Abstract 768: Diastolic Sarcomere Lengths in the Left Ventricle: Implications for Titin-Based Myocardial Stiffness
Background: In cardiac muscle strips, slack sarcomere length (SL) is ~1.85 μm, and developed tension plateaus at 2.20–2.30 μm. In earlier studies, systolic SLs determined by EM in the left ventricle (LV) were found to be <1.85 μm. Diastolic SLs were 2.00–2.10 μm at mid-range physiologic transmural filling pressure (TFP). At markedly elevated TFP, SLs did not exceed 2.20–2.30 μm. Based on these results it has been considered that LV SLs parallel those in strips and never exceed 2.20–2.30 μm. However, these studies did not take into account the influence of coronary perfusion, the EM methods were subject to shrinkage, and diastolic SLs were not measured systematically over a range of TFPs. To understand the contribution of the sarcomeric protein titin to diastolic stiffness, it is critical to know the true SL range in the LV. This study was undertaken to determine the relation between TFP, strain and diastolic SL.
Methods: TFP and a midwall segment were measured in open-chest miniswine during transient caval occlusion to determine segment length at TFP ~ 0 mmHg (l0). Diastolic arrest was induced with KCl, TFP was adjusted to a value between 0 and ~ 50 mmHg with or without coronary perfusion at a physiologic pressure, and the heart was fixed with intra-coronary glutaraldehyde. SLs were measured using a light microsocopic method that obviates the need for embedding and sectioning, processes that can induce shrinkage.
Results: At TFP ~ 0 mmHg midwall SL was 2.10–2.15 μm. Around the physiologic limit of TFP [15–20 mmHg; segment strain (l/l0) 1.3–1.4] midwall SL was 2.45–2.50 μm. There was little or no additional increase at TFP > 20 mmHg. At TFP ~ 0 mmHg subepicardial SLs were shorter (2.05–2.10 μm) and subendocardial SLs longer (2.25–2.30 μm) than midwall SLs. As TFP increased, transmural SLs equalized. Physiologic coronary perfusion pressure did not systematically influence SLs.
Conclusions: Transmural diastolic SLs in LV are longer than previous studies indicate. This suggests that the three-dimensional structure of the LV modulates SL and/or previous results were affected by shrinkage. An important implication of these findings is that extension of titin and therefore its influence on passive myocardial and chamber stiffness as the LV fills are greater than previously thought.