Arrhythmogenic atrial remodeling during pregnancy in mice.

Abstract

BACKGROUND: Pregnancy is associated with greater vulnerability to supraventricular tachyarrhythmias. OBJECTIVE: As the underlying mechanisms remain to be elucidated, we investigated whether pregnancy induces atrial remodeling that might contribute to this. METHODS: Atrial electrophysiological and contractile properties were examined in nonpregnant and pregnant (P) mice. Cell shortening and Caimaging were measured on atrial myocytes. Atrial action potential and ionic currents were recorded using the patch-clamp technique. Atrial messenger RNA and protein expression were analyzed using quantitative polymerase chain reaction and Western blot. RESULTS: The P-wave area on the electrocardiogram increased by 50% during pregnancy, suggesting atrial enlargement, confirmed by echocardiography. The atrial myocytes were longer in P mice, adding further evidence to the physiological hypertrophy associated with pregnancy. Echocardiography showed a 50% increase in atrial fractional area change during pregnancy, indicating much stronger contraction. A similar increase in cell shortening was observed in P mice and was associated with a decrease in sarcomere length and changes in myofilament protein phosphorylation. However, pregnancy did not affect L-type Cacurrent, Catransients, and SR Caload. Myocytes from P mice showed twice as many spontaneous contractions and spontaneous diastolic Careleases. Moreover, pregnancy was associated with a 50% increase in action potential duration, linked to a reduction in the density of the Ca-independent transient outward Kcurrent and the underlying K4.3 channel. CONCLUSION: During pregnancy, atrial tissues undergo substantial remodeling, potentially contributing to the development of supraventricular tachyarrhythmias.