Cardiac alternans in embryonic mouse ventricles

Area of Science:

• Cardiovascular Physiology
• Developmental Biology
• Cardiac Electrophysiology

Background:

• T-wave alternans, a known arrhythmogenic factor, has been observed in human fetuses.
• The sarcoplasmic reticulum (SR), crucial for calcium handling, is underdeveloped in embryonic hearts.

Purpose of the Study:

• To investigate if cardiac alternans can be induced in embryonic mouse hearts.
• To analyze the response of embryonic cardiac alternans to pharmacological and autonomic interventions.

Main Methods:

• Optical mapping of voltage and intracellular calcium (Ca(i)) in embryonic mouse hearts (E10.5-E12.5).
• Assessment of alternans incidence under control conditions and after interventions like thapsigargin, ryanodine, and isoproterenol.
• Measurement of action potential duration (APD) restitution slope.

Main Results:

• Cardiac alternans were induced in 57% of embryonic mouse hearts during rapid pacing.
• Alternans incidence increased to 100% with isoproterenol, correlating with a steeper APD restitution slope.
• SR Ca(i) cycling impairment did not significantly reduce alternans, indicating it's not solely SR-dependent.

Conclusions:

• Embryonic mouse ventricles can develop cardiac alternans.
• Cardiac alternans in embryos correlate with APD restitution slope and do not require fully functional SR Ca(i) cycling.
• Autonomic stimulation, like isoproterenol, can promote alternans in embryonic hearts.