UCL Discovery

Abstract

Primary rat cardiocytes were subjected to either thermal ''preconditioning'' for 30 min at 43 degrees C or 20 min metabolic ''preconditioning'' (10 mM deoxyglucose, 20 mM lactate, pH 6.5). Eighteen hours later cells were analysed either for hsp 70i expression or subjected to a subsequent lethal heat stress or simulated ischaemia (10 mM deoxyglucose, 20 mM lactate, 0.75 mM sodium dithionite, 12 mM potassium chloride, pH 6.5) for 2 hours and assessed for survival by trypan blue exclusion.Hsp 70i was induced over 100 fold by thermal ''preconditioning'' and 30 fold by metabolic ''preconditioning'' (p < 0.001, p < 0.05), hsp 90 was induced 2.71 fold and 2.24 fold (p < 0.001, p < 0.001) by thermal and metabolic ''preconditioning'' respectively, while hsp 60 was not induced by either treatment. Preconditioned cultures had improved survival against subsequent lethal heat stress or simulated ischaemia: Thermal ''preconditioning'' reduced death from 69.22% to 52.46% upon subsequent ''lethal'' heat stress and from 49.13% to 36.66% upon subsequent ''lethal'' simulated ischaemia. Metabolic ''preconditioning'' reduced cell death from 51.29% to 33.8% against subsequent ''lethal'' heat stress, and from 69.09% to 55.61% upon subsequent ''lethal'' simulated ischaemia. A second marker of cell death, the release of lactate dehydrogenase activity into the culture media, was reduced to 65% and 60% of control values for thermally preconditioned cells subjected to ''lethal'' heat or ''lethal'' simulated ischaemia respectively. Metabolically ''preconditioned'' cells demonstrated lactate dehydrogenase activity of 59% and 51% that of control values, when subjected to ''lethal'' heat or ''lethal'' simulated ''ischaemia'' respectively.