Key result
Elevated afterload induced by aortic banding caused cellular hypertrophy and increased the incidence of spontaneous calcium transients in rat left atrial myocytes from 50% to 92%.
Absolute Event Rate: 92% vs 50%
p-value: p=<0.05
Elevated afterload in a rat model causes left atrial myocyte hypertrophy and increases susceptibility to spontaneous Ca2+ release, providing a potential cellular mechanism for afterload-induced atrial fibrillation.
Suggests afterload-driven atrial myocyte changes as AF substrate; hypothesis-generating and requires human validation.
Atrial remodeling due to elevated arterial pressure predisposes the heart to atrial fibrillation (AF). Although abnormal sarcoplasmic reticulum (SR) function has been associated with AF, there is little information on the effects of elevated afterload on atrial Ca2+-handling. We investigated the effects of ascending aortic banding (AoB) on Ca2+-handling in rat isolated atrial myocytes in comparison to age-matched sham-operated animals (Sham). Myocytes were either labelled for ryanodine receptor (RyR) or loaded with fluo-3-AM and imaged by confocal microscopy. AoB myocytes were hypertrophied in comparison to Sham controls (P<0.0001). RyR labeling was localized to the z-lines and to the cell edge. There were no differences between AoB and Sham in the intensity or pattern of RyR-staining. In both AoB and Sham, electrical stimulation evoked robust SR Ca2+-release at the cell edge whereas Ca2+ transients at the cell center were much smaller. Western blotting showed a decreased L-type Ca channel expression but no significant changes in RyR or RyR phosphorylation or in expression of Na+/Ca2+ exchanger, SR Ca2+ ATPase or phospholamban. Mathematical modeling indicated that [Ca2+]i transients at the cell center were accounted for by simple centripetal diffusion of Ca2+ released at the cell edge. In contrast, caffeine (10 mM) induced Ca2+ release was uniform across the cell. The caffeine-induced transient was smaller in AoB than in Sham, suggesting a reduced SR Ca2+-load in hypertrophied cells. There were no significant differences between AoB and Sham cells in the rate of Ca2+ extrusion during recovery of electrically-stimulated or caffeine-induced transients. The incidence and frequency of spontaneous Ca2+-transients following rapid-pacing (4 Hz) was greater in AoB than in Sham myocytes. In conclusion, elevated afterload causes cellular hypertrophy and remodeling of atrial SR Ca2+-release.
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Zhang et al. (2015) studied Elevated afterload / Atrial remodeling (n=32). Ascending aortic banding vs. Sham operation was evaluated on Incidence of spontaneous Ca2+ transients following rapid pacing (p=<0.05). Elevated afterload induced by aortic banding caused cellular hypertrophy and increased the incidence of spontaneous calcium transients in rat left atrial myocytes from 50% to 92%.
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