Ca2+ transient decline and myocardial relaxation are slowed during low flow ischemia in rat hearts

Abstract

The mechanisms that impair myocardial relaxation during ischemia are believed to involve abnormalities of calcium handling. However, there is little direct evidence to support this hypothesis. Therefore, we sought to determine whether the time constant of cytosolic calcium ([Ca2+Jc) decline (τCa) was increased during low flow ischemia, and if there was a relationship between the time constant of left ventricular pressure decline (τP) and τCa. Isolated perfused hearts were studied using indo-1 fluorescence ratio as an index of [Ca2+]c. τP was used as an index of myocardial relaxation. The time constant of decline of the indo1 ratio increased from 74±5 ms to 95±4, 144±10, and to 204±16 ms when coronary flow was reduced was reduced to 50, 20, and 10% of control, respectively. Indo-1 transients were calibrated to calculate τCa. τCa increased from 67±6 ms to 108±9 and 158±19 ms when coronary flow was reduced to 20 and 10% of control, respectively. There was a linear relationship between τCa and τP (r = 0.82). These data support the hypothesis that during low flow ischemia, impaired myocardial relaxation may be caused by slowing of [Ca2+]c decline.