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From the *Department of Anesthesiology and Intensive Care Medicine; Institute of Physiology; and Institute of Clinical Pharmacology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
Address correspondence and reprint requests to Sebastian N. Stehr, Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscher St. 74, 01307 Dresden, Germany. Address e-mail to sebastian.stehr{at}gmx.de.
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 µg/mL l-bupivacaine and 9 µL/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 µL/mL plasma was necessary to effect changes in the plasma concentration of local anesthetics.
CONCLUSION: 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.
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