© 2000 American Heart Association, Inc.
Integrative Physiology |
Alterations in the Determinants of Diastolic Suction During Pacing Tachycardia
From the Cardiology Unit (S.P.B., L.N., M.D.T., M.M.L.), University of Vermont College of Medicine, Burlington, Vt, and Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology (M.M., H.G.), Washington State University, Pullman, Wash.
Correspondence to Martin M. LeWinter, MD, Cardiology Unit, Fletcher Allen Health Care, 111 Colchester Ave, Burlington, VT 05401. E-mail martin.lewinter{at}vtmednet.org
Abstract—In
cardiomyocytes, generation of restoring forces (RFs)
responsible for elastic recoil involves deformation of the sarcomeric
protein titin in conjunction with shortening below slack length. At the
left ventricular (LV) level, recoil and filling by suction
require contraction to an end-systolic volume (ESV) below
equilibrium volume (Veq) as well as large-scale deformations, for
example, torsion or twist. Little is known about RFs and suction in the
failing ventricle. We undertook a comparison of determinants of suction
in open-chest dogs previously subjected to 2 weeks of pacing
tachycardia (PT) and controls. To assess the ability of the
LV to contract below Veq, we used a servomotor to clamp left atrial
pressure and produce nonfilling diastoles, allowing
measurement of fully relaxed pressure at varying volumes. We quantified
twist with sonomicrometry. We also assessed transmural ratios of N2B to
N2BA titin isoforms and total titin to myosin heavy chain (MHC)
protein. In PT, the LV did not contract below Veq, even with marked
reduction of volume (end-diastolic pressure [EDP], 1 to
2 mm Hg), whereas in controls ESV was less than Veq when EDP was
less than 
5 mm Hg. In PT, both systolic twist and
diastolic untwisting rate were reduced, and there was exaggerated
transmural variation in titin isoform and titin-to-MHC ratios,
consistent with the more extensible N2BA being present in
larger amounts in the subendocardium. Thus, in PT, determinants of
suction at the level of the LV are markedly impaired. The altered
transmural titin isoform gradient is consistent with a decrease
in RFs and may contribute to these findings.
Key Words: suction • restoring forces • diastole • heart failure • tachycardia
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