Prevention of the oxygen paradox in hypoxic-reoxygenated hearts.
Reoxygenation after 60 min substrate-free hypoxic perfusion (modified Tyrode solution, 37 degrees C) caused isolated Langendorff hearts (from rats) to rapidly develop hypercontracture and sarcolemmal disruptions indicated by massive and sudden loss of enzymes ("oxygen paradox"). Reoxygenation (30 min) caused an augmented loss of creatine kinase by 25.8% (lactate dehydrogenase by 40.1%) of the initial total tissue activity. It was investigated whether a temporary contractile blockade by 2,3-butanedione monoxime (BDM; 20 mM) can prevent reoxygenation-induced injury. In the presence of BDM, reoxygenation no longer caused hypercontracture or increased enzyme release. Instead, ultrastructure recovered, and contents of creatine phosphate (CrP) were partially restored (60 min hypoxia: 0.4 mumol CrP/g dry wt; after subsequent 60 min reoxygenation in presence of BDM: 7.8 mumol CrP/g dry wt). When BDM was eluted after first 20 min of reoxygenation, an attenuated but distinct increase in enzyme release was still observed. When BDM was eluted after 60 min of reoxygenation, ultrastructure did not deteriorate and increase of enzyme release remained virtually absent. During first 30 min after removal of BDM, the increased loss of creatine kinase amounted to only 5.7% (lactate dehydrogenase to 6.9%) of the initial total tissue activity. The results demonstrate that the oxygen paradox can be prevented in the hypoxic-reoxygenated heart when the contractile apparatus is temporarily paralyzed during the initial phase of reoxygenation.
Schlüter
K D
KD
Physiologisches Institut I, Universität Düsseldorf, Federal Republic of Germany.
Schwartz
P
P
Siegmund
B
B
Piper
H M
HM
D000818:Animals; D004734:Energy Metabolism; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010710:Phosphates; D010100:Oxygen