Administration Of Bupivacaine Research Articles

Use of Intravenous Acetaminophen in Postoperative Pain Management After Partial and Full Bony Impacted Third Molar Extractions: A Randomized Double-Blind Controlled Trial

Currently, there is a concern at the national level of the overuse of both prescription and nonprescription opioid use. The purpose of this study was to identify whether the use of the intravenous (IV) formulation of acetaminophen (Ofirmev; Mallinckrodt Pharmaceuticals, Staines-upon-Thames, United Kingdom) is an effective tool in the reduction of postoperative pain, with a secondary goal of reduction of postoperative narcotic use. A total of 72 patients with previously diagnosed either partial bony or complete bony impacted third molars were selected with care to avoid long-acting local anesthetics or dissociative anesthetic agents. The patients' postoperative pain scores at 4 and 24hours were collected via a verbal rating scale by the primary investigator. The exclusion criteria included administration of bupivacaine or ketamine, hepatic or renal impairment, pregnancy, or allergy to any of the normally administered sedation medications. At all postoperative increments (immediately, 4hours, and 24hours), there was no significant difference at P<.05 between scores for either the IV acetaminophen or placebo group. Although there was a recorded difference in reduction of pain at both 4 and 24hours postoperatively, these were not statistically significant variables. The use of IV acetaminophen showed no statistically significant decrease in patient pain ateither 4 or 24hours postoperatively. Although there are not representative data suggesting the routine use of IV acetaminophen, on the basis of the abundance of literature on the treatment of pain for other procedures, this medication should not be discarded as ineffective.

Effects of intrathecal bupivacaine on the NR2B/CaMKIIα/CREB signaling pathway in the rat lumbar spinal cord.

Neuraxial anesthesia produces an anesthetic-sparing, sedative effect. The mechanism underlying this effect potentially involves decreased spinal afferent input. However, the neurochemical mechanisms at the spinal level remain unknown. The N-methyl-D-aspartate receptor 2B subunit/calcium-calmodulin-dependent protein kinase II α/cAMP response element-binding protein (NR2B/CaMKIIα/CREB) signaling pathway serves an important role in regulating the transmittance of peripheral noxious stimulation to supraspinal regions in the process of nociception. The present study investigated the effects of intrathecal bupivacaine on the NR2B/CaMKIIα/CREB signaling pathway. Following catheterization, 36 male Sprague-Dawley rats were randomly assigned to a normal saline (NS) or bupivacaine treatment group, in which each rat intrathecally received 20 µl normal saline or 0.5% bupivacaine, respectively. The expression levels of NR2B, CaMKIIα/p-CaMKIIα, and CREB/phosphorylated (p)-CREB in the lumbar spinal cord were investigated by western blotting, reverse transcription-quantitative polymerase chain reaction and immunohistochemistry (IHC). Following bupivacaine treatment, western blot analysis demonstrated that the protein expression levels of NR2B, p-CaMKIIα, and p-CREB in the spinal cord were reduced by approximately 54, 56 and 33%, respectively, compared with NS control rats. Similar alterations in expression were observed by IHC analysis. Additionally, mRNA expression levels of NR2B, CaMKIIα, and CREB were also downregulated following the intrathecal administration of bupivacaine. Therefore, the sedative effect of subarachnoid blockade with bupivacaine possibly occurs through de-afferentation, which may reduce cortical arousal by downregulating the spinal NR2B/CaMKIIα/CREB pathway in vivo, however further investigation is required in order to verify this.

A Comparative Evaluation of Intrathecal Administration of Hyperbaric Bupivacaine alone and in Combination of Different Low Doses of Hyperbaric Bupivacaine with Fentanyl in Cesarean Section

A Comparative Evaluation of Intrathecal Administration of Hyperbaric Bupivacaine alone and in Combination of Different Low Doses of Hyperbaric Bupivacaine with Fentanyl in Cesarean Section

Systematic review and meta-analysis of the efficacy of liposomal bupivacaine in colorectal resections

Objective: The objective of the study was to systematically investigate the outcomes of Liposomal Bupivacaine following major colorectal resections.Patients and methods: We conducted a comprehensive literature search of PubMed, Medline, Google scholar, Cochrane Central Registry and clinical trials.gov databases through May 2017 for studies published regarding liposomal bupivacaine. Studies were filtered based on relevance to perioperative analgesia in colorectal resections. Data comparing type of study, techniques of resection, mode of administration of liposomal bupivacaine, details of control group, outcomes were collected.Results: A total of 1008 patients from seven studies were included in this systematic review and meta-analysis. The studies were mostly retrospective or prospective cohort studies with one randomized controlled trial (RCT). Meta-analysis showed that liposomal bupivacaine was associated with decreased length of stay, standard mean difference in days (SMD) − 0.34, (95% confidence intervals [CI] − 0.56, −0.13, p = .001) and decreased IV opioid use (expressed as intravenous morphine equivalent in milligrams) in the first 48–72 h, SMD −0.49 (95% CI −0.69, −0.28, p < .00001). Pain scores were also significantly low in patients who received liposomal bupivacaine, SMD −0.56 (95% CI −1.07, −0.06, p = .03]. There was no significant difference in hospitalization costs between the two groups.Conclusions: Use of liposomal bupivacaine is associated with decreased IV opioid use, length of stay and lower pain scores. However, our data needs to be interpreted cautiously given the relative paucity of randomized controlled trials.

To compare efficacy of bupivacaine and bupivacaine with dexamethasone for supraclavicular brachial plexus block in patients undergoing upper-limb surgeries: A one -year randomized controlled trial

OBJECTIVE: Brachial plexus block is a viable alternative to general anaesthesia as it provides adequate muscle relaxation,excellent intraoperative and post operative analgesia. Dexamethasone ,a synthetic glucocorticoid was combined with local anaesthetics to study the effects . This study was conducted to compare the onset and duration of sensory and motor block following administration of either bupivacaine and bupivacaine- Dexamethasone in patients undergoing upper limb surgeries under USG guided supraclavicular block.MATERIALS AND METHODS: 60 ASA I / II patients between of 18 and 60 years who underwent elective upper limb surgeries randomly allocated into two groups of 30 each by a sealed envelope technique to receive 30 ml of 0.5% Bupivacaine and 2 ml of normal saline in Group BS and 30 ml of 0.5% Bupivacaine with 2ml (8mg) of Dexamethasone in Group BD. The onset duration of sensory and motor blockade were observed between the two groups.RESULTS: The onset of sensory and motor blockade was faster in Group BD when compared to Group BS (p<0.0001). The duration of sensory and motor blockade was longer in Group BD when compared to Group BS (p<0.0001). There were no significant haemodynamic changes in the study group.CONCLUSION: Dexamethasone when added to Bupivacaine in supraclavicular block shortens the onset time and prolongs the duration of sensory and motor blockade without any systemic side effects.

Intra-incisional liposomal bupivacaine and its impact on postcesarean analgesia: a retrospective study

Purpose: The efficacy of long-acting intraincisional bupivacaine in reducing postoperative opioid use among women who have undergone a cesarean is currently unknown.Materials and methods: This was a retrospective case-control study with a 1:1 allocation. We identified 40 patients in each group, for a total of 80. The treatment group was administered 266 mg of liposomal bupivacaine after completion of the cesarean and was compared to historical controls. Data regarding anesthesia administered, opioid consumption, nonsteroidal anti-inflammatory use, acetaminophen use, type of cesarean, reason for cesarean, and length of postoperative stay were recorded.Results: The treatment group used 41.51 mg of morphine equivalents, while the control group consumed 69.90 mg (p < .001); multivariate analysis demonstrated a mean difference of 26.52 mg (95%CI 12.76–40.28). Univariate analysis demonstrated mean difference in intravenous (IV) ketorolac (40.77 mg, p < .001) and IV acetaminophen (1333.33 mg, p < .001) was different and greater in the treatment group; this was controlled for in the multivariate model. There was no difference in oral and IV ibuprofen or oral acetaminophen use between groups. There were no differences between the type of anesthesia, length of stay, reason for cesarean, and classical sections between groups.Conclusions: Incisional administration of liposomal bupivacaine may be an effective adjunct in reducing opioid use postoperatively and may be a useful adjunct within an enhanced recovery program.

Multimodal Analgesia in Breast Surgical Procedures: Technical and Pharmacological Considerations for Liposomal Bupivacaine Use.

Enhanced recovery after surgery is a multidisciplinary perioperative clinical pathway that uses evidence-based interventions to improve the patient experience as well as increase satisfaction, reduce costs, mitigate the surgical stress response, accelerate functional recovery, and decrease perioperative complications. One of the most important elements of enhanced recovery pathways is multimodal pain management. Herein, aspects relating to multimodal analgesia following breast surgical procedures are discussed with the understanding that treatment decisions should be individualized and guided by sound clinical judgment. A review of liposomal bupivacaine, a prolonged-release formulation of bupivacaine, in the management of postoperative pain following breast surgical procedures is presented, and technical guidance regarding optimal administration of liposomal bupivacaine is provided.

Effectiveness of Bupivacaine after Rubber Band Ligation of Hemorrhoids for Post Procedure Pain

Introduction: Pain is the most common complication of rubber band ligation (RBL) of hemorrhoids when compared to other non-operative techniques to treat hemorrhoids. Local anesthetic injection has been used in a few studies to reduce pain after RBL but its routine use is still not established. We evaluated the effectiveness of local injection of bupivacaine after RBL of hemorrhoids to reduce pain after the procedure.Objective: To compare the mean pain scores by visual analogue scale with and without local injection of bupivacaine after RBL of 1st and 2nd degree hemorrhoids. Design: Randomized controlled trial. Material and Methods: Study was conducted in Surgical unit 1, Civil Hospital, Karachi, for a period of 2 months, from Aug 17, 2016 to Oct 17, 2016. 60 patients having first and second degree hemorrhoids were included in the study from OPD by non-probability consecutive sampling. They were randomized to either to receive local injection of bupivacaine or no injection after RBL of hemorrhoids by closed envelop method. Pain score at 2 hours after the procedure was the main outcome measured.Results: Our study showed that there was a significant reduction in the pain at 2 hours after RBL of hemorrhoids with the use of local bupivacaine injection, mean pain scores 3.30 ± 1.055 when compared to 3.93 ± 0.944 in patients without administration of bupivacaine with p-value = 0.017.Conclusion: Our study concluded that local bupivacaine injection may be used routinely after RBL of hemorrhoids to reduce pain after the procedure.

Clinical Assessment of 0.5% Levobupivacaine with 0.5% Bupivacaine Administration in the Management of Spinal Anaesthesia

Clinical Assessment of 0.5% Levobupivacaine with 0.5% Bupivacaine Administration in the Management of Spinal Anaesthesia

Low dose of dexmedetomidine as an adjuvant to bupivacaine in cesarean surgery provides better intraoperative somato-visceral sensory block characteristics and postoperative analgesia.

ObjectIn this study, we aimed to investigate the beneficial effects of dexmedetomidine on somato-visceral sensory block characteristcs, postoperative analgesia and stress response of intrathecal bupivacaine administration in women undergoing cesarean section, and to find out which dose is better.MethodsSixty parturients with the American Society of Anesthesiologists (ASA) physical status I or II were anesthetized with intrathecal bupivacaine(10mg) alone or in combination with dexmedetomidine (3 μg and 5 μg) to undergo cesarean section. The anesthetic parameters, postoperative analgesia and stress responses were monitored.ResultsCo-administration of dexmedetomidine(3 μg and 5 μg) prolonged the duration of motor and sensory block compared with bupivacaine(10mg) alone. Less supplemental dose of lidocaine and fentanyl were required in dexmedetomidine(3 μg and 5 μg) co-administration groups. Visceral traction response and abdominal muscle relaxation in operation were better in dexmedetomidine(3 μg and 5 μg) co-administration groups. No difference in haemodynamics was detected among groups. There was no significant difference in Apgar scores, neonatal umbilical pH, oxygen pressure, carbon dioxide pressure and lactate level among groups. Postoperative plasma IL-6 and cortisol levels were lower in dexmedetomidine(3 μg and 5 μg) co-administration groups. At 6 hour after operation the visual analogue scale (VAS) was smaller in dexmedetomidine(3 μg and 5 μg) co-administration groups. The uterine contraction pain at 6 and 12 hour after operation and supplemental analgesics had no difference across three groups. No difference of side effects(shivering, nausea and vomiting, itching), the first anal aerofluxus time and intraoperation tramadol dose were detected among the three groups.ConclusionThe use of dexmedetomidine especially at the dose of 3μg as an adjuvant to bupivacaine in cesarean surgery provides better intraoperative somato-visceral sensory block characteristcs and postoperative analgesia, which produced no influence on Apgar scores, side effects and stress response.

Differential effects of neural inactivation of the dorsolateral striatum on response and latent extinction.

The present study examined the role of the dorsolateral striatum (DLS) in extinction behavior. Male Long-Evans rats were initially trained on the straight alley maze, in which they were reinforced to traverse a straight runway and retrieve food reward at the opposite end of the maze. After initial acquisition, animals were given extinction training using 1 of 2 distinct protocols: response extinction or latent extinction. For response extinction, the animal was released from the same starting position and had the opportunity to perform the originally reinforced approach response to the goal end of the maze, which no longer contained food. For latent extinction, the animal was confined to the original goal location without food, allowing the animal to form a new cognitive expectation (i.e., that the goal location is no longer reinforced). Immediately before response or latent extinction training, animals received bilateral intra-DLS administration of the sodium channel blocker bupivacaine or control injections of physiological saline. Results indicated that neural inactivation of the DLS with bupivacaine impaired response extinction, but did not influence latent extinction. The dissociation observed indicates that the DLS selectively mediates extinction mechanisms involving suppression of the original response, as opposed to cognitive mechanisms involving a change in expectation. (PsycINFO Database Record

Effect of intrafragmentary bupivacaine (haematoma block) on analgesic requirements in dogs undergoing fracture repair

ObjectiveTo test the efficacy of intraoperative intrafragmentary administration of bupivacaine (haematoma block) in controlling postoperative pain in dogs undergoing osteosynthesis of long-bone isolated diaphyseal fractures. Study designRandomized, ‘blinded’, placebo-controlled, prospective study. AnimalsA total of 23 client-owned dogs with isolated long-bone fractures. MethodsDogs were allocated randomly to two groups: bupivacaine group (B) or placebo group (P). Group B dogs (n = 11) were administered an intraoperative intrafragmentary injection of 0.5% bupivacaine (1.1 mg kg–1) just before fracture fixation, whereas group P dogs (n = 12) were administered normal saline. Postoperative pain evaluations using the University of Melbourne Pain Scale (UMPS) and algometer were performed upon arrival to the recovery room and 1, 2, 4, 6, 8, 20 and 32 hours later. Algometer measurements were performed on: the incision site, a healthy region near the fracture line and the contralateral healthy limb. When the pain score exceeded 14 points in the UMPS, rescue analgesia was administered. The time-standardised area under the curve (AUCst) was used to compare UMPS scores and mechanical pain thresholds between the two groups. ResultsNone of the group B dogs required rescue analgesia, whereas eight of the 12 group P dogs did (p = 0.001). The pain threshold AUCst at the incision line was higher in group B [16.3 (2.9–41.6) N] than in group P [5.6 (2.5–17.4) N] (p = 0.029). The mean UMPS score AUCst was lower in group B (3.7 ± 1.8) than in group P (9.4 ± 4.6) (p = 0.016). In a small number of animals of both groups that were evaluated radiologically, adequate bone healing was noted. Conclusions and clinical relevanceAn intraoperative bupivacaine haematoma block is a simple, quick and effective method that can be used to aid in postoperative pain control in dogs submitted to long-bone osteosynthesis.

Cardiovascular tolerance of intravenous bupivacaine in broiler chickens (Gallus gallus domesticus) anesthetized with isoflurane

ObjectiveTo determine the median effective dose (ED50) of intravenous (IV) bupivacaine associated with a 50% probability of causing clinically relevant cardiovascular effects [defined as 30% change in heart rate (HR) or mean arterial pressure (MAP)] in chickens anesthetized with isoflurane. Study designRandomized up-and-down study. AnimalsA total of 14 Ross-708 broiler chickens (Gallus gallus domesticus) weighing 1.70–2.75 kg. MethodsAnesthesia was induced and maintained with isoflurane. Monitoring included the electrocardiogram and invasive arterial pressures. Chickens were administered bupivacaine IV over 2 minutes using a dose based on the response of the previous animal. Dose was decreased when HR and/or MAP in the previous animal increased or decreased ≥30% after bupivacaine administration, or increased when HR or MAP changed <30%. The ED50 was defined as the dose resulting in ≥30% variation in HR or MAP in 50% of the population studied. ResultsThe IV ED50 of bupivacaine was 1.94 mg kg−1 using Dixon’s up-and-down method and 1.96 mg kg−1 by logistic regression. Conclusions and clinical relevanceThese results suggest that 1.33 and 1.96 mg kg−1 of IV bupivacaine are associated with a respective 1 or 50% probability of a clinically significant change in MAP in isoflurane-anesthetized chickens. Identification of the cardiovascular changes associated with different doses of bupivacaine can be used as the basis for studies of therapeutic applications in the domestic chicken. Further studies are required to determine interspecies variation.

Serum Bupivacaine Concentration After Periarticular Injection With a Mixture of Liposomal Bupivacaine and Bupivacaine HCl During Total Knee Arthroplasty.

A relatively new technique to reduce postoperative pain for total knee arthroplasty is to inject a mixture of 266 mg of liposomal bupivacaine and 125 mg of 0.25% bupivacaine HCl with epinephrine 1:300,000 around the knee joint at the time of surgery. Currently, no publications report serum bupivacaine concentrations over time after periarticular injection of liposomal mixed with free bupivacaine. This information is important to ensure safe serum bupivacaine concentrations are maintained especially when considering supplemental or rescue peripheral nerve blocks. A total of 40 subjects scheduled for primary unilateral total knee arthroplasty with intraoperative periarticular injection of the liposomal bupivacaine and bupivacaine HCl mixture were included. Total serum bupivacaine concentrations were measured after the last injection at selected time points and calculated by gas chromatography. Quantile regression techniques were used to analyze the data over time. This study is registered with ClinicalTrials.gov (ID NCT02626559). Peak serum concentration ranged from 0.17 to 1.2 μg/mL and occurred from 10 minutes to 48 hours. Across all time points, the 48-hour interval had the highest mean concentration of total serum bupivacaine at 0.55 μg/mL (SD, 0.27). Quantile regression showed total serum bupivacaine concentrations increased over the 48 hours measured. None of the participants demonstrated signs or symptoms of local anesthetic toxicity. Total serum concentrations of bupivacaine after periarticular administration of liposomal bupivacaine mixed with bupivacaine HCl remained below the described toxicity threshold (2.5 μg/mL) within the first 48 hours, and no patients demonstrated signs or symptoms of toxicity. However, peak serum concentration time was not achieved within the 48-hour interval. Additional studies are needed to describe the course of serum bupivacaine levels after 48 hours and to ascertain the risk of toxicity when combining this method of periarticular injection with peripheral nerve blocks.

The Effects of Intrathecal Administration of Bupivacaine or Ropivacaine Following Administration of Propofol in Dogs Undergoing Ovariohysterectomy

The Effects of Intrathecal Administration of Bupivacaine or Ropivacaine Following Administration of Propofol in Dogs Undergoing Ovariohysterectomy

Evaluation of the cardiopulmonary and antinociceptive effects of bupivacaine administered epidurally at the first lumbar vertebra in awake dogs

ABSTRACT The aim of this study was to evaluate the effect of epidural bupivacaine administration at the first lumbar vertebra on cardiopulmonary variables, arterial blood gases and anti-nociception. Sixteen healthy female dogs were randomly assigned into two groups based on bupivacaine dose: G1 group, 1mg kg-1 or G2 group, 2mg kg-1, diluted in the same final volume (1mL4kg-1). Cardiopulmonary variables were measured and arterial blood gas was collected (T0), it was repeated 10 minutes after intravenous administration of butorphanol 0.4mg kg -1 (T1). Anesthesia was induced with intravenous etomidate at 2mg kg-1 and the epidural catheter was introduced and placed at the first lumbar vertebra. Thirty minutes later, bupivacaine was administered epidurally. Cardiopulmonary measurements and arterial blood gas analysis were recorded at 10 minute intervals (T2 to T6). Evaluation of pre surgical anti-nociception was performed at 5 minute intervals for 30 minutes by clamping the hind limbs, anus, vulva, and tail with the dogs awake. Subsequently, ovariohysterectomy was performed and adequacy of surgical anti-nociception was evaluated at 5 time points. Parametric data were analyzed using the F test with a &lt;0.05 significance. After bupivacaine administration, there were differences between groups just for bicarbonate means (HCO3 -) on T6 (P=0.0198), with 18.7±1.3 and 20.4±0.8 for G1 and G2, respectively. After T1, before bupivacaine administration, both groups presented a slightly lower pH, base excess (BE), the end-tidal carbon dioxide tension (PECO2), and partial pressure of carbon dioxide (PaCO2), suggesting mild metabolic acidosis. G2 showed better antinociceptive effect both before and during surgery. It was possible to perform ovariohysterectomy in 87.5% of the G2 bitches and 25% of the G1 bitches. The two doses of bupivacaine evaluated do not cause important alterations in the studied parameters and the dose of 2mg kg-1 results in a better antinociceptive effect.

Bupivacaine application reduces post thyroidectomy pain: Cerrahpasa experience.

We aimed to evaluate the impact of bupivacaine administration into the surgical field after total thyroidectomy on post-operative pain and analgesic requirement with a double-blind, prospective, clinical and randomized study. The study was performed between 2010 and 2011. Pain assessment was performed with the visual analog score (VAS). Patients were pre-operatively, randomly divided into two groups to receive either bupivacaine or saline. One group received a 10-mL of bupivacaine solution while the other group was treated with the same volume of 0.9% NaCl through the drain after completion of total thyroidectomy procedure. All patients were anesthetized and operated with the same anesthesia and surgical team. Ninety-one patients (20 males) were included in the study. No patient dropped out of the study during the procedures. No mortality was seen. The VAS scores were significantly lower in the bupivacaine administered group at post-operative minute 30 (3.7±3.2 vs. 5±2.9; P=0.03), hour one (3.04±2.4 vs. 4.2±2.8; P=0.04), and hour eight (1.8±2.04 vs. 3.2±2.1; P=0.005). Thirteen patients required analgesia during their hospital stay in the bupivacaine group while this number was twenty-two in the saline group (P=0.005). Local bupivacaine administration into the surgical field after total thyroidectomy reduces pain and analgesic requirement during the hospital stay.

Use of a perfusion index to confirm the presence of sciatic nerve blockade in dogs

ObjectivesTo evaluate perfusion index (PI) as a determinant of regional nerve block success following sciatic nerve blockade with bupivacaine in dogs undergoing stifle surgery. Study designProspective clinical trial. AnimalsTen adult dogs, aged 5.6 ± 2.6 years and weighing 36.9 ± 16.8 kg, undergoing a tibial plateau leveling osteotomy. MethodsDogs were premedicated with acepromazine (0.03 mg kg−1) and hydromorphone (0.1 mg kg−1) intramuscularly, and anesthetized with propofol (up to 4 mg kg−1) intravenously and isoflurane in oxygen. An ultrasound‐guided femoral and sciatic (F+S) nerve block was performed on the surgical limb with bupivacaine (0.75%), 0.2 mL kg−1 at the femoral site and 0.3 mL kg−1 at the sciatic site, with a maximum volume of 10 mL per site. Physiological variables were recorded every 5 minutes throughout anesthesia. A pulse co‐oximeter probe was placed between the third and fourth digits of both pelvic limbs, and the PI was recorded 5 minutes before infiltration with bupivacaine, immediately afterwards, and every 5 minutes for 30 minutes. Motor nerve conduction velocity (MNCV) of the sciatic nerve was performed on the surgical limb 5 minutes before and 20 minutes after bupivacaine administration to confirm nerve block. ResultsThe PI of the surgical limb was significantly greater than the contralateral pelvic limb at 10 minutes (p = 0.03) and 15 minutes (p < 0.01) after F+S nerve blockade. The MNCV performed after sciatic nerve blockade revealed a functional motor blockade for all dogs. There were no significant changes in physiological variables. Conclusions and clinical relevanceThe PI provided a reliable indication of successful sciatic nerve blockade in the clinical patients in this study. No increase in the PI by 15 minutes after bupivacaine administration around the sciatic nerve could indicate partial or total failure of anesthetic blockade.

Stable gastric pentadecapeptide BPC 157 and bupivacaine

Bupivacaine toxicity following accidental overdose still lacks therapeutic solution. However, there are major arguments for testing BPC 157 against bupivacaine toxicity in vivo in rats, in particular, and then finally, in vitro. These are: the lack of any known BPC 157 toxicity, a lifesaving effect via the mitigation of arrhythmias in rats underwent hyperkalemia or digitalis toxicity, the elimination of hyperkalemia and arrhythmias in rats underwent succinylcholine toxicity and finally, the reduction of potassium-induced depolarization in vitro (in HEK293 cells) in severe hyperkalemia. Most importantly, BPC 157 successfully prevents and counteracts bupivacaine cardiotoxicity; BPC 157 is effective even against the worst outcomes such as a severely prolonged QRS complex. Here, rats injected with bupivacaine (100mg/kg IP) exhibited bradycardia, AV-block, ventricular ectopies, ventricular tachycardia, T-wave elevation and asystole. All of the fatalities had developed T-wave elevation, high-degree AV-block, respiratory arrest and asystole. These were largely counteracted by BPC 157 administration (50µg/kg, 10µg/kg, 10ng/kg, or 10pg/kg IP) given 30min before or 1min after the bupivacaine injection. When BPC 157 was given 6min after bupivacaine administration, and after the development of prolonged QRS intervals (20ms), the fatal outcome was markedly postponed. Additionally, the effect of bupivacaine on cell membrane depolarization was explored by measuring membrane voltages (Vm) in HEK293 cells. Bupivacaine (1mM) alone caused depolarization of the cells, while in combination with BPC 157 (1µm), the bupivacaine-induced depolarization was inhibited. Together, these findings suggest that the stable gastric pentadecapeptide BPC 157 should be a potential antidote for bupivacaine cardiotoxicity.

The dorsolateral striatum selectively mediates extinction of habit memory

Previous research has indicated a role for the dorsolateral striatum (DLS) in acquisition and retrieval of habit memory. However, the neurobiological mechanisms guiding extinction of habit memory have not been extensively investigated. The present study examined whether the dorsolateral striatum (DLS) is involved in extinction of habit memory in a food-rewarded response learning version of the plus-maze in adult male Long-Evans rats (experiment 1). In addition, to determine whether the role of this brain region in extinction is selective to habit memory, we also examined whether the DLS is required for extinction of hippocampus-dependent spatial memory in a place learning version of the plus-maze (experiment 2). Following acquisition in either task, rats received two days of extinction training, in which the food reward was removed from the maze. The number of perseverative trials (a trial in which the rat made the same previously reinforced body-turn) and latency to reach the previously correct food well were used as measures of extinction. Animals were given immediate post-training intra-DLS administration of the sodium channel blocker bupivacaine or vehicle to determine the effect of DLS inactivation on consolidation of extinction memory in each task. In the response learning task, post-training DLS inactivation impaired consolidation of extinction memory. Injections of bupivacaine delayed 2 h post-training did not affect extinction, indicating a time-dependent effect of neural inactivation on consolidation of extinction memory in this task. In contrast, post-training DLS inactivation did not impair, but instead slightly enhanced, extinction memory in the place learning task. The present findings indicate a critical role for the DLS in extinction of habit memory in the response learning task, and may be relevant to understanding the neural mechanisms through which maladaptive habits in human psychopathologies (e.g. drug addiction) may be suppressed.