Damage induced arrhythmias: mechanisms and implications.
Little is known about the role played by non-uniform myocardial stress and strain distributions and by non-uniform excitation contraction coupling in mechanisms underlying the premature beats that initiate an arrhythmia. We will review the evidence in support of a mechanism in which both non-uniform contraction and increased Ca2+ load of cells adjacent to acutely damaged cells are essential in the "spontaneous" generation of Ca2+ transients during the relaxation phase of the electrically driven twitch. The putative mechanism of initiation of the propagating Ca2+ waves involves feedback of rapid length (or force) changes to dissociation of Ca2+ from the contractile filaments. A novel aspect of this concept is that these mechanically elicited Ca2+ transients induce propagating Ca2+ waves that travel into the adjacent normal myocardium and cause after-depolarizations, which, in turn, may cause premature action potentials. These premature action potentials will further load the cells with Ca2+, which promotes the subsequent generation of propagating Ca2+ transients and leads to triggered arrhythmias. The damage-induced premature beats may also initiate re-entry arrhythmias in non-uniform myocardium. These observations strongly support the concept that abnormal cellular Ca2+ transport plays a crucial role in the initiation of arrhythmias in damaged and non-uniform myocardium.
ter Keurs
H E
HE
Department of Medicine, The University of Calgary, Health Sciences Center, AB, Canada. terKeurs@ucalgary.ca
Zhang
Y M
YM
Davidoff
A W
AW
Boyden
P A
PA
Wakayama
Y
Y
Miura
M
M
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology*; D015220:Calcium Channels / Q000502:physiology; D006335:Heart Injuries / Q000150:complications* / Q000503:physiopathology*; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology
D015220:Calcium Channels