title: Insulin effects on myocardial function and bioenergetics in L-bupivacaine toxicity in the isolated rat heart.
abstract: OBJECTIVE
  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 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine, Dresden, Germany. sebastian.stehr@gmx.de
authors.forename: S N
authors.initials: SN
authors.lastname: Stehr
authors.forename: A
authors.initials: A
authors.lastname: Pexa
authors.forename: S
authors.initials: S
authors.lastname: Hannack
authors.forename: A
authors.initials: A
authors.lastname: Heintz
authors.forename: A R
authors.initials: AR
authors.lastname: Heller
authors.forename: A
authors.initials: A
authors.lastname: Deussen
authors.forename: T
authors.initials: T
authors.lastname: Koch
authors.forename: M
authors.initials: M
authors.lastname: Hübler
mesh_terms: D000227:Adenine Nucleotides / Q000032:analysis; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000633:toxicity; D004562:Electrocardiography / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D000077554:Levobupivacaine; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000227:Adenine Nucleotides; D000779:Anesthetics, Local; D007328:Insulin; D000077554:Levobupivacaine; D002045:Bupivacaine