A model of low-flow ischemia and reperfusion in single, beating adult cardiomyocytes

The present study was undertaken to comprehensively characterize low-flow i schemia and reperfusion in single adult cardiomyocytes and to determine whe ther it is important to control contractile activity. The ischemia-mimetic solution was hypoxic, acidic (pH 6.0), and deficient in glucose but contain ed elevated KCl. Cardiomyocytes were stimulated to contract throughout isch emia and during reperfusion with control perfusate. After the ischemia-repe rfusion insult, cells exhibited poor recovery of active cell shortening, a decrease in passive cell length, increased frequency of necrosis, lower ATP content, and evidence of the generation of oxygen-derived free radicals wi thin the cells. Intracellular lactate concentration increased, pH decreased , and Ca2+ transients were depressed during the ischemic insult, but the la tter two parameters recovered partially on reperfusion. Basal intracellular Ca2+ concentration was elevated during ischemia and early into reperfusion . Recovery was attenuated in cells that; were electrically stimulated to co ntract throughout ischemia. The duration of ischemia, stimulation frequency , and composition of the ischemia-mimetic solution were important variables . The inclusion of 10 mM lactate in the ischemia-mimetic solution significa ntly aggravated all the parameters examined above. Our data demonstrate tha t 1) an ischemia-mimetic solution administered to single, isolated adult ca rdiomyocytes can reproduce many of the responses observed in whole hearts, 2) caution should be used in adding lactate to an ischemic solution, and 3) it is important to stimulate contractile activity throughout ischemia to r eproduce the effects of ischemia in whole hearts.