Dural puncture epidural technique provides better anesthesia quality in repeat cesarean delivery than epidural technique: Randomized controlled study.

BACKGROUND: Repeat cesarean deliverys involve a longer surgery and more severe visceral traction than primary cesarean deliverys. The dural puncture epidural (DPE) technique provides faster and more effective analgesia for labor, but there is no sufficient evidence to indicate whether it is suitable for parturients undergoing repeat cesarean delivery. AIM: To determine the efficacy and safety of the DPE anesthesia technique in patients undergoing repeat cesarean delivery. METHODS: Patients undergoing repeat cesarean delivery were randomly divided into the DPE and epidural anesthesia (EA) groups. A 25-G spinal needle was used for dural puncture via a 19-G epidural needle. The patients in the two groups were injected with 5 mL of 2% lidocaine followed by 15 mL of a mixture of 1% lidocaine + 0.5% ropivacaine as the epidural dosage. The primary outcome was the onset time of sensory block to the T6 dermatome level and the sensory and motor block degree. RESULTS: A total of 115 women were included (EA: 57, DPE: 58). The mean time to sensory block to the T6 Level was significantly shorter in the DPE group than in the EA group (14.7 min vs 16.6 min; 95% confidence interval, 13.9 to 15.4 vs 15.8 to 17.4; P = 0.001). The cranial sensory block level was significantly higher at 5, 10, and 15 min after the initial dose in the DPE group than in the EA group (P < 0.05). The sacral sensory block level was significantly higher and the modified bromage score was significantly lower in the DPE group at each time point (P < 0.05). Adverse effects and neonatal outcomes were comparable between the two groups (P > 0.05). CONCLUSION: The DPE technique provided higher-quality anesthesia than the EA technique, with a rapid onset of surgical anesthesia, better cranial and sacral sensory block spread and a higher motor block degree, without increasing the incidence of maternal or fetal side effects in patients undergoing repeat cesarean delivery.

A Randomized Clinical Trial Comparing Different Concentrations of Chloroprocaine with Lidocaine for Activating Epidural Analgesia During Labor.

PURPOSE: This study aimed to explore the efficacy and safety of chloroprocaine for activating labor analgesia and the optimal concentration compared to lidocaine. PATIENTS AND METHODS: Ninety-six nulliparous parturients were randomly assigned to three groups: LD group, patients received the conventional initial dose of 6 mL of 1% lidocaine; CP1.5 group, patients received 6 mL of 1.5% chloroprocaine as the initial dose; and CP1.2 group, patients received 7.5 mL of 1.2% chloroprocaine as initial dose. Labor analgesia was maintained in all patients via a programmed intermittent epidural bolus (PIEB). The primary outcome was the analgesia onset time. Secondary outcomes included the visual analog scale (VAS) scores, the interval and duration of uterine contractions during the first 12 contractions, failure to reach adequate analgesia, labor and neonatal outcomes, maternal satisfaction and adverse effects. RESULTS: Parturients in the CP1.5 and CP1.2 groups achieved a shorter onset time than those in the LD group (hazard ratio (HR) = 6.540; 95% confidence interval (CI), 3.503-12.210; P < 0.001 and HR = 3.460; 95% CI, 1.905-6.282; P < 0.001, respectively). The median time (95% CIs) to adequate analgesia was 12.0 (10.9-13.1), 7.0 (6.2-7.8) and 8.0 (7.5-8.5) minutes in the LD, CP1.5 and CP1.2 groups, respectively. PIEB in the CP1.5 group was associated with lower VAS scores, patient-controlled epidural analgesia (PCEA) boluses, and analgesic consumption; a shorter time from epidural initiation to the first PCEA demand; and higher maternal satisfaction scores than the other two groups (P < 0.01). The interval and duration of uterine contractions, labor and newborn outcomes and adverse effects were comparable among the three groups. CONCLUSION: Chloroprocaine provided a faster onset of labor analgesia than lidocaine. Thus, 6 mL of 1.5% chloroprocaine might be a superior volume and concentration regimen to 7.5 mL of 1.2% chloroprocaine for activating labor analgesia. CLINICAL TRIAL REGISTRATION STATEMENT: The study was registered prior to subject enrollment at www.chictr.org.cn (ChiCTR2100049113).

Remifentanil preconditioning confers cardioprotection via c-Jun NH2-terminal kinases and extracellular signal regulated kinases pathways in ex-vivo failing rat heart.

Remifentanil preconditioning (RPC) exerts protection in normal hearts, but has not been investigated in heart failure. The aim of the present study was to evaluate the effect of RPC in a chronic failing rat heart model and the mechanisms involving mitogen-activated protein kinases (MAPK) and Bcl-2 protein family. The doxorubicin induced failing rat hearts were subjected to 30 min ischemia / 120 min reperfusion (IR) with or without RPC by using Langendorff apparatus. RPC was induced by three cycles of 5 min remifentanil / 5 min drug-free perfusion before IR, with three different concentrations: 25, 50 and 100 µg/l. An extracellular signal regulated kinases (ERK) inhibitor PD98059, p38MAPK inhibitor SB203580, c-Jun NH2-terminal kinases (JNK) inhibitor SP600125 were perfused at 10 min before RPC. Infarct size, cardiac function and protein kinase activity were determined. RPC significantly reduced infarct size and the rise in lactate dehydrogenase (LDH) level caused by IR injury in failing heart. The JNK inhibitor SP600125 and ERK inhibitor PD98059 abolished the RPC mediated reduction effect on the infarct size and LDH activity after reperfusion. In addition, RPC increased the phosphorylation of JNK, ERK1/2 and the downstream GSK-3ß, as well as the Bcl-2/Bax ratio, while, these changes were completely reversed by SP600125 and PD98059. And of note, SB203580 had no effect. In conclusion, our results suggested that the activation of JNK and ERK pathways, by leading to inhibition of GSK-3ß and regulating Bcl-2 protein family, is a major mechanism that RPC confers cardioprotection in failing rat heart.

Specific MicroRNAs comparisons in hypoxia and morphine preconditioning against hypoxia-reoxgenation injury with and without heart failure.

AIMS: Ischemia reperfusion (I/R) injury is an inevitable event arising during the cardiovascular diseases development and the process of potent surgical treatments. microRNAs (miRNAs) are critical regulators of multiple cell processes including I/R injury. The present study aims to quantify miRNA alterations and regulated genes upon hypoxia-reoxygenation (H/R) injury in a rat heart failure model comparing with normal cardiomyocytes. MAIN METHODS: Chronic heart failure was established by injecting doxorubicin (2mg/kg/week) for 6weeks, then H/R was performed on primary cultured cardiomyocytes isolated from normal and failed heart. Cellular injury was evaluated by detecting LDH release levels, cell variability and apoptotic rate. Dysregulated miRNAs in control, hypoxia preconditioning (HPC) and morphine preconditioning (MPC) groups under two conditions were quantified by microarray analysis. Fas protein expression was analyzed using Western Blotting analysis. KEY FINDINGS: Chronic heart failure was confirmed with lower ejection fraction (EF), and significant cellular injury. HPC could reverse the injury induced by H/R in normal heart rather than failed heart, otherwise, MPC significantly attenuated cellular injury dose dependently in both conditions. There was 12 miRNAs significantly altered after doxorubicin injection, 7 downregulated and 5 upregulated. miR-133b-5p, miR-6216, miR-664-1-5p and let7e-5p were differentially expressed after HPC and MPC treatments. The direct interaction between miR-133b-5p and target gene Fas were established. The Fas protein expression was manipulated by MPC not HPC affording protective effect against H/R injury. SIGNIFICANCE: We investigated that miR-133b-5p might play a particularly important role in the cardioprotective effect of MPC by regulating the target gene Fas.

Remifentanil preconditioning protects rat cardiomyocytes against hypoxia-reoxygenation injury via δ-opioid receptor mediated activation of PI3K/Akt and ERK pathways.

Remifentanil preconditioning has been demonstrated to reduce myocardial ischemia reperfusion injury in rat hearts, while the mechanisms are not fully understood. This study investigated the protective effects of remifentanil against hypoxia-reoxygenation injury in adult rat cardiomyocytes and the mechanisms involving opioid receptors and downstream phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinase (ERK) signaling pathways. Adult rat cardiomyocytes were pretreated with remifentanil at different concentrations and then subjected to 90min hypoxia followed by 120min reoxygenation. The δ- (naltrindole), κ- (nor-binaltorphimine), or µ-opioid receptor antagonist (CTOP), as well as ERK inhibitor (PD98059) or PI3K inhibitor (wortmannin) was added before remifentanil preconditioning, respectively. Remifentanil showed significant protective effects against hypoxia-reoxygenation injury by increasing cell survival (Trypan blue staining) while reducing LDH activity and cell apoptosis (Hoechst staining). These effects were markedly reversed by naltrindole and were partially blocked by nor-binaltorphimine. Pretreatment of either PD98059 or wortmannin also abolished the protective effects of remifentanil. Following remifentanil preconditioning, the phosphorylation level of Akt reached peak at 10min of reoxygenation. ERK phosphorylation, however, was subsequently enhanced at 120min of reoxygenation. The phosphorylation levels of Akt and ERK were both blocked by naltrindole, but not nor-binaltorphimine or CTOP. Wortmannin inhibited the phosphorylation of both Akt and ERK, whereas PD98059 suppressed the phosphorylation of ERK only. In conclusion, our results suggested that remifentanil protected adult rat cardiomyocytes from hypoxia-reoxygenation injury and its effects appears to be dependent on the δ-opioid receptor mediated activation of PI3K/Akt and subsequent ERK signaling pathways.

MicroRNA-133b-5p Is Involved in Cardioprotection of Morphine Preconditioning in Rat Cardiomyocytes by Targeting Fas.

BACKGROUND: MicroRNAs (miRNAs) have been implicated in ischemia-reperfusion injury and ischemic preconditioning. Opioid pre- and postconditioning have powerful protective effects on the heart, but it is still not known whether miRNAs are involved in opioid-induced cardioprotection. The present study was designed to investigate the role of miRNAs in morphine preconditioning (MPC)-induced cardioprotection. METHODS: MiRNA microarray analysis was performed to examine the differentially expressed miRNAs caused by MPC in adult rat cardiomyocytes. A dual-luciferase reporter assay was performed to confirm the direct regulation of miR-133b-5p on the target gene Fas. MiR-133b-5p mimic or inhibitor was separately transfected into myocardial H9c2 cells to examine the role of miR-133b-5p in morphine-induced cardioprotection. RESULTS: MPC protected adult rat cardiomyocytes against hypoxia/reoxygenation (H/R) injury by reducing cell injury and death. MiRNA microarray data showed that a total of 39 miRNAs were differentially expressed after MPC treatment. A Dual-luciferase reporter assay confirmed that miR-133b-5p directly targets the Fas gene. After H/R injury, the decrease in miR-133b-5p and a contemporaneous rise in Fas mRNA and protein levels in adult rat cardiomyocytes were prevented by MPC treatment. In H9c2 cardiomyocytes, overexpression of miR-133b-5p reduced H/R-induced cell injury and apoptosis by inhibiting Fas expression. Knockdown of miR-133b-5p blocked morphine-mediated cardioprotection by reducing miR-133b-5p levels while enhancing the expression of Fas mRNA and protein. CONCLUSIONS: MPC causes a change in miRNA expression in rat cardiomyocytes. Morphine may protect cardiomyocytes against H/R injury through upregulation of miR-133b-5p by targeting Fas.

[Effects of bacillus bifidus supplementation on the immunity in very-low-birth-weight infants].

OBJECTIVE: To study the effect of bacillus bifidus supplementation on the immunity in very-low-birth-weight (VLBW) infants. METHODS: Fifty VLBW infants who were hospitalized in the neonatal intensive care unit were equally randomized into observed and control groups. The observed group received bacillus bifidus for 14 days after birth in addition to the conventional management, which was applied in the control group. The clinical indicators and relevant immunological parameters in the peripheral blood were observed. RESULTS: The times required for brine enema was significantly fewer in the observed group than in the control group (P<0.05), while the incidence of diarrhea showed no significant difference (P>0.05). In the observed group, the proportions of CD4(+) T lymphocytes and the CD4(+)/CD8(+) ratio increased, whilst the proportion of CD3(+) and CD8(+) T lymphocytes showed no significant change. The levels of immunoglobulin A in the peripheral blood increased in the observed group, while the levels of immunoglobulin M and immunoglobulin G were not statistically changed in the observed group when compared with the control group. CONCLUSIONS: Bacillus bifidus can improve gastrointestinal symptoms of VLBW infants and have a positive effect on their immunity.