Extracellular K+ and protection against cellular damage in the rat heart

Rat hearts were perfused at 37 degrees C with three clearly-defined protocols: the Ca2+ paradox, the O2 paradox and with 20 mM caffeine. Each protocol involved an initial priming (stage 1) and a subsequent full activation (stage 2) of the damage system of the sarcolemma. Raising [K+]o from 5.4 to 6.5 mM in the Ca2+ paradox had no significant effect, but creatine kinase release was significantly inhibited (P < 0.001) at 7.5, 10.8 or 16.2 mM. Raising [K+]o to 16.2 mM only during stage 1 or only during stage 2 also inhibited creatine kinase release (P < 0.001); protection was greater than when 16.2 mM [K+]o was present throughout. [K+]o at 10.8 mM exacerbated creatine kinase release in the O2 paradox (P < 0.001) and also when present only during stage 1. However, significant protection was provided when [K+]o was raised only during stage 2 (P < 0.001). Creatine kinase release in the caffeine protocol was significantly inhibited (P < 0.001) at 10.8 mM [K+]o and when [K+]o was raised only during stage 1 or stage 2. It is concluded that raised [K+]o has two opposing effects: prevention of the activation of the membrane damage system and an exacerbation of damage via an increased Ca2+ influx.