Eight parameter changes corresponding to heart failure, as previously simulated (), are implemented in a mathematical model of the human ventricular myocyte (). *A*, the heart failure simulation predicted an increase in APD. *B*, the heart failure simulation predicted a decrease in Δ[Ca^{2+}]_{i}. *C*, the matrix multiplication approach after performing multivariable regression allows us to correctly predict these changes in APD and Δ[Ca^{2+}]_{i} by summing up the independent contributions of each of the eight parameter changes. This approach also reveals which parameter changes are most responsible for the observed changes in phenotype. For example, NCX and *G*_{K1} both contribute greatly to APD prolongation while NCX and K_{leak} are predominantly responsible for the decrease in calcium transient amplitude. *D*, compensatory changes occur to maintain APD at control value when NCX and *G*_{K1} are both reduced to 0.5 and 0.7 times their control values, respectively. For these simulations, the particular parameter changes implemented, represented graphically in *C*, are as follows: decrease in maximal slow transient outward K^{+} conductance (*G*_{toslow}), decrease in maximal fast transient outward K^{+} conductance (*G*_{tofast}), decrease in maximal slow delayed rectifier K^{+} current conductance (*G*_{Ks}), decrease in maximal inward rectifier K^{+} conductance (*G*_{K1}), increase in maximal Na^{+}–Ca^{2+} exchange current (NCX), increase in SR Ca^{2+} release (K_{s}), increase in passive SR Ca^{2+} leak (K_{leak}), and decrease in maximal rate of SR Ca^{2+} uptake (*V*_{maxSRCaP}).

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