Ultrasound-guided fascia iliaca compartment block combined with general anesthesia for amputation in an acute myocardial infarction patient after percutaneous coronary intervention: A case report.

BACKGROUND: Fascia iliaca compartment block is a technique that blocks three nerves, similar to a 3-in-1 nerve block. This block provides analgesia for patients undergoing lower limb surgery, and is a simple technique that is easy to implement. Here, we report a case of fascia iliaca compartment block in a patient with myocardial infarction who underwent emergency middle thigh amputation. CASE SUMMARY: A 78-year-old female patient weighing 38 kg with gangrene and occlusive peripheral atherosclerosis of the right leg underwent an emergency middle thigh amputation. The patient had a history of hypertension, coronary heart disease, cerebral infarction, anterior wall myocardial infarction, and had recently undergone percutaneous coronary intervention consisting of coronary angiography and right coronary artery stent implantation. Considering the patient's condition, an ultrasound-guided fascia iliaca compartment block combined with general anesthesia was implemented for amputation. The fascia iliaca compartment block provided analgesia for the operation, and reduced the dosage of general anesthetics. It also alleviated adverse cardiovascular effects caused by pain stress, and ensured the safety of the patient during the perioperative period. This block also provided postoperative analgesia. The patient had a good prognosis, and was subsequently discharged from hospital. CONCLUSION: Fascia iliaca compartment block provides surgical analgesia. It also alleviates adverse cardiovascular effects, and ensures patient safety during the perioperative period.

CaMK II γ down regulation protects dorsal root ganglion neurons from ropivacaine hydrochloride neurotoxicity.

T-type calcium channels are intimately involved in the local anesthetics neurotoxicity. Does CaMKIIγ regulate T-type calcium currents in local anesthetics neurotoxicity? This study generated pAd-CaMKIIγ and pAd-shRNA adenovirus vectors to up- and down-regulate CaMKIIγ mRNA expression in dorsal root ganglion neurons (DRG). Normal DRG (Normal group), empty vector DRG (Empty vector group), pAd-CaMKIIγ DRG (pAd-CaMKIIγ group) and pAd-shRNA DRG (pAd-shRNA group) were treated or untreated with 3 mM ropivacaine hydrochloride for 4 h. Cell viability, apoptosis rate, CaMKIIγ, pCaMKIIγ, Cav3.2, and Cav3.3 expression were detected. Ultrastructural changes in DRG were observed under a transmission electron microscope. The results demonstrated that the cell viability of DRG treated with ropivacaine hydrochloride decreased markedly, the apoptosis rate, CaMKIIγ, pCaMKIIγ, Cav3.2, Cav3.3 expression increased significantly. CaMKIIγ up-regulation aggravated ropivacaine hydrochloride-induced cell damage and increased Cav3.2 and Cav3.3 expression. In conclusion, CaMKIIγ regulated Cav3.2 and Cav3.3 expression in DRG, which was involved with ropivacaine hydrochloride-induced cell injury.

Interleukin-33 signaling contributes to renal fibrosis following ischemia reperfusion.

Acute kidney injury caused by ischemia-reperfusion injury (IRI) is a major risk factor for chronic kidney disease, which is characterized by renal interstitial fibrosis. However, the molecular mechanisms underlying renal fibrosis induced by IRI are not fully understood. Our results showed that interleukin (IL)-33 was induced markedly after IRI insult, and the kidneys of mice following IRI plus IL-33 treatment presented more severe renal fibrosis compared with mice treated with IRI alone. Therefore, we investigated whether inhibition of IL-33 protects against IRI-induced renal fibrosis. Mice were administrated with soluble ST2 (sST2), a decoy receptor that neutralizes IL-33 activity, or vehicle by intraperitoneal injection for 14 days after IRI challenge. We revealed that mice treated with sST2 exhibited less severe renal dysfunction and fibrosis in response to IRI compared with vehicle-treated mice. Inhibition of IL-33 suppressed bone marrow-derived fibroblast accumulation and myofibroblast formation in the kidneys after IRI stress, which was associated with less expression of extracellular matrix proteins. Furthermore, inhibition of IL-33 also showed a significant reduction of F4/80+ macrophages and CD3+ T cells in the kidneys of mice after IRI treatment. Finally, Treatment with IL-33 inhibitor reduced proinflammatory cytokine and chemokine levels in the kidneys of mice following IRI insult. Taken together, our findings indicate that IL-33 signaling plays a critical role in the pathogenesis of IRI-induced renal fibrosis through regulating myeloid fibroblast accumulation, inflammation cell infiltration, and the expression of proinflammatory cytokines and chemokines.

Sevoflurane attenuates platelets activation of patients undergoing lung cancer surgery and suppresses platelets-induced invasion of lung cancer cells.

STUDY OBJECTIVE: Platelets play a pivotal role in metastasis of tumor cells. The aim of this study is to explore the effects of sevoflurane and isoflurane on platelets activation of patients undergoing lung cancer surgery, and the effects of sevoflurane and isoflurane on platelets-induced invasion of lung cancer cells. DESIGN: Prospective and randomized study, and in vitro experiment. SETTING: University-affiliated teaching hospital and laboratory. PATIENTS: Forty-six patients scheduled for lung cancer radical surgery. INTERVENTIONS: Patients were randomized to two groups of 23 patients each and were received sevoflurane (group SEV) or isoflurane (group ISO) during surgery, respectively. In vitro, lung cancer cells were treated with platelets in the presence or absence anesthetics. MEASUREMENTS: Platelets activation were determined by detecting glycoproteinIIb/IIIa (GPIIb/IIIa), CD62P, and platelets aggregation rate (PAR) pre-, intra-, and postoperatively. Invasion ability of lung cancer cells were evaluated by Transwell assay. RESULTS: The levels of GPIIb/IIIa, CD62P, and PAR were reduced markedly in group SEV during perioperative period compared with group ISO. In vitro, activated platelets contributed profoundly to the invasive ability of lung cancer cells. Sevoflurane, but not isoflurane, inhibited platelets-induced invasion of lung cancer cells. Furthermore, sevoflurane suppressed the platelets activity in vitro. CONCLUSION: Sevoflurane attenuates platelets activation of patients undergoing lung cancer surgery. In vitro, sevoflurane suppresses platelets-induced invasion of lung cancer cells via decreasing platelets activity.

Neuroprotective effect of ginkgolide B on bupivacaine-induced apoptosis in SH-SY5Y cells.

Local anesthetics are used routinely and effectively. However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5Y cells were treated with different concentrations of bupivacaine alone or following preincubation with GB. Pretreatment with GB increased SH-SY5Y cell viability and attenuated intracellular ROS accumulation, apoptosis, mitochondrial dysfunction, and ER stress. GB suppressed bupivacaine-induced mitochondrial depolarization and mitochondria complex I and III inhibition and increased cleaved caspase-3 and Htra2 expression, which was strongly indicative of activation of mitochondria-dependent apoptosis with concomitantly enhanced expressions of Grp78, caspase-12 mRNA, protein, and ER stress. GB also improved ultrastructural changes indicative of mitochondrial and ER damage induced by bupivacaine. These results implicate bupivacaine-induced ROS-dependent mitochondria, ER dysfunction, and apoptosis, which can be attenuated by GB through its antioxidant property.

The effects of combined treatment with sevoflurane and cisplatin on growth and invasion of human adenocarcinoma cell line A549.

Sevoflurane, an inhalational anesthetic, and cisplatin (DDP)-based chemotherapy have been widely used during lung cancer surgery. However, the effect of sevoflurane on the sensitivity of lung cancer cells to DDP chemotherapy remains unclear. In this study, the effects of combined treatment with sevoflurane and cisplatin on the growth and invasion of human lung adenocarcinoma A549 cell line have been investigated. The underlying mechanism has also been explored. In our experiment, A549 cells were treated with 2.5% sevoflurane, 10µmol/L DDP, or the co-treatment of sevoflurane and DDP for 4h, respectively. Cell proliferation was evaluated by the MTT assay and colony formation assay. Apoptosis was assessed by flow cytometry. Cell invasion was detected by Transwell assay. The expressions of X-linked inhibitor of apoptosis protein (XIAP), Survivin, matrix metalloproteinase (MMP)-2 and MMP-9 were determined by western blotting. Our results showed that sevoflurane combined with DDP resulted in a more pronounced inhibition of tumor cells growth and invasion as compared with either drug alone. Besides, XIAP, Survivin, MMP-2, and MMP-9 were downregulated more significantly by the co-treatment of the two drugs as compared to sevoflurane treatment or DDP treatment alone. Taken together, the growth-inhibitory and invasion-inhibitory synergy between sevoflurane and DDP in human adenocarcinoma A549 cell line was found in this study. Furthermore, we showed that the growth-inhibitory synergy between sevoflurane and DDP might be associated with the downregulation of XIAP and Survivin, and the invasion-inhibitory synergy between sevoflurane and DDP might be involved in the downregulation of MMP-2 and MMP-9.

Sevoflurane inhibits proliferation, induces apoptosis, and blocks cell cycle progression of lung carcinoma cells.

PURPOSE: Sevoflurane, an inhalational anesthetic, is used extensively during lung cancer surgery. However, the effect of sevoflurane on growth of lung carcinoma cells remains unclear. The purpose of this study is to investigate effects on proliferation, apoptosis, and cell cycling in the A549 human lung adenocarcinoma cell line. METHODS: A549 cells were treated with 1.7%, 3.4%, and 5.1 % sevoflurane for 2, 4, and 6 hours. Cell proliferation was evaluated by the MTT assay and colony formation assay. Apoptosis and cell cycle was analyzed by flow cytometry. Expression of X-linked inhibitor of apoptosis protein (XIAP), survivin, Bcl-2, Bax, caspase-3, cyclin A, cyclin B1, and cdc2 was measured by Western blotting. RESULTS: Significant inhibition of cell proliferation and induction of apoptosis were found in A549 cells after sevoflurane treatment. Simultaneously, expression of XIAP and survivin was supressed, while that of caspase-3 increased significantly, but Bcl-2 and Bax were not altered. Sevoflurane caused cell cycle arrest at the G2/M phase. At the same time, data revealed that cyclin A, cyclin B1, and cdc2 expression was down-regulated after sevoflurane treatment. CONCLUSION: This study demonstrated that sevoflurane inhibited proliferation, and induced apoptosis in human lung adenocarcinoma A549 cells, associated with down-regulated expression of XIAP and suvivin, and activating caspase-3.

The effects of preloading infusion with hydroxyethyl starch 200/0.5 or 130/0.4 solution on hypercoagulability and excessive platelet activation of patients with colon cancer.

Hypercoagulability and excessive platelet activation account for a significant percentage of mortality and morbidity in cancer patients. In order to test the hypothesis that preloading infusion (PLI) with 6% hydroxyethyl starch 200/0.5 (HES 200), or 6% hydroxyethyl starch 130/0.4 (HES 130) solution can attenuate the hypercoagulable state and inhibit excessive platelet activation of patients with colon cancer, we selected 35 colon cancer patients undergoing laparoscopic-assisted radical colectomy. They were received randomly a test of 15 ml/kg of either HES 200 (n=17), or HES 130 (n=18) over a 30-min period preoperatively. In addition, fifteen healthy volunteers were selected as normal control group. Coagulation function was assessed by thrombelastography (TEG), platelet glycoprotein IIb/IIIa and CD62P was analyzed by flow cytometry before PLI, the end of PLI, 1 h after PLI, and 1 h after the end of surgery. Results demonstrated that hypercoagulable state indicated by TEG and excessive platelet activation was found in patients with colon cancer. We found that preloading infusion with HES 200/0.5 can inhibit platelet activation, and the two solutions, especially HES 200/0.5, compromised TEG parameters that indicated hypercoagulability of patients with colon cancer during perioperative period.

The roles of T-type calcium channel in the development of neuropathic pain following chronic compression of rat dorsal root ganglia.

This study aimed to elucidate the role of T-type calcium channels in the nociceptive signal transmission at the spinal level. The chronic compression of dorsal root ganglion (CCD) rat model was adopted. Three doses (50, 100 and 200 microg in groups Mib50, Mib100 and Mib200, respectively) of specific T-type Ca2+ channel inhibitors mibefradil (Mib) or normal saline (NS) were intrathecally administered on the 5th day after the CCD model had been established. The paw withdrawal latency from a noxious thermal stimulus and paw withdrawal mechanical threshold of von Frey filament was used to measure the thermal hyperalgesia and tactile allodynia, respectively. Lumbar spinal cords of the rats isolated on the 5th day after the operation were prepared to measure the mRNA expression of T-type (Cav3.1, Cav3.2 and Cav3.3) calcium channel with RT-PCR methods. The results demonstrated that CCD rats produced reliable thermal hyperalgesia and tactile allodynia after surgery. The intrathecal administration of Mib significantly suppressed thermal hyperalgesia and allodynia in CCD rats (p< 0.01), and the inhibitory effect lasted for 2 h. However, only Cav3.2 and Cav3.3 T-type calcium channel mRNA were detected in the lumbar spinal cord of rats, and there were no Cav3.1 calcium channels. Compared with native and sham groups, the Cav3.2 and Cav3.3 calcium channel mRNA expression increased significantly (p < 0.05). These data support the view that spinal T-type calcium (Cav3.2 and Cav3.3 but not Cav3.1) channels may play an important role in the pathogenesis of neuropathic pain.

Cardioprotection of sevoflurane postconditioning by activating extracellular signal-regulated kinase 1/2 in isolated rat hearts.

AIM: The activation of extracellular signal-regulated kinase (ERK)1/2 protects against ischemic-reperfusion injury. Whether ERK1/2 mediates the cardioprotection of sevoflurane postconditioning is unknown. We tested whether sevoflurane postconditioning produces cardioprotection via an ERK1/2-dependent mechanism. METHODS: In protocol 1, Langendorff-perfused Sprague-Dawley rat hearts (n=84, 12 per group), with the exception of the Sham group, were subjected to 30 min ischemia followed by 90 min reperfusion and were assigned to the untreated (control) group, followed by 4 cycles of ischemic postconditioning (25 s of each), 3% (v/v) sevoflurane postconditioning (for 5 min and 10 min of washout), and the PD98059 solvent DMSO (<0.2%), ERK1/2 inhibitor PD98059 (20 micromol/L), and Sevo+PD administration. Left ventricular hemodynamics and coronary flow at 30 min of equilibrium were recorded at 30, 60, and 90 min of reperfusion, respectively. Acute infarct size was measured by triphenyltetrazolium chloride staining. The configuration of mitochondria was observed by an electron microscope. Western blot analysis was used to determine the contents of cytosolic and mitochondrial cytochrome c at the end of reperfusion. In protocol 2, after 15 min of reperfusion, the expression of total and phosphorylated forms of ERK1/2 and its downstream target p70S6K was determined by Western blotting. RESULTS: No differences in baseline hemodynamics were observed among the experimental groups (P>0.05). After reperfusion, compared with the control group, sevoflurane postconditioning and ischemic postconditioning significantly(P<0.05) improved functional recovery and largely (P<0.05) decreased myocardial infarct size (22.9%+/-4.6% and 21.2%+/-3.8%, vs 39.4%+/- 5.7%, both P<0.05). Sevoflurane-mediated protection was abolished by PD98059. CONCLUSION: Anesthetic postconditioning by sevoflurane effectively protects against reperfusion damage by activating ERK1/2 in vitro.

Sevoflurane post-conditioning protects against myocardial reperfusion injury by activation of phosphatidylinositol-3-kinase signal transduction.

The mechanisms underlying myocardial protection by sevoflurane post-conditioning are unclear. In the present study, we tested two hypotheses: (i) that sevoflurane post-conditioning produces cardioprotection via a phosphatidylinositol-3-kinase (PI3-K)-dependent pathway; and (ii) combining sevoflurane and ischaemic post-conditioning offers an additional benefit against reperfusion injury. Rat isolated perfused hearts were exposed to 25 min ischaemia followed by 90 min reperfusion. Sevoflurane post-conditioning was induced by administration of sevoflurane (3.0 vol%) for 15 min from the onset of reperfusion. In some groups, 15 micromol/L LY294002, a selective PI3-K inhibitor, was coadministrated with sevoflurane. Other groups of hearts were exposed to ischaemic post-conditioning or combined sevoflurane plus ischaemic post-conditioning in the presence and absence of LY294002. After 15 min reperfusion, phosphorylation of Akt and glycogen synthase kinase 3beta (GSK3beta) was determined by Western blot analysis. Infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining and subsarcolemmal mitochondrial lesions were assessed by electron microscopy after 90 min reperfusion. Sevoflurane post-conditioning significantly decreased infarct size compared with control hearts (31 +/- 2 vs 42 +/- 3%, respectively; P < 0.05), diminished mitochondrial lesions and increased phosphorylation of Akt and GSK3beta, as did ischaemic post-conditioning. However, combined sevoflurane plus ischaemic post-conditioning did not further improve the cardioprotective effects compared with either intervention alone. Sevoflurane-mediated cardioprotection was abolished or inhibited by 15 micromol/L LY294002. In conclusion, sevoflurane acts during early reperfusion after ischaemia to salvage the myocardium by activating PI3-K. The combination of sevoflurane plus ischaemic post-conditioning does not offer any additional benefit over either intervention alone.

Intrathecal administration of Cav3.2 and Cav3.3 antisense oligonucleotide reverses tactile allodynia and thermal hyperalgesia in rats following chronic compression of dorsal root of ganglion.

AIM: The present study aimed to elucidate the role of T-subtype calcium channels (Cav3.1, Cav3.2, and Cav3.3) in the pathogenesis of neuropathic pain at spinal level. METHODS: The chronic compression of the dorsal root ganglion (CCD) rat model was adopted. The antisense oligonucleotide of Cav3.1, Cav3.2, and Cav3.3 or normal saline (NS) were intrathecally administered twice per day from the first day to the fourth day after operation. Paw mechanical withdrawal threshold and paw thermal withdrawal latency were measured to evaluate the tactile allodynia and thermal hyperalgesia, respectively. RESULTS: CCD rats developed reliable tactile allodynia and thermal hyperalgesia after operation. Intrathecal administration of antisense oligonucleotide of Cav3.2 and Cav3.3 significantly relieved tactile allodynia and thermal hyperalgesia in CCD rats, but not Cav3.1. CONCLUSION: Cav3.2 and Cav3.3 subtype calcium channels in the spinal cord may play an important role in the pathogenesis of neuropathic pain, which may contribute to the management of the neuropathic pain.