Spontaneous Myocardial Calcium Oscillations: Are They Linked to Ventricular Fibrillation?

Spontaneous Myocardial Calcium Oscillations. The physiological oscillation of cytosolic that underlies each heart heat is generated by the sarcoplasmic reticulum (SK) in response to an action potential (AP) and occurs relatively synchronously within and among cells. When the myocardial cell and SR loading become sufficiently high, the SK can also generate spontaneous, i.e., not triggered by sarcolemmal depolarization, oscillations The purpose of this review is to describe properties of S‐CaOs in individual cells, myocardial tissue, and the intact heart, and to examine the evidence that may link S‐CaOs to the initiation or maintenance of ventricular fibrillation (VF). The SR Ca²⁺ release that generates S‐CaOs occurs locally within cells and spreads within the cell via Ca²⁺‐induced Ca²⁺ release. The localized increase in cytosolic [Ca²⁺] due to S‐CaOs may equal that induced by an AP and causes oscillatory sarcolemmal depolarizations of cells in which it occurs. These oscillatory depolarizations are due to activation of the Na/Ca exchanger and of nonspecific cation channels. Asynchronous occurrence of diastolic S‐CaCs among cells within the myocardium causes inhomogencity of diastolic SR loading; this leads lo inhomogeneity of the systolic cytosolic [Ca2⁺] transient levels in response to a subsequent AP, which leads to heterogeneity of AP repolarization, due to heterogeneous modulation of the exchanger, nonspecific cation channels, and of the L‐type channel. In a tissue in which asynchronous S‐CaOs are occurring in diastole, the subsequent AP temporarily synchronizes SR Ca²⁺ loading and release within and among cells. Varying extents of synchronized S‐Caos then begin to occur during the subsequent diastole. The partial synchronization of this diastolic S‐CaOs among celts within myocardial tissue produces after contractions and diastolic depolarizations. When S‐CaOs are sufficiently synchronized, the resultant depolarizations summate and can be sufficient to trigger a spontaneous AP. S‐CaOs occurrence within some cells during a long AP plateau also modulates the removal of voltage inactivation of L‐type channels and increases the likelihood for “early after depoializations” to occur in myocardial tissue. S‐CaOs have an apparent modulatory role in the initiation at VF in the CV⁺ overload model and in the reflow period following ischemia. Likewise, in non‐a priori Ca²⁺ overloaded hearts, S‐CaOs modulate the threshold for VF induction (induced typically by alternating current) but may not be essential for VF induction. The role of S‐CaOs in maintenance of VF in these VF models is less clear: to date there is no evidence that inhibition of S‐CaOs can abolish VF once it has been established. The precise definition of the role of S‐CaOs in the initiation and mechanisms of VF merits further study.