Prevention of the oxygen paradox in the isolated cardiomyocyte and the whole heart.
It was investigated in hypoxic-reoxygenated cardiomyocytes and isolated perfused hearts from rat whether temporary contractile blockade by 2,3-butanedionemonoxime (20 mM: BDM) during the initial phase of reoxygenation could prevent severe reoxygenation-induced cell injury. In isolated rat cardiomyocytes, reoxygenation after 120 minutes substrate-free anoxia caused sudden hypercontracture but not cytolysis. Within 15 minutes, a nearly normal free energy change of ATP hydrolysis and a normal cytosolic Ca2+ control were reestablished, in spite of irreversible hypercontracture. When BDM was present during the initial 15 minutes reoxygenation and then eluted, hypercontracture remained absent. In the isolated perfused heart, reoxygenation after 60 minutes substrate-free hypoxic perfusion provoked rapid hypercontracture and a sudden massive loss of creatine kinase ("oxygen paradox"). When BDM was present for the first 60 minutes reoxygenation and then eluted, these characteristics of the "oxygen paradox" remained virtually absent. The results demonstrate that the reoxygenation-induced hypercontracture and severe cell injury characteristic for the "oxygen paradox" can be prevented in the hypoxic-reoxygenated heart muscle cell when the contractile apparatus is temporarily paralyzed during the initial phase of reoxygenation. This time seems to be needed for the recovery of cytosolic Ca2+ control.
Piper
H M
HM
Physiologisches Institute I, Universität Düsseldorf, Germany.
Siegmund
B
B
Schlüter
K D
KD
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
C004717:diacetylmonoxime; D003931:Diacetyl; D010100:Oxygen; D002118:Calcium