Interaction of Bupivacaine and Tetracaine with the Sarcoplasmic Reticulum Ca2+Release Channel of Skeletal and Cardiac Muscles

Komai, Hirochika; Lokuta, Andrew J.

doi:10.1097/00000542-199903000-00027

Cited by 67 publications

(42 citation statements)

References 18 publications

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“…30,31 Alteration of the SR by LAAs may occur at the level of the SR Ca 2+ release channelryanodine receptor (RyR) or with the calcium reuptake, 30,[32][33][34] and could be responsible for a decrease in amplitude of contraction and/or increase in the duration of contraction. 34 We observed an increase in time-to-peak-shortening (isotony) and time-to-peakforce (isometry) that were compatible with alteration of RyR (increase time to release Ca 2+ ). This result is in agreement with the findings of Mio et al 31 who described an increase in time-to-peak-light by measuring variation of calcium content with aequorin light intensity measurements.…”

Section: Discussionmentioning

confidence: 99%

Effects of bupivacaine, levobupivacaine and ropivacaine on myocardial relaxation

David

Ferreti

Amour

et al. 2007

Can J Anesth/J Can Anesth

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CAN J ANESTH 54: 3 www.cja-jca.org March, 2007 Purpose: Ropivacaine and levobupivacaine were developed to reduce the risk of occasional toxicity reported with bupivacaine. While the effects of long-acting local anesthetics (LAAs) on myocardial contractility (inotropy) are well described, their effects on relaxation (lusitropy) remain largely unknown. The present study aimed to compare the effects of LAAs on rat myocardium. Methods:Left ventricular papillary muscles of male Wistar rats were used to compare the inotropic and lusitropic responses of increasing concentrations of LAAs (10 -8 to 10 -3 M) under isometric and isotonic conditions. Data are mean % (SD) of baseline value.Results: Long-acting local anesthetics induced a significant impairment of relaxation in isotonic and isometric conditions. As compared to ropivacaine, bupivacaine and levobupivacaine induced greater negative lusitropic effects in isotony [at 10 -3 M, maximum unloaded shortening velocity ( max Vr) = 27 ± 11 vs 13 ± 6 and 8 ± 5%] and isometry (at 10 -3 M, time-to-halfrelaxation: 106 ± 10 vs 127 ± 17 and 133 ± 17%). When the comparison was made with equipotent concentrations, the negative lusitropic effects induced with levobupivacaine were significantly greater than those of bupivacaine and ropivacaine in isometric and isotonic conditions (at 10 -3 M, max Vr = 7 ± 4 vs 13 ± 6 and 17 ± 4 %). As previously described, LAAs also induced concentration-dependent negative inotropic effects that were greater for levobupivacaine compared to equivalent or equipotent concentrations of bupivacaine and ropivacaine.Conclusions: Long-acting local anesthetics induce marked negative inotropic and lusitropic effects. Among LAAs, levobupivacaine exerts the greater depressant effects. Impairment of calcium handling and sarcoplasmic reticulum could explain the differential responses to local anesthetics. Objectif : La ropivacaïne et la lévobupivacaïne ont été dévelop-pées pour réduire le risque d'accidents sévères observés avec la bupivacaïne. Si les effets des anesthésiques locaux (LAAs) sur la contractilité myocardique (inotropie) sont bien décrits, les effets sur la relaxation (lusitropie) restent peu explorés. Cette étude a eu pour objectif de comparer les effets des LAAs chez le rat. Méthode : Les effets de concentrations croissantes de LAAs (10 -8 à 10 -3 M) sur les réponses inotropes et lusitropes ont été comparés à l'aide d'un modèle de muscles papillaires. Les valeurs sont exprimées en % de la valeur de base (moyenne ± ET). Résultats

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Section: Discussionmentioning

confidence: 99%

Effects of bupivacaine, levobupivacaine and ropivacaine on myocardial relaxation

David

Ferreti

Amour

et al. 2007

Can J Anesth/J Can Anesth

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“…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]. The stereoselective effects induced by the bupivacaine isomers, R(+) and S(−), have been intensively studied to determine which causes less cardiotoxicity while still providing potent nerve blockade.…”

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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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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“…Die kanalvermittelte Ca 2+ -Freisetzung dominiert quantitativ: Dieses Wissen beruht v. a. auf den Beobachtungen, dass zum einen die Inkubation von SR-Vesikeln mit Rutheniumrot, einem potenten Inhibitor des Ca 2+ -Freisetzungskanals, die lokalanästhetikainduzierte Ca 2+ -Release aus diesen Organellen nicht vollständig verhindern kann [40]. Zum anderen konnten Komai [27]. Gestützt werden diese Befunde durch die Tatsache, dass höher konzentriertes Bupivacain (10 mM) kultivierte Myozyten irreversibel schädigt; dagegen werden keine derartigen Effekte bei der Verwendung niedrigerer Konzentrationen (≤0,75 mM) beobachtet [27].…”

Section: Subzelluläre Aspekteunclassified

Myotoxizität von Lokalanästhetika

et al. 2007

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Intramuscular injections of local anaesthetic agents regularly result in reversible muscle damage, with a dose-dependent extent of the lesions. All local anaesthetic agents that have been examined are myotoxic, whereby procaine produces the least and bupivacaine the most severe muscle injury. The histological pattern and the time course of skeletal muscle injury appear relatively uniform: hypercontracted myofibrils become evident directly after injection, followed by lytic degeneration of striated muscle sarcoplasmic reticulum myocyte edema and necrosis. Intriguingly, in most cases myoblasts, basal laminae and connective tissue elements remain intact which subsequently ensures complete muscular regeneration. Subcellular pathomechanisms of local anaesthetic myotoxicity are still not understood in detail. Increased intracellular Ca(2+) levels are suggested to be the most important element in myocyte injury, since denervation, inhibition of sarcolemmal Na(+) channels and direct toxic effects on myofibrils have been excluded as sites of action. Although experimental myotoxic effects are impressively intense and reproducible, only few case reports of myotoxic complications in patients after local anaesthetic administration have been published. In particular, the occurrence of clinically relevant myopathy and myonecrosis has been described after continuous peripheral blockades, infiltration of wound margins, trigger point injections, peribulbar and retrobulbar blocks.

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Interaction of Bupivacaine and Tetracaine with the Sarcoplasmic Reticulum Ca2+Release Channel of Skeletal and Cardiac Muscles

Cited by 67 publications

References 18 publications

Effects of bupivacaine, levobupivacaine and ropivacaine on myocardial relaxation

Effects of bupivacaine, levobupivacaine and ropivacaine on myocardial relaxation

Influence of age on bupivacaine cardiac arrhythmogenic effects

Myotoxizität von Lokalanästhetika

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