Document Detail

Myocardial Accumulation of Bupivacaine and Ropivacaine Is Associated with Reversible Effects on Mitochondria and Reduced Myocardial Function.
MedLine Citation:
PMID:  23223114     Owner:  NLM     Status:  Publisher    
BACKGROUND:Mechanisms of local anesthetic cardiac toxicity are still not completely understood. In this study, we analyzed whether concentrations of local anesthetics found in clinical toxicity affect myocardial mitochondrial structure and oxygen consumption.METHODS:Guinea pig isolated heart Langendorff preparations were exposed to bupivacaine (3.0 and 7.5 μg/mL) and ropivacaine (3.6 and 9.0 μg/mL) for 10 minutes. Heart rate, systolic blood pressure, the first derivative of left ventricular pressure (+dP/dt), electrocardiogram, and coronary flow were recorded. The local anesthetic tissue concentration was measured either immediately after local anesthetic exposure, or after 20- and 60-minute washout periods. In addition, electron microscopy of myocardial mitochondria was performed using a scoring system for structural damage of mitochondria. Cardiomyocyte cell culture was incubated with bupivacaine, and oxygen consumption ratio, extracellular acidification, and relative amounts of PGC-1α mRNA, a regulator of cellular energy metabolism, were determined.RESULTS:Bupivacaine and ropivacaine induced reversible PR interval and QRS prolongation, and left ventricular pressure and +dP/dt reduction. Myocardial tissue concentration of local anesthetics was 3-fold the arterial concentration. Mitochondria showed a significant concentration-dependent morphological swelling after local anesthetic application. These changes were reversed by a 20-minute washout period for ropivacaine and by a 60-minute washout for bupivacaine. Bupivacaine reduced mitochondrial oxygen consumption and increased PGC-1α expression in neonatal cardiomyocyte cell cultures, whereas fatty acid metabolism remained unaffected.CONCLUSIONS:Bupivacaine and ropivacaine accumulate in the myocardium. Reversible local anesthetic-induced mitochondrial swelling occurs at concentrations that induce a negative inotropic effect. Bupivacaine reduces cellular metabolism, whereas this reduction is reversible by fatty acids. Interaction with mitochondria may contribute to the negative inotropic effect of local anesthetics.
Nicole Hiller; Peter Mirtschink; Christine Merkel; Lilla Knels; Reinhard Oertel; Torsten Christ; Andreas Deussen; Thea Koch; Sebastian N Stehr
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-7
Journal Detail:
Title:  Anesthesia and analgesia     Volume:  -     ISSN:  1526-7598     ISO Abbreviation:  Anesth. Analg.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1310650     Medline TA:  Anesth Analg     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
From the *Department of Anesthesiology and Intensive Care Medicine, ‡Institute of Anatomy, §Institute of Clinical Pharmacology, ║Department of Pharmacology and Toxicology, and ¶Institute of Physiology, University Hospital Dresden, Dresden, Germany; and †Institute of Molecular Health Science, ETH Zurich, Switzerland.
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