The ability of heat stress and metabolic preconditioning to protect primary rat cardiac myocytes.
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 no 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.
Cumming
D V
DV
Hatter Institute for Cardiovascular Studies, University College Hospital, London, United Kingdom.
Heads
R J
RJ
Brand
N J
NJ
Yellon
D M
DM
Latchman
D S
DS
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D016923:Cell Death; D002478:Cells, Cultured; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006358:Hot Temperature; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D007770:L-Lactate Dehydrogenase