Yoko Sakai

Exendin-4 ameliorates cardiac ischemia/reperfusion injury via caveolae and caveolins-3

BackgroundExendin-4, an exogenous glucagon-like peptide-1 receptor (GLP-1R) agonist, protects the heart from ischemia/reperfusion injury. However, the mechanisms for this protection are poorly understood. Caveolae, sarcolemmal invaginations, and caveolins, scaffolding proteins in caveolae, localize molecules involved in cardiac protection. We tested the hypothesis that caveolae and caveolins are essential for exendin-4 induced cardiac protection using in vitro and in vivo studies in control and caveolin-3 (Cav-3) knockout mice (Cav-3 KO).MethodsMyocytes were treated with exendin-4 and then incubated with methyl-β-cyclodextrin (MβCD) to disrupt caveolae formation. This was then followed by simulated ischemia/reperfusion (SI/R). In addition, cardiac protection in vivo was assessed by measuring infarct size and cardiac troponin levels.ResultsExendin-4 protected cardiac myocytes (CM) from SI/R [35.6 ± 12.6% vs. 64.4 ± 18.0% cell death, P = 0.034] and apoptosis but this protection was abolished by MβCD (71.8 ± 10.8% cell death, P = 0.004). Furthermore, Cav-3/GLP-1R co-localization was observed and membrane fractionation by sucrose density gradient centrifugation of CM treated with MβCD  + exendin-4 revealed that buoyant (caveolae enriched) fractions decreased Cav-3 compared to CM treated with exendin-4 exclusively. Furthermore, exendin-4 induced a reduction in infarct size and cardiac troponin relative to control (infarct size: 25.1 ± 8.2% vs. 41.4 ± 4.1%, P < 0.001; troponin: 36.9 ± 14.2 vs. 101.1 ± 22.3 ng/ml, P < 0.001). However, exendin-4 induced cardiac protection was abolished in Cav-3 KO mice (infarct size: 43.0 ± 6.4%, P < 0.001; troponin: 96.8 ± 26.6 ng/ml, P = 0.001).ConclusionsWe conclude that caveolae and caveolin-3 are critical for exendin-4 induced protection of the heart from ischemia/reperfusion injury.

Geranylgeranylacetone protects the heart via caveolae and caveolin-3

AIMS Geranylgeranylacetone (GGA) is commonly utilized to protect the gastric mucosa in peptic ulcer disease. Recently GGA has been shown to protect the myocardium from ischemia/reperfusion by activating heat shock proteins. However, the exact mechanism as to how GGA activates these protective proteins is unknown. Caveolae and caveolin-3 (Cav-3) have been implicated in ischemia, anesthetic, and opioid induced cardiac protection. Given the lipophilic nature of GGA it is our hypothesis that GGA induced cardiac protection requires caveolae and Cav-3. MAIN METHODS We used an in vivo mouse model of ischemia-reperfusion injury and performed biochemical assays in excised hearts. KEY FINDINGS GGA treated control mice revealed increased caveolae formation and caveolin-3 in buoyant fractions, mediating heat shock protein 70 activation. Furthermore, control mice treated with GGA were protected against ischemia/reperfusion injury whereas Cav-3 knockout (Cav-3 KO) mice were not. Troponin levels confirmed myocardial damage. Finally, Cav-3 KO mice treated with GGA were not protected against mitochondrial swelling whereas control mice had significant protection. SIGNIFICANCE This study showed that caveolae and caveolin-3 are essential in facilitating GGA induced cardiac protection by optimizing spatial and temporal signaling to the mitochondria.

Quantitative measurement of femoral condyle cartilage in the knee by MRI: Validation study by multireaders

To determine reproducibility of the femoral condyle cartilage volume (CV) in cross‐sectional and longitudinal studies using various 3D imaging techniques at 1.5 T and 3 T.

Anaesthetic management of a patient with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis

PurposeA case of a patient associated with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis is presented.Clinical featuresWilliams syndrome is a rare disease associated with a characteristic facies, supravalvular aortic stenosis, and mental retardation. A 15-yr-old girl with Williams syndrome underwent aortoplasty for supravalvular aortic stenosis. Anaesthesia was induced with fentanyl and thiamylal, and maintained with nitrous oxide, oxygen, sevoflurane, and continuous intravenous infusion of fentanyl. Supravalvular aortic stenosis was evaluated using a multiplane transesophageal echocardiography (TEE) probe before and after repair.ConclusionMultiplane TEE was found to be very useful for anaesthetic management in a patient with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis.ObjectifPrésenter le cas d’une patiente atteinte du syndrome de Williams et Beuren devant subir une aortoplastie pour une sténose aortique supravalvulaire.Aspects cliniquesLe syndrome de Williams et Beuren est une maladie rare associée à un faciès caractéristique, une sténose aortique supravalvulaire et un retard mental. Une jeune patiente de 15 ans atteinte du syndrome de Williams et Beuren a subi une aortoplastie pour une sténose aortique supravalvulaire. L’anesthésie a été induite avec du fentanyl et du thiamylal et maintenue avec du protoxyde d’azote, de l’oxygène, du sévoflurane et une perfusion continue de fentanyl. Avant et après la chirurgie, on a évalué la sténose aortique supravalvulaire à l’aide d’une sonde d’échocardiographie transoesophagienne (ETO) multiplan.ConclusionLETO multiplan a été jugée très utile pour la gestion de l’anesthésie chez une patiente atteinte du syndrome de Williams et Beuren qui devait subir une aortoplastie pour une sténose aortique supravalvulaire.

Impact of newly developed, next-generation artificial endocrine pancreas.

BACKGROUND Recent studies have shown that strict perioperative blood glucose management may reduce mortality and morbidity in critically ill adult patients. The purpose of this study was to assess the accuracy and efficacy of the intraoperative application of a newly developed, next-generation artificial endocrine pancreas (STG-55, Nikkiso Co., Ltd., Tokyo, Japan). METHODS Twenty patients scheduled to undergo surgery were enrolled in this study. The STG-55 is designed to be more user-friendly than its conventional counterpart (STG-22) while maintaining the latters fundamental functions, such as a closed-loop system using algorithms for insulin and glucose infusion. After anesthetic induction, a 20G intravenous catheter was inserted into a peripheral forearm vein and connected to a continuous blood glucose monitor. The resultant 105 scores for paired blood glucose values were compared by Bland-Altman analysis. RESULTS Stable blood glucose values were maintained automatically, and there were no complications related to use of the STG-55. A close correlation (r=0.96) was observed between continuous glucose measurements using the STG-55 and conventional intermittent glucose measurements. The difficulty of manipulation using this system was decreased by improved preparation procedures. CONCLUSION The glycemic control system using the STG-55 could provide an alternative way to achieve effective and safe perioperative glycemic control.

Effectiveness of using non‐invasive continuous arterial pressure monitoring with ClearSight in hemodynamic monitoring during living renal transplantation in a recipient:a case report

We investigated the effectiveness of the ClearSight system for hemodynamic management during kidney transplantation for a recipient. The recipient was to receive a kidney transplant from his mother under general anesthesia. We used continuous noninvasive finger-cuff-based monitoring of blood pressure, provided by the ClearSight system, and stroke volume variation to predict fluid responsiveness. We used of a balanced anesthetic technique and stringent monitoring standards to ensure a successful outcome for the patient. This case demonstrated that ClearSight has the potential to improve patient monitoring in hemodynamically stable patients who received kidney transplantation under general anesthesia. J. Med. Invest. 65:139-141, February, 2018.

Noninvasive continuous blood pressure monitoring by the ClearSight system during robot‐assisted laparoscopic radical prostatectomy

Robot-assisted laparoscopic radical prostatectomy (RALRP) is commonly performed in the surgical treatment of prostate cancer. However, the steep Trendelenburg position (25) and pneumoperitoneum required for this procedure can sometimes cause hemodynamic changes. Although blood pressure is traditionally monitored invasively during RALRP, the ClearSight system (BMEYE, Amsterdam, The Netherlands) enables a totally noninvasive and simple continuous blood pressure and cardiac output monitoring based on finger arterial pressure pulse contour analysis. We therefore investigated whether noninvasive continuous arterial blood pressure measurements using the ClearSight system were comparable to those obtained invasively in patients undergoing RALRP. Ten patients scheduled for RALRP with American Society of Anesthesiologists physical status I-II were included in this study. At each of the seven defined time points, noninvasive and invasive blood pressure measurements were documented and compared in each patient using Bland-Altman analysis. Although the blood pressure measured with the ClearSight system correlated with that measured invasively, a large difference between the values obtained by the two devices was noted. The ClearSight system was unable to detect blood pressure accurately during RALRP, suggesting that blood pressure monitoring using this device alone is not feasible in this small patient population. J. Med. Invest. 65:69-73, February, 2018.

The Efficacy of Programmed Intermittent Epidural Bolus for Postoperative Analgesia after Open Gynecological Surgery: A Randomized Double-Blinded Study

Background It is well known that the programmed intermittent epidural bolus (PIEB) technique effectively provides epidural anesthesia in labor. This randomized double-blind trial compared the postoperative analgesic efficacy of PIEB with that of continuous epidural infusion (CEI) in patients undergoing gynecological surgery under combined general-epidural anesthesia. Methods Patients undergoing open gynecological surgery under combined general-epidural anesthesia were randomized at a 1 : 1 ratio to receive PIEB or CEI. In the PIEB group, the pump delivered 4 mL ropivacaine 0.2% plus fentanyl 2 μg/mL every hour. In the CEI group, the pump delivered the same solution at a rate of 4 mL/h. In both groups, additional 4 mL boluses of ropivacaine 0.2% plus fentanyl 2 μg/mL were provided, when necessary, by patient-controlled epidural analgesia after surgery. The primary outcome was the total ropivacaine dose 40 hours after surgery. The secondary outcomes were the number of PCEA boluses and postoperative pain (evaluated on an 11-point numerical rating scale) 3, 24, and 48 hours after surgery. Results In total, 57 patients were randomized (n = 28 and 29 in the PIEB and CEI groups, resp.). The two groups differ significantly in terms of the total ropivacaine dose 40 hours after surgery (mean (standard deviation): 155.38 (4.55) versus 159.73 (7.87) mL, P = 0.016). Compared to the CEI group, the PIEB group had significantly lower numerical rating scale scores 3 hours (median [lower–upper quartiles]: 0 [0–0.5] versus 3 [0–5.5], P = 0.002), 24 hours (1 [0–2] versus 3 [1–4], P = 0.003), and 48 hours (1 [0–2] versus 2 [2–3.5], P = 0.002) after surgery. Conclusion PIEB was better than CEI in terms of providing postoperative analgesia after open gynecological surgery under combined general-epidural anesthesia.

A Comparison of Fosaprepitant and Ondansetron for Preventing Postoperative Nausea and Vomiting in Moderate to High Risk Patients: A Retrospective Database Analysis

Postoperative nausea and vomiting (PONV) occur in 30–50% of patients undergoing general anesthesia and in 70–80% of high PONV risk patients. In this study, we investigated the efficacy of fosaprepitant, a neurokinin-1 (NK1) receptor antagonist, compared to ondansetron, a selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, in moderate to high PONV risk patients from our previous randomized controlled trials. Patients (171 patients from 4 pooled studies) with the Apfel simplified score ≥ 2 and undergoing general anesthesia were randomly allocated to receive intravenous fosaprepitant 150 mg (NK1 group, n = 82) and intravenous ondansetron 4 mg (ONS group, n = 89) before induction of anesthesia. Incidence of vomiting was significantly lower in the NK1 group compared to the ONS group 0–2, 0–24, and 0–48 hours after surgery (2 versus 17%, 2 versus 28%, and 2 versus 29%, resp.). However, no significant differences in PONV, complete response, rescue antiemetic use, and nausea score were observed between groups 0–48 hours after surgery. In moderate to high PONV risk patients, fosaprepitant decreased the incidence of vomiting and was superior to ondansetron in preventing postoperative vomiting 0–48 hours after surgery.

Quantitative measurement of femoral condyle cartilage in the knee by MRI: Validation study by multireaders: Quantitative Knee Cartilage Measurement

To determine reproducibility of the femoral condyle cartilage volume (CV) in cross‐sectional and longitudinal studies using various 3D imaging techniques at 1.5 T and 3 T.