Malondialdehyde and glutathione production in isolated perfused human and rat hearts.
A number of studies show the relation between oxygen-derived free radicals and cardiac ischemia/reperfusion injury. However, little is known about oxidative stress in the human heart, which can be measured by oxidized glutathione (GSSG) and malondialdehyde (MDA) formation. Furthermore, data on MDA production by rat hearts are controversial, possibly because of the use of the aspecific thiobarbituric acid assay. Therefore, GSSG and MDA were measured, with colorimetric and high-performance liquid chromatographic assays, respectively, in buffer-perfused explanted human hearts and normal rat hearts made temporarily ischemic. Human hearts received cardioplegia; rat hearts were studied in a control and an ischemic group with or without cardioplegia. Baseline GSSG release was < 0.01 nmol.min-1.g wet wt-1 in both species. During reperfusion, GSSG release from human hearts and from ischemic and cardioplegic/ischemic rat hearts peaked at 0.24 +/- 0.12, 1.1 +/- 0.4, and 0.19 +/- 0.04 nmol.min-1.g-1, respectively. MDA was undetectable (< 0.02 nmol.min-1.g-1) in the effluent of both species and in human hearts (< 4 nmol/g protein). Rat heart reduced glutathione levels decreased 32% as a consequence of cardioplegia and ischemia. Cardioplegia induced a 41% (P = .08) decrease in rat heart MDA content, whereas cumene hydroperoxide increased it 3.6 times (P < .01). Thus, after ischemia human and rat hearts release GSSG, indicating that oxidative stress has occurred. Apparently, lipid peroxidation takes place in normal rat hearts, decreases after cardioplegia, but does not increase after ischemia/reperfusion. Human hearts lack MDA under normoxic and ischemic conditions. This novel finding seems to reflect a low MDA-forming potential in both situations.(ABSTRACT TRUNCATED AT 250 WORDS)
Janssen
M
M
Thoraxcenter, Erasmus University Rotterdam, The Netherlands.
Koster
J F
JF
Bos
E
E
de Jong
J W
JW
D000818:Animals; D005609:Free Radicals; D005978:Glutathione / Q000096:biosynthesis*; D006324:Heart Arrest, Induced; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D005609:Free Radicals; D008315:Malondialdehyde; D005978:Glutathione