Mechanisms contributing to pulsus alternans in pressure-overload cardiac hypertrophy
Kotsanas, G.; Holroyd, S.M.; Young, R.; Gibbs, C.L.
American Journal of Physiology 271(6 Pt 2): H2490-H2500
1996
ISSN/ISBN: 0002-9513 PMID: 8997309 Document Number: 466328
The mechanisms underlying pulsus alternans in pressure-overload (POL) cardiac hypertrophy were investigated. Simultaneous measurements of force and intracellular Cal+ (using fura 2) in right ventricular papillary muscles under conditions that produced mechanical alternans, revealed alternation of the amplitude of the Ca-2+ transient together with alternation of force in some POL muscles. Instances when alternation of force occurred without any apparent alternation of the Ca-2+ transient were also observed. Exposure of muscles to 5 mu-M ryanodine significantly attenuated mechanical alternans, thereby implicating a role for the sarcoplasmic reticulum (SR) in this process. The time course of restitution of force and the intracellular Ca-2+ transient were, however, unchanged in POL hearts, indicating that SR Ca-2+ cycling was not appreciably slowed. The fraction of Ca-2+ recirculated intracellularly was derived from studies of postextrasystolic potentiation and was significantly reduced in the POL hearts, suggesting additional differences in cellular Ca-2+ regulation. We conclude that changes in Ca-2+ handling play an important role in the onset of mechanical alternans in POL hypertrophy, but that additional factors, most likely a slowing of crossbridge cycling rate, are also likely to be important.