Bupivacaine Inhibition of L-Type Calcium Current in Ventricular Cardiomyocytes of Hamster

Rossner, Kenneth L.; Freese, K. J.

doi:10.1097/00000542-199710000-00028

Cited by 43 publications

(23 citation statements)

References 32 publications

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“…The cardiotoxicity of RS(±) bupivacaine and its isomers is attributed to their blocking sodium [19], potassium [20], and L-type calcium channels [18,21] in the sarcolemma of cardiomyocytes. In addition, local anesthetics can either decrease [22,23] or increase Ca 2+ mobilization [24] from the sarcoplasmic reticulum and also decrease the sensitivity of myofilaments to Ca 2+ [25].…”

Section: Discussionmentioning

confidence: 99%

“…There is no data regarding the effects of bupivacaine and its S(−) isomer on the L-type Ca 2+ channel nor in the Na + /Ca 2+ exchanger in neonatal rats. The negative chronotropic effect observed with RS(±) bupivacaine may be explicated by a reduction in Ca 2+ influx into the cell, triggered by direct interaction with L-type Ca 2+ channels on phases 4 and 0 of the sinus node action potential [18,21]. Thus, we suggest that RS(±) and S(−) bupivacaine promote a more significant cardiodepressant Effects of various concentrations of RS(±) and S(−) bupivacaine on theinduction and reversion of cardiac arrhythmias in isolated perfused hearts obtained from rats of two ages Table 1.…”

Section: Discussionmentioning

confidence: 99%

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Influence of age on bupivacaine cardiac arrhythmogenic effects

Kiuchi¹,

Zapata‐Sudo²,

Trachez³

et al. 2017

Cardiovasc Disord Med

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The cardiotoxic effects of bupivacaine, a widely used local anesthetic, may be age-dependent because neonates and children tolerate a higher plasma concentration of bupivacaine after intravenous administration than adults. No studies have compared the toxicity profiles of the bupivacaine isomers in human neonates and children, but differences in the lethal dose have been observed between adult and younger rats. Here, we determined the age dependency of cardiac toxicity induced by racemic RS(±) bupivacaine and its levo S(−) isomer in hearts obtained from 2-and 16-week-old male Wistar rats (n=30 each) using a Langendorff ex vivo assay. We found that both RS(±) and S(−) bupivacaine significantly reduced heart rate and prolonged the PR interval and QRS complex duration. The effects of both compounds were significantly greater in older rats, and RS(±) bupivacaine had a greater effect than S(−) bupivacaine. Furthermore, RS(±) bupivacaine induced significantly more severe arrhythmias in 16-week-old than in 2-week-old rats. By contrast, the same concentration of S(−) bupivacaine was associated with mild arrhythmias in both age groups. Thus, although RS(±) bupivacaine induced greater cardiotoxicity than S(−) bupivacaine, the effects of both compounds were age related, with hearts from older animals showing more signs of toxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Influence of age on bupivacaine cardiac arrhythmogenic effects

Kiuchi¹,

Zapata‐Sudo²,

Trachez³

et al. 2017

Cardiovasc Disord Med

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“…Based on our study, anti-β 1 -receptor autoantibodies in HVM, as isoprenaline-like agonists for β 1 -adrenoceptors were able to prolong the plateau of APD and enhance the Ca 2+ permeability of cardiac myocytes via L-type Ca 2+ channel, which triggers early after depolarization (EAD). Ca 2+ disorder was considered to be associated with myocarditis and cardiomyopathy [30] . It was reported anti-β 1 -receptor autoantibodies in DCM could display a positive chronotropic effect on cultured neonatal rat ventricular cells without desensitization, thus increasing the metabolic pressure of myocardial cells [31] , which was further demonstrated to be mediated by I ca-L [32] .…”

Section: Discussionmentioning

confidence: 99%

Effects of autoantibodies against β₁-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca²⁺currents

Liu¹,

Liao²,

Wang³

et al. 2004

WJG

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AIM:To investigate the effects of autoantibodies against β 1 -adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca 2+ currents. METHODS:Fifteen samples of autoantibodies against β 1 -adrenoceptor positive sera of patients with hepatitis virus myocarditis were obtained and IgGs were purified by octanoic acid extraction. Binding of autoantibodies against β 1 -adrenoceptor to guinea pig cardiac myocytes was examined by immunofluorescence. Using the patch clamp technique, the effects on the action potential and I Ca-L of guinea pig cardiac myocytes caused by autoantibodies against β 1 -adrenoceptor in the absence and presence of metoprolol were investigated. Cell toxicity was examined by observing cell morphology and permeability of cardiac myocytes to trypan blue. RESULTS:The specific binding of autoantibodies against β 1 -adrenoceptor to guinea pig cardiomyocytes was observed. Autoantibodies against β 1 -adrenoceptor diluted at 1:80 prolonged APD 20 , APD 50 and APD 90 by 39.2%, 29.1% and 15.2% respectively, and only by 7.2%, 5.3% and 4.1% correspondingly in the presence of 1 µmol/L metoprolol. Autoantibodies against β 1 -adrenoceptor diluted at 1:80, 1:100 and 1:120 significantly increased the I Ca-L peak current amplitude at 0 mV by 55.87±4.39%, 46.33±5.01% and 29.29±4.97% in a concentration-dependent manner. In contrast, after blocking of β 1 -adrenoceptors (1 µmol/L metoprolol), autoantibodies against β 1 -adrenoceptor diluted at 1:80 induced a slight increase of I Ca-L peak amplitude only by 6.81±1.61%. A large number of cardiac myocytes exposed to high concentrations of autoantibodies against β 1 -adrenoceptor (1:80 and 1:100) were turned into rounded cells highly permeable to trypan blue. CONCLUSION:Autoantibodies against β 1 -adrenoceptor may result in arrhythmias and/or impairment of myocardiums in HVM, which would be mediated by the enhancement of I Ca-L .

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“…In cardiomyocytes, bupivacaine has been shown to block L-type calcium channels and participates in modulation of an as yet unidentified calcium channel. 18 Few studies on the effect of bupivacaine in neural calcium channels have been reported. In neurons, N-type channels have been found primarily (neuronal type, channels blocked with omega-conotoxin), but also L and T-type channels, which have low thresholds of activation.…”

Section: Objectif : Le Modèle Photochimique D'une Lésion Médullaire Rmentioning

confidence: 99%

Intrathecal bupivacaine protects against extension of lesions in an acute photochemical spinal cord injury model

Lopez¹,

Privat

Bernard³

et al. 2004

Can J Anesth/J Can Anesth

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P Pu ur rp po os se e: : The photochemical spinal-cord injury model reproduces extensive secondary lesions that occur after spinal injury. We have evaluated in 27 rats the functional, electrophysiological and anatomical consequences of a photochemical spinal-cord lesion induced before or after intrathecal injection of bupivacaine.M Me et th ho od ds s: : After randomization, nine rats received 20 µL of intrathecal bupivacaine 0.5% 15 min before a photochemical spinal-cord lesion (Group I) and eight rats received 20 µL intrathecal bupivacaine 15 min after such a lesion (Group II). Ten rats received 20 µL of saline 15 min before the photochemical injury (control group).Paraplegia was tested on days one, three, five, seven, nine, 12, 15 and 18 using an evaluation of hindlimb movements and an inclined plane stability test. Sensory block was evaluated by the animal's response when each hindlimb was brought into contact with a hot plate. Sympathetic injury was evaluated in terms of bladder voiding dysfunction. On day 18, residual somatosensory evoked potentials (SEP) were measured and the area of the intact spinal cord was determined using a digitalized system. R Re es su ul lt ts s: : Early paraplegia recovery was found in the two bupivacaine groups (P < 0.05). On day 12, motor recovery was complete in both bupivacaine groups whereas recovery was not complete on day 18 in the control group. Compared to the control group, inclined plane stability recovered earlier in Groups I and II, from day three to day 15. Sensory and sympathetic block scores were not different in the three groups. Nevertheless, SEP latencies were longer and amplitudes were lower in control group rats compared with the two bupivacaine groups on day 18. The intact spinal-cord cross-sectional area around the lesion was not different in the three groups.C Co on nc cl lu us si io on n: : Twenty microlitres of intrathecal bupivacaine before or after acute photochemical spinal injury improves hindlimb motor recovery and SEP parameters in rats. Objectif

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Bupivacaine Inhibition of L-Type Calcium Current in Ventricular Cardiomyocytes of Hamster

Cited by 43 publications

References 32 publications

Influence of age on bupivacaine cardiac arrhythmogenic effects

Influence of age on bupivacaine cardiac arrhythmogenic effects

Effects of autoantibodies against β₁-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca²⁺currents

Intrathecal bupivacaine protects against extension of lesions in an acute photochemical spinal cord injury model

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Bupivacaine Inhibition of L-Type Calcium Current in Ventricular Cardiomyocytes of Hamster

Cited by 43 publications

References 32 publications

Influence of age on bupivacaine cardiac arrhythmogenic effects

Influence of age on bupivacaine cardiac arrhythmogenic effects

Effects of autoantibodies against β1-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca2+currents

Intrathecal bupivacaine protects against extension of lesions in an acute photochemical spinal cord injury model

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Effects of autoantibodies against β₁-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca²⁺currents