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Insulin effects on myocardial function and bioenergetics in l-bupivacaine toxicity in the isolated rat heart

Published online by Cambridge University Press:  01 April 2007

S. N. Stehr ,
A. Pexa ,
S. Hannack ,
A. Heintz ,
A. R. Heller ,
A. Deussen ,
T. Koch  and
M. Hübler
S. N. Stehr
Affiliation:
Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine
A. Pexa
Affiliation:
Institute of Physiology, Dresden, Germany
S. Hannack
Affiliation:
Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine
A. Heintz
Affiliation:
Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine
A. R. Heller
Affiliation:
Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine
A. Deussen
Affiliation:
Institute of Physiology, Dresden, Germany
T. Koch
Affiliation:
Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine
M. Hübler
Affiliation:
Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine
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Summary

Background and objectives

A positive effect of insulin–glucose–potassium infusion in severe bupivacaine-induced cardiovascular collapse has been described in vivo. It has been speculated that an antagonistic influence of insulin on sodium channel inhibition, transient outward potassium current, calcium-dependent adenosine triphosphatase or even improved myocardial energetics may be responsible for this effect. Using an isolated heart model, we therefore sought to further elucidate insulin effects in l-bupivacaine-induced myocardial depression.

Methods

An isolated rat heart constant-pressure perfused, non-recirculating Langendorff preparation was used. Hearts were exposed to l-bupivacaine 5 μg mL−1 and insulin 10 mIU mL−1. Heart rate, systolic pressure, the first derivative of left ventricular pressure (+dP/dt), coronary flow, double product, PR and QRS intervals were recorded. Hearts were freeze-clamped and high-performance liquid chromatography measurement of the total adenine nucleotide pool was performed.

Results

l-Bupivacaine led to a significant decrease in heart rate, +dP/dt, systolic pressure, coronary flow and double product, and to an increase in PR and QRS. Insulin exerted a positive inotropic effect, significantly augmenting +dP/dt and systolic pressure in both l-bupivacaine-treated and control hearts. Heart rate, coronary flow, total adenine nucleotides, PR and QRS were not significantly changed by the insulin intervention.

Conclusion

Insulin did not have a significant effect on total adenine nucleotides in controls and in l-bupivacaine-treated hearts. However, it does exert a positive inotropic action in bupivacaine-induced myocardial depression. We conclude that the positive effect of insulin application lies in positive inotropic action and not in changes in total adenine nucleotides.

Keywords

ANAESTHETICS LOCAL, bupivacaine, toxicityDRUG TOXICITYHEARTINSULINADENOSINE TRIPHOSPHATE
Type
Research Article
Information
European Journal of Anaesthesiology , Volume 24 , Issue 4 , April 2007 , pp. 340 - 346
Copyright
Copyright © European Society of Anaesthesiology 2007

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