Twelfth thoracic vertebra erector spinae plane block for postoperative analgesia and early recovery after lumbar spine surgery in elderly patients: a single-blind randomized controlled trial.

BACKGROUND: Severe pain after lumbar spine surgery can delay recovery in elderly patients. We explored the efficacy of T12 erector spinal plane block (ESPB) in elderly patients who underwent lumbar spine surgery. METHODS: A total of 230 patients undergoing lumbar spine surgery were divided and randomly allocated to ultrasound-guided ESPB (n = 115) and control (n = 115) groups. The ESPB group received 20 mL of 0.4% ropivacaine bilaterally at the T12 level after intubation, whereas the control group did not receive a block. The primary outcome was the numeric rating scale (NRS) score at 12 h after surgery. Secondary outcomes included the NRS score and tramadol use within 72 h postoperatively, intraoperative remifentanil use, incidence of postoperative delirium (POD), complications of ESPB, ambulation time, and length of hospitalization after surgery. RESULTS: The12-hour NRS (median (IQR)) score was remarkably lower in the ESPB group than in the control group (2 (1-3) vs. 3 (2-4), p = 0.004), as well as NRS score within 48 h (P < 0.01). The ESPB group had less intraoperative remifentanil use (P < 0.001), and less tramadol use within 72 h postoperatively (P < 0.001). Seven patients (6.7%) developed POD in the ESPB group and ten patients (9.3%) in the control group, without any statistically significant difference (P > 0.05). The ambulation time and length of hospitalization after surgery were shorter in the ESPB group than in the control group (P < 0.05). No ESPB-related complications were observed. CONCLUSIONS: Bilateral T12 ESPB lowered the NRS score within 48 h after lumbar spine surgery, decreased perioperative opioid use and resulted in faster recovery in elderly patients but did not significantly reduce the incidence of POD. TRIAL REGISTRATION: The study was retrospectively registered at www.chictr.org.cn (ChiCTR2100042037) on January 12, 2021.

Adiponectin ameliorates lung ischemia-reperfusion injury through SIRT1-PINK1 signaling-mediated mitophagy in type 2 diabetic rats.

BACKGROUND: Diabetes mellitus (DM) is a key contributing factor to poor survival in lung transplantation recipients. Mitochondrial dysfunction is recognized as a critical mediator in the pathogenesis of diabetic lung ischemia-reperfusion (IR) injury. The protective effects of adiponectin have been demonstrated in our previous study, but the underlying mechanism remains unclear. Here we demonstrated an important role of mitophagy in the protective effect of adiponectin during diabetic lung IR injury. METHODS: High-fat diet-fed streptozotocin-induced type 2 diabetic rats were exposed to adiponectin with or without administration of the SIRT1 inhibitor EX527 following lung transplantation. To determine the mechanisms underlying the action of adiponectin, rat pulmonary microvascular endothelial cells were transfected with SIRT1 small-interfering RNA or PINK1 small-interfering RNA and then subjected to in vitro diabetic lung IR injury. RESULTS: Mitophagy was impaired in diabetic lungs subjected to IR injury, which was accompanied by increased oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction. Adiponectin induced mitophagy and attenuated subsequent diabetic lung IR injury by improving lung functional recovery, suppressing oxidative damage, diminishing inflammation, decreasing cell apoptosis, and preserving mitochondrial function. However, either administration of 3-methyladenine (3-MA), an autophagy antagonist or knockdown of PINK1 reduced the protective action of adiponectin. Furthermore, we demonstrated that APN affected PINK1 stabilization via the SIRT1 signaling pathway, and knockdown of SIRT1 suppressed PINK1 expression and compromised the protective effect of adiponectin. CONCLUSION: These data demonstrated that adiponectin attenuated reperfusion-induced oxidative stress, inflammation, apoptosis and mitochondrial dysfunction via activation of SIRT1- PINK1 signaling-mediated mitophagy in diabetic lung IR injury.

Activating α7nAChRs enhances endothelial progenitor cell function partially through the JAK2/STAT3 signaling pathway.

Microvascular injury is a common pathological process in ischemia-reperfusion injury. Endothelial progenitor cells (EPCs) are vital cells for angiogenesis and endothelial repair. These cells can home to injury sites and secrete angiogenic growth factors. α7nAChRs are pivotal in cholinergic angiogenesis, which is associated with endothelial cells and EPCs. Our study was designed to determine whether activating α7nAChRs enhances the function of EPCs and to explore the underlying mechanism. EPCs were derived from the bone marrow of male Sprague-Dawley rats and treated with an α7nAChR agonist (PNU282987), an α7nAChR antagonist (MLA) and a JAK2 antagonist (AG490). We then assayed the angiogenic abilities of the EPCs, including proliferation ability, adhesion ability, migration ability and in vitro tube formation ability. The levels of total JAK2 (t-JAK2), phosphorylated JAK2 (p-JAK2), total STAT3 (t-STAT3) and phosphorylated STAT3 (p-STAT3) were estimated by western blot analysis. PNU282987 treatment facilitated the angiogenic abilities of EPCs compared with the control regimen. The western blot data suggested that PNU282987 increased the levels of p-JAK2 and p-STAT3. However, the differences in t-JAK2 levels and t-STAT3 levels between the agonist-treated group and the control group were not significant. Moreover, treating EPCs with AG490 reduced STAT3 phosphorylation and attenuated the PNU282987-induced enhancement of EPCs. We demonstrated that activating α7nAChRs can enhance EPC functions partially through the JAK2/STAT3 signaling pathway. This study reveals that α7nAChRs are potential therapeutic targets for angiogenesis and that the JAK2/STAT3 pathway plays a vital role in the associated therapeutic mechanism.

α7nAChR Activation Combined with Endothelial Progenitor Cell Transplantation Attenuates Lung Injury in Diabetic Rats with Sepsis through the NF-κB Pathway.

Chronic diabetes mellitus compromises the vascular system, which causes organ injury, including in the lung. Due to the strong compensatory ability of the lung, patients always exhibit subclinical symptoms. Once sepsis occurs, the degree of lung injury is more severe under hyperglycemic conditions. The α7 nicotinic acetylcholine receptor (α7nAChR) plays an important role in regulating inflammation and metabolism and can improve endothelial progenitor cell (EPC) functions. In the present study, lung injury caused by sepsis was compared between diabetic rats and normal rats. We also examined whether α7nAChR activation combined with EPC transplantation could ameliorate lung injury in diabetic sepsis rats. A type 2 diabetic model was induced in rats via a high-fat diet and streptozotocin. Then, a rat model of septic lung injury was established by intraperitoneal injection combined with endotracheal instillation of LPS. The oxygenation indices, wet-to-dry ratios, and histopathological scores of the lungs were tested after PNU282987 treatment and EPC transplantation. IL-6, IL-8, TNF-α, and IL-10 levels were measured. Caspase-3, Bax, Bcl-2, and phosphorylated NF-κB (p-NF-κB) levels were determined by blotting. Sepsis causes obvious lung injury, which is exacerbated by diabetic conditions. α7nAChR activation and endothelial progenitor cell transplantation reduced lung injury in diabetic sepsis rats, alleviating inflammation and decreasing apoptosis. This treatment was more effective when PNU282987 and endothelial progenitor cells were administered together. p-NF-κB levels decreased following treatment with PNU282987 and EPCs. In conclusion, α7nAChR activation combined with EPC transplantation can alleviate lung injury in diabetic sepsis rats through the NF-κB signaling pathway.

SIRT1-Rab7 axis attenuates NLRP3 and STING activation through late endosomal-dependent mitophagy during sepsis-induced acute lung injury.

BACKGROUND: Acute lung injury (ALI) is a leading cause of mortality in patients with sepsis due to proinflammatory endothelial changes and endothelial permeability defects. Mitochondrial dysfunction is recognized as a critical mediator in the pathogenesis of sepsis-induced ALI. Although mitophagy regulation of mitochondrial quality is well recognized, little is known about its role in lung ECs during sepsis-induced ALI. Sirtuin 1 (SIRT1) is a histone protein deacetylase involved in inflammation, mitophagy, and cellular senescence. Here, the authors show a type of late endosome-dependent mitophagy that inhibits NLRP3 and STING activation through SIRT1 signaling during sepsis-induced ALI. METHODS: C57BL/6J male mice with or without administration of the SIRT1 inhibitor EX527 in the CLP model and lung ECs in vitro were developed to identify mitophagy mechanisms that underlie the cross-talk between SIRT1 signaling and sepsis-induced ALI. RESULTS: SIRT1 deficient mice exhibited exacerbated sepsis-induced ALI. Knockdown of SIRT1 interfered with mitophagy through late endosome Rab7, leading to the accumulation of damaged mitochondria and inducing excessive mitochondrial reactive oxygen species (mtROS) generation and cytosolic release of mitochondrial DNA (mtDNA), which triggered NLRP3 inflammasome and the cytosolic nucleotide sensing pathways (STING) over-activation. Pharmacological inhibition of STING and NLRP3 i n vivo or genetic knockdown in vitro reversed SIRT1 deficiency mediated endothelial permeability defects and endothelial inflammation in sepsis-induced ALI. Moreover, activation of SIRT1 with SRT1720 in vivo or overexpression of SIRT1 in vitro protected against sepsis-induced ALI. CONCLUSION: These findings suggest that SIRT1 signaling is essential for restricting STING and NLRP3 hyperactivation by promoting endosomal-mediated mitophagy in lung ECs, providing potential therapeutic targets for treating sepsis-induced ALI.

Effect and mechanism of propofol on myocardial ischemia reperfusion injury in type 2 diabetic rats.

BACKGROUND: Propofol has been reported to have an inhibitory effect on ischemia/reperfusion (I/R) injury in various experimental models by reducing oxidative stress, protecting mitochondrial function and suppressing apoptosis. The aim of this study was to investigate the effect and mechanism of propofol on myocardial I/R injury in type 2 diabetic rats. METHODS: A total of 24 streptozotocin (STZ)-induced diabetic rats were randomly divided into three equal groups as follows: the DI group with myocardial I/R, which was induced by occluding the left anterior descending coronary artery for 30min, followed by 2h of reperfusion; the DP group, which underwent I/R and propofol infusion at 6mg·kg(-1)·h(-1); and the DC group, which underwent sham operations without tightening of the coronary sutures. As a control, 24 healthy, age-matched, male Wistar rats were randomly divided into three equal groups: the CI, CP and CC groups. The injured cardiac tissues were removed for microscopic examination after reperfusion. The serum concentrations of nitric oxide (NO) and endothelin (ET-1); the expression of Bax, Bcl-2 and Caspase-3 within the cardiac structures; and the number of apoptotic myocardial cells were measured. RESULTS: Compared with the baseline levels before ischemia, the serum concentration of ET-1 after 2h of reperfusion was increased in the CI and DI groups, while the concentration of NO in these groups decreased after reperfusion. Compared with the I/R groups, propofol increased the content of NO and decreased the content of ET-1. Compared with the sham operation groups, I/R decreased the ratio of the anti-apoptotic protein Bcl-2 to the pro-apoptotic protein Bax, which resulted in an elevation of the index of apoptosis (AI). In contrast, compared with the I/R group, propofol increased the Bcl-2-to-Bax ratio and decreased the AI. I/R increased the expression of caspase-3 compared with the sham treatment groups, while treatment with propofol reduced caspase-3 expression relative to the I/R groups. CONCLUSIONS: These data suggest that propofol can protect against myocardial ischemia-reperfusion injury in both normal and type 2 diabetic rats, possibly by attenuating endothelial cell injury and inhibiting the apoptosis of cardiomyocytes.

[Retracted] Morphine­induced delayed pre­conditioning against anoxia/reoxygenation injury in pulmonary artery endothelial cells: The role of mitochondrial KATP channels.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that several of the flow cytometric plots featured in Fig. 2A on p. 1050 contained repeating patterns of dots, both vertically and horizontally, in addition to a variety of other apparent anomalies. The authors were asked to provide an explanation to account for the apparent anomalies in this figure, but they did not respond to the request posed by the Editorial Office. Therefore, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the journal on account of a lack of confidence in the presented data. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 1047­1053, 2016; DOI: 10.3892/mmr.2015.4629].

Reversal of isoflurane-induced depression of myocardial contraction by nitroxyl via myofilament sensitization to Ca2+.

Isoflurane (ISO) is known to depress cardiac contraction. Here, we hypothesized that decreasing myofilament Ca(2+) responsiveness is central to ISO-induced reduction in cardiac force development. Moreover, we also tested whether the nitroxyl (HNO) donor 1-nitrosocyclohexyl acetate (NCA), acting as a myofilament Ca(2+) sensitizer, restores force in the presence of ISO. Trabeculae from the right ventricles of LBN/F1 rats were superfused with Krebs-Henseleit solution at room temperature, and force and intracellular Ca(2+) ([Ca(2+)](i)) were measured. Steady-state activations were achieved by stimulating the muscles at 10 Hz in the presence of ryanodine. The same muscles were chemically skinned with 1% Triton X-100, and the force-Ca(2+) relation measurements were repeated. ISO depressed force in a dose-dependent manner without significantly altering [Ca(2+)](i). At 1.5%, force was reduced over 50%, whereas [Ca(2+)](i) remained unaffected. At 3%, contraction was decreased by ∼75% with [Ca(2+)](i) reduced by only 15%. During steady-state activation, 1.5% ISO depressed maximal Ca(2+)-activated force (F(max)) and increased the [Ca(2+)](i) required for 50% activation (Ca(50)) without affecting the Hill coefficient. After skinning, the same muscles showed similar decreases in F(max) and increases in Ca(50) in the presence of ISO. NCA restored force in the presence of ISO without affecting [Ca(2+)](i). These results show that 1) ISO depresses cardiac force development by decreasing myofilament Ca(2+) responsiveness, and 2) myofilament Ca(2+) sensitization by NCA can effectively restore force development without further increases in [Ca(2+)](i). The present findings have potential translational value because of the efficiency and efficacy of HNO on ISO-induced myocardial contractile dysfunction.

Hydrogen sulfide attenuates lung ischemia-reperfusion injury through SIRT3-dependent regulation of mitochondrial function in type 2 diabetic rats.

BACKGROUND: Lung ischemia-reperfusion injury is a complex pathophysiologic process associated with high morbidity and mortality. We have demonstrated elsewhere that diabetes mellitus aggravated ischemia-induced lung injury. Oxidative stress and mitochondrial dysfunction are drivers of diabetic lung ischemia-reperfusion injury; however, the pathways that mediate these events are unexplored. In this study using a high-fat diet-fed model of streptozotocin-induced type 2 diabetes in rats, we determined the effect of hydrogen sulfide on lung ischemia-reperfusion injury with a focus on Sirtuin3 signaling. METHODS: Rats with type 2 diabetes were exposed to GYY4137, a slow release donor of hydrogen sulfide with or without administration of the Sirtuin3 short hairpin ribonucleic acid plasmid, and then subjected to a surgical model of ischemia-reperfusion injury of the lung (n = 8). Lung function, oxidative stress, inflammation, cell apoptosis, and mitochondrial function were measured. RESULTS: Compared with nondiabetic rats, animals with type 2 diabetes at baseline exhibited significantly decreased Sirtuin3 signaling in lung tissue and increased oxidative stress, apoptosis, inflammation, and mitochondrial dysfunction (P < .05 each). In addition, further impairment in Sirtuin3 signaling was found in diabetic rats subjected to this model of lung ischemia-reperfusion. Simultaneously, the indexes showed further aggravation. Treatment with hydrogen sulfide restored Sirtuin3 expression and decreased lung ischemia-reperfusion injury in animals with type 2 diabetes mellitus by improving lung functional recovery, decreasing oxidative damage, suppressing inflammation, ameliorating cell apoptosis, and preserving mitochondrial function (P < .05). Conversely, these protective effects were largely reversed in Sirtuin3 knockdown rats. CONCLUSION: Impaired lung Sirtuin3 signaling associated with type 2 diabetic conditions was further attenuated by an ischemia-reperfusion insult. Hydrogen sulfide ameliorated reperfusion-induced oxidative stress and mitochondrial dysfunction via activation of Sirtuin3 signaling, thereby decreasing lung ischemia-reperfusion damage in rats with a model of type II diabetes.

Endothelial progenitor cells attenuate the lung ischemia/reperfusion injury following lung transplantation via the endothelial nitric oxide synthase pathway.

OBJECTIVE: Endothelial progenitor cells (EPCs) can improve endothelial integrity. This study aimed to examine the effects and the mechanism of EPCs on lung ischemia-reperfusion injury (LIRI). METHODS: Wistar rats were randomized into the sham or the left lung transplantation group. The recipients were randomized and treated with vehicle as the LIRI group, with EPC as the EPC group, or with N5-(1-iminoethyl)-l-ornithine-pretreated EPC as the EPC/L group (n = 8 per group). The ratios of arterial oxygen partial pressure to fractional inspiratory oxygen were measured. The lung wet-to-dry weight ratios, protein levels, and injury, as well as the levels of plasma cytokines, were examined. The levels of endothelin (ET)-1, endothelial nitric oxide synthase (eNOS), phosphorylated eNOS, inducible NOS, phosphorylated myosin light chain, nuclear factor-κBp65, Bax, Bcl-2, cleaved caspase-3, and myeloperoxidase in the graft lungs were detected. RESULTS: Compared with the LIRI group, EPC treatment significantly increased the ratios of arterial oxygen partial pressure to fractional inspiratory oxygen and decreased the lung wet-to-dry weight ratios and protein levels in the grafts, accompanied by increasing eNOS expression and phosphorylation, but decreasing endothelin-1, inducible NOS, phosphorylated nuclear factor-kBp65, phosphorylated myosin light chain expression, and myeloperoxidase activity. EPCs reduced lung tissue damage and apoptosis associated with decreased levels of Bax and cleaved caspase-3 expression, but increased Bcl-2 expression. EPC treatment significantly reduced the levels of serum proinflammatory factors, but elevated levels of interleukin-10. In contrast, the protective effect of EPCs were mitigated and abrogated by N5-(1-iminoethyl)-l-ornithine pretreatment. CONCLUSIONS: Data indicated that EPC ameliorated LIRI by increasing eNOS expression.

Desflurane affords greater protection than halothane in the function of mitochondria against forebrain ischemia reperfusion injury in rats.

BACKGROUND: Halothane and desflurane have been shown to attenuate neuronal injury; however, the effects of these anesthetics on mitochondria are unclear. We investigated whether halothane and desflurane affect the function of mitochondria after cerebral ischemia in rats. METHODS: Forty male Wistar rats were randomly divided into four groups (n = 10 each): sham group; 1.5 minimal alveolar concentration (MAC) halothane group; 1.0 MAC desflurane; and 1.5 MAC desflurane group. Forebrain ischemia was induced after 40-min inhalation of 1.5 MAC halothane, 1.0 MAC or 1.5 MAC desflurane by clamping the bilateral common carotid arteries and decreasing arterial blood pressure. After isolation of the brain mitochondria, mitochondrial membrane permeability was assayed spectrophotometrically with 40-200 microM Ca(2+), and mitochondrial membrane potentials were measured by a fluorospectrophotometer with the addition of rhodamine 123. The activities of mitochondrial respiratory chain complexes were also assayed spectrophotometrically. RESULTS: The results showed obvious mitochondrial swelling, loss of membrane potential with the addition of Ca(2+), and inhibition of the activities of complexes I + III and IV after forebrain ischemia reperfusion injury. Compared with the 1.5 MAC halothane group, 1.0 and 1.5 MAC desflurane reduced mitochondrial swelling by 23.9% (P < 0.001) and 23.2% (P < 0.001), whereas membrane potential dissipation was suppressed by 22.4% (P = 0.013) and 20.4% (P = 0.027). The activities of complexes I + III and IV were better preserved in 1.0 MAC and 1.5 MAC desflurane groups than in the 1.5 MAC halothane group by 34.6% (P = 0.027), 38.7% (P = 0.011), 53.9% (P = 0.009), and 55.8% (P = 0.007), respectively. CONCLUSIONS: Desflurane shows better preservation of mitochondrial function at 4 h after cerebral ischemia reperfusion injury, indicated by inhibition of mitochondrial swelling, increase of membrane potential, and improvement of functions of mitochondria respiratory complexes I + III and IV when compared with halothane.

Anti-apoptotic effect of morphine-induced delayed preconditioning on pulmonary artery endothelial cells with anoxia/reoxygenation injury.

BACKGROUND: Opioid preconditioning (PC) reduces anoxia/reoxygenation (A/R) injury to various cells. However, it remains unclear whether opioid-induced delayed PC would show anti-apoptotic effects on pulmonary artery endothelial cells (PAECs) suffering from A/R injury. The present study was conducted to elucidate this issue and to investigate the potential mechanism of opioid-induced delayed PC. METHODS: Cultured porcine PAECs underwent 16-hour anoxia followed by 1-hour reoxygenation 24 hours after pretreatment with saline (NaCl; 0.9%) or morphine (1 micromol/L). To determine the underlying mechanism, a non-selective K(ATP) channel inhibitor glibenclamide (Glib; 10 micromol/L), a nitric oxide (NO) synthase blocker NG-nitro-L-arginine methyl ester (L-NAME; 100 micromol/L), and an opioid receptor antagonist naloxone (Nal; 10 micromol/L) were given 30 minutes before the A/R load. The percentage of apoptotic cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. eNOS mRNA level was measured by real-time polymerase chain reaction (PCR). NO content of PAECs supernatants was measured with the Griess reagent. RESULTS: Compared to the A/R PAECs, morphine-induced delayed PC significantly reduced PAECs apoptosis ((18.1 +/- 1.9)% vs (5.5 +/- 0.3)%; P < 0.05), increased NO release ((11.4 +/- 1.3) micromol/L vs (20.5 +/- 2.1) micromol/L, P < 0.05), and up-regulated eNOS gene expression nearly 9 times (P < 0.05). The anti-apoptosis effect of morphine was abolished by pretreatment with Glib, L-NAME and Nal, but the three agent-selves did not aggravate the A/R injury. Furthermore, L-NAME and Nal offset the enhanced release of NO caused by pretreatment with morphine. CONCLUSIONS: Morphine-induced delayed PC prevents A/R injury of PAECs. This effect may be mediated by activation of K(ATP) channel via opioid receptor and NO signaling pathways.

Carbon monoxide inhalation ameliorates conditions of lung grafts from rat brain death donors.

BACKGROUND: Successful lung transplantation has been limited by the scarcity of donors. Brain death (BD) donors are major source of lung transplantation. Whereas BD process induces acute lung injury and aggravates lung ischemia reperfusion injury. Carbon monoxide (CO) inhalation at 50-500 parts per million (ppm) can ameliorate lung injury in several models. We examined in rats whether CO inhalation in BD donor would show favorable effects on lung grafts. METHODS: Rats were randomly divided into 4 groups. In sham group, donor rats received insertion of a balloon catheter into the cranial cavity, but the balloon was not inflated. In BD-only group, donor rats were ventilated with 40% oxygen after BD confirmation. In BD+CO250 and BD+CO500 groups, donor rats inhaled, after BD confirmation, 250 ppm or 500 ppm CO for 120 minutes prior to lung procurement, and orthotopic lung transplantation was performed. The rats were sacrificed 120 minutes after the lung transplantation by exsanguination, and their blood and lung graft samples were obtained. A total of 8 rats fulfilling the criteria were included in each group. RESULTS: The inhalation decreased the severity of lung injury in grafts from BD donors checked by histological examination. CO pretreatment reversed the aggravation of PaO2/FiO2 in recipients from BD donors. The CO inhalation down-regulated pro-inflammatory cytokines (TNF-alpha, IL-6) along with the increase of anti-inflammatory cytokine (IL-10) in recipient serum, and inhibited the activity of myeloperoxidase in grafts tissue. The inhalation significantly decreased cell apoptosis in lung grafts, inhibiting mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1) and caspase-3 in lung grafts. Further, the inhalation activated phosphorylation of p38 expression and inhibited phosphorylation of anti-extracellular signal-regulated kinase (ERK) expression in lung grafts. The effects of CO at 500 ppm were greater than those at 250 ppm. CONCLUSIONS: CO exerts potent protective effects on lung grafts from BD donor, exhibiting anti-inflammatory and anti-apoptosis functions by modulating the mitogen-activated protein kinase (MAPK) signal transduction.

CONSORT-epidural dexmedetomidine improves gastrointestinal motility after laparoscopic colonic resection compared with morphine.

BACKGROUND: We have previously shown that epidural dexmedetomidine, when used as an adjunct to levobupivacaine for control of postoperative pain after open colonic resection, improves recovery of gastrointestinal motility compared with morphine. METHODS: Sixty patients undergoing laparoscopic colonic resection were enrolled and allocated randomly to treatment with dexmedetomidine (group D) or morphine (group M). Group D received an epidural loading dose of dexmedetomidine (5 mL, 0.5 µg/kg), followed by continuous epidural administration of dexmedetomidine (80 µg) in 0.125% levobupivacaine (240 mL) at a rate of 5 mL/h for 2 days. Group M received an epidural loading dose of morphine (5 mL, 0.03 mg/kg) followed by continuous epidural administration of morphine (4.5 mg) in 0.125% levobupivacaine (240 mL) at a rate of 5 mL/h for 2 days. Verbal rating score (VRS) of pain, postoperative analgesic requirements, side effects related to analgesia, and time to postoperative first flatus (FFL) and first feces (FFE) were recorded. RESULTS: VRS and postoperative analgesic requirements were not significantly different between the treatment groups. In contrast, FFL and FFE were significant delayed in group M compared with group D (P < .05). Patients in group M also had a significantly higher incidence of nausea, vomiting, and pruritus (P < .05). No neurological deficits were observed in either group. CONCLUSIONS: Compared with morphine, epidural dexmedetomidine is a better adjunct to levobupivacaine for control of postoperative pain after laparoscopic colonic resection.

Investigation of single-dose thoracic paravertebral analgesia for postoperative pain control after thoracoscopic lobectomy - A randomized controlled trial.

BACKGROUND: Thoracoscopic lobectomy is less painful than normal thoracotomy, but pain management is still an issue in the postoperative period. Thoracic epidural analgesia (TEA) is considered as the gold standard for post-thoracotomy pain control, but is associated with numerous risks. METHODS: A total of 114 patients undergoing thoracoscopic lobectomy were randomly divided into three groups. Patients in the PVB-R group received a single-dose 0.5% ropivacaine paravertebral block (PVB), combined with patient-controlled intravenous analgesia (PCIA) after extubation during the 48-h postoperative period; those in the PVB-RD group received a single-dose 0.5% ropivacaine and dexmedetomidine (1 µg/kg) PVB, combined with the same PCIA scheme; and those in the TEA group received intraoperative thoracic epidural anesthesia with 0.5% ropivacaine, and a single dose of epidural morphine (0.03 mg/kg) after extubation combined with the same PCIA scheme. The dose and first time of postoperative analgesia, verbal rating score (VRS), change in catecholamine, cortisol and cytokine levels, change in hemodynamic parameters, and side effects during the postoperative period were recorded. RESULTS: Compared to the PVB-R group, the dose of postoperative analgesia and VRS were lower and the first time of postoperative analgesia were longer in the PVB-RD and TEA group. Patients in the PVB-RD group had a lower incidence of side effects compared to those in the TEA group. CONCLUSIONS: Single-dose 0.5% ropivacaine combined with dexmedetomidine (1 µg/kg) PVB provides satisfactory postoperative pain control after thoracoscopic lobectomy, and can reduce the incidence of postoperative side effects.

Epidural Dexmedetomidine Reduces the Requirement of Propofol during Total Intravenous Anaesthesia and Improves Analgesia after Surgery in Patients undergoing Open Thoracic Surgery.

The aim of this study was to assess the systemic and analgesic effects of epidural dexmedetomidine in thoracic epidural anaesthesia (TEA) combined with total intravenous anaesthesia during thoracic surgery. Seventy-one patients undergoing open thoracotomy were included in this study and randomly divided into three groups: Control group (Group C): patients received TEA with levobupivacaine alone and were intravenously infused with saline; Epidural group (Group E): patients received TEA with levobupivacaine and dexmedetomidine, and were intravenously infused with saline; Intravenous group (group V): patients received TEA with levobupivacaine alone and were intravenously infused with dexmedetomidine. The doses of propofol used in the induction and maintenance of general anaesthesia, cardiovascular response, dose and first time of postoperative analgesia and verbal rating scale were recorded. The induction and maintenance were significantly lower in the Groups E and V. Verbal rating scale and postoperative analgesic requirements were significantly lower in Group E than in Groups C and V. Patients in Group C had more severe cardiovascular responses, as compared with Groups E and V. Epidural administration of dexmedetomidine reduced the induction and maintenance of propofol, and inhibited the cardiovascular response after intubation and extubation. Moreover, epidural dexmedetomidine provided better analgesia after open thoracotomy.

Effect of Adding Dexmedetomidine to Ropivacaine on Ultrasound-Guided Dual Transversus Abdominis Plane Block after Gastrectomy.

OBJECTIVES: Transversus abdominis plane (TAP) block is an analgesic technique. Adding dexmedetomidine can enhance regional anesthesia. This study's aim was to evaluate whether dexmedetomidine prolonged analgesic time of TAP block after gastrectomy. METHODS: Patients scheduled for gastrectomy were randomly assigned to receive a TAP block with saline (group S), ropivacaine (group R), or ropivacaine and dexmedetomidine (group RD). Visual analogue scale (VAS) scores, postoperative nausea and vomiting (PONV) scores, sedation scores, tramadol consumption, ropivacaine concentration, and Quality of Recovery Questionnaire 40 (QoR-40) were recorded. RESULTS: Patients in group R and group RD had lower VAS scores 2, 4, 12, and 24 h after surgery compared with group S (P < 0.05). PONV scores were lower in group R and group RD compared with group S after 2, 12, 24, and 36 h (P < 0.05). Patients in group R and group RD required less tramadol and had better QoR-40 scores than those in group S (P < 0.05). The aforementioned variables and ropivacaine concentrations did not differ between group R and group RD (P > 0.05). Sedation scores were similar between three groups (P > 0.05). CONCLUSIONS: TAP block can provide analgesia and improve the quality of recovery. Adding dexmedetomidine does not significantly improve the quality or duration of TAP block.

Force development and intracellular Ca2+ in intact cardiac muscles from gravin mutant mice.

Gravin (AKAP12) is an A-kinase-anchoring-protein that scaffolds protein kinase A (PKA), ß2-adrenergic receptor (ß2-AR), protein phosphatase 2B and protein kinase C. Gravin facilitates ß2-AR-dependent signal transduction through PKA to modulate cardiac excitation-contraction coupling and its removal positively affects cardiac contraction. Trabeculae from the right ventricles of gravin mutant (gravin-t/t) mice were employed for force determination. Simultaneously, corresponding intracellular Ca2+ transient ([Ca2+]i) were measured. Twitch force (Tf)-interval relationship, [Ca2+]i-interval relationship, and the rate of decay of post-extrasysolic potentiation (Rf) were also obtained. Western blot analysis were performed to correlate sarcomeric protein expression with alterations in calcium cycling between the WT and gravin-t/t hearts. Gravin-t/t muscles had similar developed force compared to WT muscles despite having lower [Ca2+]i at any given external Ca2+ concentration ([Ca2+]o). The time to peak force and peak [Ca2+]i were slower and the time to 75% relaxation was significantly prolonged in gravin-t/t muscles. Both Tf-interval and [Ca2+]i-interval relations were depressed in gravin-t/t muscles. Rf, however, did not change. Furthermore, Western blot analysis revealed decreased ryanodine receptor (RyR2) phosphorylation in gravin-t/t hearts. Gravin-t/t cardiac muscle exhibits increased force development in responsiveness to Ca2+. The Ca2+ cycling across the SR appears to be unaltered in gravin-t/t muscle. Our study suggests that gravin is an important component of cardiac contraction regulation via increasing myofilament sensitivity to calcium. Further elucidation of the mechanism can provide insights to role of gravin if any in the pathophysiology of impaired contractility.

Morphine-induced delayed pre-conditioning against anoxia/reoxygenation injury in pulmonary artery endothelial cells: The role of mitochondrial KATP channels.

Opioids produce delayed pre-conditioning (PC) in vivo and in vitro. Our previous research revealed that opioid­induced delayed PC has an antiapoptotic effect on pulmonary artery endothelial cells (PAECs) suffering from anoxia/reoxygenation (A/R) injury. The present study hypothesized that activation of endothelial mitochondrial ATP­sensitive potassium (KATP) channels may result in antiapoptotic effects and against dysfunction in PAECs. Cultured porcine PAECs underwent 16 h anoxia treatment, followed by 1 h reoxygenation, which occurred 24 h following pretreatment with saline (0.9% NaCl; w/v) or morphine (1 µM). To determine the underlying mechanism, a selective mitochondrial KATP inhibitor, 5­hydroxydecanoic acid (5­HD; 100 µM), and an opioid receptor antagonist, naloxone (Nal; 10 µM), were administered 30 min prior to the A/R load. The percentage of apoptotic cells was assessed by Annexin V­fluorescein isothiocyanate staining, using a fluorescence­activated cell sorter. The mRNA expression of intercellular cell adhesion molecule­1 (ICAM­1) was measured by reverse transcription­quantitative polymerase chain reaction. The endothelin­1 (ET­1) content in the supernatant of PAECs cultures was estimated by radioimmunoassay. Compared with the control, A/R caused the apoptosis of PAECs, release of ET­1 and increased mRNA expression of ICAM­1. Morphine­induced delayed PC significantly reduced PAEC apoptosis, increased the release of ET­1 and reduced the mRNA expression of ICAM­1 by ~1.7­times, compared with A/R. The protective effect of morphine was abolished by pretreatment with 5­HD and Nal, however, the two agents themselves failed to aggravate the A/R injury. These results suggested that morphine-induced delayed PC has a protective effect during A/R injury of PAECs. This effect may be mediated by mitochondrial KATP channels and is opioid receptor-dependent.

Hydrogen inhalation decreases lung graft injury in brain-dead donor rats.

BACKGROUND: The process of brain death induces acute lung injury in donors and aggravates ischemia-reperfusion injury (IRI) in grafts. Hydrogen, a new anti-oxidant, attenuates IRI in several organ transplant models. We examined whether 2% inhaled hydrogen would show favorable effects on lung grafts from brain-dead donor rats. METHODS: Brain-dead donor rats inhaled mixed gases with either 50% oxygen and 50% nitrogen or mixed gases with 2% hydrogen, 50% oxygen and 48% nitrogen for 2 hours. The recipients inhaled the same gas as the donors and were euthanized 2 hours after lung transplantation. RESULTS: Hydrogen improved PaO(2)/FIO(2) and PVO(2)/FIO(2) from the arterial and pulmonary venous blood in recipients and decreased the lung injury score in grafts from brain-dead donors. Hydrogen decreased the amount of IL-8 and TNF-α in serum, inhibited the activity of malondialdehyde and myeloperoxidase, and increased the activity of superoxide dismutase in the lung grafts from brain-dead donors. Furthermore, hydrogen decreased the apoptotic index of the cells and inhibited the protein expression of intercellular adhesion molecule-1 and caspase-3 in lung grafts from brain-dead donors. CONCLUSIONS: Hydrogen can exert protective effects on lung grafts from brain-dead donors through anti-inflammatory, anti-oxidant and anti-apoptotic mechanisms.