Effects of the Anesthetic Gases Xenon, Halothane, and Isoflurane on Calcium and Potassium Currents in Human Atrial Cardiomyocytes

University Hospital RWTH Aachen, Aachen, North Rhine-Westphalia, Germany
Anesthesiology (Impact Factor: 5.88). 10/2001; 95(4):999-1006. DOI: 10.1097/00000542-200110000-00032
Source: PubMed

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: Das Ziel dieser Untersuchung war es, die Raumluftkonzentration von Xenon und Lachgas während einer balancierten Anästhesie zu vergleichen. Insgesamt wurden 64 Patienten in die Studie eingeschlossen. Die Gaskonzentrationsmessungen während der Anästhesie wurden mit einem Massenspektrometer vorgenommen. Am Kopf und am Thorax des Patienten, auf dem Fußboden und in 180cm Höhe wurde die jeweilige Gaskonzentration nach der Intubation, nach 15min, nach 30min und nach der Extubation bestimmt. In beiden Patientengruppen ergaben sich sehr hohe Werte nach der Intubation und der Extubation. Die Arbeitsplatzkonzentration von Xenon war insgesamt niedrig im Vergleich zur Lachgas. Die niedrigen Arbeitsplatzkonzentrationen von Xenon im Vergleich zu Lachgas scheinen für Patienten oder Personal mit Risikoprofil von Vorteil zu sein. The aim of this study was to compare waste gas concentrations during xenon or nitrous oxide anaesthesia. A total of 64 patients were included in this study. Gas concentrations were measured with a mass spectrometer during anaesthesia. The probes were taken beside the patient's head and thorax and at a height of 180 cm above and at the floor level. In both groups, waste gas concentrations peak after intubation and extubation. Waste gas levels during xenon anaesthesia are low compared with nitrous oxide. The low waste gas levels of xenon seem to be beneficial for personnel at risk compared to nitrous oxide.
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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.
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    ABSTRACT: Examinations about Xenon anaesthesia and right ventricular function Until these studies were performed, there was no study about the influence of xenon on right ventricular function to our knowledge. Due to its chemico-physical properties, xenon has a possible influence. A Swan-Ganz-Catheter was used to measure right ventricular ejection fraction (RVEF). Additionally we examined the influence of xenon on resuscitation. 30 pigs were anaesthetized intravenously, instrumentated and randomized into Xenon- or Control-Group. Xenon or nitrogen was added in steps of 10% with a final concentration of 75% and circulatory and respiratory parameters were registered. After that, a cardiac arrest was induced for 4 minutes, followed by cardio-pulmonary resuscitation until return of spontaneous circulation. Finally we observed circulatory and respiratory parameters for 4 hours. At 40% inspiratory Xenon-Fraction we found a significant increase of peak and mean airway pressure and of mean pulmonary artery pressure compared to baseline values. No changes in control group and no difference between the groups were registered. Neither RVEF nor cardiac output showed any changes due to the inspiratory gas mix. Resuscitation was possible without any measurable influence of Xenon, resuscitation time and required drugs were unaffected. During observation time we found a significant increase in peak airway pressure after 60 minutes of observation compared to control group. No changes of pulmonary artery pressure were seen. Changes in RVEF appeared due to resuscitation procedures. These results show the already known physical effect of xenon during wash-in without an influence on right ventricular function. The effect of raising airway pressure after one hour of anaesthesia was not seen before and leaves a question about the underlying mechanism. Further studies are required to examine these changes. Finally this effect showed no influence on right or left ventricular function or resuscitation.
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