Cross-bridge thermodynamics in pulmonary arterial hypertensive right-ventricular failure

Figures

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  Figure 1.. Energetic parameters are extracted from a series of afterloaded work-loop contractions. Steady-state stress-length work-loops at various afterloads from a single representative trabecula (A). Average values of parameters are shown (B–K), where *statistically significant differences between the CON (n = 8) and the FAIL (n = 13) trabeculae. Each inset in H–K illustrates the interpolation of the parameter of interest at the passive stress (H and I), or at the stress that maximizes work (J) or that maximizes mechanical efficiency (K), as indicated by the thin broken vertical lines. Values are presented as means ± SE. CON, control; FAIL, failing.

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  Figure 2.. Correlations among mechano-energetic and morphometric parameters. In all panels (A–F), each data point was obtained from a single trabecula. Data were fitted using linear regression, displayed as a solid line, and associated with 95% confidence intervals, displayed by the concave lines. Open symbols indicate CON group; filled symbols indicate FAIL group. Statistical significance of the correlation is indicated by the presence of an * at the top left corner. Spearman’s correlation coefficient (ρ) and R2 values are shown in each panel. CON, control; FAIL, failing; RV, right ventricle.

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  Figure 3.. Correlations among peak mechanical efficiency and mechano-energetic parameters (A–D). The plotting convention is the same as in Fig. 2, where open symbols indicate CON group; filled symbols indicate FAIL group, and statistical significance of the correlation is indicated by the presence of an * at the top left corner. Spearman’s correlation coefficient (ρ) and R2 values are shown in each panel. CON, control; FAIL, failing.

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  Figure 4.. Correlations among mechanical parameters. The plotting convention is the same as in Fig. 2, where open symbols indicate CON group; filled symbols indicate FAIL group, and statistical significance of the correlation is indicated by the presence of an * at the top left corner. CON, control; FAIL, failing.

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  Figure 5.. Correlations between heat and mechanical efficiency. A: averages of activation heat and cross-bridge (XB) heat are shown for both CON (n = 8) and the FAIL (n = 13) groups, where *statistically significant difference between groups. The left inset shows heat-stress relations from a representative FAIL trabecula for both isometric and work-loop contractions, in which both sets of data were fitted using linear regression, and both activation heat and cross-bridge heat were estimated at the active stress that gave peak mechanical efficiency (as indicated by the arrows). The right inset shows heat-stress relations from representative CON and FAIL trabeculae for both isometric and work-loop contractions. For B–E, the plotting convention is the same as in Fig. 2, where open symbols indicate CON group; filled symbols indicate FAIL group, and statistical significance of the correlation is indicated by the presence of an * at the top left corner. Values are presented as means ± SE. CON, control; FAIL, failing; RV, right ventricle.

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  Figure 6.. No correlations between cross-bridge efficiency and key indices of energetics. Cross-bridge (XB) efficiency, calculated as the ratio of work to the sum of work and cross-bridge heat (Fig. 5A inset), was not statistically different between CON (n = 8) and the FAIL (n = 13) trabeculae (A) and did not correlate with the indices shown in B–F. Values are presented as means ± SE. CON, control; FAIL, failing; RV, right ventricle.

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  Figure 7.. No correlations between cross-bridge dynamic stiffness and indices of mechano-energetics. A: single perturbed twitch stress is shown where the amplitude of oscillation provides a measure of cross-bridge dynamic stiffness. Average values of dynamic moduli at diastole and peak systolic stress from CON (n = 6) and the FAIL (n = 9) trabeculae are shown. B–G: show an absence of dependence of key indices of mechano-energetics on dynamic cross-bridge modulus. Values are presented as means ± SE. CON, control; FAIL, failing; XB, cross-bridge.