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(Circulation. 1998;98:2919-2929.)
© 1998 American Heart Association, Inc.

Basic Science Reports

Mechanoenergetic Alterations During the Transition From Cardiac Hypertrophy to Failure in Dahl Salt-Sensitive Rats

Tomoki Kameyama, MD; Zengyi Chen, MD; Stephen P. Bell, BA; Peter VanBuren, MD; David Maughan, PhD; Martin M. LeWinter, MD

From the Cardiology Unit, Department of Medicine (T.K., Z.C., S.P.B., P.v.B., M.M.L.), and the Department of Molecular Physiology and Biophysics (D.M.), The University of Vermont College of Medicine, Burlington, Vt.

Correspondence to Martin M. LeWinter, MD, Cardiology Unit, Fletcher Allen Health Care/MCHV Campus, 111 Colchester Ave, Burlington, VT 05401. E-mail martin.lewinter{at}vtmednet.org

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 (O₂)–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)–O₂ relation] was similar in HS-6 and LS-6 but higher in HS-12 versus LS-12 (218±123 versus 74±39x10³ 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<.001).

Conclusions—In DS rats, the transition to failure is associated with depressed E'_max and increased efficiency and economy. These findings are linked to myofibrillar ATPase activity and suggest that mechanisms other than isomyosin switching are important determinants of ventricular energetics. A troponin T isoform switch is one potential mechanism.

Key Words: myocardium • hypertrophy • myofibrillar ATPase activity • myosin • troponin T

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