Dexmedetomidine alleviates doxorubicin cardiotoxicity by inhibiting mitochondrial reactive oxygen species generation.

Cardiotoxicity largely limits the application of doxorubicin (Dox) for cancer treatment. Dexmedetomidine (Dex), a selective agonist of α2-adrenergic receptor, has been suggested to exert cardioprotection against myocardial injury. However, the effect and underlying mechanisms of Dex on Dox cardiotoxicity remain unknown. In this study, C57BL/6 mice were treated with Dox followed by Dex administration. Cardiomyocytes were co-incubated with Dox and Dex in vitro. The results showed that Dex markedly attenuated cardiac dysfunction induced by Dox. TUNEL staining exhibited that Dex inhibited Dox-induced cardiomyocyte apoptosis in myocardium. Moreover, the expression of anti-apoptotic protein Bcl-2 was increased, whereas the expression of pro-apoptotic protein Bax was decreased by Dex. Dox-induced the increase of reactive oxygen species (ROS), superoxide anion, and mitochondrial ROS (mROS) generation in myocardial tissues were significantly inhibited after Dex administration. In in vitro study, it was further confirmed that Dex prevented Dox-induced cardiomyocyte apoptosis and injury. However, the stimulation of mROS generation reversed the effect of Dex in cardiomyocytes. Mechanically, Dex blocked Dox-induced the ubiquitination of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), leading to the restoration of PGC-1α and downstream oxidative stress-protective molecules uncoupling protein 2 and manganese-dependent superoxide dismutase expression. Taken together, this study demonstrates that Dex exerts cardioprotection against Dox cardiotoxicity by attenuating mitochondrial dysfunction, oxidative stress, and cardiomyocyte apoptosis via inhibiting PGC-1α-signaling pathway inactivation. This suggests that Dex may be a potential therapeutic strategy for Dox cardiotoxicity treatment.

The effects of P6 electrical acustimulation on postoperative nausea and vomiting in patients after infratentorial craniotomy.

BACKGROUND: Postoperative nausea and vomiting (PONV) are frequent and harmful complications after neurosurgery. Current pharmacy-based treatment is the standard of care; it, however, lacks efficiency. Invasive and noninvasive acupuncture at the P6 meridian point has been shown to be effective in the prevention of PONV. We evaluated the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) at P6 for the prophylaxis of PONV in patients undergoing infratentorial craniotomy. METHODS: In this prospective, blind, and randomized study, patients received TEAS at P6 on the dominant side starting 30 minutes before the induction of anesthesia and up to 24 hours after surgery or sham acustimulation at P6. The anesthesia was maintained with sevoflurane/remifentanil and intermittent fentanyl/cisatracurium. Antiemetics with 4 mg ondansetron and 10 mg dexamethasone were administered intraoperatively. Data documenting postoperative episodes of nausea and vomiting and the need for antiemetic rescue (10 mg metoclopramide intramuscularly) were collected. Statistical analysis was performed using the χ test. P<0.05 was considered to be significant. RESULTS: Of the 130 patients enrolled, 119 patients completed the study. The 24-hour cumulative incidence of vomiting was significantly lower in the TEAS group than in the control group (22% vs. 41%, P=0.025). The cumulative incidences of nausea at 6 hours (27% vs. 47%, P=0.019) and 24 hours (33% vs. 58%, P=0.008) after surgery were also significantly lower in the TEAS group compared with the control group. The overall requirements of rescue antiemetics were similar between the groups. CONCLUSION: Perioperative TEAS at P6 may be an effective adjunct to the standard antiemetic drug therapy for the prevention of PONV after infratentorial craniotomy.

[Intraoperative cranial nerves monitoring under partial neuromuscular relaxation during cerebellopontine angle tumor resection].

OBJECTIVE: To evaluate the efficacy of multiple cranial nerves monitoring under partial Seventy elective neuromuscular relaxation during cerebellopontine angle (CPA) tumor resection. METHODS: patients undergoing CPA tumor resection via microneurosurgery were randomly allocated to 2 equal groups: Group FN receiving intraoperative facial nerve (NF) monitoring and Group MN receiving monitoring of multiple nerves: trigeminal nerve, glossopharyngeal nerve, accessory nerve or hypoglossal nerve other than the FN which were considered at risk by the neurosurgeon preoperatively. The manipulation procedure were modified according to cranial nerves monitoring and neuromuscular relaxation was maintained at train of four stimulation (TOF)=3 by continuous vencronium infusion during the acoustic neuroma resection. The function of the cranial nerves monitored were evaluated preoperatively and 8 days postoperatively. RESULTS: Discernable and legible images of electromyographic wave complex were obtained during cranial nerve mapping and monitoring under intraoperative partial neuromuscular relaxation form all the patients. The facial nerve function of 4 patients exacerbated (from H-B grade I-II to grade III-IV) in both groups, and one new glossopharyngeal nerve function deficiency was found in Group FN, and one new hypoglossal nerve function deficiency was found in Group MN postoperatively. CONCLUSION: Intraoperative cranial nerves monitoring under partial neuromuscular relaxation is feasible. Multiple cranial nerves combined with facial nerve monitoring seems unable to increase the short-term protective effects of nerve function after CPA tumor resection.

[The target plasma concentration of propofol required to induce electroencephalography burst suppression with target-controlled infusion].

OBJECTIVE: To determine the optimal target plasma concentration of propofol required to induce EEG burst suppression administered by TCI in order to decrease cerebral metabolic rate and increase tolerance to cerebral ischemia and hypoxia. METHODS: One hundred and fifty ASA I-II patients(aged 18-55 years-old, BMI < 30, Mallampati Score I-II) scheduled for elective surgery undergoing general anesthesia were enrolled in this study. Patients with systemic diseases or other factors effecting the electrical activity of brain were excluded. ECG, IBP, SpO2, PetCO2, Temperature and EEG (two-channel referential montage system) were continuously monitored during the procedure. Patients were induced with TCI propofol (the target plasma concentration was initially set at 5.4 microg/ml), After induction and intubation, target plasma concentration was increased by 0.3 microg/ml increment and sustained 15 minutes until EEG burst suppression appeared(stable burst suppression waveform and BSR > 50%), and this target concentration was recorded. RESULTS: The mean target plasma concentration of propofol with TCI required to induce EEG burst suppression was 6.1 +/- 0.6 microg/ml with 95% confidence interval of 5.99-6.19 microg/ml. There was no significant difference between the genders. CONCLUSIONS: The target plasma concentration of propofol reached 6.2 microg/ml can induce EEG burst suppression, which is better for intraoperative cerebral protection.

[Influence of stimulating different cords on the efficacy of infraclavicular brachial plexus block].

OBJECTIVE: Stimulating lateral or posterior cord may produce different anesthesia extent because of different anatomical position of the two plexus at the infraclavicular region. We To explore the difference in the efficacy of infraclavicular brachial plexus block by stimulating different cords of the infraclavicular brachial plexus. METHODS: 70 patients of the ASA physical status class I - II, aged 14 - 64, scheduled for elective surgical procedures below elbow underwent infraclavicular brachial plexus block with the Wilson's approach via the point 2 cm medial and caudal to the coracoid process guided by nerve stimulator, to simulate the lateral cord (n = 32) or posterior cord (n = 38). 30 ml of 0.5% ropivacaine was injected after the stimulation of the lateral or posterior cords. Anesthesia was assessed 5, 10, 20, and 30 min after the local anesthetic injection. A successful blockade was defined as analgesia in all dermatomes of the five nerves (median nerve, musculocutaneous nerve, radial nerve, ulnar nerve, and medial antebrachial cutaneous nerve). RESULTS: Stimulating the posterior cord provided complete blockade in 30 patients (78.9%) and stimulating the lateral cord provided complete blockade in 17 patients (53.1%). CONCLUSION: Stimulating the posterior cord guided by nerve stimulator increases the efficacy of infraclavicular brachial plexus block compared with stimulating the lateral cord.

[Low minimal stimulating current improves infraclavicular brachial plexus block efficacy].

OBJECTIVE: To investigate if low minimal stimulating current used in nerve stimulator localizing is associated with a greater likelihood of infraclavicular block success. METHODS: 188 patients, aged 14 to 64, of ASA physical status class I - II, and scheduled for surgical procedures below elbow were assigned to low current group (Group A, n = 118) or regular current group (Group B, n = 70) according to the last figure of admission number. The infraclavicular plexus block was performed using the Wilson's approach 2 cm medial and caudal to the coracoid process guided by nerve stimulator with 30 ml of 0.5% ropivacaine after eliciting distal motor responses. The minimal stimulating current (I) was adjusted to 0.1 mA < or = I < 0.3 mA in Group A or 0.3 mA < or = I < 0.5 mA in Group B. The 2 groups were further sub-divided into 2 subgroups: lateral cord subgroup when motor responses of wrist and finger-flexion and pronation of forearm were induced, and posterior subgroup when extension of wrist and finger was induced. Anesthesia efficacy was assessed 5, 10, 20 and 30 min after the local anesthetic injection. A successful blockade was defined as analgesia in all dermatomes of the five nerves (median nerve, musculocutaneous nerve, radial nerve, ulnar nerve, and medial antebrachial cutaneous nerve). RESULTS: The success rate of Group A was 84.7%, significantly higher than that of Group B (67.1%, P < 0.05). When divided into posterior and lateral cord subgroups, The success rate of the posterior subgroup of Group A was 96.5%, significantly higher than that of the posterior subgroup of Group B (78.9%, P < 0.05). CONCLUSION: Minimal stimulating current lower than 0.3 mA, significantly lower than the recommended value (0.5 mA), improves the efficacy of infraclavicular brachial plexus block, especially when the posterior cord is stimulated.

[Effects of intravenous and inhalational anesthetics on short-latency somatosensory evoked potentials].

OBJECTIVE: To choose suitable general anesthetics dosages when short-latency somatosensory evoked potentials (SLSEP) is monitored during operation. METHODS: 150 ASA I-II neurosurgical patients undergoing elective operations were randomly divided into intravenous anesthesia group of 90 patients and inhalation anesthesia group of 60 patients. The intravenous anesthesia group was further divided into 9 subgroups of 10 patients treated with different anesthetics of different dosages: propofol (1.5 mg/kg, 2 mg/kg, and 3 mg/kg), midazolam (0.2 mg/kg, 0.3 mg/kg, and 0.4 mg/kg), and etomidate (0.15 mg/kg, 0.3 mg/kg, and 0.4 mg/kg). The intravenous anesthetics were given and upper limb SLSEP was monitored continuously. The inhalation anesthesia group was further divided into enflurane, isoflurane and desflurane subgroups of 20 patients each. The inhalational anesthetics were given at the concentrations corresponding to the end-expiratory concentrations of 0 to 0.3, 0.5, 0.75, 1.0 and 1.5 MAC. The changes of N(14), N(20) and central conduction time (CCT) were recorded. In addition to SLSEP, EKG, NIBP, SpO(2), P(ET) CO(2) were monitored as well as end-tidal anesthetic concentration. During the experiment SpO(2) was maintained > 95% and P(ET) CO(2) was maintained at the range of 35 - 45 mmHg by mask oxygen or assisted ventilation. RESULTS: The intravenous anesthetic propofol significantly decreased N(20) amplitude and produced less effect on the latency of N(14), N(20) and CCT. Midazolam significantly decreased the N(20) amplitude and prolonged the latency of N(20) and CCT. Etomidate significantly increased the N(20) amplitude, and the change did not recover when the patients had opened their eyes 10 minutes after medication. All three inhalational anesthetics significantly decreased the N(20) amplitude and prolonged the N(20) latency and CCT. N(20) amplitude disappeared in some patients treated with enflurane when the end-expiratory concentration was 1.0 MAC, while disappeared in some patients treated with isoflurane and desflurane when the end-expiratory concentration was 1.5 MAC for these 2 drugs. CONCLUSION: When using SLSEP monitoring, the most suitable general anesthetic is etomidate during the induction stage and isoflurane and desflurane during the maintenance stage with the end-expiratory concentration below 1.0 MAC.