Spontaneous calcium release in tissue from the failing canine heart

Area of Science:

• Cardiovascular Physiology
• Cardiac Electrophysiology
• Heart Failure Pathophysiology

Background:

• Abnormal calcium handling is linked to electrical instability in heart failure (HF).
• Previous research focused on isolated myocytes, leaving tissue-level mechanisms unclear.
• The role of spontaneous calcium release in triggering arrhythmias in HF tissue requires further investigation.

Purpose of the Study:

• To investigate the tissue-level mechanisms of triggered activity (TA) in tachycardia-induced heart failure (HF).
• To determine if spontaneous calcium release from the sarcoplasmic reticulum (SCR) in myocardial cell aggregates causes TA.
• To identify whether SCR amplitude or rate of rise is associated with TA in HF.

Main Methods:

• Utilized calcium and voltage optical mapping in canine ventricular wedge preparations.
• Compared HF and normal canine hearts under control and beta-adrenergic stimulation.
• Analyzed steady-state calcium transients, SCR characteristics, and triggered activity incidence.

Main Results:

• HF hearts exhibited reduced calcium transient amplitude and increased duration compared to normal.
• TA was significantly more frequent in HF, particularly during beta-adrenergic stimulation.
• The rate of SCR rise was significantly greater for events triggering beats (0.41 RU/ms) versus those that did not (0.18 RU/ms).
• No significant difference in SCR amplitude was observed between triggering and non-triggering events.

Conclusions:

• Tissue-level triggered activity in HF is associated with abnormal calcium regulation.
• Spontaneous calcium release from the sarcoplasmic reticulum in myocardial cell aggregates mediates TA in HF.
• The rate of spontaneous calcium release rise, not peak amplitude, is critically associated with triggered activity in HF tissue.