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NHE Inhibition Does Not Improve Na+ or Ca2+ Overload During Reperfusion: Using Modeling to Illuminate the Mechanisms Underlying a Therapeutic Failure
Figure 5
Changes in ion concentrations and pH during simulated reperfusion.
(A) intracellular sodium (
), (B) maximum and minimum intracellular calcium (
), and (C) intracellular pH (
) during simulated ischemia (gray region) and reperfusion during four simulations: Control (with no NHE inhibition) (black), NHE inhibition beginning with reperfusion at 50 percent (blue) or 100 percent (green) reduction, and 100 percent NHE blockade beginning with ischemia (light blue). In (B), the three insets, plotted on the same vertical axis as the main figure, show 2000 ms of intracellular calcium transients corresponding to the regions denoted by the vertical dashed lines: just prior to the onset of ischemia (left); during late ischemia, demonstrating alternans (middle); and late in the observed reperfusion window (right).
doi: https://doi.org/10.1371/journal.pcbi.1002241.g005