Myocardial relaxation is accelerated by fast stretch, not reduced afterload

Area of Science:

• Cardiovascular Physiology
• Biophysics
• Cardiac Mechanics

Background:

• Fast myocardial relaxation is essential for efficient diastolic function.
• Previous research focused on molecular factors, neglecting mechanical influences on relaxation rate.
• The established theory that reducing afterload accelerates relaxation has not translated to improved clinical outcomes in diastolic dysfunction.

Purpose of the Study:

• To reevaluate the theory that afterload reduction accelerates myocardial relaxation.
• To investigate the role of myocardial relengthening at end systole (end systolic strain rate) as a modulator of relaxation rate.
• To test the hypothesis that end systolic strain rate, rather than afterload, determines relaxation speed.

Main Methods:

• Utilized electrically-stimulated trabeculae from mice, rats, and humans.
• Employed load-clamp techniques to independently manipulate afterload and end systolic strain rate.
• Conducted computer simulations to model the observed mechanical behaviors.

Main Results:

• Myocardial relaxation rate increased monotonically with end systolic strain rate.
• Afterload did not significantly alter the rate of myocardial relaxation.
• Computer simulations supported the experimental findings, suggesting relengthening accelerates cross-bridge detachment.

Conclusions:

• Myocardial relaxation is mechanically modulated by the rate of stretch at end systole (end systolic strain rate).
• This finding challenges the prevailing theory that afterload is the primary mechanical determinant of relaxation rate.
• End systolic strain rate may serve as a novel diagnostic indicator or therapeutic target for diastolic dysfunction.