Dataset Information

Insights From Computational Modeling Into the Contribution of Mechano-Calcium Feedback on the Cardiac End-Systolic Force-Length Relationship.

ABSTRACT: In experimental studies on cardiac tissue, the end-systolic force-length relation (ESFLR) has been shown to depend on the mode of contraction: isometric or isotonic. The isometric ESFLR is derived from isometric contractions spanning a range of muscle lengths while the isotonic ESFLR is derived from shortening contractions across a range of afterloads. The ESFLR of isotonic contractions consistently lies below its isometric counterpart. Despite the passing of over a hundred years since the first insight by Otto Frank, the mechanism(s) underlying this protocol-dependent difference in the ESFLR remain incompletely explained. Here, we investigate the role of mechano-calcium feedback in accounting for the difference between these two ESFLRs. Previous studies have compared the dynamics of isotonic contractions to those of a single isometric contraction at a length that produces maximum force, without considering isometric contractions at shorter muscle lengths. We used a mathematical model of cardiac excitation-contraction to simulate isometric and force-length work-loop contractions (the latter being the 1D equivalent of the whole-heart pressure-volume loop), and compared Ca2+ transients produced under equivalent force conditions. We found that the duration of the simulated Ca2+ transient increases with decreasing sarcomere length for isometric contractions, and increases with decreasing afterload for work-loop contractions. At any given force, the Ca2+ transient for an isometric contraction is wider than that during a work-loop contraction. By driving simulated work-loops with wider Ca2+ transients generated from isometric contractions, we show that the duration of muscle shortening was prolonged, thereby shifting the work-loop ESFLR toward the isometric ESFLR. These observations are explained by an increase in the rate of binding of Ca2+ to troponin-C with increasing force. However, the leftward shift of the work-loop ESFLR does not superimpose on the isometric ESFLR, leading us to conclude that while mechano-calcium feedback does indeed contribute to the difference between the two ESFLRs, it does not completely account for it.

SUBMITTER: Guidry ME

PROVIDER: S-EPMC7273927 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Insights From Computational Modeling Into the Contribution of Mechano-Calcium Feedback on the Cardiac End-Systolic Force-Length Relationship.

Guidry Megan E ME Nickerson David P DP Crampin Edmund J EJ Nash Martyn P MP Loiselle Denis S DS Tran Kenneth K

Frontiers in physiology 20200529

In experimental studies on cardiac tissue, the end-systolic force-length relation (ESFLR) has been shown to depend on the mode of contraction: isometric or isotonic. The isometric ESFLR is derived from isometric contractions spanning a range of muscle lengths while the isotonic ESFLR is derived from shortening contractions across a range of afterloads. The ESFLR of isotonic contractions consistently lies below its isometric counterpart. Despite the passing of over a hundred years since the first ...[more]

PMID: 32547426

Similar Datasets

Project description:AimsIn a hypertensive population with optimal blood pressure control with a long-term follow-up, we aimed at analysing possible predictors of left ventricular (LV) ejection fraction (LVEF) reduction, including indexed mechano-energetic efficiency (MEEi), a well-recognized echo-derived parameter of LV performance.Methods and resultsThe study population included 5673 hypertensive patients from the Campania Salute Network with a long-term follow-up, normal baseline LVEF (≥50%), and no prevalent cardiovascular (CV) disease. Patients developing LVEF impairment (LVEF < 50% or a reduction of at least 10 percentage points compared with baseline) were compared with patients with persistently normal LVEF. Optimal blood pressure control was achieved in about 80% of patients. Patients who experienced LVEF reduction were 2.41% during a long-term follow-up (mean duration 5.6 ± 3.9 years). At baseline, they were older (59.46 ± 11.58 vs. 53.40 ± 11.41, P < 0.0001) and showed higher LV mass index (53.3 ± 12.83 vs. 47.56 ± 9.58, P < 0.0001), left atrial (LA) volume index (14.4 ± 4.2 vs. 13.1 ± 2.8, P < 0.0001) and carotid intima-media thickness (1.99 ± 0.86 vs. 1.61 ± 0.73, P < 0.0001), lower MEEi (0.32 ± 0.08 vs. 0.34 ± 0.07, P = 0.037), and higher prevalence of CV events during follow-up (13.9% vs. 3%, P < 0.0001) compared with patients with persistently normal LVEF. A logistic regression analysis, performed after running univariate analyses and selecting parameters significantly associated with LVEF reduction, showed that having a CV event [odds ratio (OR) 7.57, P < 0.0001], being in the lowest MEEi quartile (OR 2.43, P = 0.003), and having a larger LA volume index (OR 1.08, P = 0.028) were all parameters independently associated with the development of LV systolic dysfunction. A further logistic regression model, performed by excluding patients experiencing CV events, demonstrated that the lowest MEEi quartile was independently associated with the evolution towards LVEF reduction (OR 2.35, P = 0.004), despite significant impact of LA volume index (OR 1.08, P = 0.023) and antiplatelet therapy (OR 1.89, P < 0.01). Receiver operating characteristic curves showed that the model including MEEi had higher accuracy than the model without MEEi in predicting LVEF reduction (areas under the curve 0.68 vs. 0.63, P = 0.046).ConclusionsLower values of MEEi at baseline identify hypertensive patients more liable to develop LVEF reduction. In hypertensive setting, MEEi evaluation improves risk stratification for development of LV systolic dysfunction during long-term follow-up.

Dataset Information

Insights From Computational Modeling Into the Contribution of Mechano-Calcium Feedback on the Cardiac End-Systolic Force-Length Relationship.

Publications

Insights From Computational Modeling Into the Contribution of Mechano-Calcium Feedback on the Cardiac End-Systolic Force-Length Relationship.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets