Fig. 5.
Pharmacokinetic–pharmacodynamic model of cardiac output relative to baseline (1.0) after bupivacaine-induced cardiac depression and subsequent recovery with different treatments. (A) Treatment-specific curves matched to experimental conditions for 30% intravenous lipid emulsion (ILE30), 20% ILE (ILE20), 0.9% saline (saline), and no treatment (null). For ILE30 and ILE20, the modeled response includes mathematical contributions from a volume effect, a sink effect, and an inotropic effect. (B) Mechanism-specific contributions to recovery from bupivacaine cardiac depression after an infusion of 30% ILE; mechanisms represented are no effect (null), volume effect only (volume; equivalent to 0.9% saline model), sink and volume, inotropy and volume, and a combination of sink, inotropy, and volume. Specific mechanisms and combinations were probed by turning on and off individual mathematical components as described in the Computational Modeling section of the Materials and Methods.