Endocardial versus epicardial differences of intracellular free calcium under normal and ischemic conditions in perfused rat hearts

Transmural heterogeneity of myocardial metabolism and function are present in the left ventricle under normal and ischemic conditions. To determine if endocardial versus epicardial differences of [Ca²⁺]_i are also present, perfused rat heart studies using indo-1 fluorescence as an index of [Ca²⁺]_i were performed in the left ventricular epicardium and endocardium. Hearts were studied during control conditions and low-flow ischemia. Results demonstrated the following: 1) At a pacing rate of 1.5 Hz, endocardial levels of diastolic and systolic [Ca²⁺]_i (470±40 and 1,240±170 nM) were higher than epicardial levels (290±30 and 920±150 nM). 2) At a more physiological pacing rate of 5 Hz, endocardial levels of diastolic and systolic [Ca²⁺]_i (680±50 and 1,230±70 nM) were also higher than epicardial levels (390±20 and 950±60 nM). 3) During low-flow ischemia, endocardial levels of diastolic [Ca²⁺], rose to a greater degree (from 680±50 to 1,050±70 nM at 10% of control coronary flow) compared with epicardial levels (from 390±20 to 580±40 nM at 10% of control flow), suggesting that the endocardium is more susceptible to low-flow ischemia. 4) The amplitude of the [Ca²⁺]_i transient was the same at the endocardium (540±50 nM) and epicardium (560±50 nM) and did not change during low-flow ischemia, despite marked contractile dysfunction. These findings are consistent with the hypothesis that endocardial versus epicardial differences of [Ca²⁺]_i exist under normal and low-flow ischemic conditions and may, in part, account for the previous observations of transmural metabolic and functional gradients in the left ventricle of the whole heart. Furthermore, the contractile failure associated with low-flow ischemia is not due to a decrease of the [Ca²⁺]_i transient amplitude.