Interventricular comparison of the energetics of contraction of trabeculae carneae isolated from the rat heart

Abstract

We compare the energetics of right ventricular and left ventricular trabeculae carneae isolated from rat hearts. Using our work-loop calorimeter, we subjected trabeculae to stress-length work (W), designed to mimic the pressure-volume work of the heart. Simultaneous measurement of heat production (Q) allowed calculation of the accompanying change of enthalpy (H = W + Q). From the mechanical measurements (i.e. stress and change of length), we calculated work, shortening velocity and power. In combination with heat measurements, we calculated activation heat (Q(A)), crossbridge heat (Q(xb)) and two measures of cardiac efficiency: 'mechanical efficiency' ((mech) = W/H) and 'crossbridge efficiency' ((xb) = W/(H - Q(A))). With respect to their left ventricular counterparts, right venticular trabeculae have higher peak shortening velocity, and higher peak mechanical efficiency, but with no difference of stress development, twitch duration, work performance, shortening power or crossbridge efficiency. That is, the 35% greater maximum mechanical efficiency of right venticular than left ventricular trabeculae (13.6 vs. 10.2%) is offset by the greater metabolic cost of activation (Q(A)) in the latter. When corrected for this difference, crossbridge efficiency does not differ between the ventricles.

Figure 1. Steady-state traces of twitch stress, extent of shortening and rate of heat production of a representative trabecula

A and B, twitch stress (A) and muscle length (B), as functions of time, of a trabecula at L_o and at 1 Hz undergoing isometric (a), unloaded-isotonic (f), and isotonic afterloaded work-loop (b to f) contractions. The thick segments of length traces in B represent the 30 ms periods used to estimate the initial velocity of shortening (indexed by the slope of each length–time trace). C, records of rate of heat production during each of the three modes of contraction. The vertical scale bar corresponds to 10 kW m⁻³. The trabecula was from the RV and had length of 2.75 mm and diameter of 375 μm.

Figure 2. Steady-state total stress and passive stress as functions of relative trabecula length

A, stress–length work-loops of a representative RV trabecula (length 2.75 mm, diameter 275 μm) undergoing isometric (a), unloaded-isotonic (f) and variable-afterload work-loop (b to e) contractions at 1 Hz, at preloads of L_o (thick lines) and L_r (thin lines, approximately 0.95 L_o). The combined end-systolic points and end-diastolic points were fitted using cubic regression (upper and lower broken lines, respectively). B, end-systolic and end-diastolic lines were averaged across 14 trabeculae from each ventricle. Thick lines, RV; thin lines, LV; continuous lines, 0.5 Hz; broken lines, 1 Hz. The isometric stresses at both L_o and L_r were averaged and superimposed. Symbols are mean ± SEM; filled symbols, RV; open symbols, LV; circles, 0.5 Hz; triangles, 1 Hz. There were no statistically significant differences of either total stress or passive stress between ventricles.

Figure 3. Twitch duration–afterload relations

A, individual data at 1 Hz from representative muscles (RV, thick lines, filled symbols; LV, thin lines, open symbols). Data of L_o (circles) and L_r (triangles) were grouped and fitted by linear regression. RV trabecula: length 3.75 mm, diameter 275 μm; LV trabecula: length 2.00 mm, diameter 325 μm. B, average relations for the 14 trabeculae at 0.5 Hz (continuous lines) and 1 Hz (broken lines) isolated from RV (thick lines) and LV (thin lines). There was no difference of twitch duration between ventricles.

Figure 4. Initial shortening velocity and power as functions of relative afterload

A and B, averaged (n= 14 regression lines) initial shortening velocities (V_max) at L_o (thick lines), L_r (thin lines) and at 0.5 Hz (continuous lines) and 1 Hz (broken lines) isolated from LV (A) and RV (B). The measured peak values of V_max were averaged and superimposed (filled symbols, L_o; open symbols, L_r; circles, 0.5 Hz; triangles, 1 Hz). The average peak V_max values were greater for RV than for LV trabeculae and greater at L_o than at L_r. C and D, initial shortening power () as functions of relative afterload. The estimated peak values of (calculated from each of the individual 14 fitted curves) were averaged and superimposed. There was no significant difference of the average peak values of between RV and LV. At peak , no difference of V_max between ventricles. Insets show data from representative trabeculae at 1 Hz and at L_o (RV trabecula: length 3.50 mm, diameter 325 μm; LV trabecula: length 2.00 mm, diameter 325 μm).

Figure 5. Heat as a function of afterload

A, data at 1 Hz from representative trabeculae of RV (thick line, filled symbols) and LV (thin line, open symbols). B, averaged regression lines of the 14 trabeculae from each ventricle: thick lines, RV; thin lines, LV; continuous lines, 0.5 Hz; dotted lines, 1 Hz. All data fitted by linear regression. There was no difference of slopes, but significant difference of intercepts, between ventricles. There was no effect of stimulus frequency.

Figure 6. Twitch energy (heat or change of enthalpy), external mechanical work density, mechanical efficiency and crossbridge efficiency as functions of relative afterload

The curves in each panel are the averages of fitted functions from 14 trabeculae; the insets show data from representative muscles at 1 Hz and at L_o. Superimposed on the averaged curves are the respective average values, estimated from each of the fitted functions (same plotting conventions as in Fig. 4). The straight grey lines in A and B denote the relations between heat and relative afterload. The broken vertical lines have been located to pass through the point of peak work (right-hand line) or peak mechanical efficiency (left-hand line). No significant difference of the peak values of work density or crossbridge efficiency between RV and LV trabeculae. Peak mechanical efficiency and mechanical efficiency at peak work were greater in RV than in LV.

Figure 8. Output of a finite element model of the measurement chamber of the microcalorimeter

Temperature sensitivity of the upstream and downstream thermocouples and their difference, for trabeculae of three lengths: 1 mm (filled circles), 2 mm (stars) and 3 mm (open circles). The vertical dotted line denotes the optimal location of the centre of the trabecula – approximately 0.75 mm downstream of the centre of the measurement chamber.

Figure 9. Dependence of measured twitch heat production on muscle length

Maximum rates of heat production observed for all 28 trabeculae (RV, filled symbols; LV, open symbols) at both stimulus frequencies (circles, 0.5 Hz; triangles, 1 Hz) at L_o. Average regression equation: Heat = 27.7 kJ m⁻³– 3.37 kJ m⁻³ mm⁻¹× Length (r²= 0.29; s_y.x= 3.6 kJ m⁻³).

Figure 7. Simulations arising from our implementation of the mathematical model of muscle energetics of Landesberg et al. (2000)

A, effect of increasing crossbridge viscosity (η) between 0 (straight line) and 0.9 (in steps of 0.1) on the number of attached crossbridges (N_xb) as a function of the relative force generated by the muscle (F_rel). B, normalised heat (Q) and change of enthalpy (ΔH) from Fig. 6. Knowing F_rel and V_rel (see text) allows calculation of work (W) from which are derived mechanical efficiency (ɛ_mech=W/ΔH) and crossbridge efficiency (ɛ_xb=W/(ΔH–Q_A), where ((relative) Q_A= 0.3) with η= 0. C, faint lines: same dependent variables as in B, but plotted as functions of N_xb; note identical graphs (faint lines). Thick lines: effect of increased viscosity (η= 0.5). D, identical data as in B but with dependent variables plotted as functions of V_rel.