Alterations in the determinants of diastolic suction during pacing tachycardia

Stephen P. Bell, Lori Nyland, Marc D. Tischler, Mark McNabb, Hendrikus "Henk" Granzier, Martin M. LeWinter

Research output: Contribution to journalArticle

146 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)235-240
Number of pages6
JournalCirculation Research
Volume87
Issue number3
StatePublished - 2000
Externally publishedYes

Fingerprint

Connectin
Suction
Tachycardia
Protein Isoforms
Myosin Heavy Chains
Blood Pressure
Atrial Pressure
Cardiac Myocytes
Proteins
Thorax
Dogs
Pressure

Keywords

  • Diastole
  • Heart failure
  • Restoring forces
  • Suction
  • Tachycardia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Bell, S. P., Nyland, L., Tischler, M. D., McNabb, M., Granzier, H. H., & LeWinter, M. M. (2000). Alterations in the determinants of diastolic suction during pacing tachycardia. Circulation Research, 87(3), 235-240.

Alterations in the determinants of diastolic suction during pacing tachycardia. / Bell, Stephen P.; Nyland, Lori; Tischler, Marc D.; McNabb, Mark; Granzier, Hendrikus "Henk"; LeWinter, Martin M.

In: Circulation Research, Vol. 87, No. 3, 2000, p. 235-240.

Research output: Contribution to journalArticle

Bell, SP, Nyland, L, Tischler, MD, McNabb, M, Granzier, HH & LeWinter, MM 2000, 'Alterations in the determinants of diastolic suction during pacing tachycardia', Circulation Research, vol. 87, no. 3, pp. 235-240.
Bell SP, Nyland L, Tischler MD, McNabb M, Granzier HH, LeWinter MM. Alterations in the determinants of diastolic suction during pacing tachycardia. Circulation Research. 2000;87(3):235-240.
Bell, Stephen P. ; Nyland, Lori ; Tischler, Marc D. ; McNabb, Mark ; Granzier, Hendrikus "Henk" ; LeWinter, Martin M. / Alterations in the determinants of diastolic suction during pacing tachycardia. In: Circulation Research. 2000 ; Vol. 87, No. 3. pp. 235-240.
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