title: Daily reoxygenation decreases myocardial injury and improves post-ischaemic recovery after chronic hypoxia.
abstract: OBJECTIVE
  In contrast to the clinical evidence, experimental studies showed that chronic hypoxia (CH) confers a certain degree of protection against ischaemia-reperfusion damage. We studied the effects of daily reoxygenation during CH (CHReox) on hearts exposed to ischaemia-reperfusion. We also separated the intrinsic effects on the myocardium of CH and CHReox from those related to circulatory and nervous factors.
  
  
  METHODS
  Fifty-one Sprague-Dawley rats were maintained for 15 days under CH (10% O(2)) or CHReox (10% O(2)+1 h day(-1) exposure to air). Normoxic (N, 21% O(2)) rats were the control. The animals were randomly assigned to one of the three following protocols: (1) protocol A: hearts (n=7 per group) were subjected to 30-min occlusion of the left anterior descending (LAD) coronary artery followed by 3-h reperfusion, with measurement of the injury by tetrazolium staining; (2) protocol B: the end-diastolic pressure (EDP) and left ventricular developed pressure x heart rate (LVDP x HR) were measured in Langendorff-perfused isolated hearts (n=5 per group) during 30-min global ischaemia and 45-min reperfusion; and (3) protocol C: hearts (n=5 per group) were frozen for the determination of levels of endothelial nitric oxide synthase (eNOS) by Western blotting.
  
  
  RESULTS
  CHReox hearts displayed greater phosphorylation of the eNOS and enhanced plasma level of nitrates and nitrites in comparison to CH hearts (P<0.0001, Bonferroni's post-test). The infarct size was greater in CH than in N hearts (P<0.0001, Bonferroni's post-test) while it was reduced in CHReox in comparison to CH and N hearts (P<0.0001). At the end of reperfusion, EDP was higher in CH than CHReox and N hearts (P=0.01, Bonferroni's post-test) while LVDP x HR was higher in CHReox and N than in CH hearts (P=0.03, Bonferroni's post-test).
  
  
  CONCLUSIONS
  Exposure to CH results in impairment of myocardial tolerance to ischaemia-reperfusion, greater injury and reduced recovery of performance, in agreement with clinical evidence. Infarct size, diastolic contracture and myocardial performance have been reduced, respectively, by 63%, 64% and 151% with daily reoxygenation compared with chronic hypoxia by accelerating intrinsic adaptive changes.
authors.affiliation: Cardiovascular Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. giuseppina.milano@chuv.ch
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Milano
authors.forename: Antonio F
authors.initials: AF
authors.lastname: Corno
authors.forename: Michele
authors.initials: M
authors.lastname: Samaja
authors.forename: Sandrine
authors.initials: S
authors.lastname: Morel
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vassalli
authors.forename: Ludwig K
authors.initials: LK
authors.lastname: von Segesser
mesh_terms: D000818:Animals; D001835:Body Weight; D002908:Chronic Disease; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D000860:Hypoxia / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D009566:Nitrates / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000097:blood; D009573:Nitrites / Q000097:blood; D010101:Oxygen Consumption / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006454:Hemoglobins; D009566:Nitrates; D009573:Nitrites; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat