Long-term heart rate reduction induced by the selective I(f) current inhibitor ivabradine improves left ventricular...

Area of Science:

• Cardiology
• Pharmacology
• Physiology

Background:

• Heart rate reduction (HRR) offers benefits in congestive heart failure (CHF) by improving left ventricular (LV) filling and optimizing myocardial oxygen balance.
• The long-term impact of HRR on cardiac function and remodeling in CHF remains incompletely understood.

Purpose of the Study:

• To investigate the long-term effects of HRR on cardiac function and remodeling in a rat model of CHF.
• To assess the role of the selective I(f) current inhibitor ivabradine in achieving HRR and its subsequent impact.

Main Methods:

• Rats with CHF were treated with ivabradine for 90 days to induce long-term HRR.
• Cardiac function, hemodynamics, LV geometry, and tissue characteristics (collagen and capillary density) were evaluated during treatment and after cessation.
• Parameters were reassessed 3 days post-treatment to determine persistent effects.

Main Results:

• Ivabradine effectively reduced heart rate by 18% without altering blood pressure or LV filling pressures.
• LV end-systolic diameter was reduced, leading to preserved cardiac output through increased stroke volume.
• Long-term HRR decreased LV collagen density and increased capillary density, with functional improvements persisting after treatment withdrawal.

Conclusions:

• Long-term HRR using ivabradine improves LV function and stroke volume, maintaining cardiac output in CHF rats.
• The observed cardiac benefits are attributed to both the direct effects of HRR and secondary adaptations in the extracellular matrix and myocyte function.