The effects of levosimendan on myocardial function in ropivacaine toxicity in isolated guinea pig heart preparations.
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.


CONCLUSIONS
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.
Stehr
Sebastian N
SN
Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. sebastian.stehr@gmx.de
Christ
Torsten
T
Rasche
Berit
B
Rasche
Stefan
S
Wettwer
Erich
E
Deussen
Andreas
A
Ravens
Ursula
U
Koch
Thea
T
Hübler
Matthias
M
D000200:Action Potentials / Q000187:drug effects; D000577:Amides / Q000633:toxicity*; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects* / Q000503:physiopathology; D011724:Pyridazines / Q000494:pharmacology*; D000077212:Ropivacaine; D000077464:Simendan; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
D000577:Amides; D000779:Anesthetics, Local; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D000077212:Ropivacaine