Effects of bupivacaine, levobupivacaine and ropivacaine on myocardial relaxation.
OBJECTIVE
Ropivacaine and levobupivacaine were developed to reduce the risk of occasional toxicity reported with bupivacaine. While the effects of long-acting local anesthetics (LAAs) on myocardial contractility (inotropy) are well described, their effects on relaxation (lusitropy) remain largely unknown. The present study aimed to compare the effects of LAAs on rat myocardium.


METHODS
Left ventricular papillary muscles of male Wistar rats were used to compare the inotropic and lusitropic responses of increasing concentrations of LAAs (10(-8) to 10(-3) M) under isometric and isotonic conditions. Data are mean % (SD) of baseline value.


RESULTS
Long-acting local anesthetics induced a significant impairment of relaxation in isotonic and isometric conditions. As compared to ropivacaine, bupivacaine and levobupivacaine induced greater negative lusitropic effects in isotony [at 10(-3) M, maximum unloaded shortening velocity ((max)Vr) = 27 +/- 11 vs 13 +/- 6 and 8 +/- 5%] and isometry (at 10(-3) M, time-to-half-relaxation: 106 +/- 10 vs 127 +/- 17 and 133 +/- 17%). When the comparison was made with equipotent concentrations, the negative lusitropic effects induced with levobupivacaine were significantly greater than those of bupivacaine and ropivacaine in isometric and isotonic conditions (at 10(-3) M, (max)Vr = 7 +/- 4 vs 13 +/- 6 and 17 +/- 4 %). As previously described, LAAs also induced concentration-dependent negative inotropic effects that were greater for levobupivacaine compared to equivalent or equipotent concentrations of bupivacaine and ropivacaine.


CONCLUSIONS
Long-acting local anesthetics induce marked negative inotropic and lusitropic effects. Among LAAs, levobupivacaine exerts the greater depressant effects. Impairment of calcium handling and sarcoplasmic reticulum could explain the differential responses to local anesthetics.
David
Jean-Stéphane
JS
Laboratoire d'Anesthésiologie, Université Claude Bernard et Département d'Anesthésie-Réanimation, Hôpital Edouard Herriot et Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France. js-david@univ-lyon1.fr
Ferreti
Christian
C
Amour
Julien
J
Vivien
Benoit
B
Eve
Olivier
O
Petit
Paul
P
Riou
Bruno
B
Gueugniaud
Pierre-Yves
PY
D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000494:pharmacology*; D003864:Depression, Chemical; D003971:Diastole / Q000187:drug effects* / Q000502:physiology; D000077554:Levobupivacaine; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000077212:Ropivacaine; D018709:Statistics, Nonparametric
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D000077554:Levobupivacaine; D002045:Bupivacaine