Limb Remote Ischemic Preconditioning Applied During Sevoflurane Anesthesia Does Not Protect the Lungs in Patients Undergoing Adult Heart Valve Surgery.

BACKGROUND: Two consistent overall cell protective preconditioning treatments should provide more protection. We hypothesized that limb remote ischemic preconditioning (RIPC, second preconditioning stimulus) applied during sevoflurane inhalation (first preconditioning stimulus) would provide more protection to the lungs of patients undergoing adult heart valve surgery. METHODS: In this randomized, placebo-controlled, double-blind trial, 50 patients were assigned to the RIPC group or the placebo group (1:1). Patients in the RIPC group received three 5-min cycles of 300 mmHg cuff inflation/deflation of the left-side lower limb before aortic cross-clamping. Anesthesia consisted of opioids and propofol for induction and sevoflurane for maintenance. The primary end point was comparison of the postoperative arterial-alveolar oxygen tension ratio (a/A ratio) between groups. Secondary end points included comparisons of pulmonary variables, postoperative morbidity and mortality and regional and systemic inflammatory cytokines between groups. RESULTS: In the RIPC group, the a/A ratio and other pulmonary variables exhibited no significant differences throughout the study period compared with the placebo group. No significant differences in either plasma or bronchoalveolar lavage levels of TNF- α were noted between the groups at 10 min after anesthetic induction and 1 h after cross-clamp release. The percentage of neutrophils at 12 h postoperation was significantly increased in the RIPC group compared with the placebo group (91.34±0.00 vs. 89.42±0.10, P = 0.023). CONCLUSIONS: Limb RIPC applied during sevoflurane anesthesia did not provide additional significant pulmonary protection following adult valvular cardiac surgery.

Serratus Anterior Plane Block Combined with General Analgesia and Patient-Controlled Serratus Anterior Plane Block in Patients with Breast Cancer: A Randomized Control Trial.

INTRODUCTION: Anterior serratus muscle plane block is a novel regional block technique for blockade of the sensory plane of the lateral cutaneous branch of the intercostal nerve (T2-T9), which effectively relieves the pain of patients and improves the quality of recovery. This study aimed to observe the early effectiveness and safety of serratus anterior plane block combined with general anesthesia and patient-controlled serratus anterior plane block in early postoperative recovery in breast cancer. METHODS: The study involved a total of 84 patients undergoing radical mastectomy in our hospital. The patients were randomly divided into three groups: the serratus anterior block + general anesthesia + patient-controlled serratus anterior plane block group (PCSAPB group), the serratus anterior block + general anesthesia + patient-controlled intravenous analgesia group (PCIA group), and the general anesthesia + PCIA group (control group), with n = 28 cases in each group. RESULTS: The visual analogue scale (VAS) scores of the three groups were compared before and after the operation (P < 0.001), and the anxiety visual analogue scale (AVAS) scores after operation were compared among the three groups (P < 0.001). The total number of postoperative analgesic pumps in the PCSAPB group was significantly lower than that in the control group (P < 0.05). The incidence of adverse reactions in the three groups was statistically significant (P < 0.05). CONCLUSION: The combination of anterior serratus plane block and general anesthesia and patient-controlled anterior serratus plane block reduced pain and adverse events, alleviating anxiety, improving the quality of early postoperative recovery among patients with breast cancer after modified radical mastectomy.

Over-expression of P2X7 receptors in spinal glial cells contributes to the development of chronic postsurgical pain induced by skin/muscle incision and retraction (SMIR) in rats.

Many patients suffer from chronic postsurgical pain (CPSP) following surgery, and the underlying mechanisms are poorly understood. In the present work, with use of the skin/muscle incision and retraction (SMIR) model, the role of P2X7 receptors (P2X7Rs) in spinal glial cells in the development of CPSP was evaluated. Consistent with previous reports, we found that SMIR decreased the ipsilateral 50% paw withdrawal threshold (PWT), lasting for at least 2weeks. No injury was done to L3 dorsal root ganglia (DRG) neurons and no axonal or Schwann cell damage at the retraction site in the saphenous nerve was observed 7days after SMIR. The results of immunofluorescence showed that both microglia and astrocytes were activated in the spinal dorsal horn following SMIR. In addition, both P2X7Rs and tumor necrosis factor-alpha (TNF-α) were up-regulated following SMIR. Double immunofluorescence staining revealed that the up-regulated P2X7R immunoreactivity was mainly located in microglia, and to a lesser extent in astrocytes, but not in neurons. Intrathecal delivery of specific P2X7R antagonist BBG (10µM in 10µl volume) or A438079 (10µM in 10µl volume), started 30min before the surgery and once daily thereafter for 7days, prevented the mechanical allodynia. Intrathecal injection of BBG inhibited the activation of microglia and astrocytes, and the up-regulation of TNF-α induced by SMIR. These data suggest that P2X7Rs in the spinal dorsal horn might mediate the development of CPSP via activation of glial cells and up-regulation of TNF-α.

[Effects of dexmedetomidine hydrochloride on ERK1/2 activation in a rat model of ventilator-induced lung injury].

OBJECTIVE: To investigate the effect of dexmedetomidine hydrochloride on inflammatory lung injury and phosphorylation of extracellular regulated protein (ERK1/2) in a rat model of ventilator-induced lung injury (VILI). METHODS: Thirty-six adult male SD rats were randomized into 3 groups (n=12) to receive a 4-h standard ventilation (group C, with tidal volume of 8 ml/kg and respiratory rate of 90/min), high-tidal volume ventilation (group H, with tidal volume of 20 ml/kg and respiratory rate of 50 /min), and high-tidal volume ventilation plus 0.5 µg·kg(-1)·h(-1) dexmedetomidine infusion (group D), with the maintenance of a positive end expiratory pressure (PEEP) of 0 cmH(2)O. After mechanical ventilation the rats were sacrificed to collect the lung lavage liquid and lung tissue to examine the pulmonary inflammatory changes and tumor necrosis factor-α (TNF-α) expression as well as the expressions of ERK1/2 and p-ERK1/2. RESULTS: Groups H and D showed obvious lung injury and significant elevations of the total protein, WBC, MPO, TNF-α, and ERK1/2 phosphorylation as compared with those of group C. The rats in group D showed milder lung pathologies with significantly lower levels of phosphorylation of ERK1/2 and TNF-α compared with those in group H. CONCLUSION: Dexmedetomidine can significantly attenuate VILI, decrease the production of the inflammatory molecules, and inhibit the activation of ERK1/2, demonstrating a protective effect against VILI.

[Effect of dexmedetomidine on patient-controlled intravenous analgesia with fentanyl in elderly patients after total hip replacement].

OBJECTIVE: To investigate the effect of a continuous infusion of low-dose dexmedetomidine on patient-controlled analgesia (PCA) with fentanyl in elderly patients after total hip replacement. METHODS: Forty patients (ASA I-II) aged 66-81 years after total hip replacement were randomized equally into the control and test groups. The patients in the test group received continuous infusion of dexmedetomidine at the rate of 0.2 µg·kg(-1)·h(-1) from the beginning to the end of PCA with fentanyl after the surgery, while those in the control group received normal saline. The cumulative fentanyl dose, VAS pain scores and Ramsay sedation score were recorded at 0, 4, 8, 12 and 24 h after the surgery. RESULTS: All the patients in the two groups reported good pain relief and none needed additional fentanyl. The VAS pain score was significantly lower (P<0.05 or 0.01), while the Ramsay sedation scores higher (P<0.05) in the test group than in the control group. The cumulative fentanyl dose was significantly lower in the test group (P<0.05 or 0.01). The incidence of such adverse effects as nausea and vomiting was significantly lower in the test group (P<0.05). CONCLUSION: PCA with fentanyl combined with low-dose dexmedetomidine infusion is safe for elderly patients, and can decrease fentanyl consumption and improve the effect of PCA with fentanyl.

[Effects of morphine and pethidine on the expression of P-glycoprotein in mouse brain microvascular endothelial cells].

OBJECTIVE: To observe the effects of morphine and pethidine on P-glycoprotein (P-gp) expression in mouse brain microvascular endothelial cells and investigate the role of nuclear factor-kappaB (NF-kappaB) signaling pathway in morphine-induced up-expression of P-gp. METHODS: The mouse brain microvascular endothelial cell line (b.END3) was subjected to pre-incubation with NF-kappaB inhibitor PDTC (5 micromol/L) for 1 h followed by stimulation with morphine (1 microg/ml) or pethidine (1 microg/ml) for 24 h. The bEnd.3 cells were then collected for Western blotting for P-gp expression. RESULTS: A 24-h morphine stimulation induced an up-expression of P-gp in bEnd.3 cells by almost 200%. Pethidine in similar conditions did not affect P-gp expression in the cells. PDTC, the specific inhibitor of NF-kappaB, inhibited morphine-induced up-expression of P-gp in the cells. CONCLUSION: Morphine can induce up-expression of endogenous P-gp in mouse brain microvascular endothelial cells. NF-kappaB signaling pathway is involved in the morphine-induced up-expression of P-gp.

[Effect of dexmedetomidine on bispectral index and auditory evoked potential index during anesthesia with target controlled infusion of propofol and remifentanyl].

OBJECTIVE: To evaluate the effect of dexmedetomidine (Dex) on bispectral index (BIS) and auditory evoked potential index (AAI) during anesthesia with target controlled infusion (TCI) of propofol and remifentanyl. METHODS: Thirty adult patients (ASA I approximate, equalsII) who were scheduled for elective thyroidectomy were monitored with BIS, AAI, ECG, blood pressure, end-tidal CO(2), and pulse oximeter before and during anesthesia. Anesthesia was induced by TCI with propofol 4 mg/L and remifentanyl 1 mu g/kg. After loss of consciousness the patients were intubated after rocuronium 0.6 mg/kg intravenous injection, remifentanyl was then infused at 0.2 microg/(kg x min)(-1) and propofol infusion (Ct) was titrated to maintain a BIS value at 50 +/- 3. At 10 min after stabilization of anesthesia the patients were randomly and double-blindly divided into 2 groups: Group D (n=15) received Dex 0.4 mu g/kg iv administered over 5 min and Group C (n=15) received equal volume of normal saline. Values of BIS, AAI, MAP, HR were recorded every 2 min within 20 min after the administration of the drugs. RESULTS: Before anesthesia the BIS index was 90 +/- 2 in Group D and 92 +/- 2 in Group C, AAI was 81 +/- 1 in Group D and 78 +/- 1 in Group C. In anesthesia with target controlled infusion of propofol, BIS index showed a significant decrease with the i.v. administration of Dex 0.4 microg/kg, while AAI remained unchanged. In Group C, both of BIS and AAI remained unchanged after saline injection. CONCLUSION: During propofol and remifentanyl anesthesia, after the administration of Dex, BIS value demonstrates a predominant decrease, whereas AAI shows no changes.

[Effect of mitogen-activated protein kinase kinase 6-p38 alpha signal pathway on receptor for advanced glycation end-product expression in alveolar epithelial cells induced by mechanical stretch].

OBJECTIVE: To investigate the role of mitogen-activated protein kinase kinase 6 (MKK6) p38 alpha in mechanical stretch induced receptor for advanced glycation end-product (RAGE) expression in alveolar epithelial cells (A549). METHODS: Recombinant plasmids were transfected into A549 cells with liposome DOTAP. A549 cells transfected with p38 alpha (AF)/pGFP and MKK6b (E)/pGFP plasmids were taken as treated groups, while the groups that transfected with pcDNA3 plasmid and pGFP plasmid served as blank transfection group and control group, respectively. All the groups were then cultured in 6-well Bioflex cell culture plates and exposed to cyclic mechanical stretch at 20% elongation. The infection and expression of gene were assessed by Western blotting analysis. The activity of p38 kinase in A549 cells and the expression of RAGE protein and mRNA were observed. RESULTS: The transfection of MKK6b (E) led to a markedly increase in p38 kinase activity compared with control group. In contrast, the transfection of p38 alpha (AF) significantly inhibited p38 kinase activity. Compared with control group, stretch markedly increased RAGE protein and mRNA expression in MKK6b (E) transfected cells, while it markedly decreased RAGE expression in p38 alpha (AF) transfected cells. CONCLUSION: MKK6 p38 alpha signaling pathway regulates the expression of RAGE induced by mechanical stretch in A549 cells.

[Regulation of P38 and MKK6 on HMGB1 expression in alveolar macrophages induced by cyclic mechanical stretch.].

The aim of the present study was to investigate the role of mitogen-activated protein kinase kinase 6 (MKK6)-P38 signaling pathway in cyclic mechanical stretch-induced high mobility group box 1 protein (HMGB1) expression in alveolar macrophages. In the study, Sprague-Dawley rats were anesthetized and then sacrificed by bloodletting. The lungs were lavaged six times with prechilled PBS. Alveolar macrophages were isolated from lavage samples. Recombinant plasmids were transfected into alveolar macrophages with liposome DOTAP. Alveolar macrophages transfected with P38(AF)/pGFP and MKK6b(E)/pGFP plasmids were taken as treated groups, while the groups that transfected with pcDNA3 plasmid and pGFP plasmid served as blank transfection group and control group, respectively. All the groups were then cultured in 6-well Bioflex cell culture plates and exposed to cyclic mechanical stretch at 20% elongation using Flexercell 4000T cell stretching unit. The results showed that the transfection of MKK6b(E) led to a marked increases in P38 kinase activity compared with control group. In contrast, the transfection of P38(AF) significantly inhibited P38 kinase activity. Compared with control group, HMGB1 protein and mRNA expression in MKK6b(E) transfected cells increased markedly, while HMGB1 expression in P38(AF) transfected cells decreased markedly. These results suggest that MKK6-P38 MAPK signaling pathway regulates the expression of HMGB1 induced by cyclic mechanical stretch in alveolar macrophages.

[Effect of intrathecal administration of sufentanil at different doses on bupivacaine spinal anesthesia in gynecologic laparoscopy].

OBJECTIVE: To investigate the effect of sufentanil administered intrathecally at different doses on the clinical effect of bupivacaine spinal anesthesia in gynecologic laparoscopy. METHODS: Sixty patients with ectopic pregnancy undergoing elective laparoscopy (ASA class I-II) were randomized into 4 groups (groups A, B, C and D), and received spinal anesthesia with 15 mg bupivacaine and sufentanil at 0, 2.5, 5 and 7.5 microg, respectively. When the patients complained of discomforts, showed bodily movements, had heart rate over 100 beats/min, or showed blood pressure increment by 20%, additional doses of propofol were given. The onset time of sensory block, time to Bromage scale 3 motor block, time to the highest sensory block level, time of operation and recovery from anesthesia, and the total dosages of propofol were recorded along with the sedative score and the side effects. RESULTS: The 4 groups were comparable for age, body weight, height and operation time (range 60-65 min) (P>0.05). Both the onset time of sensory block and the time of Bromage scale 3 motor block in groups C and D were significantly shorter than those in groups A and B (P<0.05). The time of the highest sensory block in group D was shorter than that in group A (P<0.05). Compared to the group A, the dose of propofol was reduced in groups B, C, and D by 7.1%, 28.1%, and 34.8%, respectively; propofol doses in groups C and D were significantly lower than those in groups A and B (P<0.05). Pruritus associated with the spinal anesthesia occurred in 4 (26.7%), 3 (20%), and 6 (40%) cases in groups B, C and D, respectively. CONCLUSIONS: Intrathecal sufentanil dose-dependently affect the effect of bupivacaine spinal anesthesia, and larger sufentanil dose produces better effects but more side effects. According to our results, 5.0 microg is the optimal dose for sufentanil.

[Effects of epidural clonidine pretreatment in epidural patient-controlled analgesia using sufentanil combined with levobupivacaine].

OBJECTIVE: To investigate the clinical effects of epidural clonidine pretreatment in epidural patient-controlled analgesia (PCA) using sufentanil combined with levobupivacaine. METHODS: Sixty patients undergoing abdominal hysterectomy of ASA status I-II were randomly divided into 3 equal groups: C2 group was pretreated with epidural clonidine 2 microg/kg at the L2-3 interspace, 15 min later, epidural anesthesia was performed with 0.5% levobupivacaine, and then 0. 4 microg/ml combined with levobupivacaine 2 mg/ml was given for postoperative epidural patient-controlled analgesia. C4 group was pretreated with epidural clonidine 4 microg/kg, and C0 group was pretreated with normal saline. The analgesic effect, PCA drug dosage, adverse reaction, and visual analog scale (VAS) score were recorded. RESULTS: Anesthesia was clinically satisfactory in all patients. The rate of atropine use of the C4 group was 30%, significantly higher than those of the C2 group (15% ) and C0 group (5%, both P < 0.05). The rate of VAS < or = 3 at rest 24 h postoperatively of the C2 and C4 groups were 88% and 93% respectively, both significantly higher than that of the C0 group (75%, P < 0.01 and P < 0.01). The rate of VAS < or = 3 while coughing 24 h postoperatively of the C2 and C4 groups were 61% and 79% respectively, both significantly higher than that of the C0 group (48%). The dosages of PCA drug of the C2 and C4 groups were significantly lower than that of the C0 group by 11.8% and 22.8% respectively (both P < 0.05). The dosage of PCA drug 0-4 h after operation of the C2 was significantly higher than that of the C4 group. The sedative degree of the C4 group was higher than that of the C0 group. The rate of postoperative vomiting of the C0 group was 40%, significantly higher than that of the C4 group (10%, P < 0.05). CONCLUSION: Epidural clonidine 2-4 microg/kg pretreatment improves the clinical effects of epidural PCA using sufentanil combined with levobupivacaine.