The relation between the release of endogenous catecholamines and the rise in extracellular potassium concentration [( K+]0) was studied during global ischemia in the isolated perfused rabbit heart. An increase in release of catecholamines was observed only after ischemic periods longer than 10 min. In agreement with other studies, [K+]0 initially rose until a plateau phase was established after 8 min. During this phase [K+]0 actually decreased in several hearts. In these hearts, lactate release was larger (116.9 +/- 22.4 mumol/g dry wt, n = 5) than in hearts in which no decrease in [K+]0 was observed (83.3 +/- 16.0 mumol/g dry wt, n = 6). Blockade of the alpha- and beta-adrenoceptors by phentolamine (5 x 10(-6) M) and propranolol (10(-6) M), respectively, prevented the decrease in [K+]0. These findings show that the secondary decrease in [K+]0 is associated with increased glycolytic flux. Moreover, catecholamines are a prerequisite for this decrease and are frequently observed between 8 and 15 min of ischemia.