A cardiolipina é o alvo da cardiotoxicidade dos anestésicos locais?

XiaoFeng Shen; FuZhou Wang; ShiQin Xu; YanNing Qian; YuSheng Liu; HongMei Yuan; QingSong Zha; ShanWu Feng; XiRong Guo; JianGuo Xu; Jie Yang

doi:10.1590/S0034-70942010000400013

Review Article

A cardiolipina é o alvo da cardiotoxicidade dos anestésicos locais?

Is cardiolipin the target of local anesthetic cardiotoxicity?

XiaoFeng Shen; FuZhou Wang; ShiQin Xu; YanNing Qian; YuSheng Liu; HongMei Yuan; QingSong Zha; ShanWu Feng; XiRong Guo; JianGuo Xu; Jie Yang

http://dx.doi.org/10.1590/S0034-70942010000400013 Braz J Anesthesiol, vol.60, n4, p.445-454, 2010

PDF

Downloads: 0

Resumo

JUSTIFICATIVA E OBJETIVOS: Os anestésicos locais são amplamente utilizados na prevenção ou na reversão de dor aguda e no tratamento de dor crônica. A reação de cardiotoxicidade induzida pelos anestésicos locais é um evento acidental sem terapia farmacológica, exceto a infusão de intralípides relatados recentemente cujo mecanismo de ação ainda não é bem compreendido. CONTEÚDO: A cardiolipina, um fosfolipídio aniônico, desempenha papel relevante na determinação de reação respiratória mitocondrial, metabolismo de ácidos graxos e apoptose celular. A disfunção do metabolismo energético mitocondrial é sugerida em associação com a cardiotoxicidade dos anestésicos locais, a partir de um estudo in vitro de que ela talvez se deva a fortes ligações eletrostáticas entre os anestésicos locais e a cardiolipina na membrana mitocondrial. Não há, contudo, evidência experimental. Portanto, levantamos a hipótese de que as interações anestésico-cardiolipina sejam o principal determinante associado à reação de cardiotoxicidade, o que pode ser estabelecido com a adoção de métodos teóricos e biológicos estruturais. Esse modelo de interação nos daria uma pista sobre o mecanismo da cardiotoxicidade dos anestésicos locais, visando a futuras pesquisas na área de desenvolvimento de fármacos de prevenção a esse evento na prática clínica. CONCLUSÕES: A interação entre a cardiolipina mitocondrial e os anestésicos locais pode ser a principal fonte de sua cardiotoxicidade, em função de seus efeitos sobre o metabolismo energético e o estado eletrostático.

Palavras-chave

ANESTÉSICOS, Local, CARDIOLIPINA, COMPLICAÇÕES, Arritmias, cardíacas, parada cardíaca, induzida

Abstract

BACKGROUND AND OBJECTIVES: Local anesthetics are used broadly to prevent or reverse acute pain and treat symptoms of chronic pain. Local anesthetic-induced cardiotoxic reaction has been considered the accidental event without currently effective therapeutic drugs except for recently reported intralipid infusion whose possible mechanism of action is not well known. CONTENTS: Cardiolipin, an anionic phospholipid, plays a key role in determining mitochondrial respiratory reaction, fatty acid metabolism and cellular apoptosis. Mitochondrial energy metabolism dysfunction is suggested as associated with local anesthetic cardiotoxicity, from an in vitro study report that the local anesthetic cardiotoxicity may be due to the strong electrostatic interaction of local anesthetics and cardiolipin in the mitochondria membrane, although there is a lack for experimental evidence. Herein we hypothesized that local anesthetic-cardiolipin interactions were the major determinant of local anesthetic-associated cardiotoxic reaction, established by means of theoretic and structural biological methods. This interacting model would give an insight on the underlying mechanism of local anesthetic cardiotoxicity and provide clues for further in depth research on designing preventive drugs for such inadvertent accidence in routine clinical practice. CONCLUSIONS: The interaction between local anesthetic and mitochondrial cardiolipin may be the underlying mechanism for cardiotoxicity affecting its energy metabolism and electrostatic status.

Keywords

ANESTHETICS, Local, CARDIOLIPINS, COMPLICATIONS, Arrhythmias, cardiac, heart arrest, induced

References

Howell BA, Chauhan A. Bupivacaine binding to pegylated liposomes. Anesth Analg. 2009;109:678-682.

Clark MK. Lipid emulsion as rescue for local anesthetic-related cardiotoxicity. J Perianesth Nurs. 2008;23:111-117.

Mazoit JX, Le Guen R, Beloeil H. Binding of long-lasting local anesthetics to lipid emulsions. Anesthesiology. 2009;110:380-386.

McCutchen T, Gerancher JC. Early intralipid therapy may have prevented bupivacaine-associated cardiac arrest. Reg Anesth Pain Med. 2008;33:178-180.

Sirianni AJ, Osterhoudt KC, Calello DP. Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine. Ann Emerg Med. 2008;51:412-415.

Felice K, Schumann H. Intravenous lipid emulsion for local anesthetic toxicity: a review of the literature. J Med Toxicol. 2008;4:184-191.

Leskiw U, Weinberg GL. Lipid resuscitation for local anesthetic toxicity: is it really lifesaving?. Curr Opin Anaesthesiol. 2009;22:667-671.

Marwick PC, Levin AI, Coetzee . Recurrence of cardiotoxicity after lipid rescue from bupivacaine-induced cardiac arrest. Anesth Analg. 2009;108:1344-1346.

Weinberg GL. Limits to lipid in the literature and lab: what we know, what we don't know. Anesth Analg. 2009;108:1062-1064.

Hicks SD, Salcido DD, Logue ES. Lipid emulsion combined with epinephrine and vasopressin does not improve survival in a swine model of bupivacaine-induced cardiac arrest. Anesthesiology. 2009;111:138-146.

de Jong RH. Lipid infusion for cardiotoxicity: promise? Yes-panacea?. Not. Anesthesiology. 2007;106:635-636.

Mather LE, Chang DH. Cardiotoxicity with modern local anaesthetics: is there a safer choice?. Drugs. 2001;61:333-342.

Vanderkooi G, Chazotte B, Biethman R. Temperature dependence of anesthetic effects on succinate oxidase activity in uncoupled submitochondrial particles. FEBS Lett. 1978;90:21-23.

Chazotte B, Vanderkooi G. Multiple sites of inhibition of mitochondrial electron transport by local anesthetics. Biochim Biophys Acta. 1981;636:153-161.

Saeki H, Nozawa Y, Shimonaka H. Effects of anesthetics, dibucaine and methoxyflurane on the ATPase activity and physical state of Tetrahymena surface membranes. Biochem Pharmacol. 1979;28:1095-1098.

Vanderkooi G, Shaw J, Storms C. On the mechanism of action of anesthetics: Direct inhibition of mitochondrial F1-ATPase by n-butanol and tetracaine. Biochim Biophys Acta. 1981;636:200-203.

Adade AB, O'Brien KL, Vanderkooi G. Temperature dependence and mechanism of local anesthetic effects on mitochondrial adenosinetriphosphatase. Biochemistry. 1987;26:7297-7303.

Azzi A, Scarpa A. Inhibition of K+ transport in liver mitochondria. Biochim Biophys Acta. 1967;135:1087-1088.

Selwyn MJ, Fulton DV, Dawson AP. Inhibition of mitochondrial anion permeability by local anaesthetics. FEBS Lett. 1978;96:148-151.

Barritt GJ. Inhibition by local anaesthetics of anion transport in isolated rat heart mitochondria. Biochem Pharmacol. 1979;28:1017-1021.

Dawson AP, Selwyn MJ, Fulton DV. Inhibition of Ca2+ efflux from mitochondria by nupercaine and tetracaine. Nature. 1979;277:484-486.

Garlid KD, Nakashima RA. Studies on the mechanism of uncoupling by amine local anesthetics: Evidence for mitochondrial proton transport mediated by lipophilic ion pairs. J Biol Chem. 1983;258:7974-7980.

Dabadie P, Bendriss P, Erny P. Uncoupling effects of local anesthetics on rat liver mitochondria. FEBS Lett. 1987;226:77-82.

Terada H, Shima O, Yoshida K. Effects of the local anesthetic bupivacaine on oxidative phosphorylation in mitochondria: Change from decoupling to uncoupling by formation of a leakage type ion pathway specific for H+ in cooperation with hydrophobic anions. J Biol Chem. 1990;265:7837-7842.

Houtkooper RH, Vaz FM. Cardiolipin, the heart of mitochondrial metabolism. Cell Mol Life Sci. 2008;65:2493-2506.

Chicco AJ, Sparagna GC. Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am J Physiol Cell Physiol. 2007;292:C33-44.

Önyüksel H, Sethi V, Weinberg GL. Bupivacaine, but not lidocaine, disrupts cardiolipin-containing small biomimetic unilamellar liposomes. Chem Biol Interact. 2007;169:154-159.

Mulroy MF. Systemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive measures. Reg Anesth Pain Med. 2002;27:556-561.

Farid IS, Hernandez-Popp V, Youssef GN. Bupivacaine induces transient neurological symptoms after subarachnoid block. Pain Pract. 2002;2:53-55.

de La Coussaye JE, Aya AG, Eledjam JJ. Neurally-mediated cardiotoxicity of local anesthetics: direct effect of seizures or of local anesthetics?. Anesthesiology. 2003;98:1295-1296.

Gould DB, Aldrete JA. Bupivacaine cardiotoxicity in a patient with renal failure. Acta Anaesthesiol Scand. 1983;27:18-21.

Conklin KA, Ziadlou-Rad F. Bupivacaine cardiotoxicity in a pregnant patient with mitral valve prolapse. Anesthesiology. 1983;58:596.

Soltesz EG, van Pelt F, Byrne JG. Emergent cardiopulmonary bypass for bupivacaine cardiotoxicity. J Cardiothorac Vasc Anesth. 2003;17:357-358.

Ho AM, Dion PW, Karmakar MK. Estimating with confidence the risk of rare adverse events, including those with observed rates of zero. Reg Anesth Pain Med. 2002;27:207-210.

Lambeth JD. Cytochrome P-450scc: Cardiolipin as an effector of activity of a mitochondrial cytochrome P-450. J Biol Chem. 1981;256:4757-4762.

Claypool SM, Oktay Y, Boontheung P. Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane. J Cell Biol. 2008;182:937-950.

Chen S, Tarsio M, Kane PM. Cardiolipin mediates cross-talk between mitochondria and the vacuole. Mol Biol Cell. 2008;19:5047-5058.

Müller M, Moser R, Cheneval D. Cardiolipin is the membrane receptor for mitochondrial creatine phosphokinase. J Biol Chem. 1985;260:3839-3843.

Petrosillo G, Portincasa P, Grattagliano I. Mitochondrial dysfunction in rat with nonalcoholic fatty liver: involvement of complex I, reactive oxygen species and cardiolipin. Biochim Biophys Acta. 2007;1767:1260-1267.

Sparagna GC, Chicco AJ, Murphy RC. Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure. J Lipid Res. 2007;48:1559-1570.

Sztark F, Malgat M, Dabadie P. Comparison of the effects of bupivacaine and ropivacaine on heart cell mitochondrial bioenergetics. Anesthesiology. 1998;88:1340-1349.

Sztark F, Nouette-Gaulain K, Malgat M. Absence of stereospecific effects of bupivacaine isomers on heart mitochondrial bioenergetics. Anesthesiology. 2000;93:456-462.

Nouette-Gaulain K, Forestier F, Malgat M. Effects of bupivacaine on mitochondrial energy metabolism in heart of rats following exposure to chronic hypoxia. Anesthesiology. 2002;97:1507-1511.

Grouselle M, Tueux O, Dabadie P. Effect of local anaesthetics on mitochondrial membrane potential in living cells. Biochem J. 1990;271:269-272.

Porter JD, Edney DP, McMahon EJ. Extraocular myotoxicity of the retrobulbar anesthetic bupivacaine hydrochloride. Investig Ophthalmol Vis Sci. 1988;29:163-174.

Steer JH, Mastaglia FL, Papadimitriou JM. Bupivacaineinduced muscle injury: The role of extracellular calcium. J Neurol Sci. 1986;73:205-217.

Sztark F, Tueux O, Erny P. Effects of bupivacaine on cellular oxygen consumption and adenine nucleotide metabolism. Anesth Analg. 1994;78:335-339.

Bernardi P. Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol Rev. 1999;79:1127-1155.

Irwin W, Fontaine E, Agnolucci L. Bupivacaine myotoxicity is mediated by mitochondria. J Biol Chem. 2002;277:12221-12227.

David JS, Ferreti C, Amour J. Effects of bupivacaine, levobupivacaine and ropivacaine on myocardial relaxation. Can J Anaesth. 2007;54:208-217.

Nouette-Gaulain K, Sirvent P, Canal-Raffin M. Effects of intermittent femoral nerve injections of bupivacaine, levobupivacaine, and ropivacaine on mitochondrial energy metabolism and intracellular calcium homeostasis in rat psoas muscle. Anesthesiology. 2007;106:1026-1034.

Kowaltowski AJ, Naia-da-Silva ES, Castilho RF. Ca2+- stimulated mitochondrial reactive oxygen species generation and permeability transition are inhibited by dibucaine or Mg2+. Arch Biochem Biophys. 1998;359:77-81.

Arita K, Utsumi T, Kato A. Mechanism of dibucaine-induced apoptosis in promyelocytic leukemia cells (HL-60). Biochem Pharmacol. 2000;60:905-915.

Werdehausen R, Braun S, Essmann F. Lidocaine induces apoptosis via the mitochondrial pathway independently of death receptor signaling. Anesthesiology. 2007;107:136-143.

Corman SL, Skledar SJ. Use of lipid emulsion to reverse local anesthetic-induced toxicity. Ann Pharmacother. 2007;41:1873-1877.

Edelman LB, Ripper R, Kelly K. Metabolic context affects hemodynamic response to bupivacaine in the isolated rat heart. Chem Biol Interact. 2008;172:48-53.

Malhotra A, Xu Y, Ren M. Formation of molecular species of mitochondrial cardiolipin 1: A novel transacylation mechanism to shuttle fatty acids between sn-1 and sn-2 positions of multiple phospholipid species. Biochim Biophys Acta. 2009;1791:314-320.

Schlame M. Formation of molecular species of mitochondrial cardiolipin 2: A mathematical model of pattern formation by phospholipid transacylation. Biochim Biophys Acta. 2009;1791:321-325.

Beranek A, Rechberger G, Knauer H. Identification of a cardiolipin-specific phospholipase encoded by the gene CLD1 (YGR110W) in yeast. J Biol Chem. 2009;284:11572-11578.

Sorice M, Manganelli V, Matarrese P. Cardiolipin-enriched raft-like microdomains are essential activating platforms for apoptotic signals on mitochondria. FEBS Lett. 2009;583:2447-2450.

Schug ZT, Gottlieb E. Cardiolipin acts as a mitochondrial signalling platform to launch apoptosis. Biochim Biophys Acta. 2009;1788:2022-2031.

Takashi T, Inoue K, Nojima S. Immune reactions of liposomes containing cardiolipin and their relation to membrane fluidity. J Biochem (Tokyo). 1980;87:679-685.

Shimooka T, Seto S, Terada H. Increase in water permeability of negatively charged liposomal membrane by local anesthetics. Chem Pharm Bull (Tokyo). 1992;40:1880-1882.

Wilschut J, Holsappel M, Jansen R. Ca2+-induced fusion of cardiolipin/phosphatidylcholine vesicles monitored by mixing of aqueous contents. Biochim Biophys Acta. 1982;690:297-301.

Larsen SW, Frost AB, Østergaard J. On the mechanism of drug release from oil suspensions in vitro using local anesthetics as model drug compounds. Eur J Pharm Sci. 2008;34:37-44.

Dahlberg M, Maliniak A. Molecular dynamics simulations of cardiolipin bilayers. J Phys Chem B. 2008;112:11655-11663.

Sinibaldi F, Fiorucci L, Patriarca A. Insights into cytochrome ccardiolipin interaction: Role played by ionic strength. Biochemistry. 2008;47:6928-6935.

Sani MA, Dufourc EJ, Gröbner G. How does the Bax-alpha1 targeting sequence interact with mitochondrial membranes?: The role of cardiolipin. Biochim Biophys Acta. 2009;1788:623-631.

Muhonen J, Holopainen JM, Wiedmer SK. Interactions between local anesthetics and lipid dispersions studied with liposome electrokinetic capillary chromatography. J Chromatogr A. 2009;1216:3392-3397.

Padera R, Bellas E, Tse JY. Local myotoxicity from sustained release of bupivacaine from microparticles. Anesthesiology. 2008;108:921-928.

A cardiolipina é o alvo da cardiotoxicidade dos anestésicos locais?

Is cardiolipin the target of local anesthetic cardiotoxicity?

XiaoFeng Shen; FuZhou Wang; ShiQin Xu; YanNing Qian; YuSheng Liu; HongMei Yuan; QingSong Zha; ShanWu Feng; XiRong Guo; JianGuo Xu; Jie Yang

Resumo

Palavras-chave

Abstract

Keywords

References

Links

Share

Braz J Anesthesiol