Interactive effects of K+, acidosis, and catecholamines on isolated rabbit heart: implications for exercise

Intense exercise can double arterial K+ concentration, decrease pH by 0.4 units, and increase catecholamines 15-fold. Any one of these changes may be cardiotoxic in a subject at rest, yet these changes are well tolerated in exercise. We tested the interactive effects of extracellular K+ concentration ([K+]o), metabolic acidosis (pH 7.0), and raised catecholamines in the isolated working rabbit heart when they were changed with similar kinetics and concentrations to those seen in exercise. Raised [K+]o (8 and 12 mM) significantly decreased aortic flow (AF) by 23 and 76%, respectively (P < 0.01). Acidosis decreased AF by 19% (P < 0.05) and by 38% in combination with 8 mM [K+]o (P < 0.05), making their combined effect additive. Either epinephrine (80 nM), norepinephrine (80 nM) or extracellular Ca2+ concentration (5 mM) offset the negative effects of 8 and 12 mM [K+]o on AF. Norepinephrine also improved AF in 8 mM [K+]o with acidosis. Thus, there may be a beneficial interaction among changes in K+, catecholamines, and acidosis during exercise such that each could offset the others' potentially harmful effects.