Advances in mesenchymal stem cells therapy for tendinopathies / 中华创伤杂志(英文版)

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.

Comparison of a minimally invasive osteosynthesis technique with conventional open surgery for transverse patellar fractures / 中华创伤杂志(英文版)

PURPOSE@#The study aims to compare the efficacy and safety of a new minimally invasive osteosynthesis technique with those of conventional open surgery for transverse patellar fractures.@*METHODS@#It was a retrospective study. Adult patients with closed transverse patellar fracture were included, and with open comminuted patellar fracture were excluded. These patients were divided into minimally invasive osteosynthesis technique (MIOT) group and open reduction and internal fixation (ORIF) group. Surgical time, frequency of intraoperative fluoroscopy, visual analogue scale score, flexion, extension, Lysholm knee score, infection, malreduction, implant migration and implant irritation in two groups were recorded and compared. Statistical analysis was performed by the SPSS software package (version 19). A p < 0.05 indicated statistical significance.@*RESULTS@#A total of 55 patients with transverse patellar fractures enrolled in this study, the minimally invasive technique was performed in 27 cases, and open reduction was performed in 28 cases. The surgical time in the ORIF group was shorter than that in the MIOT group (p = 0.033). The visual analogue scale scores in the MIOT group were significantly lower than those in the ORIF group only in the first month after surgery (p = 0.015). Flexion was restored faster in the MIOT group than that in the ORIF group at one month (p = 0.001) and three months (p = 0.015). Extension was recovered faster in the MIOT group than that in the ORIF group at one month (p = 0.031) and three months (p = 0.023). The recorded Lysholm knee scores in the MIOT group were always greater than those in the ORIF group. Complications, such as infection, malreduction, implant migration, and implant irritation, occurred more frequently in the ORIF group.@*CONCLUSION@#Compared with the ORIF group, the MIOT group reduced postoperative pain and had less complications and better exercise rehabilitation. Although it requires a long operation time, MIOT may be a wise choice for transverse patellar fractures.

Clinical observation on syndrome-differentiation acupuncture combined with rehabilitation training for autism spectrum disorder / 中国针灸

OBJECTIVE@#To compare the clinical efficacy and safety between syndrome-differentiation acupuncture combined with rehabilitation training and simple rehabilitation training for children with autism spectrum disorder (ASD).@*METHODS@#A total of 60 children with ASD were randomly divided into an observation group and a control group, 30 cases in each group. In the control group, routine rehabilitation training was applied; in the observation group, syndrome-differentiation acupuncture (the main points were Baihui [GV 20], Dingshenzhen, Niesanzhen, etc., the supplementary acupoints were selected according to syndrome-differentiation) combined with rehabilitation training were applied, all the treatments were given once a day, 5-day continuous treatment with 2-day interval, 12 weeks were required. Before treatment and after 6, 12 weeks of treatment, the autism treatment evaluation checklist (ATEC), childhood autism rating scale (CARS) and autism behavior checklist (ABC) scores were observed, the therapeutic effect and safety were evaluated in the two groups.@*RESULTS@#After 6 and 12 weeks of treatment, except for the sensory perception score after 6 weeks of treatment in the control group, the item scores and total scores of ATEC, CARS scores and ABC scores were decreased compared with those before treatment in the two groups (P<0.05). After 6 weeks of treatment, the social score and total score of ATEC, CARS score in the observation group were lower than those in the control group (P<0.05); after 12 weeks of treatment, the item scores and total score of ATEC, CARS score and ABC score in the observation group were lower than those in the control group (P<0.05). The total effective rate in the observation group was 80.0% (24/30), which was higher than 56.7% (17/30) in the control group (P<0.05). There was no serious adverse reactions in the two groups, and there was no significant difference in the incidence rate of adverse reactions between the two groups (P>0.05).@*CONCLUSION@#Syndrome-differentiation acupuncture combined with rehabilitation training could improve the core symptoms in children with ASD, especially sensory perception and social ability, and with good safety, which is superior to simple rehabilitation training.

Effect of psoralen on rat osteoblasts injuries induced by TCP wear particles in vitro and its mechanism / 中国应用生理学杂志

To investigate the effect and mechanism of psoralen on calvarial osteoblasts injuries caused by tricalcium phosphate (TCP) wear particles in vitro. Primary osteoblasts were obtained from the calvaria of neonatal SD rat by the series of digestion and were identified with ALP staining. Calvarial osteoblasts were treated with TCP wear particles for 48 h to establish the in vitro model of osteoblasts injuries. The rat osteoblasts were randomly divided into control group, TCP wear particles (0.1 mg/ml) group, psoralen treated (at the concentrations of 10, 10, 10 mol/L) groups. WST assay and the flow cytometry were used to detect the cell viability of osteoblasts and apoptosis, respectively. Chemical colorimetry was performed to examine ALP activity of osteobalsts. When the osteoblasts were treated for 14 day, mineral nodules formation was observed with alizarin red S staining. Western blot was applied to examine protein expressions of glucose regulated protein78/94(GRP78/94), inositol dependent enzyme 1 alpha (IREα), spliced X-box binding protein 1 (XBP1s) and phosphorylated c-Jun N-terminal kinase (p-JNK) in calvarial osteoblasts. Compared with control group, the cell viability of osteoblasts, ALP activity and mineral nodules formation in TCP group were decreased significantly (P＜0.05), while the percentage of apoptosis and protein expressions of GRP78/94, IRE1α, XBP1 and p-JNK were obviously increased in calvarial osteoblasts (P＜0.05). Compared with TCP group, the injuries of calvarial osteoblasts and cell apoptosis in psoralen treated groups were obviously decreased (P＜0.05), and the expression levels of GRP78/94, IRE1α, XBP1 and p-JNK were down-regulated remarkably (P＜0.05). Psoralen prevents osteoblasts injuries caused by TCP wear particles through IRE1α-XBP1s-JNK signaling pathway activation.

Minimally-invasive internal fixation for mid-lateral 1/3 clavicle fracture with distal clavicular anatomic locking plate / 中国骨伤

OBJECTIVE@#To investigate clinical effects of minimally-invasive internal fixation for mid-lateral 1/3 clavicle fracture with distal clavicular anatomic locking plate.@*METHODS@#From February 2016 to March 2017, 32 patients with mid-lateral 1/3 clavicle fractures treated by minimally-invasive internal fixation with distal clavicular anatomic locking plate, including 24 males and 8 females with an average of (42.3±12.7) years old (ranged from 22 to 68 years old). According to Robinson classification, 6 patients were type 2A2, 18 patients were type 2B1 and 8 patients were type 2B2. No vessel and nerve injury occurred before operation. The time from injury to operation ranged from 0 to 6 days with an average of (3.1±1.4) days. Length of bilateral clavicule were compared before and after operation to evaluate fracture reduction. Constant score at 6 months after operation was applied to assess recovery of shoulder function.@*RESULTS@#Thirty patients were followed up from 11 to 18 months with an average of (13.3±2.2 ) months. No vessel and nerve injury, implant failure, nonunion or delayed union occurred after operation, and facture wound healed at stage I, the time ranged from 8 to 12 weeks with an average of(10.2±1.1) weeks. Shortened length of clavicle decreased from(11.2±3.6) % before operation to (0.4±0.3)% after operation at 2 days. Ten patients removed internal fixation at 8 months after operation without re-fracture occurred after remove plate. Constant score increased from 23.53±5.21 before operation to 94.30±5.60 after operation at 6 months, and 26 patients got excellent results, and 4 good. Patients were satisfied aesthetic degree of scar and shoulder joint function.@*CONCLUSIONS@#Minimally-invasive internal fixation for mid-lateral 1/3 clavicle fracture with distal clavicular anatomic locking plate, which has advantages of less trauma, rapid recover, less scar, could receive good clinical effects and not effect beauty.

Effect of oxidative stress on periprosthetic osteolysis induced by TCP wear particles in mouse calvaria and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To explore the effect of oxidative stress on periprosthetic osteolysis induced by TCP wear particles in mouse calvaria and its mechanism.@*METHODS@#Thirty-six male ICR mice were randomly divided into three groups (=12):sham group, TCP wear particles (TCP) group and N-acetyl-L-cysteine (NAC) group. Aperiprosthetic osteolysis model in mouse was established by implanting 30 mg of TCP wear particles onto the surface of bilateral parietal bones following removal of the periosteum. On the 2nd day post-operation, NAC (1.0 mg/kg) was locally injected to the calvarium under the periosteum every other day for 2 weeks. Then, all the mice were sacrificed to obtain blood and the calvaria. Periprosthetic osteolysis in the mouse calvaria was observed by tartrate resistant acid phosphatase (TRAP) staining; serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6); total anti-oxidation capacity (T-AOC) and superoxide dismutase (SOD) activity were examined by ELISA and chemical colorimetry, respectively; protein levels of glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), phospho-PERK (p-PERK), eukaryotic initiation factor 2α (eIF2α) and phospho-eIF2α (p-eIF2α) in periprosthetic bone tissue were detected by Western blot.@*RESULTS@#Compared with sham group, serum levels of TNF-α, IL-1β and IL-6, and osteolysis area were increased obviously in TCP group (<0.05), and serum level of T-AOC and SOD activity were decreased significantly in TCP group (<0.05), GRP78 expression, the ratio of p-PERK and PERK, p-eIF2α and eIF2α in the mouse calvaria of TCP group were up-regulated markedly. Compared with TCP group, serum levels of TNF-α, IL-1β and IL-6, and osteolysis area were decreased markedly in NAC group (<0.05), serum level of T-AOC and SOD activity were increased obviously in NAC group (<0.05), and GRP78 expression, the ratio of p-PERK/PERK and p-eIF2α/eIF2α were obviously down-regulated.@*CONCLUSIONS@#Inhibition of oxidative stress can prevent periprosthetic osteolysis induced by TCP wear particles, which may be mediated by inactivation of PERK/eIF2α signaling pathway.

Descending branch of anterior lateral malleolar artery based anterograde island flaps for reconstruction of foot and ankle defects / 中国骨伤

<p><b>OBJECTIVE</b>To explore surgical method and clinical effects of descending branch of the anterior lateral malleolar artery based anterograde island flap for repairing foot and ankle wounds.</p><p><b>METHODS</b>Nine patients with skin defects of foot and ankle repaired by descending branch of the anterior lateral malleolar artery based anterograde island flap were studied from June 2015 to January 2017, including 6 males and 3 females aged from 32 to 63 years old. The wound were located on foot and ankle and associated with exposure of bone, tendon, blood vessels or nerves. The surface of wound located on foot in 6 patients, and 3 patients in ankle joint. The area of defect ranged from 1.5 cm×2.0 cm to 6.0 cm×13.0 cm, and the area of flap ranged from 2.0 cm×3.0 cm to 7.0 cm×15.0 cm. The donor site was skin grafted with split-thickness skin from abdomen. Appearance, texture, condition of donor site of island flaps after operation were observed, satisfied degree of clinical effects were evaluated by ZHANG Hao's evaluation, and AOFAS score were used to evaluate function.</p><p><b>RESULTS</b>Circulations of flaps in 9 cases were stable without blockage, and healed well at 2 weeks after operation. All patients were followed up from 2 to 18 months with an average of(8.0±2.3) months. All flap were survived at stage I, pedicles looked smooth and tidy, no cat-ear formed, the texture of flap was soft with satisfied appearance, the color was near to surrounding skin. The surface of wound were tidy after skin graft of donor sites without scar hypertrophy. Nine patients got satisfied results according to ZHANG Hao's evaluation, and AOFAS score was excellent.</p><p><b>CONCLUSIONS</b>Descending branch of the anterior lateral malleolar artery based anterograde island flap for repairing foot and ankle wounds, which has advantages of protect main vessel, thin flap, is a simple and effective method.</p>

Role of the dynamic contrast-enhanced MRI in assessing the response to neoadjuvant chemotherapy of breast cancer / 中国癌症杂志

Background and purpose:Neoadjuvant chemotherapy to breast cancer has become a mature treat-ment method. The purpose of this study was to evaluate the dynamic contrast-enhanced MRI in assessing the response to neoadjuvant chemotherapy (NAC).Methods:Twenty-four female patients with breast carcinoma (24 were all inva-sive ductal carcinoma) underwent dynamic contrast-enhanced MRI (DCE-MRI) before, after the second and ifnal cycle of NAC. For each patient and each MRI examination, the maximum diameter of tumor, volume transfer constant (Ktrans), exchange rate constant (Kep), and extravascular extracellular volume fraction (Ve) were compared. According to the method of response evaluation criteria in solid tumor (RECIST), the results of neoadjuvant chemotherapy were divided into responder and non-responder.Results:All 24 patients were unilateral and single breast cancer; there were 17 cases of responders and 7 cases of non-responders according to RECIST criteria. For 17 cases of responders, both the average values ofKtrans andKepwere signiifcantly descended after neoadjuvant chemotherapy (allP<0.05).Conclusion:The quantitative parameters ofKtrans andKep can evaluate objectively and veridically the response to neoadjuvant chemother-apy for breast cancer in dynamic contrast-enhanced MRI.

Indirect reduction technique using a distraction support in minimally invasive percutaneous plate osteosynthesis of tibial shaft fractures / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>To describe an indirect reduction technique during minimally invasive percutaneous plate osteosynthesis (MIPPO) of tibial shaft fractures with the use of a distraction support.</p><p><b>METHODS</b>Between March 2011 and October 2014, 52 patients with a mean age of 48 years (16-72 years) sustaining tibial shaft fractures were included. All the patients underwent MIPPO for the fractures using a distraction support prior to insertion of the plate. Fracture angular deformity was assessed by goni- ometer measurement on preoperative and postoperative images.</p><p><b>RESULTS</b>Preoperative radiographs revealed a mean of 7.6°(1.2°-28°) angulation in coronal plane and a mean of 6.8°(0.5°-19°) angulation in sagittal plane. Postoperative anteroposterior and lateral radio- graphs showed a mean of 0.8°(0°-4.0°) and 0.6°(0°-3.6°) of varus/valgus and apex anterior/posterior angulation, respectively. No intraoperative or postoperative complications were noted.</p><p><b>CONCLUSIONS</b>This study suggests that the distraction support during MIPPO of tibial shaft fractures is an effective and safe method with no associated complications.</p>

Treatment of complete acromioclavicular joint dislocation with transfer of the medial half of the coracoacromial ligament to reconstruct the coracoclavicular ligament / 中国骨伤

<p><b>OBJECTIVE</b>To explore the operation methods and clinical effects of transfer of the medial half of the coracoacromial ligament to reconstruct the coracoclavicular ligament in treating complete acromioclavicular joint dislocation.</p><p><b>METHODS</b>From January 2006 to June 2012,26 patients with acute complete acromioclavicular joint dislocation underwent surgery. Transfer of the medial half of the coracoacromial ligament to reconstruct the coracoclavicular ligament, additional clavical hoot plate and Kirschner wires fixation, were performed in all the patients. Among the patients, 18 patients were male and 8 patients were female, with an average age of 36.7 years old (ranged from 25 to 51 years). The duration from injury to operation was from 3 to 12 days with an average of 5 days. According to the Rockwood classification, 4 cases were grade III and 22 cases were grade V . Clinical manifestation included local swelling, tenderness with snapping, limitation of shoulder joint motion. In preoperative bilateral shoulder joint X-rays, the injured coracoclavicular distance was (16.2 ± 5.0) mm which was significantly wider than that of uninjured sides (7.6 ± 1.0) mm. Clinical results were evaluated according to X-rays and Constant-Murley score.</p><p><b>RESULTS</b>All incisions obtained primary healing after operation without complication of infection, internal fixation breakage, redislocation. All the patients were followed up from 12 to 30 months with an average of 18 months. Kirschner wires and internal fixation plate were removed at 1 month and 8-10 months after operation, respectively. At final follow-up, the motion of shoulder joint recovered to normal and a no pain joint was obtained. According to Constant-Murley score, 24 cases got excellent results and 2 cases good. There was no significant difference after operation between the injured coracoclavicular distance and the uninjured contralateral side [(7.7 ± 1.2) mm vs (7.6 ± 1.0) mm), P > 0.05].</p><p><b>CONCLUSION</b>Transfer of the medial half of the coracoacromial ligament to reconstruct the coracoclavicular ligament, additional fixation using hook plate and Kirschner wires is the effective surgical method in treating complete acute acromioclavicular joint dislocation.</p>

Percutaneous fixation for the treatment of un-displaced scaphoid fractures with herbert cannulated screws through volar approach / 中国骨伤

<p><b>OBJECTIVE</b>To summarize the experience of percutaneous fixation of scaphoid fractures with Herbert screws through volar approach, and provide a reliable and efficient treatment method for scaphoid fractures.</p><p><b>METHODS</b>From April 2008 to September 2012,15 patients with scaphoid fractures were treated by percutaneous fixation with Herbert cannulated screws through volar approach including 14 males and 1 female with an average age of 35 years ranging from 25 to 45 years old. Among them, 10 cases were on left side and 5 cases were on right side. Durations from injury to operation ranged from 3 to 10 days with an average of 5 days. All these cases were identified as B2 type according to the Herbert classification based on X-ray and CT scan. In order to assess the function of wrist, all patients were calculated according to Krimmer's score postoperatively.</p><p><b>RESULTS</b>The follow-up period were from 5 to 18 months with an average of 10 months. At 3 months after operation,X-ray was re-checked every month. All the patients achieved bone union with a mean time of 10 weeks (ranged from 7 to 14 weeks) postoperatively. According to Krimmer's score, 14 cases gained 100 scores as perfect and one case got 90 scores as good. The small volar incision of all patients were union at the first period. No operation complications such as infection and nonunion occurred.</p><p><b>CONCLUSION</b>Percutaneous fixation with Herbert cannulated screws through volar approach is a reliable and efficient treatment method for scaphoid fractures with small invasion, high bone union rate, and fewer complications.</p>

The study of effects and mechanism of U50, 488H on electrical coupling during ischemia in the perfused isolated rat heart / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To determine the effect of activation of lambda-opioid receptor with U50, 488H, a selective kappa-opioid receptor agonist, on the changes in electrical coupling during prolonged ischemia and to explore the possible mechanism.</p><p><b>METHODS</b>The isolated rat heart was perfused in a Langendorff apparatus. The effect of U50, 488H on electrical coupling parameters including onset of uncoupling, plateau time, slope and fold increase in r(t) was observed in isolated perfused rat heart subjected to global no-flow ischemia. The effect of U50, 488H on connexin 43 (Cx43) expression of ventricular muscle during ischemia was determined by immunohistochemistry.</p><p><b>RESULTS</b>In the prolonged ischemia model, U50, 488H concentration dependently delayed the onset of uncoupling, increased time to plateau, and decreased the maximal rate of uncoupling during ischemia. The effect of U50, 488H on electrical uncoupling parameters during ischemia was abolished by a selective kappa-opioid receptor antagonist nor-BNI or a PKC inhibitor chelerythrine. The amount of Cx43 immunoreactive signal in ventricular muscle was greatly reduced after ischemia. U50, 488H markedly increased Cx43 expression during ischemia and its effect was also attenuated by nor-BNI or chelerythrine.</p><p><b>CONCLUSION</b>These results demonstrated that U50, 488H delayed the onset of uncoupling and plateau time, decreased the maximal rate of uncoupling and increased Cx43 expression of ventricular muscle during ischemia, and these effects of U50, 488H were mediated by kappa-opioid receptor, in which activation of PKC was involved. The effect of U50, 488H on electrical coupling during ischemia was probably correlated with preservation of Cx43 in cardiac muscle.</p>

Effect of gap junction on the cardioprotection of ischemic postconditioning in rat heart / 中国应用生理学杂志

<p><b>AIM</b>To determine whether the cardioprotection of ischemic postconditioning and heptanol in ischemic heart against ischemia/reperfusion (I/R) is mediated by gap junction.</p><p><b>METHODS</b>The effect of ischemic postconditioning, heptanol at different doses (0.03, 0.06, 0.30, and 0.60 mg/kg) and AAP10 (10 mg/kg) on the intact rat heart during 30 min ischemia and 2 h of reperfusion was observed. Ischemic postconditioning was achieved by 3 cycles of 10 s reperfusion/10 s regional ischemia starting at the beginning of the reperfusion. The infarct size and the arrhythmia scores were measured. The effect of ischemic postconditioning, heptanol at different doses (0.05, 0.10, 0.50 and 1.00 mmol/L) and AAP10 (1 x 10(-7)mol/L) on the isolated heart during 30 min ischemia and 2 h of reperfusion was observed. Ischemic postconditioning was achieved by 6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of the reperfusion. The arrhythmia scores and conduction velocity of ventricle muscle were measured.</p><p><b>RESULTS</b>In the intact rat heart model, ischemic postconditioning and heptanol reduced infarct size and arrhythmia scores. In the Langendorff perfused rat heart model, ischemic postconditioning and heptanol reduced arrhythmia scores and conduction velocity of ventricle muscle. Administration of AAP10, an opener of gap junction attenuated the cardioprotection of ischemic postconditioning and heptanol.</p><p><b>CONCLUSION</b>The cardioprotection of ischemic postconditioning and heptanol may be related to the attenuation of gap junction communication on myocardiac ischemia/reperfusion injury.</p>

Clinical and prognostic analysis of nasopharyngeal carcinoma in 44 children and adolescents / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the clinical effect and prognostic factors of nasopharyngeal carcinoma in 44 children and adolescents.@*METHODS@#From June 1987 to December 2003,44 children and adolescents with nasopharyngeal carcinoma were treated by radiotherapy, and some patients also received chemotherapy. Kaplan-Meier method was used for the survival rate and univariate analysis, and Cox proportional hazard model was used in multivariate analysis.@*RESULTS@#The 3.5 year survival rate was 84.2% and 62.3%.In the univariate analysis, clinical stage, lymph node (N) stage, radiotherapy dose and chemotherapy were significant prognostic factors of survival.In the multivariate analysis, N stage and chemotherapy were the prognostic factors in the survival rate.@*CONCLUSION@#Most nasopharyngeal carcinomas belong to the advanced degree. These patients are sensitive to radiotherapy and chemotherapy. Combined modality therapy can improve the clinical effect of nasopharyngeal carcinoma in children and adolescents.

Delayed electrical uncoupling is involved in kappa-opioid receptor activation -induced cardioprotective effect in the isolated rat heart / 中国应用生理学杂志

<p><b>AIM</b>To determine whether activation of kappa-opioid receptor with U50,488H, a selective kappa-opioid receptor agonist, produces any changes in electrical uncoupling during prolonged ischemia and whether these changes in electrical uncoupling is associated with the cardioprotection induced by kappa-opioid receptor activation, and to explore the possible mechanism.</p><p><b>METHODS</b>(1) To observe the effect of U50,488H (10(-7), 10(-6), 3 x10(-6) and 10(-5) mol/L), a selective kappa-opioid receptor agonist, or with a selective kappa-opioid receptor antagonist nor-BNI (5 x 10(-6) mol/L), or with a mitochondrial K(ATP) channel inhibitor 5-HD on myocardium during ischemia/reperfusion in isolated perfused rat heart. Parameters of measurements include hemodynamic data, formazan content, heart rate, coronary flow, and lactate dehydrogenase (LDH). (2) To examine the effect of U50,488H of different concentration on electrical coupling parameters (including onset of uncoupling, plateau time, slope, and fold increase in r1) during 70 min myocardial ischemia in isolated perfused rat heart.</p><p><b>RESULTS</b>(1) Pretreatment with U50,488H concentration dependently increased formazan content and reduced LDH release induced by 30 min of ischemia and 120 min of reperfusion. (2) The onset of electrical uncoupling and plateau time during prolonged ischemia was delayed by kappa-opioid receptor activation with U50,488H. (3) Linear regression analysis shown that the increase in formazan content and decrease in LDH release produced by kappa-opioid receptor activation was associated with delayed electrical uncoupling during prolonged ischemia. (4) The effects of U50,488H on formazan content, LDH release and on electrical coupling were abolished by nor-BNI, or 5-HD.</p><p><b>CONCLUSION</b>This results demonstrate that the onset of electrical uncoupling during prolonged ischemia is delayed by kappa-opioid receptor activation with a selective kappa-opioid receptor agonist U50,488H, and that delayed electrical uncoupling is associated with the cardioprotection induced by kappa-opioid receptor activation with U50,488H. These effects of kappa-opioid receptor activation with U50,488H are mediated by mitochondrial K(ATP) channels.</p>