Effects of the anesthetic gases xenon, halothane, and isoflurane on calcium and potassium currents in human atrial cardiomyocytes
ABSTRACT Negative inotropic and proarrhythmic side effects on the heart are well known for the volatile anesthetics halothane and isoflurane but not for the noble gas xenon. We investigated the effects of halothane, isoflurane, and xenon on calcium and potassium currents in human atrial myocytes to elucidate the cellular and molecular basis of their cardiac actions.
Atrial myocytes were prepared from the right auricles obtained from patients undergoing heart surgery. Ion currents were measured with the whole cell patch clamp technique during superfusion of the cells with solutions that contained halothane, isoflurane, or xenon at concentrations corresponding to their respective minimum alveolar concentration (MAC); gas concentrations were determined with the head space-gas chromatography/mass spectrometry/selected ion monitoring method.
L-type calcium currents were significantly depressed by 31.9 +/- 4.1%, from -1.8 +/- 0.3 to -1.2 +/- 0.4 picoampere (pA)/picofarad (pF) (n = 4; P < 0.05) at 1 MAC halothane and by 21.7 +/- 9.2%, from -1.6 +/- 0.7 to -1.2 +/- 0.6 pA/pF (n = 7; P < 0.05) at 1 MAC isoflurane, but not affected by 70% xenon (1 MAC). Inwardly rectifying potassium currents were not influenced by any anesthetic. Halothane (1 MAC) significantly inhibited the transient as well as the sustained part of voltage-gated potassium outward currents, by 19.4 +/- 6.7%, from 6.7 +/- 2.1 to 5.4 +/- 1.6 pA/pF (n = 8; P < 0.05), and by 8.6 +/- 4.8%, from 5.5 +/- 1.7 to 5.0 +/- 1.5 pA/pF (n = 8; P < 0.05), respectively. Transient K+ outward currents were even more inhibited, by 25.8 +/- 4.8%, from 9.8 +/- 3.1 to 7.3 +/- 2.1 pA/pF (n = 5; P < 0.05) at 1 MAC isoflurane, whereas xenon evoked only a slight (albeit significant) inhibition, by 6.1 +/- 3.7%, from 8.2 +/- 6.0 to 7.7 +/- 5.8 pA/pF (n = 10; P < 0.05). Isoflurane and xenon did not affect sustained potassium currents. All effects of the anesthetics were fully reversible after washout.
Halothane and isoflurane exhibited considerable inhibitory effects on voltage-gated cardiac Ca2+ and K+ currents important for the duration of action potentials and the repolarization. Xenon, in contrast, did not affect Ca2+ currents and only slightly inhibited transient K+ outward currents, in line with the almost absent cardiac side effects of the noble gas.
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ABSTRACT: Xenon has minimal haemodynamic side effects when compared to volatile or intravenous anaesthetics. Moreover, in in vitro and in animal experiments, xenon has been demonstrated to convey cardio- and neuroprotective effects. Neuroprotection could be advantageous in paediatric anaesthesia as there is growing concern, based on both laboratory studies and retrospective human clinical studies, that anaesthetics may trigger an injury in the developing brain, resulting in long-lasting neurodevelopmental consequences. Furthermore, xenon-mediated neuroprotection could help to prevent emergence delirium/agitation. Altogether, the beneficial haemodynamic profile combined with its putative organ-protective properties could render xenon an attractive option for anaesthesia of children undergoing cardiac catheterization. In a phase-II, mono-centre, prospective, single-blind, randomised, controlled study, we will test the hypothesis that the administration of 50% xenon as an adjuvant to general anaesthesia with sevoflurane in children undergoing elective cardiac catheterization is safe and feasible. Secondary aims include the evaluation of haemodynamic parameters during and after the procedure, emergence characteristics, and the analysis of peri-operative neuro-cognitive function. A total of 40 children ages 4 to 12 years will be recruited and randomised into two study groups, receiving either a combination of sevoflurane and xenon or sevoflurane alone. Children undergoing diagnostic or interventional cardiac catheterization are a vulnerable patient population, one particularly at risk for intra-procedural haemodynamic instability. Xenon provides remarkable haemodynamic stability and potentially has cardio- and neuroprotective properties. Unfortunately, evidence is scarce on the use of xenon in the paediatric population. Our pilot study will therefore deliver important data required for prospective future clinical trials. EudraCT: 2014-002510-23 (5 September 2014).Trials 12/2015; 16(1):587. DOI:10.1186/s13063-015-0587-3 · 2.12 Impact Factor
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ABSTRACT: The purpose of this study was to investigate whether adding emulsified isoflurane to St Thomas cardioplegia solution could enhance the cardiac protection after cardioplegic arrest in rats. A randomized, blind study. A university laboratory. Thirty male Sprague-Dawley rats. Thirty isolated heart preparations were randomly divided into 3 groups (n = 10/group) according to the different cardioplegia solutions being given: St Thomas solution mixed with emulsified isoflurane (containing 2.8% of isoflurane, group EI), St Thomas solution mixed with emulsified Intralipid (Huarui Pharmacy, Wuxi, Jiangsu, China) (group EL), and St Thomas solution alone (group St). In the 35-minute normothermic ischemia period, infusion of cardioplegia solution was repeated every 15 minutes. After the 35-minute ischemia period, the heart was perfused with Krebs-Henseleit buffer for another 2 hours. The functional parameters of the heart were monitored throughout the experiments. The coronary effluent was collected for measuring the activity of CK-MB 30 minutes after reperfusion, and the infarct size was assessed at the end of reperfusion. The infarct size in group EI (24% +/- 4%) was reduced when compared with that in group EL (31% +/- 8%, p < 0.05) and group St (43% +/- 9%, p < 0.001). The CK-MB activity in group EI was decreased significantly when compared with that in group EL and group St (p < 0.05). The functional recovery in group EI also was improved. Compared with standard St Thomas solution alone, adding 30% Intralipid alone also significantly reduced the infarct size and the CK-MB leakage and improved the recovery of the mechanical function. St Thomas cardioplegia solution supplemented with emulsified isoflurane enhanced its cardioprotection in an isolated heart ischemia reperfusion injury model in rats.Journal of cardiothoracic and vascular anesthesia 02/2010; 24(1):99-103. DOI:10.1053/j.jvca.2009.10.016 · 1.48 Impact Factor
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ABSTRACT: Myokardiale Stunning ist eine postischämische kontraktile Dysfunktion, die nach Wiederherstellung der Perfusion trotz fehlender irreversibler Zellschädigung und trotz eines normalen koronaren Blutflusses persistiert. Untersucht wurden die Effekte der periischämischen Applikation des Inhalationsanästhetikums Xenon auf den Schweregrad und die Erholung von myokardialem Stunning, sowie auf die transmyokardiale Perfusionsverteilung. Die Untersuchungen zeigen, dass die Applikation von 75 Vol% Xenon während einer Fentanyl-Midazolam Basisanästhesie zu einer signifikant besseren Erholung der WTF bis zur 12. Stunden der Reperfusion führt. Der Anstieg der Plasmaadrenalinspiegel während der Aufwachphase und der frühen Reperfusionsphase war in der Xenongruppe signifikant niedriger als in der Kontrollgruppe. Hinsichtlich der globalen hämodynamischen Parameter, der koronaren Blutflussgeschwindigkeit und des regionalen myokardialen Blutflusses gab es keine signifikanten Unterschiede.