Changes in intracellular Ca²⁺concentration of rabbit coronary artery smooth muscle cell during ischemic cardioplegic period

Abstract

To elucidate the possibility whether an elevation of intracellular Ca2+ concentration ([Ca2+]i) in rabbit coronary artery myocytes during ischemic cardioplegic period may serve as one of the mechanisms of the "no-reflow' phenomenon or not, the changes in [Ca2+]i were measured under ischemic cardioplegia conditions using a fluorescent Ca2+ indicator, fura 2/AM. When single cells were perfused with cardioplegic or ischemic cardioplegic solutions, [Ca2+]i was significantly increased and the degree of [Ca2+]i elevation was further augmented by the ischemic cardioplegic solution. Pretreatment of a sarcoplasmic reticulum emptying agent, 20 mM caffeine, had no effect on ischemic cardioplegia-induced [Ca2+]i changes, but application of a Ca2+ channel blocker, 5 x 10 (-1)M nifedipine, or an antagonist of Na+/Ca2+ exchange, 5 mM Ni2+, significantly inhibited the [Ca2+]i elevation, respectively. The magnitude of ischemic cardioplegia-induced [Ca2+]i elevation was dependent on the Ca2+ concentration of perfusate in the range of 0 and 25 mM. When Ni2+ was added to the reperfusion solution, recovery of ischemic cardioplegia-induced [Ca2+]i elevation was very rapid compared with the controls. It is concluded that ischemic cardioplegia-induced [Ca2+]i elevation may serve as one of the mechanisms of the "no-reflow' phenomenon in rabbit coronary artery smooth muscle cells. We propose that Na+/Ca2+ exchange may serve as a key function in ischemic cardioplegia-induced [Ca2+]i elevation.

Intracellular free calcium accumulation in ferret vascular smooth muscle during crystalloid and blood cardioplegic infusions

“…Depolarization-induced Ca 2+ influx through voltage-operated Ca 2+ channels, Ca 2+ -induced Ca 2+ release from the sarcoplasmic reticulum, and Na + /Ca 2+ exchange mechanisms are 3 major potential causes of Ca 2+ accumulation during cardioplegic infusion. However, the exact cause of accumulation is controversial and dependent on the cell type, 6,7 age, 8 species, and other factors. According to the Nernst equation, 9,10 the open probability of voltage-operated Ca 2+ channels is low during hyperkalemic (25 mmol/L K + ) cardioplegic infusion, and maintained depolarization theoretically inhibits Ca 2+ influx by inactivation of L-type Ca 2+ channels.…”

“…11,12 However, it has been reported that the increase in [Ca 2+ ] i during cardioplegic infusion may be inhibited by a calcium-channel blocker. 7 A contribution of Ca 2+ in the sarcoplasmic reticulum to [Ca 2+ ] i accumulation is both probable and predicted, 13 but researchers have reported variable findings. 6,7 Furthermore, increased intracellular free Na + as a result of Na + /H + exchange and depolarization of the membrane by hyperkalemic cardioplegic infusion can increase Ca 2+ influx through the Na + /Ca 2+ exchange system.…”

“…7 A contribution of Ca 2+ in the sarcoplasmic reticulum to [Ca 2+ ] i accumulation is both probable and predicted, 13 but researchers have reported variable findings. 6,7 Furthermore, increased intracellular free Na + as a result of Na + /H + exchange and depolarization of the membrane by hyperkalemic cardioplegic infusion can increase Ca 2+ influx through the Na + /Ca 2+ exchange system. 14 Decreased activity of the Na + /Ca 2+ exchange mechanism during cardioplegic infusion may theoretically account for some of the increase in [Ca 2+ ] i .…”