Figure 1. Threshold-based recovery of cardiac output and the cardiotonic effect of ILE.

(A) Treatment with ILE (10mL/kg 30% Intralipid) at t=0.5 over 1 minute (ILE, n=11) improves recovery of carotid flow following a 10mg/kg infusion of bupivacaine ending at t=0, (null, n=9) Mean ± SEM. (B) Treatment with ILE increases removal of bupivacaine from cardiac tissue as assessed by fitting curves to single-phase exponential decay with plateau=0 and shared y-intercept (n=24 animals for ILE, n=28 for null). (C) Carotid flow does not recover until achieving a bupivacaine concentration below ~100nmol/g corresponding to IC₅₀ of bupivacaine inhibition from Clarkson & Hondeghem, 1985. Below 100nmol/g, the curves diverge with a greater improvement in flow at equivalent bupivacaine concentrations for animals treated with ILE (ILE, n=11, mean line) compared to control (null, n=4, mean line). (D) Accompanying Mann-Whitney U-test between Null and ILE for “C” (39-300 nmol/g) demonstrating significant difference in carotid flows for concentrations <56nmol/g. A transient drop at ~250nmol/g corresponds to infusion of lipid. (E) In vivo experimental data (95% confidence intervals) with in silico prediction overlaid demonstrating that incorporating the bupivacaine disassociation constant from the sodium channel produces a robust fit between in vivo and in silico data sets.