What is the clinical evidence from this study?

Study design: Other. Population: Myocardial contractile kinetics. Intervention: 10% α-MHC expression vs. 0% α-MHC expression. Primary outcome: Maximal rate of rise of force (dF/dt(max)) (92% increase).

What question did this study set out to answer?

This study aims to evaluate the influence of low-level α-myosin heavy chain (α-MHC) expression on contraction kinetics in porcine myocardium.

January 8, 2011AJP Heart and Circulatory PhysiologyOpen Access

Effects of low-level α-myosin heavy chain expression on contractile kinetics in porcine myocardium

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Key result

Mathematical modeling predicts that 10% α-MHC expression increases the maximal rate of rise of force by 92% compared with 0% α-MHC, suggesting accelerated myocardial twitch kinetics.

Population

Porcine myocardium model, using right atrial and left ventricular tissue preparations.

Comparison

Expression of 100% α-MHC and mathematical… vs Expression of 100% β-MHC and 0% α-MHC in…

Design

Preclinical

Authors

MLMatthew R. LocherUniversity of Wisconsin–Madison MRMaria V. RazumovaUniversity of Washington JSJulian E. StelzerCase Western Reserve University

Discussion

Member takes

Implication

Should not alter HF management yet; leaves open whether restoring low-level α-MHC could enhance systolic function.

Key Points

This study aims to evaluate the influence of low-level α-myosin heavy chain (α-MHC) expression on contraction kinetics in porcine myocardium.
Examined right atrial and left ventricular tissues from porcine myocardium expressing 100% α-MHC or 100% β-MHC.
Measured myosin ATPase activity, isometric force, and force redevelopment rate (k(tr)) in varying Ca(2+) concentrations.
Calculated composite rate constants for cross-bridge attachment and detachment (f(app) and g(app)).
k(tr) was approximately ninefold higher in atrial myocardium than in ventricular myocardium.
Rate constants f(app) and g(app) were approximately 10-fold and 8-fold higher in α-MHC compared to β-MHC, respectively.
Low-level expression of α-MHC increases the maximal rate of rise of force (dF/dt(max)) by 92% compared to 0% α-MHC.

Structured PICO

Population

Porcine myocardium model (n=4 adolescent Yorkshire pigs, weighing 45 ± 3 kg), using right atrial (~100% α-MHC) and left ventricular (~100% β-MHC) tissue preparations.

Intervention

Expression of 100% α-MHC (atrial tissue) and mathematical modeling of 10-30% α-MHC expression

Comparator

Expression of 100% β-MHC (ventricular tissue) and 0% α-MHC in mathematical modeling

Outcome

Composite rate constants of cross-bridge attachment (f(app)) and detachment (g(app)), myosin ATPase activity, isometric force, and rate constant of force redevelopment (k(tr))surrogate

Main Result

Effect estimate: 92% increase

Low-level expression of α-MHC significantly accelerates myocardial twitch kinetics, suggesting its loss in human heart failure may impair systolic function.

Cite This Study

Locher et al. (2011) studied Myocardial contractile kinetics. 10% α-MHC expression vs. 0% α-MHC expression was evaluated on Maximal rate of rise of force (dF/dt(max)) (92% increase). Mathematical modeling predicts that 10% α-MHC expression increases the maximal rate of rise of force by 92% compared with 0% α-MHC, suggesting accelerated myocardial twitch kinetics.

synapsesocial.com/papers/6a0d514268ddba849a09b285 https://doi.org/10.1152/ajpheart.00452.2010

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Effects of low-level α-myosin heavy chain expression on contractile kinetics in porcine myocardium

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Effects of low-level α-myosin heavy chain expression on contractile kinetics in porcine myocardium

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Also Consider

Also Consider