title: Responses of chronically hypoxic rat hearts to ischemia: KATP channel blockade does not abolish increased RV tolerance to ischemia.
abstract: Chronic hypoxia may precondition the myocardium and protect from ischemia-reperfusion damage. We therefore examined the recovery of left and right ventricular function after ischemia and reperfusion (15 min each) in isolated blood-perfused working hearts from normoxic (Norm) and hypoxic (Hypo; 14 days, 10.5% O(2)) adult rats. In addition, the mRNA expression of hypoxia-inducible factor (HIF)-1alpha and the protein expression of endothelial nitric oxide synthase (eNOS) were measured. Postischemic left ventricular function recovered to 66 +/- 6% and 67 +/- 5% of baseline in Norm and Hypo, respectively. In contrast, postischemic right ventricular function was 93 +/- 2% of baseline in Hypo vs. 67 +/- 3% in Norm (P < 0.05). Improved postischemic right ventricular function in Hypo (93 +/- 2% and 96 +/- 2% of baseline) was observed with 95% O(2) or 21% O(2) in the perfusate, and it was not attenuated by glibenclamide (5 and 10 micromol/l) (86 +/- 4% and 106 +/- 6% recovery). HIF-1alpha mRNA and eNOS protein expression were increased in both left and right hypoxic ventricles. In conclusion, postischemic right, but not left, ventricular function was improved by preceding chronic hypoxia. ATP-sensitive K(+) channels are not responsible for the increased right ventricular tolerance to ischemia after chronic hypoxia in adult rat hearts.
authors.affiliation: Division of Cardiothoracic Surgery, University of Essen, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Forkel
authors.forename: Xiaochao
authors.initials: X
authors.lastname: Chen
authors.forename: Susanne
authors.initials: S
authors.lastname: Wandinger
authors.forename: Florian
authors.initials: F
authors.lastname: Keser
authors.forename: Alexey
authors.initials: A
authors.lastname: Duschin
authors.forename: Uwe
authors.initials: U
authors.lastname: Schwanke
authors.forename: Stilla
authors.initials: S
authors.lastname: Frede
authors.forename: Parwis
authors.initials: P
authors.lastname: Massoudy
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Heinz
authors.initials: H
authors.lastname: Jakob
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001835:Body Weight; D002245:Carbon Dioxide / Q000097:blood; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D066298:In Vitro Techniques; D054086:KATP Channels; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009929:Organ Size; D010100:Oxygen / Q000097:blood; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D014157:Transcription Factors; C092520:uK-ATP-1 potassium channel; D002245:Carbon Dioxide; D010100:Oxygen