Mechanoenergetic alterations during the transition from cardiac hypertrophy to failure in Dahl salt-sensitive rats

Abstract

Background - The time course and mechanisms of altered mechanoenergetics and depressed cross-bridge cycling in hypertrophied and failing myocardium are uncertain. Methods and Results - We studied mechanoenergetics in Dahl salt-sensitive (DS) rats fed high-salt diet (HS) for 6 (HS-6) and 12 (HS-12) weeks to produce compensated hypertrophy and failure. The slope of the end- systolic pressure-volume relation (E'(max)) was similar in HS-6 and low-salt controls (LS-6), but reduced in HS-12 compared with controls (LS-12). Efficiency [1/slope of oxygen consumption (V̇O2)-pressure-volume area (PVA) relation] was similar in HS-6 and LS-6 but higher in HS-12 versus LS-12 (59±16% versus 44±7%, P<0.05). Economy [1/slope of the force-time integral (FTI)-V̇O2 relation] was similar in HS-6 and LS-6 but higher in HS-12 versus LS-12 (218±123 versus 74±39 X 103 g · s · mL O2-1 · g; P<0.05). Compared with controls, myofibrillar ATPase activity was reduced by 24% in HS-6 and 44% in HS-12. V3 Isomyosin was increased in HS-6 (40+ 12% versus 9±8%; P<0.05) and further increased in HS-12 (76±10% versus 22±18%; P<0.05). Hypothyroid LS-12 rats had 100% V3 isomyosin, yet efficiency, economy, and ATPase values were intermediate between LS-12 and HS-12. HS-12 rats demonstrated increased troponin T3 isoform (17±2 versus 23±2%, P<0.05). There were no changes in troponin I or tropomyosin isoforms. However, the proportion of phosphorylated troponin T was reduced in HS-12 versus LS-12 hearts (P