Mechanisms contributing to pulsus alternans in pressure overload
cardiac hypertrophy.
Kotsanas, George, Sean M. Holroyd, Ross Young, Colin L. Gibbs.
Department of Physiology, Monash University, Clayton, Victoria
3168, Australia
APStracts 3:0273H, 1996.
The mechanisms underlying pulsus alternans in pressure overload (POL)
cardiac hypertrophy were investigated. Simultaneous measurements of
force and intracellular Ca2+ (using fura-2) in right ventricular
papillary muscles under conditions that produced mechanical
alternans, revealed alternation of the amplitude of the Ca2+
transient together with alternation of force in some POL muscles.
Instances where alternation of force occurred without any apparent
alternation of the Ca2+ 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 Ca2+ transient were, however, unchanged in POL hearts,
indicating that SR Ca2+ cycling was not appreciably slowed. The
fraction of Ca2+ recirculated intracellularly was derived from
studies of post-extrasystolic potentiation and was significantly
reduced in the POL hearts suggesting additional differences in
cellular Ca2+ regulation. We conclude that changes in Ca2+ 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.
Received 12 September 1995; accepted in final form 30 May 1996.
APS Manuscript Number H858-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96