Abstract Body:
Atrial fibrillation (AFib) is the most common cardiac rhythm disturbance. Treatment of AFib involves restoration of the atrial electrical rhythm. Following rhythm restoration, a period of depressed mechanical function, including decreased blood flow velocity and reduced atrial contractility, known as atrial stunning, occurs. This suggests that defects in contractility occur in AFib and are revealed upon restoration of rhythm. To assess contractile function, we used a canine atrial tachypacing model of induced AFib. Mass spectrometry analysis showed dysregulation of contractile proteins in samples from AFib compared to sinus rhythm atria. In atrial cardiomyocytes that were useable for skinned single cardiomyocyte force-calcium studies, we found reduced force of contraction. There were no significant differences in myosin heavy chain isoform expression. Resting tension is decreased in the AFib samples correlating with reduced full-length titin in the sarcomere. We measured degradation of other myofilament proteins including cMyBP-C, actinin, MHC, and cTnI, showing significant degradation in the AFib samples compared to sinus rhythm atria. Many of the protein degradation products appeared as discrete cleavage products that are generated by calpain proteolysis. We assessed calpain activity and found it to be significantly increased. Skinned cardiomyocytes from AFib atria showed increased calcium sensitivity that was consistent with increased cTnI degradation and decreased TnI phosphorylation. These results provide an understanding of the contractile remodeling that occurs in AFib.