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Enantiomer-Specific Effects of an Intravenously Administered Arrhythmogenic Dose of Bupivacaine on Neurons of the Nucleus Tractus Solitarius and the Cardiovascular System in the Anesthetized Rat
  1. Donald D. Denson, PH.D.*,
  2. Michael M. Behbehani, PH.D.** and
  3. Richard V. Gregg, M.D.*
  1. *From the Departments of Anesthesia and Physiology and
  2. **Biophysics, University of Cincinnati College of Medicine, Ohio.
  1. Address correspondence to Donald D. Denson, Ph.D., Department of Anesthesiology, Emory University School of Medicine, 1364 Clifton Rd. NE, Atlanta, GA 30322.


Background and Objective. This investigation was designed to determine whether the effects on the cell firing rate (CFR) at the nucleus tractus solitarius (NTS) and on the cardiovascular system, which are associated with a toxic dose of bupivacaine, have an enantiomer-specific component.

Methods. Adult Sprague-Dawley rats were anesthetized with chloral hydrate, and a femoral artery and vein were cannulated. After the cranial surface was exposed, a 3-mm hole was drilled 2 mm caudal and 1.5 mm lateral with respect to lambda for placement of a 1-μm tungsten microelectrode. Cells of the NTS were located 6-6.5 mm from the brain surface, and CFR was continuously recorded. Lead II electrocardiogram and arterial blood pressure were also recorded. Twenty-four animals received either d- or l-bupivacaine (2 mg/kg) in random order.

Results. Cell firing rates decreased from 21 ± 13 to 0 ± 0 impulses/second ( p < 0.001) at 34 ± 15 seconds after the injection of d-bupivacaine. Cell firing rates decreased from 22 ± 17 to 2 ± 4 impulses/second ( p < 0.01) at 68 ± 45 seconds after injection of l-bupivacaine. In addition to the decreases in blood pressure and heart rate that were found, all animals exhibited an inversion in electrical axis beginning within 2-3 seconds after bupivacaine administration. Mild bradycardia was noted in four of the animals receiving the l-bupivacaine, whereas severe bradycardia was observed in all animals receiving d-bupivacaine. Most important, this severe bradycardia was accompanied by progressive hypotension. In addition, all animals receiving d-bupivacaine became apneic and died, whereas all animals receiving l-bupivacaine continued to breathe and all but two of the animals survived.

Conclusions. Data in the current report support the hypothesis that effects of bupivacaine on neurons of the NTS and on the cardiovascular system have an enantiomer-specific component.

  • Anesthetics
  • local
  • bupivacaine
  • toxicity
  • local anesthetic
  • central nervous system
  • medulla
  • nucleus tractus solitarius.

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  • This work was supported in part by the Department of Anesthesia, University of Cincinnati College of Medicine, and in part by a Carl Koller Research Grant awarded to one of the authors (DDD) by the American Society of Regional Anesthesia.