1.Low-dose Simvastatin Increases Skeletal Muscle Sensitivity to Caffeine and Halothane.
Xu-Lei CUI ; Ying-Lin WANG ; Gang TAN ; Ai-Lun LUO ; Xiang-Yang GUO
Chinese Medical Sciences Journal 2016;31(2):107-115
Objective To determine whether the myotoxic side effects of statin simvastatin affect skeletal muscle's sensitivity to caffeine and halothane.Methods Primary cultured neonate rat skeletal myotubes were treated with 0.01-5.0 μmol/L simvastatin for 48 hours. MTT was used to evaluate cellular viability. The gross morphology and microstructure of the myotubes were observed with a light and electron microscope, respectively. The intracellular calcium concentrations ([Ca]i) at rest and in response to caffeine and halothane were investigated by fluorescence calcium imaging. Data were analyzed by analysis of variance (ANOVA) test.Results Simvastatin (0.01-5.0 μmol/L) decreased myotube viability, changed their morphological features and microstructure, and increased the resting [Ca]i in a dose-dependent manner. Simvastatin did not change myotube's sensitivity to low doses of caffeine (0.625-2.5 mmol/L) or halothane (1.0-5.0 mmol/L). In response to high-dose caffeine (10.0 mmol/L, 20.0 mmol/L) and halothane (20.0 mmol/L, 40.0 mmol/L), myotubes treated with 0.01 μmol/L simvastatin showed a significant increase in sensitivity, but those treated with 1.0 μmol/L and 5.0 μmol/L simvastatin showed a significant decrease. The sarcoplasmic reticulum Castorage peaked in the myotubes treated with 0.01 μmol/L simvastatin, but it decreased when cells were treated with higher doses of simvastatin (0.1-5.0 μmol/L).Conclusions The myotoxic side effect of simvastatin was found to change the sensitivity of myotubes in response to high-dose caffeine and halothane. When dose was low, sensitivity increased mainly because of increased Cacontent in the sarcoplasmic reticulum, which might explain why some individuals with statin-induced myotoxic symptoms may show positive caffeine-halothane contracture test results. However, when the dose was high and the damage to the myotubes was severer, sensitivity was lower. It is here supposed that the damage itself might put individuals with statin-induced myotoxic symptoms at greater risks of presenting with rhabdomyolysis during surgery or while under anesthesia.
2.Expressions of cystathionine-beta-synthase and cystathionine-gamma-lyase in the corpus cavernosum smooth muscle of castrated rats.
Hua LUO ; Lun-Bo LIU ; Ai-Ping FENG ; Yang GAO ; Gao-Yuan LIAO ; Ming-Quan QIU
National Journal of Andrology 2013;19(7):599-603
OBJECTIVETo study the expressions of cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) in the corpus cavernosum smooth muscle of castrated rats and their roles in erectile dysfunction after castration.
METHODSWe randomly assigned 40 eight-week-old male SD rats to groups A (2-week sham-operation), B (4-week sham-operation), C (2-week castration) and D (4-week castration). We determined the level of serum testosterone (T) and the expressions of CBS and CSE in the corpus cavernosum smooth muscle of the rats after operation using immunohistochemistry and RT-PCR.
RESULTSThe T level was significantly decreased in groups C ([11.85 +/- 6.73] nmol/L) and D ([1.96 +/- 1.23] nmol/L) as compared with A ([89.65 +/- 17.13] nmol/L) and B ([106.75 +/- 19.68] nmol/L) (P < 0.05). CBS and CSE were expressed in all groups of rats, but the relative expressions of CBS and CSE mRNA were significantly lower in groups C (0.93 +/- 0.14 and 0.87 +/- 0.20) and D (0.79 +/- 0.17 and 0.71 +/- 0.12) than in A (2.13 +/- 0.65 and 1.93 +/- 0.15) and B (2.07 +/- 0.53 and 1.89 +/- 0.45) (P < 0. 05), so were the optical density values (IA) of the CBS and CSE proteins, 130.35 +/- 23.56 and 93.56 +/- 36.64 in group C and 80.29 +/- 29.65 and 58.56 +/- 19.95 in group D, as compared with 310.57 +/- 130.56 and 269.56 +/- 116.76 in group A and 349.68 +/-112.35 and 298.35 +/- 100.76 in group B (P < 0.05). The androgen level was positively correlated with the expressions of CBS and CSE in the corpus cavernosum smooth muscle of the rats.
CONCLUSIONAndrogen regulates erectile function via the expressions of CBS and CSE.
Animals ; Cystathionine beta-Synthase ; metabolism ; Cystathionine gamma-Lyase ; metabolism ; Male ; Muscle, Smooth ; enzymology ; Orchiectomy ; Penis ; enzymology ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood
3.Influence of different tranexamic acid administration methods during and after cardiac surgery on coagulation function and postoperative blood loss.
Jing-jie WANG ; Guang-jun CHEN ; Wei LIU ; Yu-guang HUANG ; Ai-lun LUO ; Qi MIAO
Acta Academiae Medicinae Sinicae 2013;35(2):145-149
OBJECTIVETo evaluate the influence of different tranexamic acid administration methods during and after cardiac surgery with cardiopulmonary bypass(CPB) on coagulation function and postoperative bleeding.
METHODSPatients undergoing elective cardiac surgery with use of CPB (n=60) were randomized in a double-blind fashion to one of two treatment groups:group A(n=30) , administered with tranexamic acid 10 mg/kg (intravenous injection slowly before skin incision) , followed by infusion of normal saline until postoperative 12 hours;and group B(n=30) , administered with tranexamic acid 10 mg/kg(intravenous injection slowly before skin incision) , followed by infusion of tranexamic acid 1 mg/(kg·h) until postoperative 12 hours. Hemoglobin, platelet count, and coagulation function were assessed before anesthesia induction, after surgery, 8am next day and 24 hours after surgery. Bleeding, allogeneic blood transfusion, and fluid infusion during the postoperative 24 hours were recorded.
RESULTNo differences were found between groups in terms of coagulant function, postoperative bleeding, allogeneic blood transfusion, and fluid infusion(P>0.05) .
CONCLUSIONCompared with intraoperative administration alone, prolonged treatment with tranexamic acid after cardiac surgery shows no advantage because it can not further improve coagulant function, reduce bleeding, or reduce allogeneic blood transfusion.
Adolescent ; Adult ; Aged ; Antifibrinolytic Agents ; administration & dosage ; therapeutic use ; Blood Coagulation ; drug effects ; Cardiac Surgical Procedures ; Cardiopulmonary Bypass ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Perioperative Period ; Postoperative Hemorrhage ; prevention & control ; Postoperative Period ; Tranexamic Acid ; administration & dosage ; therapeutic use ; Young Adult
4.Prevalence and risk factors of chronic post-thoracotomy pain in Chinese patients from Peking Union Medical College Hospital.
Hai-Tang WANG ; Wei LIU ; Ai-Lun LUO ; Chao MA ; Yu-Guang HUANG
Chinese Medical Journal 2012;125(17):3033-3038
BACKGROUNDIn clinical practice, the mechanisms underlying chronic post-surgical pain (CPSP) remain insufficiently understood. The primary goals of this study were to determine the incidence of chronic pain after thoracic surgery and to identify possible risk factors associated with the development of chronic post-thoracotomy pain in Chinese patients. The secondary goal was to determine whether the difference between pre- and post-operative white blood cell (WBC) counts could predict the prevalence of CPSP after thoracotomy. The impact of chronic pain on daily life was also investigated.
METHODSWe contacted by phone 607 patients who had undergone thoracotomy at our hospital during the period February 2009 to May 2010. Statistical comparisons were made between patients with or without CPSP.
RESULTS
RESULTSwere ultimately analyzed from 466 qualified patients. The overall incidence of CPSP was 64.5%. Difference between pre- and post-operative WBC counts differed significantly between patients with or without CPSP (P < 0.001) and was considered as an independent risk factor for the development of CPSP following thoracotomy (P < 0.001). Other predictive factors for chronic pain included younger age (< 60 years, P < 0.001), diabetes mellitus (P = 0.023), acute post-operative pain (P = 0.005) and the duration of chest tube drainage (P < 0.001). At the time of interviews, the pain resulted in at least moderate restriction of daily activities in 15% of the patients, of which only 16 patients had paid a visit to the doctor and only three of them were satisfied with the therapeutic effects.
CONCLUSIONSChronic pain is common after thoracotomy. WBC count may be a new independent risk factoring surgical patients during peri-operative period. Besides, age, diabetes mellitus, acute post-operative pain, and duration of chest tube drainage may also play a role in chronic post-surgical pain occurrence.
Adult ; Aged ; Chronic Pain ; epidemiology ; etiology ; Drainage ; Female ; Humans ; Leukocyte Count ; Male ; Middle Aged ; Pain, Postoperative ; epidemiology ; etiology ; Prevalence ; Risk Factors ; Thoracotomy ; adverse effects
5.Analgesic effect of calpain inhibitor ALLN on the zymosan-induced paw inflammatory pain and its effect on the expression of cyclooxygenase-2 in the spinal dorsal horn.
Jing-Jie WANG ; Guang-Jun CHEN ; Wen CHEN ; Jin DU ; Ai-Lun LUO ; Yu-Guang HUANG
Acta Academiae Medicinae Sinicae 2012;34(1):25-31
OBJECTIVETo examine the analgesic effect of calpain inhibitor ALLN on the zymosan-induced paw inflammatory pain and its effect on the expression of cyclooxygenase-2 (COX-2) in the spinal dorsal horn.
METHODSForty-eight Sprague-Dawley rats were equally divided into three groups: control group, sham-operated group, and zymosan group. According to Meller's method, zymosan (1.25 mg) was injected intraplantarly to induce paw inflammation in zymosan group; an equal volume of PBS was administered in the sham-operated group. Mechanical withdrawal threshold (MWT) and maximum thickness of paw were tested or measured before and 0.5, 1, 2, 4, 8, and 24 hours after injection. All rats were killed at different occasions following surgery to examine calpain activity in the spinal dorsal horn with Western blot analysis. Another sixty-four Sprague-Dawley rats were divided into three groups: sham-operated group, zymosan-induced paw inflammation with intraperitoneal dimethyl sulphoxide (DMSO) treatment group, and zymosan-induced paw inflammation with intraperitoneal calpain inhibitor ALLN treatment group. MWT and maximum thickness of paw were tested or measured before and 0.5, 1, 2, 4, 8, and 24 hours after injection. All rats were killed at different occasions following surgery to examine the COX-2 expression in the spinal dorsal horn with Western blot analysis.
RESULTSMWT significantly decreased in the rats with zymosan-induced paw inflammation, while the maximum thickness of paw significantly increased, compared with control and sham-operated rats (P < 0.05). Calpain in the ipsilateral spinal dorsal horn was dramatically activated after zymosan injection (P < 0.01). Intraperitoneal ALLN injection significantly increased zymosan-induced MWT and decreased paw edema at the same time points after zymosan injection compared with DMSO treatment group (P < 0.05). Meanwhile, calpain inhibitor ALLN treatment significantly decreased the COX-2 expression in the spinal dorsal horn compared with DMSO treatment (P < 0.01).
CONCLUSIONAdministration of calpain inhibitor ALLN is effective to attenuate zymosan-induced paw inflammatory pain. Calpain activation may be one aspect of the signaling cascade that increases the COX-2 expression in the spinal cord and contributes to mechanical hyperalgesia after peripheral inflammatory injury.
Analgesics ; pharmacology ; Animals ; Cyclooxygenase 2 ; metabolism ; Disease Models, Animal ; Glycoproteins ; pharmacology ; Male ; Pain ; chemically induced ; drug therapy ; enzymology ; Posterior Horn Cells ; drug effects ; enzymology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; drug effects ; enzymology ; Zymosan ; adverse effects
6.Effects of residual paralysis after a single intubating dose of rocuronium on postoperative pulmonary function of patients undergoing laparoscopic gynecological surgeries.
Yu-he BAI ; Hong-zhi REN ; Ai-lun LUO ; Yu-guang HUANG ; Tie-hu YE ; Xiang-yang GUO
Acta Academiae Medicinae Sinicae 2010;32(1):102-107
OBJECTIVETo evaluate the residual paralysis after a single intubating dose of rocuronium and its effect of residual paralysis after a single dose of rocuronium on the postoperative pulmonary function of patients undergoing laparoscopic gynecological surgeries.
METHODSSixty American Society of Anesthesiologists (ASA) I - II patients undergoing laparoscopic gynecological surgeries were randomly divided into rocuronium (R) group (n = 30) and rocuronium + neostigmine (R + N) group (n = 30).All patients received midazolam (0.02 mg/kg), fentanyl (1 microg/kg), propofol(1.5-2 mg/kg), and rocuronium (0.6 mg/kg) to facilitate tracheal intubation and no more relaxant thereafter. Anesthesia was maintained with isoflurane and nitrous oxide in oxygen (N(2)O:O(2) = 1:1). At the end of the procedure, neuromuscular blockade was not reversed in R group, while antagonism was accomplished with neostigmine (0.04 mg/kg) and atropine (0.02 mg/kg) in R + N group. Immediately after tracheal extubation and on arrival in the PACU, the train-of-four (TOF) ratio at the adductor pollicis of all patients were measured using acceleromyography. Forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)), and peak expiratory flow rate (PEFR) of all patients were measured using spirometry before surgery, after administration of midazolam and fentanyl, immediately after tracheal extubation, on arrival in the PACU, and after the TOF ratio recovered to 1.0. The TOF ratio and pulmonary function between two groups were compared.
RESULTSImmediately after tracheal extubation and on arrival in the PACU, the mean TOF ratio in R group was significantly lower than that in R + N group (P < 0.05). The mean time to achieve TOF ratio of 0.9 and 1.0 in R group was significantly longer than in R + N group (P < 0.05). Immediately after tracheal extubation and on arrival in the PACU, FVC, FEV(1), and PEFR were significantly lower in R group than in R + N group (P < 0.05). FVC, FEV(1), and PEFR after administration of midazolam and fentanyl and after TOF ratio recovered to 1.0 were significantly lower than the baseline values in all patients (P < 0.01).
CONCLUSIONSAfter a single intubating dose of rocuronium, residual paralysis exists in the majority of patients undergoing laparoscopic gynecological surgeries. The pulmonary function is impaired after the surgery, even after recovery of TOF ratio to 1.0.
Adolescent ; Adult ; Airway Extubation ; Androstanols ; administration & dosage ; adverse effects ; Female ; Gynecologic Surgical Procedures ; Humans ; Intubation, Intratracheal ; Laparoscopy ; Middle Aged ; Neuromuscular Nondepolarizing Agents ; administration & dosage ; adverse effects ; Paralysis ; chemically induced ; Postoperative Period ; Respiratory Function Tests ; Young Adult
7.Application of propofol target controlled infusion combined with dribbled and nebulized lidocaine in tracheal intubation under spontaneous respiration.
Jian-qing XU ; Tie-hu YE ; Yu-guang HUANG ; Ai-lun LUO
Acta Academiae Medicinae Sinicae 2010;32(5):569-573
OBJECTIVETo evaluate the value of propofol target-controlled infusion combined with dribbled and nebulized lidocaine in tracheal intubation under spontaneous breathing.
METHODSTotally 40 elective surgery patients to accept tracheal intubation under unconsciousness and spontaneous breathing were randomly divided into 2 groups: 6-8 cm of endotracheal tube was inserted subglottic ally in the complete intubation group (n=20) while 3-4 cm was inserted temporarily in the partial intubation group (n=20).
RESULTSThe tracheal intubation was successfully completed under spontaneous breathing in all patients; meanwhile,the hemodynamic status was stable without any severe respiratory complications. Eleven patients suffered from moderate coughing response in the complete intubation group while no such response was noted in the partial intubation group (P<0.01).
CONCLUSIONSApplication of propofol target-controlled infusion combined with dribbled and nebulized lidocaine provides a good condition for tracheal intubation under unconsciousness and spontaneous breathing. The partial intubation can effectively prevent the occurrence of coughing response.
Adolescent ; Adult ; Aged ; Cough ; etiology ; prevention & control ; Female ; Humans ; Intubation, Intratracheal ; adverse effects ; methods ; Lidocaine ; administration & dosage ; Male ; Middle Aged ; Propofol ; administration & dosage ; Young Adult
8.Application of lumber plexus blockade for hip fracture repair in elderly patients.
Zhong-Huang XU ; Shuai TANG ; Ai-Lun LUO ; Yu-Guang HUANG
Acta Academiae Medicinae Sinicae 2010;32(3):328-331
OBJECTIVETo evaluate the lumber plexus blockade as anesthesia technique for hip fracture repair in elderly patients.
METHODSWe retrospectively analyzed the peri-operative data of 87 hip fracture patients, aged 70 years or older, who underwent surgical repair at our hospital between 2003 and 2006. Patients were divided into three groups according the anesthesia techniques applied: general anesthesia (GA) group (n=21), epidural anesthesia (EA) group (n=37), and lumber plexus blockade (LPB) group (n=29).
RESULTSThe peri-operative data were comparable among three groups, except that intra-operative the dosage of fentanyl was significantly lower in LPB group compared with in GA group(P0.05), and the blood urea nitrogen 1 day after surgery was significantly increased in GA group(P0.05).
CONCLUSIONLumber plexus blockade combined with small-dose intravenous anesthesia is an optional anesthetic technique for elderly patients undergoing hip fracture repair.
Aged ; Aged, 80 and over ; Female ; Hip Fractures ; surgery ; Hip Joint ; surgery ; Humans ; Lumbosacral Plexus ; Male ; Nerve Block ; Retrospective Studies
9.Clinical features and diagnosis for Chinese cases with malignant hyperthermia: a case cluster from 2005 to 2007.
Ying-lin WANG ; Ai-lun LUO ; Gang TAN ; Xu-lei CUI ; Xiang-yang GUO
Chinese Medical Journal 2010;123(10):1241-1245
BACKGROUNDMalignant hyperthermia (MH), manifesting as MH crisis during and/or after general anesthesia, is a potentially fatal disorder in response to volatile anesthetics and depolarizing muscle relaxants. Though typical features of MH episode can provide clues for clinical diagnosis, MH susceptibility is confirmed by in vitro caffeine-halothane contracture test (CHCT) in western countries. It is traditionally thought that MH has less incidence and fewer typical characteristics in Chinese population than their western counterparts because of the different genetic background. In this study, we investigated the clinical features of MH in Chinese cases and applied the clinical grading scale and CHCT for diagnosis of MH.
METHODSA cluster of three patients with MH, from January 2005 to December 2007, were included in the study. Common clinical presentations and the results of some lab examinations were reported in detail. The method of the clinical grading scale of diagnosis of MH was applied to estimate the qualitative likelihood of MH and predict MH susceptibility. Muscle fibers of femoral quadriceps of the patients were collected and CHCT was performed to confirm the diagnosis of MH.
RESULTSThe clinical grading scales of diagnosis of the disease for these cases were all ranked grade D6, suggesting almost diagnosed ones. And the results of caffeine test were positive correspondingly, indicating that the patients should be diagnosed as MH susceptibility (MHS) according to diagnostic criteria of the North America MH group, which were already confirmed by clinical presentations and biochemical results.
CONCLUSIONSThese Chinese cases manifest as MH crisis. The clinical grading scale of diagnosis of MH may provide clues for clinical diagnosis. CHCT can also be used in confirming diagnosis of MH in Chinese cases though they have different genetic background from their western counterparts.
Adolescent ; Adult ; Caffeine ; Child ; China ; Female ; Halothane ; Humans ; In Vitro Techniques ; Male ; Malignant Hyperthermia ; diagnosis ; Muscle Contraction ; drug effects ; Young Adult
10.Application of caffeine-halothane contracture test in the diagnosis of malignant hyperthermia.
Ying-Lin WANG ; Xiang-Yang GUO ; Zhong-Huang XU ; Yu-Guang HUANG ; Ai-Lun LUO
Acta Academiae Medicinae Sinicae 2008;30(2):182-186
OBJECTIVETo explore the application of caffeine-halothane contracture test (CHCT) in the confirmation of malignant hyperthermia (MH).
METHODSOne patient who underwent radical gastrectomy presented with clinical manifestations of MH during routine intravenous-inhalation anesthesia process. Isoflurane inhalation and the operation were ceased immediately and emergency management approaches such as physical cooling therapy were taken. Meanwhile, the levels of serum creatine kinase (CK), serum myoglobin, and urinary myoglobin were examined and rectus abdominis was taken and then CHCT was performed to confirm the clinical diagnosis. Total genome was extracted from the patient and then exons 2-18, 39-46, and 90-104 of ryanodine receptor 1 (RYR1) gene were screened to detect mutations using DNA sequencing technique.
RESULTSThe patient was diagnosed as MH episode by clinical characteristics and postoperatively continuous elevation of the levels of CK, serum myoglobin, and urinary myoglobin (30 times higher than normal level). Despite halothane test was negative, the diagnosis of MH was verified by the positive result of caffeine test. DNA sequencing of RYR1 gene of the patient revealed c. 6724C > T (p. T 2 206M).
CONCLUSIONCHCT can be used to confirm the diagnosis of MH.
Anesthetics, Inhalation ; therapeutic use ; Caffeine ; Creatine Kinase ; blood ; Enzyme-Linked Immunosorbent Assay ; Halothane ; Humans ; Isoflurane ; therapeutic use ; Malignant Hyperthermia ; blood ; diagnosis ; genetics ; Muscle, Skeletal ; drug effects ; physiopathology ; Myoglobin ; blood ; Ryanodine Receptor Calcium Release Channel ; genetics

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