Document Detail

The effects of levosimendan on myocardial function in ropivacaine toxicity in isolated guinea pig heart preparations.
MedLine Citation:
PMID:  17717217     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Levosimendan is a novel drug used for inotropic support in heart failure, but its efficacy in local anesthetic-induced myocardial depression is not known. Therefore, we investigated the effects of levosimendan on the negative inotropic response to ropivacaine in isolated heart preparations of guinea pigs. METHODS: Action potentials and force of contraction were studied with conventional techniques in guinea-pig papillary muscles. Heart rate, systolic pressure, the first derivative of left ventricular pressure (+dP/dt(max)), coronary flow, and PR and QRS intervals were measured in isolated constant-pressure perfused, nonrecirculating Langendorff heart preparations. Single or cumulatively increasing concentrations of levosimendan and ropivacaine were used either alone or in combination. RESULTS: In isolated papillary muscle, ropivacaine reduced force of contraction in a concentration-dependent manner. Exposure to 10 microM levosimendan in the presence of 10 muM ropivacaine almost completely reversed the negative inotropic response. Sensitivity to the positive inotropic effect of levosimendan was not altered by 10 muM ropivacaine (-logEC50 [M] = 7.03 without versus 6.9 with ropivacaine, respectively). Action potential parameters were influenced only at the highest concentration. In the Langendorff heart, levosimendan significantly reversed the ropivacaine-induced reduction in heart rate, systolic pressure, coronary flow, and +dP/dt(max) to baseline values. CONCLUSION: Levosimendan is an effective inotropic drug in ropivacaine-induced myocardial depression and levosimendan myocardial sensitivity, and efficacy was not affected by the local anesthetic. Our results suggest that the calcium-sensitizing action of levosimendan is effective in local anesthetic-induced cardiac depression.
Sebastian N Stehr; Torsten Christ; Berit Rasche; Stefan Rasche; Erich Wettwer; Andreas Deussen; Ursula Ravens; Thea Koch; Matthias Hübler
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesia and analgesia     Volume:  105     ISSN:  1526-7598     ISO Abbreviation:  Anesth. Analg.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-24     Completed Date:  2007-09-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1310650     Medline TA:  Anesth Analg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  641-7     Citation Subset:  AIM; IM    
Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
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MeSH Terms
Action Potentials / drug effects
Amides / toxicity*
Anesthetics, Local / toxicity*
Cardiotonic Agents / pharmacology*
Coronary Circulation / drug effects
Dose-Response Relationship, Drug
Guinea Pigs
Heart / drug effects*,  physiopathology
Heart Rate / drug effects
Hydrazones / pharmacology*
Myocardial Contraction / drug effects*
Papillary Muscles / drug effects*,  physiopathology
Pyridazines / pharmacology*
Time Factors
Ventricular Function, Left / drug effects*
Ventricular Pressure / drug effects
Reg. No./Substance:
0/Amides; 0/Anesthetics, Local; 0/Cardiotonic Agents; 0/Hydrazones; 0/Pyridazines; 131741-08-7/simendan; 84057-95-4/ropivacaine

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