Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes

Objectives: Indirect evidence suggests a role for Ca2+-overload in electrical and mechanical alterations caused by atrial tachycardia. The present study assessed the alterations in cellular [Ca2+] and contractile function caused by rapid atrial cellular activation. Methods: Intracellular Ca2+ transients (CaT) and cell shortening (CS) were measured by microfluorometry (Indo-1 AM) and video edge-detection in isolated, field-stimulated canine atrial myocytes (37 degreesC). Results: Abrupt increases in frequency (0.3-3 Hz) caused rapid increases in diastolic [Ca2+](i) (DCa) that were maintained during rapid-pacing for up to 50 min. When short-term (3-min) rapid-pacing was imposed, CaT and CS increased initially upon returning to 0.3 Hz, but then declined rapidly to 64 +/- 5 and 49 +/- 7%, respectively, of pre-tachycardia values, returning to control after similar to 15 min. Post-tachycardia CaT and CS reductions were prevented by decreasing [Ca2+ ](o) during tachycardia to prevent Ca2+-overload. CS reductions correlated with indices of Ca2+ loading during tachycardia. Restoration of CaT to normal during post-tachycardia contractile dysfunction (by increasing [Ca2+](o)) returned CS to normal, indicating that reduced Ca2+ release, not reduced myofilament Ca2+-sensitivity, caused post-tachycardia contractile failure. Estimation of sarcoplasmic-reticulum Ca2+-stores (caffeine-induced Ca2+ release) confirmed tachycardia-induced Ca2+-loading and suggested that reduced Ca2+-stores decreased Ca2+-release post-tachycardia. Conclusions: Atrial tachycardia increases cellular Ca2+-loading, leading to post-tachycardia abnormalities in Ca2+-handling that produce contractile dysfunction. These findings are the first direct evidence for the frequently postulated role of Ca2+-overload in tachycardia-induced abnormalities of atrial function. (C) 2001 Elsevier Science B.V. All rights reserved.