title: Mechanisms contributing to pulsus alternans in pressure-overload cardiac hypertrophy.
abstract: The mechanisms underlying pulsus alternans in pressure-over-load (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 when alternation of force occurred without any apparent alternation of the Ca2+ transient were also observed. Exposure of muscles to 5 microM 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 postextrasystolic 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.
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Kotsanas
authors.forename: S M
authors.initials: SM
authors.lastname: Holroyd
authors.forename: R
authors.initials: R
authors.lastname: Young
authors.forename: C L
authors.initials: CL
authors.lastname: Gibbs
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D005117:Cardiac Complexes, Premature / Q000503:physiopathology; D006332:Cardiomegaly / Q000209:etiology* / Q000503:physiopathology*; D004558:Electric Stimulation; D006706:Homeostasis; D006973:Hypertension / Q000150:complications*; D007537:Isometric Contraction; D009200:Myocardial Contraction; D010210:Papillary Muscles / Q000503:physiopathology; D011674:Pulse / Q000187:drug effects; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology
chemical_list: D012433:Ryanodine