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.