Consensus statement on smoking cessation in patients with pain.

Smoking is closely associated with the development of various cancers and tobacco-related illnesses such as cardiovascular and respiratory disorders. However, data are scarce on the relationship between smoking and both acute and chronic pain. In addition to nicotine, tobacco smoke contains more than 4000 different compounds. Although nicotine is not the sole cause of smoking-induced diseases, it plays a critical role in pain-related pathophysiology. Despite the acute analgesic effects of nicotine, long-term exposure leads to tolerance and increased pain sensitivity due to nicotinic acetylcholine receptor desensitization and neuronal plastic changes. The purpose of smoking cessation interventions in smoking patients with pain is primarily not only to reduce their pain and associated limitations in activities of daily living, but also to improve the outcomes of underlying pain-causing conditions and reduce the risks of tobacco-related disorders. This statement aims to summarize the available evidence on the impact of smoking on pain and to inform medical professionals of the significance of smoking cessation in patients with pain.

Low Skeletal Muscle Mass Is Associated With Perioperative Neurocognitive Disorder Due To Decreased Neurogenesis in Rats.

BACKGROUND: Perioperative neurocognitive disorder (PND) is a postsurgical complication associated with neuroinflammation and impaired hippocampal neurogenesis, in which brain-derived neurotrophic factor (BDNF) plays a key role. Sarcopenia refers to age-related muscle loss that causes cognitive decline, muscle atrophy, and postoperative delirium. Rats with tail suspension (TS) were used to represent a low-activity model, which involves decreased hind limb function by TS. This hind limb unloading by TS can induce sarcopenia in 2 weeks. However, the relationship between PND and muscle atrophy is unclear. In this experiment, we investigated whether preoperative muscle atrophy induced by TS would affect neurogenesis and accelerate PND in rats. METHODS: Sixty 21-week-old rats were assigned to 4 groups: the TS group, the TS with surgery (TS + S) group, the control group, and the control with surgery (control + S) group. After the abdominal manipulation under 3% sevoflurane anesthesia, cognitive function was assessed using the Morris water maze test and a fear-conditioning test. Neurogenesis was evaluated by checking BDNF secretion and immunohistochemical staining in the hippocampus. RESULTS: The TS + S group showed impaired swimming latency (difference of means = 12.4 versus control + S; 95% confidence interval [CI], 2.0-22.7; P = .016) (difference of means = 15.2 versus TS; 95% CI, 0.4-30.1; P = .043) and path length (difference of means = 147.8 versus control + S; 95% CI, 20.7-274.9; P = .020) in the maze test and cued fear memory (difference of means = -26.0 versus TS; 95% CI, -46.4 to -5.6; P = .006) (difference of means = -22.3 versus control + S; 95% CI, -42.7 to -1.9; P = .026) in the fear-conditioning test. The postoperative levels of BDNF in the TS + S and TS groups were reduced compared with the other groups (P = .002). The number of neural precursors in the dentate gyrus was significantly lower in the TS + S group (P < .001). CONCLUSIONS: We observed that preoperative hind limb muscle atrophy, indicated by TS, was associated with an increased occurrence of PND through the reduction in BDNF and neurogenesis after abdominal surgery in young adult rats. Therefore, we concluded that preoperative low skeletal muscle mass can induce PND due to impaired postoperative neurogenesis. Our findings might indicate that low-cost perioperative interventions, such as preoperative exercise, is beneficial to preventing PND.

Tail suspension is useful as a sarcopenia model in rats.

BACKGROUND: Sarcopenia promotes skeletal muscle atrophy and exhibits a high mortality rate. Its elucidation is of the highest clinical importance, but an animal experimental model remains controversial. In this study, we investigated a simple method for studying sarcopenia in rats. RESULTS: Muscle atrophy was investigated in 24-week-old, male, tail-suspended (TS), Sprague Dawley and spontaneously hypertensive rats (SHR). Age-matched SD rats were used as a control group. The skeletal muscle mass weight, muscle contraction, whole body tension (WBT), cross-sectional area (CSA), and Muscle RING finger-1 (MuRF-1) were assessed. Enzyme-linked immunosorbent assay was used to evaluate the MuRF-1 levels. Two muscles, the extensor digitorum longus and soleus muscles, were selected for representing fast and slow muscles, respectively. All data, except CSA, were analyzed by a one-way analysis of variance, whereas CSA was analyzed using the Kruskal-Wallis test. Muscle mass weight, muscle contraction, WBT, and CSA were significantly lower in the SHR (n = 7) and TS (n = 7) groups than in the control group, whereas MuRF-1 expression was dominant. CONCLUSIONS: TS and SHR presented sarcopenic phenotypes in terms of muscle mass, muscle contraction and CSA. TS is a useful technique for providing muscle mass atrophy and weakness in an experimental model of sarcopenia in rats.

The Effect of Tranexamic Acid Administration on Perioperative Bleeding in Patients Undergoing Knee or Hip Arthroplasty: A Single-Centre Retrospective Study.

OBJECTIVE: Tranexamic acid (TXA) has been used to reduce perioperative bleeding in various surgeries because of its antifibrinolytic effect. Recently, patients undergoing orthopaedic surgery in our institution received a loading dose of TXA (10 00 mg) before surgery, followed by 100 mg h-1 until the end of surgery. The purpose of the present study was to evaluate the efficacy of TXA administration on the perioperative blood loss in patients undergoing knee arthroplasty or hip arthroplasty. METHODS: A retrospective cross-sectional study was conducted for the records in patients who underwent surgery without TXA administration (control group) and patients who underwent surgery with TXA administration (TXA group). Amount of intraoperative blood loss, intraoperative infusion volume, intraoperative blood transfusion volume, postoperative blood transfusion volume, changes in haemoglobin concentrations (ΔHb) and estimated blood loss were collected. Data were adjusted by propensity score method. RESULTS: A total of 126 (63 in the control group and 63 in the TXA group) patients were included during the study period. Intraoperative infusion, postoperative transfusion, ΔHb and estimated blood loss were significantly reduced in the TXA group, although there were no significant differences in the volumes of intraoperative transfusion and blood loss. CONCLUSION: The administration of TXA (loading dose of 1000 mg and continuous infusion of 100 mg h-1) reduced postoperative transfusion and perioperative blood loss. These results indicated that TXA administration is useful for reducing perioperative blood loss in patients undergoing knee or hip arthroplasty.

Dexmedetomidine reduced sevoflurane-induced neurodegeneration and long-term memory deficits in neonatal rats.

Exposure to sevoflurane and other inhalational anesthetics can induce neurodegeneration in the developing brain. Although dexmedetomidine (DEX) has provided neuroprotection against hypoxic ischemic injury, relatively little is known about whether it has the neuroprotective effects against anesthetic-induced neurodegeneration. This study examined whether DEX improves the long-term cognitive dysfunction observed after exposure of neonatal rats to 3% sevoflurane. Seven-day-old rats received intraperitoneal saline (DEX 0) or DEX (6.6, 12.5, 25 µg/kg) 30 min before exposure to 3% sevoflurane with 21% oxygen for 4 h (n = 10 per group). The pups in the control group received only DEX 25 µg/kg without anesthesia. The escape latency in the Morris water maze was significantly increased in the DEX 0 group compared with the sham and control group, and the escape latency, but not the swimming path length, was significantly shorter at post-natal day 47 in the DEX 25 than in the DEX 0 group. The percent time spent in the quadrant was significantly decreased in the DEX 0 group compared with the sham and control group, and the percent time spent in the quadrant was significantly increased in the DEX 25 group compared with the DEX 0 groups. The freezing times of the DEX 0 and 6.6 groups were significantly decreased compared with those in the sham, control and DEX 25 groups. The number of NeuN-positive cells in the CA1 region was significantly decreased in the DEX 0 and 6.6 groups compared with the sham, control and DEX 25 groups. These findings indicate pre-treatment with DEX may improve long-term cognitive function and ameliorate the neuronal degeneration induced by sevoflurane exposure in neonatal rats.

Erythropoietin Reduces Neurodegeneration and Long-Term Memory Deficits Following Sevoflurane Exposure in Neonatal Rats.

Exposure to general anesthetics induces neural apoptosis and degeneration in the immature neonatal brain. Erythropoietin (EPO) has been shown to protect neonatal animals against hypoxic-ischemic injury and general anesthesia-induced developmental neurotoxicity. However, preventive strategy caused by EPO against neurotoxicity due to general anesthesia is still uncertain. This study examined the effects of EPO administration on brain cytology and cognitive function in adolescent rats exposed to 3% sevoflurane as neonates. Seven-day-old rats received intraperitoneal saline (EPO 0 U group) or EPO (60, 120, or 600 U) 30 min before exposure to 3% sevoflurane with 21% oxygen for 4 h. The rats only received 21% oxygen without EPO and sevoflurane as the sham group. The Morris water maze task was performed time-dependently among the groups, 3 weeks post-anesthesia exposure. Escape latency and % quadrant in the EPO 600 U group were significantly reduced and increased, respectively, compared with those in the EPO 0 U group 6 weeks post-exposure. In addition, freezing time in response to the conditioned stimulus and the number of NeuN-positive cells in the hippocampal CA1 region were significantly increased in the EPO 120 and 600 U groups than in the EPO 0 U group 6 weeks after exposure. Moreover, the statistical parameter mapping of positive cell density was increased in the EPO-treated rats. These results support the observations that pretreatment with EPO reduced long-term cognitive deficits and neuronal degeneration in cortex and hippocampus induced by sevoflurane exposure with low oxygen concentration in neonatal rats.

The additional oxygen as a carrier gas during long-duration sevoflurane exposure ameliorate the neuronal apoptosis and improve the long-term cognitive function in neonatal rats.

The effects of the oxygen concentration as a carrier gas and long duration anesthesia exposure on neuroapoptosis and cognitive impairments in the developing brain are not fully understood. This study shows that long-duration sevoflurane anesthesia with or without additional oxygen induces neuroapoptosis and long-term cognitive dysfunction in neonatal rats. Seven-day-old rats were exposed to sevoflurane anesthesia for 2, 4, and 6 h with 21% or 30% oxygen. The control group received 21% oxygen alone for 6 h. Post-anesthesia blood gas analysis resulted in hypoxia and hypercapnia. Moreover, PO2 and base excess in the 30% oxygen group were significantly higher than the 21% oxygen group. The numbers of caspase-3-positive cells in both cortical layer 3 and the CA1 region in the hippocampus in the 6 h anesthesia exposure group with 21% oxygen were increased compared with the 6 h anesthesia exposure with 30% oxygen and control groups. Cognitive function was assessed in an additional group of rats, and the brains were stained for NeuN 6 weeks post-anesthesia. Although the Morris water maze task was acquired equally by all rats 3 weeks post-anesthesia, the escape latency was significantly longer in the 6 h sevoflurane with 21% oxygen group than the 6 h with 30% oxygen groups 6 weeks post-exposure. No difference was found with regard to freezing time among the groups in the fear conditioning test. The number of NeuN-positive cells in the CA1 region of the hippocampus in the control group was increased compared with the other groups. These findings indicate that long-duration sevoflurane exposure with 30% oxygen as a carrier gas would ameliorate neuronal apoptosis and improve long-term cognitive function in neonatal rats.

The suppressive effects of landiolol administration on the occurrence of postoperative atrial fibrillation and tachycardia, and plasma IL-6 elevation in patients undergoing esophageal surgery: A randomized controlled clinical trial.

STUDY OBJECTIVE: To determine whether perioperative landiolol administration suppresses postoperative atrial fibrillation (AF) and the plasma cytokines elevation in patients undergoing esophageal cancer surgery. DESIGN: A prospective, randomized controlled trial. SETTING: Akita University Hospital, Akita, Japan, from April 2012 to January 2015. PATIENTS: Forty American Society of Anesthesiologists grade I-II patients undergoing elective esophagectomy. INTERVENTIONS: Patients were randomly divided into two groups, landiolol group (landiolol: 5µg/kg/min) and control group (the same volume of covered saline). Landiolol or saline was infused continuously from the induction of anesthesia until next morning. MEASUREMENTS: We examined the new onset of AF and sinus tachycardia, and measured plasma concentrations of cytokines (IL-1ß, IL-6, IL-8, IL-10, and TNF-α) just before surgery, at the end of surgery, the next day, and 2days after surgery. Data (mean±SD) were analyzed using two-way ANOVA followed by the Bonferroni"s test for post hoc comparison; a P<0.05 was considered statistically significant. MAIN RESULTS: Demographic data were similar between the landiolol and the control groups. The incidence of AF was significantly lower in the landiolol group (1/19=5.3%) compared with the control group (7/20=35%) as well as sinus tachycardia (landiolol group, 0/19=0% vs. control group, 5/20=25%). Plasma IL-6 level at the end of surgery was significantly lower in the landiolol group compared with the control group, but the other plasma cytokines levels were similar between the two groups during the entire study period. CONCLUSIONS: Perioperative landiolol administration suppressed the incidence of new-onset of AF as well as sinus tachycardia, and the plasma IL-6 elevation in patients undergoing esophageal cancer surgery.

Evaluation of postoperative pregabalin for attenuation of postoperative shoulder pain after thoracotomy in patients with lung cancer, a preliminary result.

OBJECTIVE: Thirty-one to 97% of patients who undergo thoracotomy for lung cancer experience ipsilateral shoulder pain, marring the otherwise excellent relief provided by thoracic epidural analgesia. The aim of this study was to test whether the addition of pregabalin to the treatment for shoulder pain would provide a significant benefit. METHODS: Twenty patients undergoing thoracic surgery for lung cancer were enrolled in the control group between May 2012 and December 2012, and 20 patients were enrolled in the pregabalin group between January 2013 and July 2013, consecutively. All patients had standard pre- and intraoperative care. Patients received pregabalin 150 mg po POD 1 and then non-steroidal anti-inflammatory drugs (NSAIDs) po 2 h later (pregabalin group), or they received only NSAIDs po at exactly the same times (control group). Pain severity was then measured using a 100-mm visual analog scale (VAS) scoring system. RESULTS: The VAS scores indicated that patients in the pregabalin group had significantly less shoulder pain on postoperative day (POD) 2 than those in the control group (control: 27.9 ± 28.1 vs. pregabalin: 11.8 ± 14.4; p = 0.030). No differences in pain were observed between the two groups on other POD. There were significant differences on only POD 2 in the patients with shoulder pain immediately after surgery. Three of the pregabalin-treated patients showed mild somnolence. CONCLUSIONS: Postoperative administration of pregabalin provided significant relief of postoperative shoulder pain during earlier POD after thoracic surgery for lung cancer when received multimodal analgesia in combination with NSAIDs.

Dexmedetomidine improves the histological and neurological outcomes 48 h after transient spinal ischemia in rats.

Dexmedetomidine, an α2 adrenoceptor agonist, provides neuroprotection against various cerebral ischemia models through its anti-apoptotic effects. Dexmedetomidine also improves paraplegia induced by intrathecal morphine after short-term spinal ischemia. However, there are no reports regarding dexmedetomidine׳s ability to provide neuroprotection solely against transient spinal ischemia. We investigated whether dexmedetomidine would provide spinal protection following transient spinal ischemia in rats. Adult male Sprague Dawley rats were randomly assigned to one of the following five groups: (1) intravenous infusion of 0.9% NaCl at the rate of 0.5 mL/h (control), (2) dexmedetomidine 0.1 µg/kg/h, (3) dexmedetomidine 1 µg/kg/h, (4) dexmedetomidine 10 µg/kg/h, or (5) intravenous infusion of 0.9% NaCl without spinal ischemia (sham). The rats received saline solution or dexmedetomidine from 30 min before spinal cord ischemia to 48 h after ischemia. Spinal cord ischemia was induced by intraaortic balloon occlusion combined with proximal arterial hypotension for 10 min. Ischemic injury was assessed by neurological deficit scores and the number of viable motor nerve cells in the anterior spinal cord at 48 h after reperfusion. Neurological deficit scores in the dexmedetomidine-treated rats were significantly lower than the scores in the control group at 24 and 48 h after ischemia (P<0.05). The number of viable motor nerve cells was significantly larger in the dexmedetomidine-treated rats than in the control rats (P<0.05), but the number of motor nerve cells in the dexmedetomidine group was significantly smaller than the sham group. Our results indicate that the continuous administration of dexmedetomidine improves neurological and histological outcomes 48 h after transient spinal ischemia in rats.

Combination of oral clonidine and intravenous low-dose ketamine reduces the consumption of postoperative patient-controlled analgesia morphine after spine surgery.

OBJECTIVE: Because ketamine, clonidine, and morphine modulate nociceptive pain, coadministration of these drugs would augment the activity of postoperative analgesic drugs. The purpose of this study was to evaluate the effects of coadministration of ketamine and clonidine on postoperative morphine consumption in patients after spine surgery. METHODS: The patients undergoing spine surgery were allocated randomly to one of the four study groups, which are as follows: group M (n = 12), intravenously (IV) administered patient-controlled analgesia (PCA) morphine alone; group MK (n = 12), IV-PCA morphine plus intra- and postoperative ketamine; group MC (n = 13), IV-PCA morphine plus oral clonidine premedication; group MCK (n = 12), IV-PCA morphine plus intra- and postoperative ketamine and clonidine premedication. The patients in the MC and MCK groups received 4 µg/kg clonidine orally, whereas those in the MK and MCK groups received IV bolus of ketamine (10 mg) at a rate of 2 mg/kg/hour during anesthesia. Patients were arranged to use IV-PCA mode for administration of drugs, which was programmed to deliver a bolus dose of 2-mg morphine (groups M and MC), or boluses of 2-mg morphine and 2-mg ketamine (groups MK and MCK). Scores of visual analog scale (VAS) for pain, morphine requirement, vital signs, nausea, sedation, and other side effects were followed up to 60 hours after surgery. RESULTS: Although there were significant differences in VAS pain scores at rest 24-48 hours after the surgery, the VAS pain score at movement was similar among the groups. The number of PCA request and cumulative morphine requirement were significantly lower in the MCK group than in the M group. CONCLUSION: This study results show that the administration of perioperative low-dose ketamine combined with clonidine premedication could reduce the consumption of postoperative PCA morphine following spine surgery.

[Comparative performance of Airway Scope, Trueview EVO2, and Fibertech video laryngoscope used by inexperienced medical students in a simulated manikin with normal and difficult airways].

BACKGROUND: Many kinds of video-typed laryngoscopes are widely used for tracheal intubation in many clinical situations. The present study was performed to compare the ease in the use of the Airway Scope (AWS), Trueview EVO2 (TVE), and Fibertech Video Laryngoscope (FVL). METHODS: Twenty-seven inexperienced medical students used AWS, TVE and FVL in a simulated manikin with normal and difficult airways. We measured the time of tracheal intubation and start of ventilation, performance levels of tracheal intubations, dental clicks, difficulty of tracheal intubation, and ease of tracheal intubation, and performer's liking. RESULTS: The use of TVE was associated with the longest time to tracheal intubation with dental click and ventilation than the other devices in normal and difficult airways, whereas the performance levels of tracheal intubation were similar among the three devices. VAS score (easy to use) and the degree of liking were lower in AWS than TVE. CONCLUSIONS: This study suggests that inexperienced medical students would perform tracheal intubation using AWS in a short time without dental click in a simulated manikin.

Neuroprotective effects of selective ß-1 adrenoceptor antagonists, landiolol and esmolol, on transient forebrain ischemia in rats; a dose-response study.

Although selective beta-1 adrenoceptor antagonists are known to provide neuroprotective effects after brain ischemia, dose-response relationships of their neuroprotective effects have not been examined. The present study was conducted to evaluate whether the degree of brain protection against transient forebrain ischemia would be influenced by different doses of selective beta-1 adrenoceptor antagonists, esmolol and landiolol, in rats. Adult male S.D. rats received intravenous infusion of saline 0.5 ml/h, esmolol 20, 200, 2,000 µg/kg/min, or landiolol 5, 50, 500 µg/kg/min. Infusion was initiated 30 min prior to ischemia and continued for 24h. Ten-minute forebrain ischemia was induced by hemorrhagic hypotension and occlusion of the bilateral carotid arteries. Neurological and histological examinations were performed. Neurological deficit scores at 1, 4 and 7 days were lower, and the number of intact neurons in CA1 hippocampal region was larger in the rats treated with esmolol and landiolol after ischemia, compared with saline-treated rats (P<0.05), whereas no difference was found among different doses of esmolol and landiolol. These results suggested that selective beta-1 adrenoceptor antagonists improved neurological and histological outcomes following forebrain ischemia in rats, irrespective of their doses.

Neuroprotective effects and suppression of ischemia-induced glutamate elevation by ß1-adrenoreceptor antagonists administered before transient focal ischemia in rats.

BACKGROUND: ß-Adrenoreceptor antagonists provide neuroprotective effects after focal cerebral ischemia in experimental settings. This study was conducted to compare the neuroprotective effects of low-dose and high-dose of selective ß1-adrenoreceptor antagonists in rats after focal cerebral ischemia. We also investigated whether glutamate and norepinephrine contribute to neuroprotection of the ß-adrenoreceptor antagonists. METHODS: Sprague-Dawley rats were subjected to 120 minutes middle cerebral artery occlusion. The rats received intravenous infusion of saline 0.5 mL/h, esmolol 200, esmolol 2000, landiolol 50, or landiolol 500 µg/kg/min. Infusion of all the drugs were started 30 minutes before ischemia and continued for 24 hours. Neurological deficit scores were evaluated at 1, 4, and 7 days, whereas the brains were removed and stained at 7 days after ischemia. In the esmolol 200, and landiolol 50 µg/kg/min groups of additional rats, glutamate and norepinephrine concentrations in the striatum were measured separately by microdialysis during ischemia (glutamate, 120 min; norepinephrine, 110 min) and reperfusion (40 min). RESULTS: Neurological deficit scores were smaller in rats treated with esmolol or landiolol than in saline-treated rats at 1, 4, and 7 days. The cortical and striatal infarct volumes were smaller in rats receiving ß-adrenoreceptor antagonists than in the saline-treated rats. There were no significant differences in neurological score or infarct volume between the groups receiving the different doses of ß1-adrenoreceptor antagonists. The area under the curve of glutamate in the esmolol-treated or landiolol-treated rats was significantly smaller than that in the saline-treated rats, whereas no significant differences were noted in the norepinephrine concentration among the groups. CONCLUSIONS: This study indicates that the improvement in neurological and histologic outcomes by selective ß1-adrenoreceptor antagonists after transient focal cerebral ischemia is partly attributed to attenuation of glutamate release.

[Comparison of levobupivacaine and ropivacaine for postoperative epidural analgesia].

BACKGROUND: Levobupivacaine is a long acting local anesthetic with less cardiovascular toxicity. Recently we can use levobupivacaine for postoperative analgesia. We retrospectively compared levobupivacaine with ropivacaine for the postoperative epidural analgesia in patients undergoing gynecological abdominal surgery. METHODS: The patients who had received epidural and general anesthesia from October 2008 to April 2009 were allocated into two groups. Analgesia intensity, the time to receive the first analgesic, and the number of times to use the additional analgesics were observed for three postoperative days. RESULTS: There was no difference in demographic data between the levobupivacaine and ropivacaine groups. In the levobupivacaine group (n=23) the patient received epidural 0.24% levobupivacaine and fentanyl, while the patients in the ropivacaine group (n=43) epidural 0.19% ropivacaine and fentanyl, at the rate of 3.5 ml x hr(-1). The volume of epidural fentanyl was similar between the groups. The time from the end of surgery to receive the first analgesic was longer in the levobupivacaine group than in the ropivacaine group. The number of the patients who did not require additional analgesia was greater in the levobupivacaine group than in the ropivacaine group. The patients who received metocropramide to treat nausea were fewer in the levobupivacaine group, compared with the ropivacaine group. CONCLUSIONS: These results suggest that the use of epidural 0.24% levobupivacaine in the patients undergoing the gynecological surgery is superior to the use of 0.19% ropivacaine.

Post-treatment with selective ß1 adrenoceptor antagonists provides neuroprotection against transient focal ischemia in rats.

We have reported the neuroprotective effects of pre-treatment with beta-adrenoceptor antagonists on the cerebral infarction at 1 and 7 days after focal ischemia in rats. However, the protective effect of post-treatment with beta-adrenoceptor antagonists has not been investigated yet. This study was conducted to evaluate the post-treatment effects of selective beta(1)-adrenoceptor antagonists in the rat focal cerebral ischemia. Halothane anesthetized, normothermic adult male Sprague-Dawley rats were subjected to 2h of middle cerebral artery occlusion (MCAO) using the intraluminal suture technique confirmed by laser Doppler flowmetry. Rats received intravenous infusion of saline 0.5 mL/h, esmolol 200 microg/kg/min, or landiolol 50 microg/kg/min (n=8 in each group). Infusion was initiated 30 min after MCAO and continued for 24h. Rats were allowed to survive for 7 days, and the neurological deficit score was evaluated at 1, 4 and 7 days after reperfusion. The brains were removed and stained with triphenyltetrazolium chloride at 7 days after reperfusion. Neurological deficit scores were lower in the rats treated with esmolol or landiolol, compared with saline-treated rats at 1 day as well as 4 and 7 days. The infarct volumes of cortical and striatum were less in the rats receiving beta-adrenoceptor antagonists than in saline-treated rats (P<0.05). The current study indicates that administration of selective beta1-adrenoceptor antagonists after the onset of ischemia also improved neurological and histological outcomes following transient focal cerebral ischemia in rats.

Esmolol and landiolol, selective beta1-adrenoreceptor antagonists, provide neuroprotection against spinal cord ischemia and reperfusion in rats.

BACKGROUND: Paraplegia is a devastating and unpredictable complication occasionally resulting from surgery of the thoracic and thoracoabdominal aorta. Because ultrashort-acting selective beta(1)-adrenoreceptor antagonists provide neuroprotective effects after brain ischemia, we hypothesized that they would also ameliorate spinal cord injury after transient ischemia and reperfusion in rats. METHODS: Male Sprague-Dawley rats were randomly assigned to one of the following 4 groups: saline (received IV infusion of 0.9% saline at a rate of 0.5 mL/h, n = 8), esmolol (esmolol 200 microg/kg/min, n = 8), landiolol (landiolol 50 microg/kg/min), or sham surgical (n = 6). Infusion of saline or drugs was initiated 30 minutes before spinal cord ischemia and continued for the subsequent 24-hour reperfusion. Spinal cord ischemia was induced by intraaortic balloon occlusion combined with proximal arterial hypotension for 10 minutes. The spinal cord was then reperfused for 24 hours. Ischemic injury was assessed in terms of the motor deficit index score of the hindlimb and the number of viable motor nerve cells in the anterior spinal cord at 24 hours after reperfusion. RESULTS: The motor deficit index scores were significantly lower in the esmolol and landiolol groups compared with the saline group (P < 0.05). Histopathologic evaluation of the spinal cord showed less damage in the esmolol and landiolol groups than in the saline group (P < 0.05). CONCLUSIONS: These data show that ultrashort-acting selective beta(1)-adrenoreceptor antagonists can reduce neurological injury in a rat model of spinal cord ischemia-reperfusion.

Epoxyeicosanoid signaling in CNS function and disease.

Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites of cytochrome P450 epoxygenase enzymes recognized as key players in vascular function and disease, primarily attributed to their potent vasodilator, anti-inflammatory and pro-angiogenic effects. Although EETs' actions in the central nervous system (CNS) appear to parallel those in peripheral tissue, accumulating evidence suggests that epoxyeicosanoid signaling plays different roles in neural tissue compared to peripheral tissue; roles that reflect distinct CNS functions, cellular makeup and intercellular relationships. This is exhibited at many levels including the expression of EETs-synthetic and -metabolic enzymes in central neurons and glial cells, EETs' role in neuro-glio-vascular coupling during cortical functional activation, the capacity for interaction between epoxyeicosanoid and neuroactive endocannabinoid signaling pathways, and the regulation of neurohormone and neuropeptide release by endogenous EETs. The ability of several CNS cell types to produce and respond to EETs suggests that epoxyeicosanoid signaling is a key integrator of cell-cell communication in the CNS, coordinating cellular responses across different cell types. Under pathophysiological conditions, such as cerebral ischemia, EETs protect neurons, astroglia and vascular endothelium, thus preserving the integrity of cellular networks unique to and essential for proper CNS function. Recognition of EETs' intimate involvement in CNS function in addition to their multi-cellular protective profile has inspired the development of therapeutic strategies against CNS diseases such as cerebral ischemia, tumors, and neural pain and inflammation that are based on targeting the cellular actions of EETs or their biosynthetic and metabolizing enzymes. Based upon the emerging importance of epoxyeicosanoids in cellular function and disease unique to neural systems, we propose that the actions of "neuroactive EETs" are best considered separately, and not in aggregate with all other peripheral EETs functions.

[Emergent percutaneous coronary intervention therapy after renal transplantation].

A 54-year-old man was scheduled for renal transplantation. There was no cardiac event except ST-segment depression during surgery. One hour after surgery, the patient complained of a chest pain, and received immediate percutaneous coronary intervention therapy, which was successfully performed. We need close monitoring after surgery even if the patients have no cardiac complication before surgery.