm with either treatment (this horse had the highest VS before treatments were administered). The decrease in VS to <8.5 mm lasted for 150 min in both treatment groups. CONCLUSION: The outcomes of the median and ulnar nerve blocks performed with 2% lidocaine with epinephrine did not differ from blocks performed with 2% mepivacaine. CLINICAL RELEVANCE: Two percent lidocaine with epinephrine may serve as an adequate replacement for proximal nerve blocks when mepivacaine is unavailable.

MicroRNA-183-5p protects human derived cell line SH-SY5Y cells from mepivacaine-induced injury.

With the gradual recognition of the side effects of local anesthetics, the nerve injury caused by local anesthetics has received growing attention. This research intended to delve into miR-183-5p changes in mepivacaine-mediated SH-SY5Y cell injury, as well as its modulatory mechanism on cell apoptosis. RT-qPCR was adopted for assaying miR-183-5p and PDCD4 mRNA expression. Our team respectively transfected miR-183-5p mimic and inhibitor to enhance or inhibit miR-183-5p function. We employed Western blot for detecting PDCD4 protein levels, as well as flow cytometry and Hoechst 33342/PI double staining for determining cell apoptosis rate. Additionally, our crew applied an ELISA kit for measuring TNF-α, IL-1ß, IL-6, and IL-8 contents. The level of reactive oxygen species (ROS) production was examined by the Image-iT LIVE Green ROS detection Kit. As well as dual-luciferase reporter experiment for verifying the targeting link of miR-183-5p with PDCD4. In mepivacaine-induced cell apoptosis in SH-SY5Y cells, miR-183-5p expression was down-regulated. TNF-α, IL-1ß, IL-6, and IL-8 contents were elevated. The rate of apoptosis increased visibly, cleaved caspase-3 and Bax levels waxed, whereas Bcl-2 level waned. MiR-183-5p could alleviate the damaging impact of mepivacaine. Dual-luciferase reporter experiments demonstrated that miR-183-5p directly targeted PDCD4. Collectively, we concluded that a high concentration of mepivacaine can cause SH-SY5Y cell damage, miR-183-5p functions crucially in mepivacaine-mediated cell damage. This study provides a theoretical basis for elucidating the mechanism of mepivacaine-induced nerve cell damage, and overexpressed miR-183-5p likely become a novel strategy to combat mepivacaine-induced nerve damage.Abbreviations:miRNA: Micro RNA; PDCD4: Programmed Cell Death 4; MDA: Malondialdehyde; SOD: Superoxide Dismutase; ROS: Reactive Oxygen Species; WT: Wild Type; Mut: Mutant; UTR: Untranslated Region; IL-6: Interleukin-6; IL-1ß: Interleukin-1ß; TNF-α: Tumor Necrosis Factor-α; IL-8: Interleukin-8; COX-2: Cyclooxygenase-2; iNOS: inducible NOS; MEP: Mepivacaine.

The effect of intra-articular mepivacaine administration prior to carpal arthroscopy on anesthesia management and recovery characteristics in horses.

OBJECTIVE: To evaluate the effects of intra-articular (IA) mepivacaine administration prior to carpal arthroscopy on anesthetic drug requirements, blood pressure support, hemodynamic variables, and quality of recovery in horses. STUDY DESIGN: Experimental, analytical, cohort study. SAMPLE POPULATION: Twenty-two horses (n = 11 horses/group). METHODS: Horses were anesthetized by using the same protocol, but an IA injection of mepivacaine or saline was performed before carpal arthroscopy. End-tidal isoflurane concentration, heart rate, and mean arterial pressure were recorded at specific time points. Quality of recovery was scored by the anesthetist, who was unaware of group assignment. Data were analyzed by using two-way repeated-measures analysis of variance. RESULTS: Mean arterial pressure was higher during joint distension in the control group compared with baseline (7% higher, P = .02) and with the treatment group (10% higher, P = .04). Heart rate was higher in the control group compared with the treatment group during joint distension (8% higher, P = .04) and chip removal (11% higher, P = .03). Heart rate was higher in the control group compared with baseline during chip removal (5.5% higher, P = .04). Two horses in the control group required additional ketamine vs none in the treatment group. Quality of recovery was not different between groups. CONCLUSION: Intra-articular mepivacaine resulted in fewer detectable reactions to surgical stimulation, with similar recovery scores and blood pressure support requirements. CLINICAL SIGNIFICANCE: Intra-articular anesthesia prior to arthroscopy can be used safely in the horse and should be considered as a part of balanced anesthetic protocols.

Prospective randomized investigation of topical anesthesia during unilateral laparoscopic ovariectomy in horses.

OBJECTIVE: To compare pain-related responses in mares receiving topical or injected anesthesia of the ovarian pedicle prior to standing unilateral laparoscopic ovariectomy. STUDY DESIGN: Prospective randomized, blinded, placebo-controlled study. ANIMALS: Fifteen healthy research mares. METHODS: Mares were restrained in stocks and administered sedation. A right or left paralumbar ovariectomy was performed by using a laparoscopic portal and two instrument portals. Mares were divided into two treatment groups, and equal volumes of mepivacaine anesthesia were administered either topically (n = 8) or by injection into the ovarian pedicle (n = 7). Saline controls were simultaneously administered topically (n = 7) or by injection (n = 8), and surgeons were blinded to the treatment group. Ovarian removal was performed with traumatic forceps and a blunt tip vessel sealer and divider. Pain responses were measured by operative visual analog scale (VAS) scoring and perioperative serum cortisol response. Visual analog scale and serum cortisol were compared between groups by using Mann-Whitney testing. Serum cortisol concentrations were evaluated using repeated-measures one-way analysis of variance. RESULTS: Ovaries were removed in all mares by using the described technique without operative complications. Quantity of sedation required to complete the procedure, operative VAS scores, and perioperative cortisol concentrations did not differ between treatment groups. CONCLUSION: Application of topical mepivacaine to the ovary provided intraoperative analgesia similar to injection of the ovarian pedicle when performing unilateral standing laparoscopic ovariectomy in mares. CLINICAL SIGNIFICANCE: Topical anesthesia application to the ovary could provide an alternative to laparoscopic needle use, reducing the risk of inadvertent trauma to the pedicle or other visceral organs during laparoscopic ovariectomy.

Retrospective case review of combined local mepivacaine and steroid injections into vaginal trigger points for the management of moderate-to-severe perineal pain after childbirth.

OBJECTIVE: After an obstetric trauma, a non-negligible number of postpartum women complain of perineal pain and dyspareunia. These symptoms clearly diminish their quality of life. Many treatment options have been suggested, such as oral analgesia, local anaesthetic, or steroid injections… Regretfully, none of these have yet demonstrated their efficacy with the validated trials. The objective of this review is to retrospectively evaluate the response to vaginal infiltrations into the trigger points (where the vaginal/perineal examination sets off the maximum intensity of pain) combining local anaesthetic and corticosteroids. METHODS: Our goal is to detect women who complain of sexual disfunction and perineal pain 2 and 6 months after childbirth. All reviewed cases correspond to vaginal deliveries made between June 2016 and April 2017. Trigger points were detected through a vaginal examination. Patients with moderate-to-severe perineal pain were determined using a visual analogue score (VAS 0-10). We suggested a treatment of vaginal infiltration specifically into the trigger points. Patients underwent local injections with a combination of mepivacaine hydrochloride 2% (8 ml) and betamethasone acetate (2 ml). RESULTS: Twenty-seven women were treated with vaginal injections directly into the trigger points. Seven of them [7/27 (25.92%)] were treated 2 months after delivery and experienced complete recovery of their perineal pain 4 months after the treatment. Those who first chose conservative treatment [20/27 (74.08%)] were also assessed 6 months after giving birth. This group continued to suffer the same symptoms and they then subsequently underwent vaginal injections. As well as the first group, these women experienced complete recovery of their perineal pain after treatment. No side effects have been registered so far. CONCLUSION: Women treated with vaginal injection into the trigger points improved in a fast and effective way. It seems to be a well-tolerated and safe option for women with moderate-to-severe pain.

Duration of action of mepivacaine and lidocaine in equine palmar digital perineural blocks in an experimental lameness model.

OBJECTIVE: To establish and compare the onset and duration of action of 2 local anesthetics based on objective lameness and skin sensitivity assessment. STUDY DESIGN: Interventional crossover experimental trial with balanced randomization. ANIMALS: Eight horses. METHODS: Reversible forelimb lameness was induced in 8 horses. A palmar digital nerve block (PDNB) was applied with mepivacaine or lidocaine (both 2%). Quantitative lameness and skin sensitivity data were collected with an inertial sensor system and a force gauge, respectively. The times to lameness resolution/skin desensitization (T1), consistent lameness detection/partial return of skin sensitivity (T2), and complete return of lameness/skin sensitivity (T3) were determined and compared between treatments and assessment methods. RESULTS: Mepivacaine blocks resolved lameness in 8/8 horses, compared to 3/8 horses with lidocaine blocks. Both agents led to skin desensitization in 8/8 horses. Skin desensitization occurred sooner than lameness resolution after mepivacaine (P = .047). Duration of action was longer with mepivacaine than lidocaine (mean T3_lameness mepivacaine 366 minutes, lidocaine 113 minutes (P = .038); T3_skin mepivacaine 195 minutes, lidocaine 63 minutes [P ≤ .001]). Skin sensitivity returned sooner than lameness after lidocaine block at T3 (P = .015). CONCLUSION: The use of lidocaine in PDNBs for the purpose of lameness diagnosis should be reassessed, as it may not resolve lameness despite loss of skin sensation. Mepivacaine is superior, with a reliable onset and longer duration of action. Skin desensitization as an indicator for the onset of action or effectiveness of PDNBs for mepivacaine and lidocaine, or as a measure of the duration of action of lidocaine PDNBs should be interpreted with caution.

Quantification of the vasodilatory effect of axillary plexus block. A prospective controlled study.

BACKGROUND: Axillary plexus block is a common method for regional anesthesia, especially in hand and wrist surgery. Local anesthetics (e.g., mepivacaine) are injected around the peripheral nerves in the axilla. A vasodilatory effect due to sympathicolysis has been described, but not quantified. MATERIALS AND METHODS: In a prospective controlled study between October 2012 and July 2013, we analyzed 20 patients with saddle joint arthritis undergoing trapeziectomy under axillary plexus block. Patients received a mixture of mepivacaine 1% and ropivacaine 0.75% in a 3:1 ratio. The measurements were carried out on the plexus side and the contralateral hand, which acted as the control. Laser-Doppler spectrophotometry (oxygen to see [O2C] device) was used to measure various perfusion factors before and after the plexus block, after surgery and in 2-h intervals until 6 h postoperatively. RESULTS: Compared with the contralateral side, the plexus block produced an enhancement of tissue oxygen saturation of 117.35 ± 34.99% (cf. control SO2: 92.92 ± 22.30%, P < 0.010) of the baseline value. Furthermore, blood filling of microvessels (rHb: 131.36 ± 48.64% versus 109.12 ± 33.25%, P < 0.0062), peripheral blood flow (219.85 ± 165.59% versus 129.55 ± 77.12%, P < 0.018), and velocity (163.86 ± 58.18% versus 117.16 ± 45.05%, P < 0.006) showed an increase of values. CONCLUSIONS: Axillary plexus block produces an improvement of peripheral tissue oxygen saturation of the upper extremity over the first 4 h after the inception of anesthesia.

Influence of commonly used pharmaceutical agents on equine bone marrow-derived mesenchymal stem cell viability.

REASON FOR PERFORMING STUDY: To provide evidence to support recommendations regarding the co-administration of drugs with mesenchymal stem cell (MSC) therapy. OBJECTIVES: To determine the influence of sedatives, local anaesthetic and corticosteroids on MSC viability and proliferation, in comparison to somatic cells derived from tendon (TDCs). STUDY DESIGN: In vitro cell culture. MATERIALS AND METHODS: MSCs (n = 3) and TDCs (n = 2) were cultured in media containing a clinically relevant dose range of xylazine, romifidine, detomidine and butorphanol, mepivacaine, methylprednisolone, or triamcinolone acetonide. Cell viability in suspension culture was assessed at intervals up to 4 h using the trypan blue dye assay. MSCs in monolayer culture were exposed to the highest concentrations of drug and proliferation was measured using the alamarBlue fluorescence assay. RESULTS: Exposure to romifidine or mepivacaine did not significantly affect viability or proliferation rate of MSCs or TDCs at any of the dosages tested. At the highest concentration of detomidine and butorphanol, MSC viability was significantly reduced compared to controls. Although xylazine exposure caused a significant (P < 0.001), dose-dependent reduction in MSC viability compared to controls, overall population viability remained good. Conversely, both methylprednisolone and triamcinolone resulted in the rapid death of significant numbers of MSCs (P < 0.001). CONCLUSIONS: Clinicians can sedate horses and administer nerve blocks to assist in intratendinous or intrathecal injection of MSCs with confidence that these drugs will not impact the viability of implanted cells. However, the concomitant use of corticosteroids is likely to have a severely detrimental effect on cell viability and should not be performed. Similarly, steroid administration into the sheath of a damaged tendon is not recommended.

The Effects of Mepivacaine Hydrochloride on Antimicrobial Activity and Mechanical Nociceptive Threshold During Amikacin Sulfate Regional Limb Perfusion in the Horse.

OBJECTIVE: To determine the effect of intravenous regional limb perfusion (IVRLP) with a combination of mepivacaine hydrochloride and amikacin sulfate on synovial fluid amikacin sulfate concentration, antimicrobial activity, and mechanical nociceptive threshold (MNT). STUDY DESIGN: Experimental study. ANIMALS: Healthy adult horses (n=9). METHODS: One IVRLP treatment was randomly administered by cephalic vein of each limb: amikacin alone (1 g amikacin in 60 mL saline) or amikacin with mepivacaine (1 g amikacin and 500 mg mepivacaine in 60 mL saline). Opposite treatments were repeated after a 24 hour wash-out period. Amikacin concentration and antimicrobial activity were determined for synovial fluid from middle carpal joints at tourniquet removal and 30 minutes following. Zone of inhibition was determined for Staphylococcus aureus and Escherichia coli. MNT was determined at 3 dorsal metacarpal locations prior to and after sedation, after Esmarch tourniquet application, and 30 minutes after IVRLP prior to and after tourniquet removal. RESULTS: Two limbs from each treatment group were removed because of undetectable amikacin concentrations for a total of 14 data sets analyzed. Synovial fluid amikacin concentrations and zone of inhibition were not significantly different between treatments at any time point. MNT were significantly increased 30 minutes after IVRLP prior to and following tourniquet removal using amikacin and mepivacaine (median, range; 40.0 µg/mL, 38.7-40.0 and 40.0, 25.8-40.0, respectively) compared to amikacin alone (19.5 µg/mL, 18.7-25.6 and 15.3, 13.2-20.5, respectively). CONCLUSION: Addition of mepivacaine to amikacin for IVRLP in the horse as a means of providing analgesia without decreasing antimicrobial activity.

Effect of local anesthetic concentration, dose and volume on the duration of single-injection ultrasound-guided axillary brachial plexus block with mepivacaine: a randomized controlled trial.

BACKGROUND: In what way volume, concentration and dose affect block duration is controversial. The purpose of the present study is to investigate the effect of dose, volume and concentration of mepivacaine on the duration of sensory and motor blockade in ultrasound-guided single shot axillary brachial plexus blockade. METHODS: In this parallel group randomized trial conducted in the Sint Maartenskliniek Nijmegen, 45 adult patients undergoing minor orthopaedic forearm, wrist or hand surgery were randomized to 3 groups. Group A: 20 mL mepivacaine 1.5 %, Group B: 30 mL mepivacaine 1 % and Group C: 30 mL mepivacaine 1.5 %. Randomization was computer-generated, with allocation concealment by opaque sequentially numbered sealed envelopes. Patients and observers were blinded to group allocation. PRIMARY OUTCOME MEASURE: duration of sensory block. RESULTS: Forty-five patients were randomized, four patients were excluded and replaced, and 15 patients in each group were included in the analysis. Mean (95 % CI) sensory and motor block duration was 256 (230-282) and 254 (226-282) minutes in Group A, 226 (209-243) and 220 (200-240) minutes in Group B and 270 (249-291) and 264 (244-284) minutes in Group C. Duration of sensory and motor block duration differed significantly between groups (p = 0.012 and p = 0.016 respectively). Post-hoc analysis showed a significantly reduced sensory and motor block duration in Group B when compared to Group C of 44 min. No local anesthetic systemic toxicity was reported. CONCLUSIONS: When using mepivacaine for axillary brachial plexus block, a higher dose and concentration was associated with a longer duration of sensory and motor blockade, but not a higher volume. TRIAL REGISTRATION: The Netherlands National Trial Register NTR3648 . Registered October 3, 2012.

The effect of mepivacaine on swine lingual, pulmonary and coronary arteries.

BACKGROUND: Although mepivacaine has a known biphasic action on the aortic and coronary artery in several animal species, its effects on the lingual and pulmonary artery are not well understood and it is not yet known whether mepivacaine produces vasoconstriction in these vessels. The present study aims to investigate the direct effects of mepivacaine on swine lingual, pulmonary and coronary arterial endothelium-denuded rings. METHODS: Artery rings were perfused with isotonic 40 mM KCl until a stable constricted plateau was reached. The rings were then perfused with isotonic 40 mM KCl plus a particular concentration of mepivacaine (0.4 µM, 4.0 µM, 40 µM, 0.4 mM and 4.0 mM). The isometric tension strengths in each experiment were normalized to the strength of the isometric tension immediately before mepivacaine perfusion and expressed as a percentage. RESULTS: Mepivacaine at 0.4 to 40 µM did not significantly alter 40 mM KCl-induced contraction in the lingual, pulmonary and coronary arterial rings. In contrast, mepivacaine at 4 mM produced attenuated vasoconstriction in the lingual, pulmonary and coronary arterial compared with isotonic 40 mM KCl. CONCLUSIONS: Mepivacaine produced vasoconstriction at lower concentrations, followed by attenuated vasoconstriction at higher concentrations on swine lingual, pulmonary and coronary arterial endothelium-denuded rings. Mepivacaine (4 µM) appeared to increase isotonic 40 mM KCl-induced contraction, followed by attenuated vasoconstriction at 4 mM. Dentists using 3 % mepivacaine should take into consideration that the risk of complications may be increased if more than six mepivacaine cartridges are used in dental treatment or minor surgery, or if over 15 ml of mepivacaine is administered to a patient with cardiovascular complications during general anesthesia for oral maxillofacial surgery.

Amide-type local anesthetics and human mesenchymal stem cells: clinical implications for stem cell therapy.

In the realm of regenerative medicine, human mesenchymal stem cells (hMSCs) are gaining attention as a cell source for the repair and regeneration of tissues spanning an array of medical disciplines. In orthopedics, hMSCs are often delivered in a site-specific manner at the area of interest and may require the concurrent application of local anesthetics (LAs). To address the implications of using hMSCs in combination with anesthetics for intra-articular applications, we investigated the effect that clinically relevant doses of amide-type LAs have on the viability of bone marrow-derived hMSCs and began to characterize the mechanism of LA-induced hMSC death. In our study, culture-expanded hMSCs from three donors were exposed to the amide-type LAs ropivacaine, lidocaine, bupivacaine, and mepivacaine. To replicate the physiological dilution of LAs once injected into the synovial capsule, each anesthetic was reduced to 12.5%, 25%, and 50% of the stock solution and incubated with each hMSC line for 40 minutes, 120 minutes, 360 minutes, and 24 hours. At each time point, cell viability assays were performed. We found that extended treatment with LAs for 24 hours had a significant impact on both hMSC viability and adhesion. In addition, hMSC treatment with three of the four anesthetics resulted in cell death via apoptosis following brief exposures. Ultimately, we concluded that amide-type LAs induce hMSC apoptosis in a time- and dose-dependent manner that may threaten clinical outcomes, following a similar trend that has been established between these particular anesthetics and articular chondrocytes both in vitro and in vivo.

Effect of retrobulbar nerve block on heart rate variability during enucleation in horses under general anesthesia.

OBJECTIVE: Analysis of any effect of retrobulbar block during ocular surgery on heart rate variability and oculocardiac reflex. STUDY DESIGN: Prospective study. ANIMAL STUDIED: Horses (n = 16) undergoing eye enucleation due to chronic ophthalmologic diseases. PROCEDURE: Eye enucleation was performed under general anesthesia. The horses were randomly assigned to the first (inhalation anesthesia only, n = 10) or second group (inhalation and local retrobulbar anesthesia, n = 6). The retrobulbar block was performed using 12 mL of mepivacaine hydrochloride 2%. ECG data were taken by a Telemetric ECG before, during, and after surgery. Heart rate variability was analyzed in the time domain as mean heart rate, mean beat-to-beat interval duration, and standard deviation of continuous beat-to-beat intervals. The frequency domain analysis included the low- and high-frequency components of heart rate variability and the sympathovagal balance (low/high frequency). The low frequency represents mainly sympathetic influences on the heart, whereas high frequency is mediated by the parasympathetic tone. RESULTS: All horses without a retrobulbar block showed a significant decrease in the heart rate during traction on the globe and pressure on the orbital fat pad for homoestasis (P = 0.04). Simultaneously, high-frequency power, as an indicator of vagal stimulation, increased significantly. High-frequency and low-frequency power in the retrobulbar block group increased in five horses, and heart rate decreased in only one horse. Both were not significant within the group, but there was a significant difference between both groups relating to the incidence of heart rate decrease occurring at globe traction. CONCLUSIONS AND CLINICAL RELEVANCE: Heart rate variability is a sensitive, non-invasive parameter to obtain sympathovagal stimulations during general anesthesia. The retrobulbar block can prevent heart rate decrease associated with initiation of the oculocardiac reflex.

Nisoxetine blocks sodium currents and elicits spinal anesthesia in rats.

BACKGROUND: Although nisoxetine has been shown to elicit infiltrative cutaneous local anesthesia, the inhibition of voltage-gated Na(+) channels by nisoxetine has not been reported. The aim of this study was to evaluate the effect of nisoxetine on Na(+) currents and its efficacy on spinal anesthesia. METHODS: In in vitro studies, the voltage-clamp method was employed to examine whether nisoxetine blocked Na(+) currents in mouse neuroblastoma N2A cells. RESULTS: Mepivacaine showed concentration- and state-dependent effect on tonic blockade of voltage-gated Na(+) currents (IC50 of 3.7 and 74.2 µM at holding potentials of -70 and -100 mV, respectively). Nisoxetine was more potent (IC50 of 1.6 and 28.6 µM at holding potentials of -70 and -100 mV, respectively). In in vivo studies, after rats were intrathecally injected with nisoxetine and mepivacaine, the dose-response curves were constructed. Nisoxetine acted like local anesthetic mepivacaine and induced spinal anesthesia with a more sensory-selective action (p < 0.05) over motor blockade in a dose-related fashion. Intrathecal 5% dextrose (vehicle) produced no spinal anesthesia. On the 50% effective dose (ED50) basis, nisoxetine elicited more potent spinal anesthesia than did mepivacaine (p < 0.05). CONCLUSIONS: Our results showed that nisoxetine displayed a more potent and prolonged spinal anesthesia with a more sensory/nociceptive-selective action over motor blockade, compared with mepivacaine. The local anesthetic effect of nisoxetine could be probably due to the suppression of Na(+) currents.

Diagnostic intra-articular anaesthesia of the elbow in dogs with medial coronoid disease.

OBJECTIVE: Assessment of the effect of intra-articular anaesthesia on lameness caused by medial coronoid disease. METHODS: This study included 90 dogs that were evaluated for the complaint of unilateral forelimb lameness. All dogs were suspected of having an elbow problem for which orthopaedic examination and radiographs showed inconclusive findings. Following a short sedation, mepivacaine was injected intra-articularly to determine whether lameness was caused by a suspected elbow problem. This effect was compared with the final diagnosis based on computed tomography and arthroscopy. RESULTS: Out of 90 dogs, 78 (87%) dogs had an improvement of lameness after injection of the local anaesthetic, which confirmed the elbow joint as the primary source of lameness. A positive response was seen in all types of medial coronoid lesions. A false negative result was observed in 12 dogs (13%). CLINICAL RELEVANCE: Medial coronoid disease is represented by different types of pathologic lesions including chondromalacia, fissures, fragments, and medial compartment disease. Diagnosis may be difficult because of limited clinical or radiographic signs or a combination of both. Intra-articular anaesthesia can be a helpful diagnostic tool to localize the problem by eliminating pain and reducing lameness to a great extent in all types of coronoid lesions.

A controlled study evaluating a novel surgical treatment for kissing spines in standing sedated horses.

OBJECTIVE: To compare the results of a novel minimally invasive surgical technique with intralesional corticosteroid medication, as treatment for overriding dorsal spinous processes (ORDSP) in horses. STUDY DESIGN: Retrospective controlled clinical case series. ANIMALS: Horses (n = 68) with ORDSP. METHODS: ORDSP was diagnosed based on history, clinical, and radiographic examination. All narrowed spaces were treated. Horses undergoing medical treatment had methylprednisolone acetate injected directly in the affected space under radiographic control. Surgical cases had interspinous ligament desmotomy (ISLD) using Mayo scissors; supraspinous ligaments were left intact. All horses had the same controlled exercise plan and returned to work 3-6 weeks after treatment. RESULTS: Methylprednisolone was administered in 1-7 spaces in 38 cases, compared with ISLD in 3-8 spaces in 37 cases. Thirty-four horses (89%) treated medically initially resolved signs of back compared with 35 horses (95%) treated surgically. From these, back pain recurred in 19 medical cases and in none of the surgical cases. Horses having ISLD were 24 times more likely to experience long-term resolution of signs of back pain (OR 24; 95%CI: 5-115; P = < .0001). Repeat radiographs in 19 surgical cases indicated that interspinous spaces widened significantly postoperatively (P = < .0001). CONCLUSIONS: This surgical technique allowed horses with back pain and radiographic ORDSP to return to work without further clinical signs of back pain and to show radiographic evidence of improvement.

Submucous tramadol increases the anesthetic efficacy of mepivacaine with epinephrine in inferior alveolar nerve block.

The purpose of this study was to evaluate the effect of submucous tramadol as adjuvant of mepivacaine with epinephrine in inferior alveolar nerve block. A double-blind, randomized, placebo-controlled, crossover clinical trial was conducted. Twenty healthy young volunteers were randomized into two treatment sequences using a series of random numbers. Sequence 1: Group A, 2% mepivacaine with 1:100,000 epinephrine plus submucous tramadol 50mg (1mL of saline) and one week later Group B, 2% mepivacaine with 1:100,000 epinephrine plus submucous placebo (1mL of saline). Sequence 2: Group B and one week later Group A. All treatments were administered 1min after that patient informed anesthesia of lower lip. We evaluated the duration of anesthesia of lower lip, anesthetic efficacy, and local and systemic adverse events. Anesthetic efficacy was better in group receiving submucous tramadol during the first 2h compared with group receiving submucous placebo (P<0.05). Submucous tramadol increased the anesthetic efficacy of mepivacaine with epinephrine of soft tissue in inferior alveolar nerve block.