Effects of halothane and isoflurane on rat ventricular action potentials recorded in situ

Hayes, Eric; Barrett, Terrance D.; Burrill, Dean E.; Walker, Michael J.

doi:10.1016/0024-3205(96)00104-x

Cited by 7 publications

(3 citation statements)

References 28 publications

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“…However, the effects have been extremely inhomogeneous. Hayes et al (14) reported that halothane prolonged the APD measured at 50% repolarization (APD 50 ), whereas others found a shortening of APD 50 by halothane (11,15,16). Similar varied results were shown for isoflurane (11,13) and sevoflurane (17,18).…”

Section: Basic Electrophysiology Of the Cardiomyocyte And Arrhythmiassupporting

confidence: 71%

Effects of volatile anesthetics on cardiac ion channels

Hüneke¹,

Fassl²,

Rossaint³

et al. 2004

Acta Anaesthesiol Scand

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The focus of the present review is on how interference with various ion channels in the heart may be the molecular basis for cardiac side-effects of gaseous anesthetics. Electrophysiological studies in isolated animal and human cardiomyocytes have identified the L-type Ca(2+) channel as a prominent target of anesthetics. Since this ion channel is of fundamental importance for the plateau phase of the cardiac action potential as well as for Ca(2+)-mediated electromechanical coupling, its inhibition may facilitate arrhythmias by shortening the refractory period and may decrease the contractile force. Effective inhibition of this ion channel has been shown for clinically used concentrations of halothane and, to a lesser extent, of isoflurane and sevoflurane, whereas xenon was without effect. Anesthetics furthermore inhibit several types of voltage-gated K(+) channels. Thereby, they may disturb the repolarization and bear a considerable risk for the induction of ventricular tachycardia in predisposed patients. In future, an advanced understanding of cardiac side-effects of anesthetics will derive from more detailed analyses of how and which channels are affected as well as from a better comprehension of how altered channel function influences heart function.

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Section: Basic Electrophysiology Of the Cardiomyocyte And Arrhythmiassupporting

confidence: 71%

Effects of volatile anesthetics on cardiac ion channels

Hüneke¹,

Fassl²,

Rossaint³

et al. 2004

Acta Anaesthesiol Scand

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“…Studies implicate halocarbons in alterations of a number of ion channels, and these changes may contribute to their arrhythmic effect. Halocarbon effects include activation of hyperpolarizing, background potassium channels [37,38], reduction of gap junction conductance between cells [39], alterations of voltagegated calcium channel activity [40], increases in calcium release from the sarcoplasmic reticulum [41][42][43][44] and depression of the sodium current [36,[45][46][47].…”

Section: Halocarbons and Arrhythmic Riskmentioning

confidence: 99%

A possible mechanism of halocarbon-induced cardiac sensitization arrhythmias

Jing

Jesús

Iravanian

et al. 2006

Journal of Molecular and Cellular Cardiology

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Cardiac sensitization is the term used for malignant ventricular arrhythmias associated with exposure to inhaled halocarbons in the presence of catecholamines. We investigated the electrophysiological changes associated with cardiomyocyte exposure to epinephrine and a halocarbon known to be associated with cardiac sensitization (halon 1301, CF 3 Br). Cardiomyocytes (CMs) were isolated from neonatal rats and grown on multielectrode arrays (MEAs). Upon exposure to epinephrine, the CM inter-spike interval (ISI) was decreased 14% at 10 µg/L (P<0.05) and 27% at 100 µg/L (P<0.05) as compared to baseline. Halon alone (50 mg/L) mildly prolonged the field potential (FP) duration (7%). CMs exposed to combinations of epinephrine (100 µg/L) and halon (50 mg/L) for 15 min showed a blunted increase in the ISI (35±12%) and a 38% decrease in conduction velocity (P<0.05) when compared to epinephrine alone. There was no change in field potential properties, but dephosphorylated connexin 43 (Cx43) was increased 60±16% with the combination as compared to epinephrine alone (P<0.05). Treatment with okadaic acid, a phosphatase inhibitor, prevented the Cx43 dephosphorylation and the reduction in conduction velocity upon exposure to halon and epinephrine. Moreover, the electrophysiological changes induced by epinephrine and halon were indistinguishable from those seen with the gap junction inhibitor heptanol. In conclusion, the combination of a halocarbon and epinephrine results in a unique electrophysiological signature including slow conduction that may explain, in part, the basis for cardiac sensitization. The slowing of conduction is most likely related to changes in the phosphorylation state of Cx43.

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“…As such the overall effect of halothane on action potential configuration will depend on the relative density of expression of the various halothane‐sensitive ion channels between species and tissues. For example, exposure to halothane led to an overall reduction of action potential duration in rat ventricular myocytes ( Harrison et al ., 1999 ; Hayes et al ., 1996 ), guinea‐pig papillary muscles ( Ozaki et al ., 1989 ), canine Purkinje fibres ( Polic et al ., 1991 ) and human atrial fibres ( Luk et al ., 1988 ) which is consistent with a dominant inhibitory action of halothane on I Ca in these preparations. However, ( Bosnjak & Kampine, 1986 ) reported in cat papillary muscles that halothane induced a considerable negative inotropic effect but had little effect on the duration of action potentials.…”

Section: Discussionmentioning

confidence: 99%

Effects of halothane on the transient outward K⁺ current in rat ventricular myocytes

Davies

Hopkins

Boyett

et al. 2000

British J Pharmacology

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Halothane has been shown to affect several membrane currents in cardiac tissue including the L‐type calcium current (ICa), sodium current and a variety of potassium currents. However, little is known about the effects of halothane on the transient outward K+ current (Ito). Single ventricular myocytes from rat hearts were voltage clamped using the whole cell patch configuration and an EGTA‐containing pipette solution to record the Ca2+‐independent, 4‐aminopyridine sensitive component of Ito. 300 μM Cd2+ or 10 μM nifedipine was used to block ICa. At +80 mV, Ito (peak current minus current at the end of the pulse) was 1.8±0.2 nA under control conditions which was reduced to 1.3±0.2 nA by 1 mM halothane (P<0.001, mean±s.e.mean, n=9). The inhibition of Ito by halothane was concentration‐dependent (K0.5, 1.1±0.2 mM). One mM halothane led to a 16 mV shift in the steady‐state inactivation curve towards negative membrane potentials (P=0.005, n=8) but had no significant effect on the activation‐voltage relationship (P=0.724). One mM halothane also increased the rate of inactivation of Ito; the dominant time constant of inactivation was reduced from 14±1 to 9±1 ms (P=0.017, mean±s.e.mean, n=6). These data show that halothane reduced Ito; 0.3 mM, close to the MAC50 value for halothane, inhibited the current by 15% and as such, the inhibition of Ito will be relevant to the clinical situation. Halothane induced a shift in the steady‐state inactivation curve and accelerated the inactivation process of Ito which could be responsible for its inhibitory effect. Due to the differential transmural expression of Ito in ventricular tissue, inhibition of Ito would reduce the transmural dispersion of refractoriness which could contribute to the arrhythmogenic properties of halothane. British Journal of Pharmacology (2000) 131, 223–230; doi:

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Effects of halothane and isoflurane on rat ventricular action potentials recorded in situ

Cited by 7 publications

References 28 publications

Effects of volatile anesthetics on cardiac ion channels

Effects of volatile anesthetics on cardiac ion channels

A possible mechanism of halocarbon-induced cardiac sensitization arrhythmias

Effects of halothane on the transient outward K⁺ current in rat ventricular myocytes

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Effects of halothane and isoflurane on rat ventricular action potentials recorded in situ

Cited by 7 publications

References 28 publications

Effects of volatile anesthetics on cardiac ion channels

Effects of volatile anesthetics on cardiac ion channels

A possible mechanism of halocarbon-induced cardiac sensitization arrhythmias

Effects of halothane on the transient outward K+ current in rat ventricular myocytes

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Product

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Effects of halothane on the transient outward K⁺ current in rat ventricular myocytes