Effect of creatine depletion on myocardial mechanics.
The physiological significance of energy transport by means of shuttling creatine (C) and creatine phosphate (CP) between mitochondria and the energy utilizing sites was examined in C-depleted rat hearts. Feeding a diet containing structural analogues of C [either 1% guanidinoproprionic acid (GPA) or 2% guanidinobutyric acid (GBA)] led to the decrease of total myocardial C (C + CP) by 78% and 75% after seven weeks and by 89% and 82% after ten weeks. Mechanics of isolated papillary muscles were examined under isometric conditions at different temperatures, muscle lengths and frequencies of stimulation. No differences were found in the basic characteristics of contraction and relaxation among the hearts of normal, GPA- and GBA-treated rats at low workloads. However, when paired stimulation was applied, the interval at which fusion occurred was significantly longer in C-depleted than in controls. At high workloads, the developed force (DF) in C-depleted decreased in the same way as in controls, but its subsequent recovery took significantly longer and the recovered DF in C-depleted muscles was smaller than in controls. We conclude that C depletion has greater effects on the excitation to contraction coupling and recovery rather than on the DF during stimulation at high frequencies.
Korecky
B
B
Department of Physiology, School of Medicine, University of Ottawa, Canada.
Brandejs-Barry
Y
Y
D000818:Animals; D003401:Creatine / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D006146:Guanidines; D011422:Propionates; D010725:Phosphocreatine; C032267:beta-guanidinobutyric acid; D003401:Creatine; C005775:guanidinopropionic acid