Effects of hyperoxia and cardiovascular risk factors on myocardial ischaemia-reperfusion injury: a randomized, sham-controlled parallel study.

Recent studies on O2 supplementation in acute coronary syndrome patients are equivocal. We tested the hypothesis that oxidative stress is increased in rodents with cardiovascular risk factors and enhances ischaemia-reperfusion injury in the presence of hyperoxia. A total of 43 Wistar rats (WR), 30 spontaneously hypertensive rats (SHR) and 33 obese Zucker rats (ZR) were randomized in a sham procedure (one-third) or underwent a left anterior descending ligation of the coronary artery for 60 min (two-thirds). This was followed by 3 h of reperfusion while animals were randomized either in a hyperoxic (HR) or a normoxic reperfusion (NR) group. Myocardial infarction size and oxidative stress biomarkers (myeloperoxidase (MPO), malondialdehyde and total free thiols) were assessed in blood samples. Baseline troponin T was higher in SHR and ZR than in WR (both P < 0.001). Baseline total MPO was elevated in ZR in comparison to SHR and WR (both P < 0.001). SHR had lower thiol concentration compared to WR and ZR (P < 0.000001). HR was associated with a lower troponin T rise in SHR and ZR than in NR (both P < 0.001), while the reverse occurred in WR (P < 0.001). In SHR, HR limited total MPO increase as compared to NR (P = 0.0056) and the opposite effect was observed with total MPO in WR (P = 0.013). NR was associated with a drastic reduction of total thiols as compared to HR both in SHR and in ZR (both P < 0.001). Despite a heightened baseline oxidative stress level, HR limited myocardial necrosis and anti/pro-oxidant imbalance in SHR and ZR whereas this effect was exacerbated in healthy WR.