The effects of lipid infusion on myocardial function and bioenergetics in l-bupivacaine toxicity in the isolated rat heart.
BACKGROUND
It is unclear whether improved metabolism or a "lipid sink" effect of lipid infusion is responsible for the positive effects in local anesthetic-induced myocardial depression.


METHODS
We used an isolated rat heart, constant-pressure perfused, nonrecirculating Langendorff preparation and exposed hearts to 5 mug/mL l-bupivacaine and 9 microL/mL lipid emulsion. Hearts were freeze-clamped and energy was charge measured by HPLC. In a second experiment the effects of pacing hearts was evaluated. The effects of lipid addition on local anesthetic concentrations in Krebs-Henseleit buffer and human plasma were examined by using a mass spectrometer.


RESULTS
With spontaneously beating hearts l-bupivacaine led to a significant decrease in heart rate (to 74% +/- 7% of baseline), +dP/dt (69% +/- 7%), systolic pressure (78% +/- 6%), coronary flow (61% +/- 8%), and to an increase in PR (177% +/- 52%) and QRS intervals (166% +/- 36%). Lipid infusion exerted a positive inotropic effect, significantly augmenting +dP/dt and systolic pressure back to 94% +/- 11% and 102% +/- 16% of baseline in l-bupivacaine-treated hearts. Heart rate, coronary flow, PR, and QRS intervals remained unchanged after lipid intervention. Lipid infusion in paced hearts had a significant effect on +dP/dt, systolic pressure, and Mvo2. Neither l-bupivacaine nor lipids had an effect on energy charge. A lipid concentration of 500 muL/mL plasma was necessary to effect changes in the plasma concentration of local anesthetics.


CONCLUSIONS
Lipid application in l-bupivacaine-induced cardiac depression had a significant positive inotropic effect, which we would attribute to a direct inotropic effect. However, in an isolated heart model, indirect, local anesthetic plasma-binding effect of lipids cannot be excluded.
Stehr
Sebastian N
SN
Department of Anesthesiology and Intensive Care Medicine, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany. sebastian.stehr@gmx.de
Ziegeler
Jörg C
JC
Pexa
Annette
A
Oertel
Reinhard
R
Deussen
Andreas
A
Koch
Thea
T
Hübler
Matthias
M
D000818:Animals; D002045:Bupivacaine / Q000633:toxicity*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008055:Lipids / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D023421:Models, Animal; D051381:Rats
D008055:Lipids; D002045:Bupivacaine