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

• Published in: European journal of anaesthesiology Vol. 24; no. 4; p. 340
• Main Authors: Stehr, S N, Pexa, A, Hannack, S, Heintz, A, Heller, A R, Deussen, A, Koch, T, Hübler, M
• Format: Journal Article
• Language: English
• Published: England 01.04.2007
• Subjects: Adenine Nucleotides - analysis; Anesthetics, Local - toxicity; Animals; Bupivacaine - analogs & derivatives; Bupivacaine - toxicity; Electrocardiography - drug effects; Energy Metabolism - drug effects; Heart - drug effects; Heart Rate - drug effects; Insulin - pharmacology; Rats; Rats, Wistar
• ISSN: 0265-0215
• DOI: 10.1017/S0265021506002109

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. An isolated rat heart constant-pressure perfused, non-recirculating Langendorff preparation was used. Hearts were exposed to l-bupivacaine 5 microg 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. 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. 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.