Albumin protects the ultrastructure of the endothelial glycocalyx of coronary arteries in myocardial ischemia-reperfusion injury in vivo.

Myocardial ischemia-reperfusion (I/R) injury induces endothelial glycocalyx (GCX) degradation. Several candidate GCX-protective factors including albumin have been identified, few have been demonstrated in in vivo studies and most albumins used to date have been heterologous. Albumin is a carrier protein for sphingosine 1-phosphate (S1P), which has protective effects on the cardiovascular system. However, changes inhibited by albumin in the endothelial GCX structure in I/R in vivo via the S1P receptor has not been reported. In this study, we aimed to determine whether albumin prevents the shedding of endothelial GCX in response to I/R in vivo. Rats were divided into four groups: control (CON), I/R, I/R with albumin preload (I/R + ALB), and I/R + ALB with S1P receptor agonist fingolimod (I/R + ALB + FIN). FIN acts as an initial agonist of S1P receptor 1 and downregulates the receptor in an inhibitory manner. The CON and I/R groups received saline and I/R + ALB and I/R + ALB + FIN groups received albumin solution before left anterior descending coronary artery ligation. Our study used rat albumin. Shedding of endothelial GCX was evaluated in the myocardium by electron microscopy, and the concentration of serum syndecan-1 was measured. Thus, albumin administration maintained the structure of endothelial GCX and prevented shedding of endothelial GCX via the S1P receptor in myocardial I/R, and FIN annihilated the protective effect of albumin against I/R injury.

Tmem45b is essential for inflammation- and tissue injury-induced mechanical pain hypersensitivity.

Persistent mechanical pain hypersensitivity associated with peripheral inflammation, surgery, trauma, and nerve injury impairs patients' quality of life and daily activity. However, the molecular mechanism and treatment are not yet fully understood. Herein, we show that chemical ablation of isolectin B4-binding (IB4+) afferents by IB4-saporin injection into sciatic nerves completely and selectively inhibited inflammation- and tissue injury-induced mechanical pain hypersensitivity while thermal and mechanical pain hypersensitivities were normal following nerve injury. To determine the molecular mechanism involving the specific types of mechanical pain hypersensitivity, we compared gene expression profiles between IB4+ neuron-ablated and control dorsal root ganglion (DRG) neurons. We identified Tmem45b as one of 12 candidate genes that were specific to somatosensory ganglia and down-regulated by IB4+ neuronal ablation. Indeed, Tmem45b was expressed predominantly in IB4+ DRG neurons, where it was selectively localized in the trans Golgi apparatus of DRG neurons but not detectable in the peripheral and central branches of DRG axons. Tmem45b expression was barely detected in the spinal cord and brain. Although Tmem45b-knockout mice showed normal responses to noxious heat and noxious mechanical stimuli under normal conditions, mechanical pain hypersensitivity was selectively impaired after inflammation and tissue incision, reproducing the pain phenotype of IB4+ sensory neuron-ablated mice. Furthermore, acute knockdown by intrathecal injection of Tmem45b small interfering RNA, either before or after inflammation induction, successfully reduced mechanical pain hypersensitivity. Thus, our study demonstrates that Tmem45b is essential for inflammation- and tissue injury-induced mechanical pain hypersensitivity and highlights Tmem45b as a therapeutic target for future treatment.

A Case of Decreased Amplitude in Motor Evoked Potentials Under Remimazolam Anesthesia.

Remimazolam is a newly developed benzodiazepine derivative. Although one case report on the use of remimazolam for motor evoked potential (MEP) monitoring has been reported, there has been no report of changes in the MEP response under remimazolam anesthesia, which is associated with impairment of the corticospinal motor track. This is a case of a 54-year-old woman who was diagnosed with an extradural extramedullary tumor. The patient reported being allergic to chicken eggs. We used remimazolam instead of propofol for anesthesia management. During tumor resection, the amplitudes of MEP responses at the left quadriceps femoris, left tibialis anterior, and left abductor hallucis muscle decreased. The surgery was scaled down and the tumor was removed in a reduced size. The patient had muscle weakness immediately after surgery but eventually recovered. In this case, we could detect changes in MEP response under remimazolam anesthesia, which suggested impairment of the motor tracts during surgery.

Usefulness and accuracy of a handheld ultrasound device for epidurssal landmark and depth assessment by anesthesiology residents.

PURPOSE: The aim of this study was to assess the usefulness and accuracy of a handheld ultrasound device (Accuro, Rivanna Medical, Charlottesville, VA, USA) for epidural landmark and depth assessment when epidural anesthesia is performed by residents. METHODS: Patients scheduled to receive epidural anesthesia were randomly assigned to the Accuro group (group A) or control group (group C). In group A, the depth to the epidural space and the appropriate place for epidural insertion according to Accuro was recorded. In group C, epidural anesthesia was performed using a conventional method. The following were recorded and compared between the groups: time from puncture of the Tuohy needle to loss of resistance, number of Tuohy needle redirects, and epidural-related complications. In group A, depth to the epidural space estimated by Accuro (Accuro Depth) and the actual depth measured with a marker on the needle (Needle Depth) were recorded and compared. RESULTS: Sixty patients were enrolled during the study period. There was no significant difference between the groups regarding the median or range of time required to locate the epidural space. The number of Tuohy needle redirects was 0 (0-3) in group A and 1.5 (0-7) in group C (P = 0.012). Accuro Depth was less than Needle Depth [mean difference, 0.85 cm (95% CI-1.10 to - 0.62), SD = 0.62]. CONCLUSIONS: Although there was no significant difference in time from Tuohy needle puncture to loss of resistance, Accuro reduced the number of Tuohy needle redirects and accurately indicated the depth to the epidural space. Accuro may be useful for identifying the needle insertion point and estimating depth to the epidural space when residents perform epidural anesthesia.

Validation of the relationship between coagulopathy and localization of hydroxyethyl starch on the vascular endothelium in a rat hemodilution model.

Various anticoagulant properties have been associated with hydroxyethyl starch (HES). However, the mechanism remains unclear and it has not been fully considered whether these properties are beyond the dilutional effect itself. The aim of this study was to reproduce the coagulopathy induced by HES and to test the hypothesis that the coagulopathy is caused by endothelial or glycocalyx damage due to localization of HES on the endothelium, which is caused by the high shear viscosity of dilutional blood. Using a rat model, we compared blood coagulability measured by Sonoclot, levels of endothelial and glycocalyx damage markers and coagulation factors, and blood shear viscosity when hemodilution was performed with physiological saline (PS), 6% HES 130/0.4 in PS, and 10% HES 200/0.5 in PS. We also evaluated the localization rates of fluorescently labeled HES on endothelium in the isolated aorta. HES decreased the fibrin gel formation rate more than did PS. HES was shown to cover the endothelium, possibly due to its high shear viscosity, and this mechanism potentially acted to protect, rather than damage, the endothelium and glycocalyx. However, this covering effect may be the cause of coagulopathy due to inhibition of von Willebrand factor secretion from the endothelium.

Successful removal of a central venous catheter misplaced in the right subclavian artery using an intravascular stent: a case report.

BACKGROUND: Cannulation of a central venous catheter is sometimes associated with serious complications. When arterial cannulation occurs, attention must be given to removal of a catheter. CASE PRESENTATION: A 62-year-old man was planned for emergency thoracic endovascular aortic repair. After the induction of anesthesia, a central venous catheter was unintentionally inserted into the right subclavian artery. We planned to remove the catheter. Since we considered that surgical repair would be highly invasive for the patient, we decided to remove it using a percutaneous intravascular stent. A stent was inserted through the right axillary artery. The stent was expanded immediately after the catheter was removed. Post-procedural angiography revealed no leakage from the catheter insertion site and no occlusion of the right subclavian and vertebral arteries. There were no obvious hematoma or thrombotic complications. CONCLUSIONS: A catheter that has been misplaced into the right subclavian artery was safely removed using an intravascular stent.

Generic rocuronium reduces withdrawal movements compared to original rocuronium under target-controlled infusion induction with propofol.

PURPOSE: Rocuronium-induced injection pain often causes withdrawal movements leading to accidental disruption of indwelling needles. Generic rocuronium (Maruishi Pharmaceutical Co., Ltd, Osaka, Japan) with a novel solution has been reported to reduce the injection pain compared to original rocuronium [Esmeron® (Eslax®), MSD Co. Ltd, Tokyo, Japan], however, no reports have compared the injection pain under sedation with propofol, the most frequently used general anesthetic. This study was carried out to compare the injection pain caused by generic rocuronium and that caused by original rocuronium in patients anesthetized by propofol with a target-controlled infusion system. METHODS: Forty patients were randomly assigned to two groups in this single-center, prospective, randomized, double-blind study. One group was administered generic rocuronium after sedation with propofol with a target-controlled infusion system. The other group was administered original rocuronium after anesthesia with propofol. Patient's withdrawal movements were assessed with the scale. The primary outcome was the total incidence of movement after administration of rocuronium. Secondary outcome was the incidence of moderate or severe movement after administration of rocuronium. RESULTS: The total incidence of movement after administration of generic rocuronium (11%) was significantly lower than that after the administration of original rocuronium (79%) (p < 0.01). The incidence of moderate or severe movement after administration of generic rocuronium (0%) was significantly lower than that after the administration of original rocuronium (53%) (p < 0.01). CONCLUSION: Generic rocuronium was considered more suitable than the original rocuronium for induction of anesthesia by propofol performed with a target-controlled infusion system.

Head Rotation Reduces Oropharyngeal Leak Pressure of the i-gel and LMA® Supreme™ in Paralyzed, Anesthetized Patients: A Randomized Trial.

BACKGROUND: Second-generation supraglottic airway (SGA) devices are useful for airway management during positive pressure ventilation in general anesthesia and emergency medicine. In some clinical settings, such as the anesthetic management of awake craniotomy, SGAs are used in the head-rotated position, which is required for exposure of the surgical field, although this position sometimes worsens the efficiency of mechanical ventilation with SGAs. In this study, we investigated and compared the influence of head rotation on oropharyngeal leak pressures (OPLP) of the i-gel and LMA® Supreme™, which are second-generation SGA devices. METHODS: Patients who underwent elective surgery under general anesthesia were enrolled in this study and randomly divided into i-gel or LMA Supreme groups. After induction of anesthesia with muscle relaxation, the i-gel or LMA Supreme was inserted according to computerized randomization. The primary outcome was the OPLP at 0°, 30°, and 60° head rotation. The secondary outcomes were the maximum airway pressure and expiratory tidal volume when patients were mechanically ventilated using a volume-controlled ventilation mode with a tidal volume of 10 mL/kg (ideal body weight), ventilation score, and fiber-optic views of vocal cords. RESULTS: Thirty-four and 36 participants were included in the i-gel and LMA Supreme groups, respectively. The OPLPs of the i-gel and LMA Supreme significantly decreased as the head rotation angle increased (mean difference [95% confidence interval], P value: i-gel; 0° vs 30°: 3.5 [2.2-4.8], P < .001; 30° vs 60°: 2.0 [0.6-3.5], P = .002; 0° vs 60°: 5.5 [3.3-7.8], P < .001, LMA Supreme; 0° vs 30°: 4.1 [2.6-5.5], P < .001; 30° vs 60°: 2.4 [1.1-3.7], P < .001; 0° vs 60°: 6.5 [5.1-8.0], P < .001). There were statistically significant differences in expiratory tidal volume and ventilation score between 0° and 60° in the i-gel group and in ventilation score between 30° and 60° in the LMA Supreme group. There was no statistically significant difference between the 2 devices in all outcome measures. The incidences of adverse events, such as hoarseness or sore throat, were not significantly different between i-gel and LMA Supreme. CONCLUSIONS: Head rotation to 30° and 60° reduces OPLP with both i-gel and LMA Supreme. There is no difference in OPLP between i-gel and LMA Supreme in the 3 head rotation positions.

Efficacy of Automatic Retention Pressure of a Double-Lumen Tube Cuff: An Artificial Intubation Model.

BACKGROUND: The movement of a double-lumen endotracheal tube (DLT) out of its appropriate position during thoracic surgery can result in the loss of one-lung ventilation (OLV), especially during pulmonary resection and node dissection. Our study aimed to validate the efficacy of automatic retention pressure control of the DLT bronchial cuff in maintaining OLV in an artificial intubation model. MATERIALS AND METHODS: A 35-Fr left-sided DLT was intubated to the left main bronchus in an intubation simulator and connected to an anesthesia machine. The inspiratory volume, respiratory rate, and inspiratory-expiratory ratio were set at 500 mL, 12 times/min, and 1:2, respectively. A 1-kg right main bronchial traction in the lateral right was provided after OLV was established. SmartCuff (Smiths Medical, Minneapolis, Minnesota, USA) was used to maintain cuff pressure. The efficacy of retention pressure with SmartCuff (Group S) and without SmartCuff (Group WS) was compared. The primary outcome was the rate of tidal volume (TV) reduction following bronchial traction in the two groups. RESULTS: The TVs were 289.8 ± 28.9 mL and 242.8 ± 31.9 mL in Group S and Group WS, respectively (P = 0.003). The rate of TV reduction after bronchial traction was significantly lower in Group S (29 ± 5%) than in Group WS (43 ± 6%) (P < 0.001). CONCLUSIONS: Automatic retention pressure control of the DLT bronchial cuff improves the rate of TV reduction during right main bronchial traction in an artificial intubation model. Continuous retention cuff pressure may be useful in maintaining OLV during thoracic surgery.

Preoperative Prediction of Communication Difficulties during Awake Craniotomy in Glioma Patients: A Retrospective Evaluation of 136 Cases at a Single Institution.

Awake craniotomy has been widely performed in patients with glioma in eloquent areas to minimize postoperative brain dysfunction. However, neurological examination in awake craniotomy is sometimes problematic due to communication difficulties during the intraoperative awake period. We evaluated preoperative predictors of these difficulties in awake craniotomy for patients with glioma. In all, 136 patients with glioma who underwent awake craniotomy at our institution between January 2012 and January 2020 were retrospectively evaluated. Patients were divided into two groups (appropriately awake group and inappropriately awake group) depending on their state during the intraoperative awake period, and the relationship between communication difficulties in awake craniotomy and both clinical and radiological characteristics were assessed. The appropriately awake group included 110 patients, and the inappropriately awake group included 26 patients. Reasons for inclusion in the inappropriately awake group were insufficient wakefulness in 15 patients, restless state in 6, and intraoperative seizures in 5. In multivariate analysis, the likelihood of being inappropriately awake was inversely correlated with preoperative seizures (odds ratio [OR], 0.23; 95% confidence interval [CI], 0.06-0.89; p = 0.033) and positively correlated with left-sided lesions (OR, 7.31; 95% CI, 1.54-34.62; p = 0.012). Both lack of preoperative seizures and left-sided lesions were identified as risk factors for intraoperative difficulties in awake craniotomy for patients with glioma. Understanding these risk factors may lead to more appropriate determination of eligibility for awake craniotomy.

Effects of anesthetic agents on contractions of the pregnant rat myometrium in vivo and in vitro.

BACKGROUND: Several anesthetic agents are used in cesarean sections for both regional and general anesthesia purposes. However, there are no data comparing the in vivo effects of propofol, sevoflurane, and dexmedetomidine on the contraction of the myometrium in pregnant rats. The aim of this study was to investigate the effect of these anesthetic agents on myometrial contraction and elucidate the underlying mechanisms. METHODS: Contraction force and frequency changes in response to propofol, dexmedetomidine, or sevoflurane were evaluated in vivo and in vitro. To test the effect of arachidonic acid on myometrial contraction enhanced by dexmedetomidine, changes in myometrial contraction with dexmedetomidine after administration of indomethacin were evaluated. The amount of phosphorylated myosin phosphatase target subunit 1 (MYPT1) in the membrane fraction was expressed as a percentage of the total fraction by Western blot analysis. RESULTS: This study demonstrated that dexmedetomidine enhances oxytocin-induced contraction in the myometrium of pregnant rats, whereas propofol and sevoflurane attenuate these contractions. The dexmedetomidine-induced enhancement of myometrial contraction force was abolished by the administration of indomethacin. Propofol did not affect oxytocin-induced MYPT1 phosphorylation, whereas sevoflurane attenuated oxytocin-induced MYPT1 phosphorylation. CONCLUSIONS: Inhibition of myofilament calcium sensitivity may underlie the inhibition of myometrial contraction induced by sevoflurane. Arachidonic acid may play an important role in the enhancement of myometrial contraction induced by dexmedetomidine by increasing myofilament calcium sensitivity. Dexmedetomidine may be used as a sedative agent to promote uterine muscle contraction and suppress bleeding after fetal delivery.

Remote ischemic preconditioning reduces myocardial ischemia-reperfusion injury through unacylated ghrelin-induced activation of the JAK/STAT pathway.

Remote ischemic preconditioning (RIPC) offers cardioprotection against myocardial ischemia-reperfusion injury. The humoral factors involved in RIPC that are released from parasympathetically innervated organs have not been identified. Previous studies showed that ghrelin, a hormone released from the stomach, is associated with cardioprotection. However, it is unknown whether or not ghrelin is involved in the mechanism of RIPC. This study aimed to determine whether ghrelin serves as one of the humoral factors in RIPC. RIPC group rats were subjected to three cycles of ischemia and reperfusion for 5 min in two limbs before left anterior descending (LAD) coronary artery ligation. Unacylated ghrelin (UAG) group rats were given 0.5 mcg/kg UAG intravenously 30 min before LAD ligation. Plasma levels of UAG in all groups were measured before and after RIPC procedures and UAG administration. Additionally, JAK2/STAT3 pathway inhibitor (AG490) was injected in RIPC and UAG groups to investigate abolishment of the cardioprotection of RIPC and UAG. Plasma levels of UAG, infarct size and phosphorylation of STAT3 were compared in all groups. Infarct size was significantly reduced in RIPC and UAG groups, compared to the other groups. Plasma levels of UAG in RIPC and UAG groups were significantly increased after RIPC and UAG administration, respectively. The cardioprotective effects of RIPC and UAG were accompanied by an increase in phosphorylation of STAT3 and abolished by AG490. This study indicated that RIPC reduces myocardial ischemia and reperfusion injury through UAG-induced activation of JAK/STAT pathway. UAG may be one of the humoral factors involved in the cardioprotective effects of RIPC.

Video Glasses Reduce Preoperative Anxiety Compared With Portable Multimedia Player in Children: A Randomized Controlled Trial.

PURPOSE: Preoperative anxiety in children is challenging for anesthesia providers and nurses. The use of video glasses (VG), an immersive head mount display, helps conceal the unfamiliar operating room environment from the patient's visual field. The aim of this study was to determine the anxiolytic effect of VG compared with that of a portable multimedia player (PMP) during the preoperative period in children. DESIGN: Prospective randomized trial. METHODS: Participants were randomized into VG or PMP groups. Patients watched their favorite animation videos using the allocated device from the time of entering the preanesthetic holding area to the end of anesthetic induction. We evaluated modified Yale Preoperative Anxiety Scale scores during anesthetic induction. FINDINGS: The modified Yale Preoperative Anxiety Scale score in the VG group was significantly lower than that in the PMP group (P = .001). CONCLUSIONS: In children, the anxiolytic effect of VG during the preoperative period is larger than that of PMP.

Lipid emulsion, but not propofol, induces skeletal muscle damage and lipid peroxidation.

PURPOSE: Prolonged propofol infusion induces skeletal muscle damage. However, it is well known that the lipid emulsion that is the solvent of propofol causes various types of tissue damage via lipid peroxidation, and that propofol, conversely, has an anti-lipid peroxidative effect. The purpose of this study was to determine whether propofol or the lipid emulsion is the cause of muscle damage following prolonged administration. METHODS: Rats were divided into four groups: NI group (no intervention), Cath group (venous catheter insertion only), Prop group (1% propofol (Maruishi) intravenous infusion at 10 mg/kg/h), and Lipid group (10% Lipofundin® intravenous infusion at 100 mg/kg/h) (n = 10, each group). 1% Propofol (Maruishi) or Lipofundin was infused at 1 mL/kg/h for 72 h. The solvent of 1% propofol (Maruishi) is a 10% lipid emulsion. Lipofundin consists of 50% long-chain triacylglycerols and 50% medium-chain triacylglycerols, similar to the propofol solvent. Plasma concentrations of creatine kinase and myoglobin, superoxide production level, and 4-hydroxynonenal and malondialdehyde expression in the gastrocnemius muscle were evaluated 72 h after the interventions. RESULTS: Plasma concentrations of creatine kinase and myoglobin in the Lipid group were significantly higher than those in the other three groups. The superoxide production level, and 4-hydroxynonenal and malondialdehyde expression in the Lipid group were also significantly higher than in the other three groups. CONCLUSION: Lipofundin induces skeletal muscle damage via lipid peroxidation, and 1% propofol (Maruishi) conversely suppresses the muscle damage via antioxidant effects.

Sevoflurane Promotes Regeneration of the Endothelial Glycocalyx by Upregulating Sialyltransferase.

BACKGROUND: During ischemia-reperfusion injury, the endothelial glycocalyx is damaged by oxidative stress-induced release of hydrogen peroxide, leading to decreased endothelium-dependent vasodilation. The regenerative effects of sevoflurane on the endothelial glycocalyx and endothelium-dependent vasodilation in oxidative stress remain unclear. Sialic acid, which is a component of the glycocalyx, plays a key role in antioxidant activity and is catalyzed by the sialyltransferase, ST6Gal-I. We hypothesized that ST6Gal-I is involved in the sevoflurane-induced promotion of endothelial glycocalyx restoration and endothelium-dependent vasodilation after oxidative stress. MATERIALS AND METHODS: To assess vasodilation, isometric tension in the rat aorta was measured. Aortic rings were treated with 0.5 mM hydrogen peroxide pre-exposure or post exposure to sevoflurane, with or without an ST6Gal-I inhibitor. The rings were then used for glycocalyx imaging using fluorescein isothiocyanate-labeled lectin staining and for immunohistochemistry for ST6Gal-I. RESULTS: Vasodilation was significantly decreased by treatment with hydrogen peroxide compared to controls. Application of sevoflurane after treatment with hydrogen peroxide revived endothelium-dependent vasodilatation, whereas pretreatment with sevoflurane had no such effect. Sevoflurane after-treatment revived the intensity of fluorescence of the endothelial glycocalyx compared to the hydrogen peroxide group. However, pretreatment with sevoflurane had no such effect. Sevoflurane significantly upregulated the reduced expression of ST6Gal-I induced by hydrogen peroxide treatment. CONCLUSIONS: Sevoflurane exerts regenerative effects on endothelium-dependent vasodilation and the endothelial glycocalyx following oxidative stress in the rat aorta.

Epidural anesthesia combined with sedation with dexmedetomidine for appendectomy in a patient with amyotrophic lateral sclerosis: a case report.

BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) present increased risks for anesthesia-related complications. We present a case of epidural anesthesia combined with sedation with dexmedetomidine for open appendectomy in a patient with ALS who refused invasive mechanical ventilation. CASE PRESENTATION: A 50-year-old man with a 3-year history of ALS was scheduled to undergo open appendectomy due to repeated appendicitis. He refused to undergo invasive mechanical ventilation using an endotracheal tube. Hence, we decided to administer epidural anesthesia combined with sedation with dexmedetomidine for anesthesia during the surgical procedure. The patient underwent open appendectomy without complications and with no pain or discomfort during surgery. There were no neurological complications at the 3-month follow-up after surgery. CONCLUSIONS: Epidural anesthesia combined with sedation with dexmedetomidine may be effective for the anesthetic management of patients who would benefit from regional anesthesia.

Desflurane inhibits endothelium-dependent vasodilation more than sevoflurane with inhibition of endothelial nitric oxide synthase by different mechanisms.

The effects of desflurane on endothelium-dependent vasodilation remain uncertain, whereas sevoflurane is known to inhibit it. Endothelium-dependent vasodilation is mainly mediated by endothelial nitric oxide synthase. The effects of desflurane on endothelium-dependent vasodilation were compared with those of sevoflurane, and inhibition mechanisms, including phosphorylation of endothelial nitric oxide synthase and the calcium pathway, were evaluated for the two anesthetics. We hypothesized that desflurane would inhibit endothelium-dependent vasodilation in a concentration-dependent manner more than sevoflurane, with inhibition of a calcium pathway. Isolated rat aortic rings were randomly assigned to treatment with desflurane or sevoflurane for measurements of the vasodilation ratio. To determine NO production with desflurane and sevoflurane, an in vitro assay was performed with cultured bovine aortic endothelial cells. These cells were also used for measurement of intracellular calcium or Western blotting. For endothelium-dependent vasodilation, the ratio of vasodilation was more significantly inhibited by 11.4% desflurane than by 4.8% sevoflurane. Inhibition did not between 5.7% desflurane and 2.4% sevoflurane. No inhibitory effect of desflurane or sevoflurane was observed in endothelium-denuded aorta. Desflurane inhibited nitric oxide production caused by stimulation of bradykinin significantly more than sevoflurane. Desflurane had a greater suppressive effect on the bradykinin-induced increase in intracellular calcium concentration than did sevoflurane. Sevoflurane, but not desflurane, inhibited phosphorylation of the serine 1177 residue by bradykinin stimulation. Desflurane inhibited endothelium-dependent vasodilation more than sevoflurane through inhibition of a calcium pathway. Sevoflurane inhibited endothelium-dependent vasodilation by inhibition of phosphorylation of the serine 1177 residue of endothelial nitric oxide synthase.

Dexmedetomidine Maintains Its Direct Cardioprotective Effect Against Ischemia/Reperfusion Injury in Hypertensive Hypertrophied Myocardium.

BACKGROUND: Dexmedetomidine (DEX) has a direct cardioprotective effect against ischemia/reperfusion injury through endothelial nitric oxide synthase (eNOS) phosphorylation via α2-adrenoreceptor (α2-AR). By using spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat models, the cardioprotective effect of DEX in hypertrophied myocardium and the differential characteristics of cardiac α2-AR and the I1 imidazoline receptor (I1R) were examined. METHODS: Langendorff-perfused rat hearts underwent 40 minutes of global ischemia followed by 120 minutes of reperfusion in the presence or absence of DEX before ischemia. Infarct size was measured, and eNOS phosphorylation was assessed by Western blotting. The presence and expression of the receptors were assessed by immunohistochemistry, real-time reverse transcriptase polymerase chain reaction, and Western blotting. RESULTS: In WKY, DEX significantly decreased infarct size and increased phosphorylated-eNOS/eNOS. These effects were counteracted by yohimbine (α2-AR antagonist) and efaroxan (α2-AR and I1R antagonist). In SHR, DEX significantly decreased infarct size, and the effect was counteracted by efaroxan but not yohimbine. DEX did not alter phosphorylated-eNOS/eNOS in SHR. α2-AR and I1R were observed in WKY and SHR hearts. Although alpha2A-AR and alpha2B-AR messenger RNA and protein levels were upregulated in SHR, I1R expression was comparable between the 2 species. CONCLUSIONS: In the hypertrophied heart, DEX maintains its direct cardioprotective effect against ischemia/reperfusion injury via I1R in an eNOS-nondependent manner despite upregulation of α2-AR.

Nitrite administration improves sepsis-induced myocardial and mitochondrial dysfunction by modulating stress signal responses.

PURPOSE: A specific therapeutic strategy in sepsis-induced myocardial dysfunction remains to be determined. Nitrite may have cardioprotective effects against sepsis-induced myocardial dysfunction. This study investigated the cardioprotective effects of nitrite on myocardial function, mitochondrial bioenergetics, and its underlying molecular mechanisms in severe septic rats. METHODS: Sepsis was induced in male Wistar rats by cecal ligation and puncture (CLP). After CLP, we administered normal saline (NS group) or nitrite (nitrite group) subcutaneously. We administered nitrite at different doses (0.1-10 mg/kg) to ascertain the most effective dose and examined cardiac function in an isolated heart experiment 8 h after CLP. We investigated mitochondrial bioenergetics and molecular mechanisms underlying the administration of nitrite in vitro. RESULTS: In isolated heart experiments, the left ventricular developed pressure (96 ± 5 mmHg) at a moderate nitrite dose (1.0 mg/kg) was significantly higher than that in the NS group (75 ± 4 mmHg, P < 0.05). Mitochondrial oxidative phosphorylation in the nitrite group was significantly higher than that in the NS group (P < 0.01). Immunoblotting revealed that nitrite significantly increased the phosphorylation of Akt (P < 0.05) and reduced the nuclear translocation of NF-κB (P < 0.05) compared with the NS group. Nitrite was also shown to improve the rate of survival in severe septic rats (P < 0.001). CONCLUSIONS: Our results showed that a moderate nitrite dose improved septic myocardial dysfunction at organ, cellular, and molecular levels via modulation of stress signal responses, which resulted in an improvement in survival.