Skeletal Muscle Growth Following Mechanical Overload Is Absent in HFpEF
(A) Unilateral synergistic surgical ablation of the tibialis anterior (TA) was performed to induce myofiber hypertrophy in the extensor digitorum longus (EDL) in HFpEF and control (CON) rats. (B) Representative images of nonoverload, contralateral (CL) and overload (OL) EDL muscles stained for Type I (red), Type IIa (green), and Type IIb/IIx (unstained/black) fibers and capillaries (bright green). (C) Total EDL FCSA and (D) fiber type distribution of CL (CON n = 8, HFpEF n = 8) and OL (CON n = 7, HFpEF n = 8). Absolute (E) twitch and (F) maximal forces (CL muscles: CON n = 8 and HFpEF n = 8; OL muscles: CON n = 7 and HFpEF n = 6). (G) Capillary-to-fiber ratio (C:F), (H) capillary density (CD) (CL muscles: CON n = 8 and HFpEF n = 8; OL muscles: CON n = 7 and HFpEF n = 8), and (I and J) muscle oxygen tension at maximal rate of oxygen consumption (CL muscles: CON n = 8 and HFpEF n = 8; OL muscles: CON n = 5 and HFpEF n = 7). In situ femoral artery blood flow at (K) rest and (L) during muscle stimulation (CL muscles: CON n = 6 and HFpEF n = 5; OL muscles: CON n = 6 and HFpEF n = 7). (M) In situ mitochondrial respiratory states of permeabilized EDL fibers presented as fold change relative to baseline CL muscle (each group n = 4). (N) Respiratory control ratio (RCR) (each group n = 4). Protein contents of (O) OPA1, PGC-1α, Drp1, (P) ACC, and ACL (each group n = 4). Differences were assessed by 2-way analysis of variance followed by Bonferroni post hoc test. Data are presented as mean ± SD, and the level of significance was accepted as ∗P < 0.05; ∗∗P < 0.01; and ∗∗∗P < 0.001 for all analyses. CIV = complex IV activity; EI+II = uncoupled respiration in the presence of complex I+II substrates; EII = uncoupled respiration in the presence of complex II substrates; LI = leak respiration with complex I substrates; PI = oxidative phosphorylation with complex I substrates; PI+II = oxidative phosphorylation with complex I+II substrates; other abbreviations as in Figure 1.