Key result
An ischemia-mimetic solution applied to single adult cardiomyocytes reproduced whole-heart ischemic responses, which were aggravated by adding 10 mM lactate and attenuated without electrical stimulation.
Electrical stimulation of single adult cardiomyocytes during exposure to an ischemia-mimetic solution accurately reproduces the effects of ischemia-reperfusion injury seen in whole hearts.
Poor recovery in stimulated single cardiomyocytes warrants model refinement; leaves open in vivo and clinical relevance of contractile control.
The present study was undertaken to comprehensively characterize low-flow ischemia and reperfusion in single adult cardiomyocytes and to determine whether it is important to control contractile activity. The ischemia-mimetic solution was hypoxic, acidic (pH 6.0), and deficient in glucose but contained elevated KCl. Cardiomyocytes were stimulated to contract throughout ischemia and during reperfusion with control perfusate. After the ischemia-reperfusion 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 within the cells. Intracellular lactate concentration increased, pH decreased, and Ca(2+) transients were depressed during the ischemic insult, but the latter two parameters recovered partially on reperfusion. Basal intracellular Ca(2+) concentration was elevated during ischemia and early into reperfusion. Recovery was attenuated in cells that were electrically stimulated to contract 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 significantly aggravated all the parameters examined above. Our data demonstrate that 1) an ischemia-mimetic solution administered to single, isolated adult cardiomyocytes 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 reproduce the effects of ischemia in whole hearts.
No takes yet. Share an insight, caveat, or question.
Maddaford et al. (1999) studied Low-flow ischemia and reperfusion. Ischemia-mimetic solution and electrical stimulation vs. Control perfusate / unstimulated cells was evaluated on Cellular responses including active cell shortening, necrosis, ATP content, and Ca(2+) transients. An ischemia-mimetic solution applied to single adult cardiomyocytes reproduced whole-heart ischemic responses, which were aggravated by adding 10 mM lactate and attenuated without electrical stimulation.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: