A cardiolipina é o alvo da cardiotoxicidade dos anestésicos locais?

Abstract

Is Cardiolipin the Target of Local Anesthetic Cardiotoxicity?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.

Terapia lipídica com dois agentes na intoxicação por ropivacaína: estudo experimental em suínos

“…This effect is achieved by chelating LA molecules and is known as "lipid sink" in Anglo-Saxon literature 14 . The second is based on the notion that local anesthetics are known to inhibit carnitine acetyltransferase, which is essential for transporting fatty acids into mitochondria 15 , and LE could overcome this inhibition and the metabolic and toxic effect by "mass effect" alone or some other yet unknown mechanism. The third mechanism is based on the fact that fatty acids are known to increase the calcium levels of cardiac myocytes and thus may activate a direct inotropic route 14,16 .…”

“…The third mechanism is based on the fact that fatty acids are known to increase the calcium levels of cardiac myocytes and thus may activate a direct inotropic route 14,16 . The hypothesis that lipid emulsions with in vitro long-chain triglycerides would be more effective 15 motivated this study to evaluate the hemodynamic effects of ropivacaine-induced toxicity in swine. In our experiments, we observed no significant differences in blood pressure using LE with long-chain triglycerides and mixed with long-and medium-chain.…”

Lipídeos nas intoxicações por anestésicos locais

“…The hypothesis formulated is that lipid emulsions would counteract the reduction in the main source of myocardial energy 4 . Finally, the third mechanism originates from evidence that lipid emulsions have a positive inotropic effect on the isolated heart and may reverse myocardial depression due to bupivacaine at lipid levels lower than those needed to reduce the aqueous bupivacaine concentration 26 , occurring with increased levels of intracellular Ca++. Thus, physiologic, metabolic or inotropic pathways may all contribute to antagonize local anesthetic toxicity 32 .…”

Estimulação elétrica transcutânea para tratamento da dor após cirurgia cardíaca: uma revisão sistemática

“…As evidências mostram que o uso combinado com anti-inflamatórios não esteroidais pode reduzir o consumo de morfina; no entanto, esses agentes não estão livres de efeitos indesejáveis, incluindo a inibição da agregação plaquetária, que pode causar hemorragias. Há também relatos de uso de anestésicos locais que bloqueiam a resposta ao estresse associada aos procedimentos cirúrgicos, no entanto, sua cardiotoxicidade é uma grande preocupação, pois compromete a vida do paciente 8,9 .…”

“…Nesse cenário, a estimulação elétrica nervosa transcutânea (TENS) é considerada um tratamento alternativo, pois atua de forma não invasiva e é de fácil aplicação, atuando por estimulação sensorial, gerando efeitos terapêuticos a partir da combinação de frequência e comprimento de onda 9,10 . Assim, é necessário realizar um levantamento de evidências científicas sobre o uso da TENS, visando à redução de complicações dolorosas após a cirurgia cardíaca e seu impacto nos parâmetros ventilatórios.…”