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Effects of intravenous anaesthetics on cyclopiazonic acid-induced contractions in isolated rat aorta
ABSTRACT PRESENTATIONS: THURSDAY, MAY 12, 2016 Poster Session PS03 Thursday, May 12, 2016 08:30-10:30, Poster Exhibition Lounge
clinically relevant concentration which is related with the inhibition of Orai1 protein activity by them.
P-13 Effects of intravenous anaesthetics on cyclopiazonic acid-induced contractions in isolated rat aorta Seokyoung Song, W. Roh, B. Kim, S. Lee, H. Sung School of Medicine, Catholic University of Daegu, Department of Anesthesiology and Pain Medicine, Daegu, Korea Introduction. Sarcoplasmic-endoplasmic reticulum Ca2þ ATPase (SERCA) inhibitor, cyclopiazonic acid (CPA) makes store empty of Ca2þ in sarcoplasmic reticulum (SR) which activates Ca2þ influx through store-operated Ca2þ channels (SOCCs) to lead store-operated calcium entry (SOCE). The molecular biological structure of SOCCs recently known to contribute to the above is calcium releasing activated calcium channel protein 1(Orai1). The overall goal of this ex-vivo study is to investigate the effects of intravenous anaesthetics on SOCE which is induced by CPA in isolated thoracic aorta of rat. The effect of SERCA inhibitor, CPA in endotheliumdenuded rings is different to that of endothelium-intact rings in the isometric tension study. And the inhibitory effects of intravenous anaesthetics on CPA-induced contractions in endothelium-denuded rat aorta and these anaesthetics attenuated the expression of Orai1 protein activated by CPA. Method. Research has shown that isometric tension experiments with the isolated aorta of Male Sprague Dawley rats (n¼49) cofirm that CPA is able to make SOCE. Further more, the contractile responses in endothelium-denuded rat aortic rings showed that intravenous anaesthetics inhibits SOCE caused by CPA. Finally, Western blotting showed these intravenous anaesthetics inhibit the expression of Orai1. Results. Contractile response to CPA appeared hardly or a little in the endothelium-intact rings but markedly and sustained in endothelium-denuded rings. Application of Nω -nitro-L-arginine methyl ester (L-NAME) as a inhibitor to nitric oxide synthase and indomethacin as a inhibitor to cycolooxygenase in endotheliumintact rings before 30 minutes of CPA produced the similar contractile responses with those of endothelium-denuded rings. These contractile responses were inhibited by 2-aminoethyl diphenyl borinate (2APB), SOCE inhibitor (P o 0.05). The inhibition of contractile responses appeared in 30 μM and 100 μM of propofol, 100 μM of thiopental, 10 μM of midazolam and 100 μM of ketamine (P o 0.05). However, dexmedetomidine showed no effects to contractile responses of CPA. The expression of Orai1 decreased significantly in the group of 100 μM of thiopental and 10 μM of midazolam in comparison with the control (Po0.05). Discussion. In conclusion, the intravenous anaesthetics like propofol, thiopental, midazolam and ketamine inhibit SOCCs at
S18
REFERENCE 1. Yang B, Gwozdz T, Dutko-Gwozdz J, Bolotina VM: Orai1 and Ca2þ-independent phospholipase A2 are required for storeoperated Icat-SOC current, Ca2þ entry, and proliferation of primary vascular smooth muscle cells. Am J Physiol Cell Physiol 302(5):C748-C756, 2012. P-14 Does glycemic level affect neurologic outcomes during cardiopulmonary bypass? Elvin Kesimci, E. Erkýlýc, F. Alaybeyoglu, C. Balcý, T. Dulkadiroglu, T. Gumus, O. Kanbak Ataturk Training and Research Hospital, Ankara, Turkey Introduction. Perioperative hyperglycaemia, aggravated by cardiopulmonary bypass (CPB), is associated with adverse outcomes. Increased potential for stroke in these patients may be improved by different interventions. Blood glucose level changes as an intrinsic response to both stress and extrinsic sources; might affect early mortality and morbidity. In this study, we tried to identify a relationship existence between cerebral arterial oxygen saturation (rSO2) and blood glucose levels, and thus; evaluate changes in rSO2 caused by changes in blood glucose levels measured at predetermined time points of CPB. Methods. Forty six patients with American Society of Anaesthesiologists (ASA) physical status at least III and even IV, undergoing elective open cardiac surgery were prospectively studied. Preparation for surgery, anaesthesia and perioperative vital data monitoring (five-channel) ECG, pulse oximetry,
Journal of Cardiothoracic and Vascular Anesthesia, Vol 30, No S1 (May), 2016: pp S18–S35
clinically relevant concentration which is related with the inhibition of Orai1 protein activity by them.
P-13 Effects of intravenous anaesthetics on cyclopiazonic acid-induced contractions in isolated rat aorta Seokyoung Song, W. Roh, B. Kim, S. Lee, H. Sung School of Medicine, Catholic University of Daegu, Department of Anesthesiology and Pain Medicine, Daegu, Korea Introduction. Sarcoplasmic-endoplasmic reticulum Ca2þ ATPase (SERCA) inhibitor, cyclopiazonic acid (CPA) makes store empty of Ca2þ in sarcoplasmic reticulum (SR) which activates Ca2þ influx through store-operated Ca2þ channels (SOCCs) to lead store-operated calcium entry (SOCE). The molecular biological structure of SOCCs recently known to contribute to the above is calcium releasing activated calcium channel protein 1(Orai1). The overall goal of this ex-vivo study is to investigate the effects of intravenous anaesthetics on SOCE which is induced by CPA in isolated thoracic aorta of rat. The effect of SERCA inhibitor, CPA in endotheliumdenuded rings is different to that of endothelium-intact rings in the isometric tension study. And the inhibitory effects of intravenous anaesthetics on CPA-induced contractions in endothelium-denuded rat aorta and these anaesthetics attenuated the expression of Orai1 protein activated by CPA. Method. Research has shown that isometric tension experiments with the isolated aorta of Male Sprague Dawley rats (n¼49) cofirm that CPA is able to make SOCE. Further more, the contractile responses in endothelium-denuded rat aortic rings showed that intravenous anaesthetics inhibits SOCE caused by CPA. Finally, Western blotting showed these intravenous anaesthetics inhibit the expression of Orai1. Results. Contractile response to CPA appeared hardly or a little in the endothelium-intact rings but markedly and sustained in endothelium-denuded rings. Application of Nω -nitro-L-arginine methyl ester (L-NAME) as a inhibitor to nitric oxide synthase and indomethacin as a inhibitor to cycolooxygenase in endotheliumintact rings before 30 minutes of CPA produced the similar contractile responses with those of endothelium-denuded rings. These contractile responses were inhibited by 2-aminoethyl diphenyl borinate (2APB), SOCE inhibitor (P o 0.05). The inhibition of contractile responses appeared in 30 μM and 100 μM of propofol, 100 μM of thiopental, 10 μM of midazolam and 100 μM of ketamine (P o 0.05). However, dexmedetomidine showed no effects to contractile responses of CPA. The expression of Orai1 decreased significantly in the group of 100 μM of thiopental and 10 μM of midazolam in comparison with the control (Po0.05). Discussion. In conclusion, the intravenous anaesthetics like propofol, thiopental, midazolam and ketamine inhibit SOCCs at
S18
REFERENCE 1. Yang B, Gwozdz T, Dutko-Gwozdz J, Bolotina VM: Orai1 and Ca2þ-independent phospholipase A2 are required for storeoperated Icat-SOC current, Ca2þ entry, and proliferation of primary vascular smooth muscle cells. Am J Physiol Cell Physiol 302(5):C748-C756, 2012. P-14 Does glycemic level affect neurologic outcomes during cardiopulmonary bypass? Elvin Kesimci, E. Erkýlýc, F. Alaybeyoglu, C. Balcý, T. Dulkadiroglu, T. Gumus, O. Kanbak Ataturk Training and Research Hospital, Ankara, Turkey Introduction. Perioperative hyperglycaemia, aggravated by cardiopulmonary bypass (CPB), is associated with adverse outcomes. Increased potential for stroke in these patients may be improved by different interventions. Blood glucose level changes as an intrinsic response to both stress and extrinsic sources; might affect early mortality and morbidity. In this study, we tried to identify a relationship existence between cerebral arterial oxygen saturation (rSO2) and blood glucose levels, and thus; evaluate changes in rSO2 caused by changes in blood glucose levels measured at predetermined time points of CPB. Methods. Forty six patients with American Society of Anaesthesiologists (ASA) physical status at least III and even IV, undergoing elective open cardiac surgery were prospectively studied. Preparation for surgery, anaesthesia and perioperative vital data monitoring (five-channel) ECG, pulse oximetry,
Journal of Cardiothoracic and Vascular Anesthesia, Vol 30, No S1 (May), 2016: pp S18–S35