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American journal of physiology. Heart and circulatory physiology, 2000-02, Vol.278 (2), p.H643-H651
Ort / Verlag
United States
Erscheinungsjahr
2000
Quelle
MEDLINE
Beschreibungen/Notizen
1 Restoration of Appearance and Function Trust, Institute
of Plastic Surgery, Mount Vernon Hospital, Northwood HA6 2RN;
2 Vascular Biology Unit, Department of Surgical Research,
Northwick Park Institute for Medical Research, Harrow HA1 3UJ, United
Kingdom
Bilirubin is a potent antioxidant generated
intracellularly during the degradation of heme by the enzyme heme
oxygenase. The purpose of this study was to determine the role of
increased cardiac bilirubin in protection against postischemic
myocardial dysfunction. Rat hearts were isolated and perfused according
to the Langendorff technique to evaluate the recovery of myocardial
function after 30 min of global ischemia and 60 min of
reperfusion. We found that upregulation of the inducible isoform of
heme oxygenase (HO-1) by treatment of animals with hemin 24 h before
ischemia ameliorated myocardial function and reduced infarct
size (tetrazolium staining) on reperfusion of isolated hearts. Tin
protoporphyrin IX, an inhibitor of heme oxygenase activity, completely
abolished the improved postischemic myocardial performance observed
after hemin-mediated HO-1 induction. Likewise, cardiac tissue injury
was exacerbated by treatment with tin protoporphyrin IX. Increased
cardiac HO-1 expression and heme oxygenase activity were associated
with enhanced tissue bilirubin content and an increased rate of
bilirubin release into the perfusion buffer. Furthermore, exogenously
administered bilirubin at concentrations as low as 100 nanomolar
significantly restored myocardial function and minimized both infarct
size and mitochondrial damage on reperfusion. Our data provide strong
evidence for a primary role of HO-1-derived bilirubin in
cardioprotection against reperfusion injury.
antioxidant genes; heat shock proteins; preconditioning; infarct
size; carbon monoxide