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Firstly, as will be discussed below, LCACs induce Ca 2+ overload within cardiomyocytes via release of sarcoplasmic reticulum (SR) Ca 2+ and inhibition of mitochondrial Ca 2+ uptake ( 2+ overload effect has been shown to depend on LCAC fatty acyl chain length, suggesting that longer LCACs have greater membrane penetration and, therefore, cause greater membrane disruption ( Opposing these findings of membrane perturbation and potentially irreversible sarcolemma disruption are the reports of reversible electrophysiological and inotropic effects following exogenous LCACs wash out or after/during normoxic reperfusion post ischemia ( In sum, the evidence strongly supports membrane perturbation and altered phospholipid packing in mediating the electrophysiological and inotropic effects of LCACs in the heart