Adenosine prevents cardioplegia-induced Ca²⁺ loading in cardiac cells

Hyperkalemic cardioplegia is used to arrest the heart during open heart surgery by depolarizing the sarcolemma. A recognized adverse effect of hyperkalemic cardioplegia is ventricular dysfunction related to intracellular Ca²⁺ loading, but no effective means of protection under these conditions have been established. Whether adenosine, a known cardioprotective agent, could prevent intracellular Ca²⁺ loading without altering cardioplegia-induced depolarization was investigated using epifluorescent and laser confocal microscopy, and perforated patch-clamp electrophysiology. In ventricular myocytes isolated from guinea pig hearts, and loaded with a Ca²⁺-sensitive fluorescent probe, exposure of myocytes to 16 mM K⁺ induced intracellular Ca²⁺ loading, and membrane depolarization. Yet, adenosine (1 mM) effectively prevented Ca²⁺ loading whithout reducing the magnitude of cardioplegia-induced depolarization. The preventing effect of adenosine on Ca²⁺ loading was antagonized by inhibitors of protein kinase C. Adenosine did slow the rate of K⁺-induced membrane depolarization which could be repsonsible for a decrease in net Ca²⁺ influx. The property of adenosine to prevent hyperkalemia-induced Ca²⁺ loading may contribute to the cytoprotective efficacy of this agent as an adjunct to conventional hyperkalemic cardioplegia used in cardiac surgery.