Effects of ropivacaine and bupivacaine on rabbit myocardial energetic metabolism and mitochondria oxidation

Abstract

To compare the cardiotoxicity induced by ropivacaine and bupivacaine and to investigate the mechanism of cardiotoxicity, 24 mature New Zealand rabbits were divided randomly into control group (group C), ropivacaine group (group R) and bupivacaine group (group B). Hearts were drawn out rapidly from the anesthetized animals and cardiac perfusion was performed immediately. Ropivacaine 500 ng/ml (group R) or bupivacaine 500 ng/ml (group B) was added to the perfusion solution. Ventricular myocardial ATP, ADP and AMP were measured with high performance liquid chromatogram. The ability of myocardial mitochondria oxidation to pyruvate or palmitoylcarnitine was detected with Clark electrode. Our results showed that myocardial ATP and ADP decreased significantly (P<0.05) in group R and most significantly (P<0.01) in group B as compared with group C. Myocardial ATP and ADP decreased most significantly (P<0.01) in group B as compared with group R. The changes of myocardial AMP revealed significant difference among three groups. The changes of pyruvate oxidation exibited no significant difference among the three groups. Palmitoylcarnitine oxidation decreased markedly (P<0.05) in group R and most significantly (P<0.01) in group B as compared with group C. The present study indicated that the inhibition of lipid substrate oxidation may be responsible for the cardiotoxicity induced by bupivacaine and ropivacaine. The cardiotoxicity induced by ropivacaine is far more less than bupivacaine.

Keywords

bupivacaine / ropivacaine / toxicity / mitochondria

References

[1] FredmanB, ShapiroA, ZoharE, et al. . The analgesic efficacy of patient-controlled ropivacaine instillation after cesarean delivery. Anesth Analg, 2000, 911436-1436

[2] StocchiV, CucchiariniL, CanestraiF, et al. . A very fast ion-pair reversephase HPLC method for the separation of the most significant nucleotides and their degradation products in human red blood cells. Anal Biochem, 1987, 167181-181

[3] PalmerJ W, TandlerB, HoppelC L. Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac muscle. J Biol Chem, 1977, 2528731-8731

[4] WeinbergG L, PalmerJ W, VadeBoncouerT R, et al. . Bupivacaine inhibits acylcarnitine exchange in cardiac mitochondria. Anesthesiology, 2000, 92523-523

[5] ClarksonC W, HondeghemL M. Mechanism for bupivacaine depression of cardiac conduction: Fast block of sodium channels during the action potenial with slow recovery from block during diastole. Anesthesiology, 1985, 62396-396

[6] ButterworthJ, JamesR, GrimesJ. Structure-affinity relationships and stereospecificity of several homologous series of local anesthetics for beta2-adrenergic receptor. Anesth Analg, 1997, 85336-336

[7] HeavnerJ E. Cardiac dysehythmias induced by infusion of local anesthetics into the lateral cerebral ventricle of cats. Anest Analg, 1986, 65133-133

[8] ChazotteB, VanderkooiG. Multiple sites of inhibition of mitochondrial electron transport by local anesthetics. Biochem Biophys Acta, 1981, 636151-151

[9] Collins-NakaiR L, NoseworthyD, LopaschukG D. Epinephrine increases ATP production in hearts by preferentially increasing glucose metabolism. Am J Physiol, 1994, 267H867-H867

[10] FloridiA, Di PadovaM, BarbieriR, et al. . Effect of local anesthetic ropivacaine on isolated rat liver mitochondria. Biochem Pharmacol, 1999, 151009-1009

[11] SztarkF, MalgatM, DabadieP, et al. . Comparison of effects of bupivacaine and ropivacaine on heart cell mitochondrial bioenergetics. Anesthesiology, 1998, 881340-1340