Effects of bupivacaine, levobupivacaine and ropivacaine on myocardial relaxation

Abstract

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

Anesthetic Management of a Patient with Dilated Cardiomyopathy for Inguinal Hernia Repair

“…Injection ropiva caine 0.5% was used as it is less cardiotoxic and produces less motor blockade. 9 Injection fentanyl was preferred as an additive as it has minimal depressing effect on cardiac function and improves quality of analgesia. Fluid management is also critical and preloading the patient in the preoperative period is not desirable because it may precipitate a congestive heart failure.…”

A cardiolipina é o alvo da cardiotoxicidade dos anestésicos locais?

“…In addition, active oxidative metabolism is a key determinant in bupivacaine toxicity, and bupivacaine myotoxicity is a relevant model of mitochondrial dysfunction involving the permeability transition pore (PTP), a cyclosporin A-sensitive inner membrane channel that plays a key role in many forms of cell death, and Ca 2+ dysregulation, and that it represents a promising system to test new PTP inhibitors that may prove relevant in spontaneous myopathies where mitochondria have long been suspected to play a role 49 . Longacting local anesthetics induce marked negative inotropic and lusitropic effects on cardiomyocytes and such effect was mainly because of the impairment of calcium handling 50 . To the regulation of Ca 2+ homeostasis, different local anesthetics possess different functions; bupivacaine, levobupivacaine, and ropivacaine can induce a deleterious effect in mitochondrial energy, though levobupivacaine disturbs Ca 2+ homeostasis in the greatest degree 51 .…”

“…In view of recently reported successful cases resuscitated with intralipid administration 1-6 ; the facts related to a mitochondrial dysfunction during local anesthetic cardiotoxicity [13][14][15][16][17][18][19][20][21][22][23][24][44][45][46][47][48][49][50][51] , and the key role of cardiolipin in mitochondrial functioning [35][36][37][38][39][40] , we therefore propose that the interaction between the local anesthetic and cardiolipin determines the toxic effect of local anesthetics on cardiomyocytes by interfering with the mitochondrial energy metabolism. This interaction model can be produced with methods of theoretic and structural biology which gives insights of the potential interacting relation and clues for designing interventional drugs for such inadvertent events.…”

Validação de metodologia analítica por cromatografia líquida de alta eficiência para quantificação de bupivacaína (S75-R25) em nanoesferas de poli(lactídeo-co-glicolídeo)

“…A longa duração de ação, aliada à tendência em fornecer bloqueio mais sensorial que motor, tornou-a de uso popular para promover anestesia prolongada durante o trabalho de parto ou no período pós-operatório. [3][4][5] Porém, sua supremacia foi questionada devido a relatos de cardiotoxicidade. [6][7][8] Clinicamente, a cardiotoxicidade da BVC manifesta-se por arritmias ventriculares graves e depressão miocárdica após administração intravascular inadvertida de grandes doses.…”