Postischemic myocardial recovery and oxidative stress status of vitamin C deficient rat hearts.
OBJECTIVE
To investigate the role of vitamin C tissue content as a protective agent during myocardial ischemia-reperfusion injury, we have evaluated the postischemic functional recovery and free radical release of osteogenic disorder Shionogi (ODS) inherently scorbutic rat hearts and compared them to healthy Wistar rat hearts.


METHODS
Isolated perfused hearts of ODS or Wistar rats underwent 30 min of a global total normothermic ischemia followed by 30 min of reperfusion. The lipid-soluble spin trap alpha-phenyl N-tert-butylnitrone (3 mM) was perfused upstream of the coronary bed. Functional parameters were recorded and samples of coronary effluents were analysed using electron spin resonance spectroscopy to characterise and quantify the amount of radical species released.


RESULTS
From the onset of reperfusion, a large and long-lasting release of alkyl/alkoxyl radicals was detected, with a peak value of 29.0+/-3.2 nM obtained after 13 min, which was associated with a persistent contractile dysfunction. However, ODS rat hearts showed a higher myocardial recovery with lower left ventricular end diastolic pressure (44.34+/-1.74 vs. 55.03+/-1.57 mmHg for Wistar), higher recovery of rate pressure product (12.3+/-1.4 vs. 1.9+/-1.7x10(3) mmHg beats/min for Wistar) and shorter duration of contractile abnormalities during reperfusion (3.7+/-1.0 vs. 20.8+/-5.3 min for Wistar). Moreover, free radical release was identical in ODS rat hearts as compared to control Wistar rats. Ascorbic acid tissue content was significantly altered in ODS rats (31.9+/-3.3 vs. 591.0+/-54.9 mmol/g of tissue for Wistar) but superoxide dismutases, glutathion peroxidases and inducible heat shock protein 70 genes were up-regulated.


CONCLUSIONS
This study shows that ascorbic-acid-deficient ODS rat hearts are more resistant to an ischemic insult than control Wistar rats, probably through the development of alternative protective defences, like the induction of heat shock proteins. These paradoxical results raise the question of the relative importance of each endogenous antioxidant in the cardiac resistance to ischemia-reperfusion injury.
Vergely
C
C
Laboratoire de Physiopathologie et Pharmacologie Cardio-vasculaires Expérimentales, Facultés de Médecine et Pharmacie, 7 Boulevard Jeanne d'Arc, 21000 Dijon, France. catherine.vergely@u-bourgogne.fr
Perrin
C
C
Laubriet
A
A
Oudot
A
A
Zeller
M
M
Guilland
J C
JC
Rochette
L
L
D000704:Analysis of Variance; D000818:Animals; D001205:Ascorbic Acid / Q000032:analysis / Q000097:blood; D001206:Ascorbic Acid Deficiency / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000032:analysis*; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D008297:Male; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D010477:Perfusion; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics; D014527:Uric Acid / Q000097:blood; D014810:Vitamin E / Q000097:blood
D005609:Free Radicals; D018840:HSP70 Heat-Shock Proteins; D014810:Vitamin E; D014527:Uric Acid; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001205:Ascorbic Acid