Hyperoxia confers myocardial protection in mechanically ventilated rats through the generation of free radicals and opening of mitochondrial ATP-sensitive potassium channels.
1. One hour exposure to hyperoxia has been shown previously to limit a subsequent ischaemia-reperfusion injury in spontaneously breathing rats. We tested the cardioprotective effect of a shorter period of hyperoxia during mechanical ventilation and the possible contribution of reactive oxygen species (ROS) and mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels. 2. Mechanically ventilated rats were exposed to normoxia (Fi O2 = 0.3) or hyperoxia (Fi O2 = 1.0) for 30 min and pH, P CO2, PO2, heart rate, airway and blood pressure were measured at baseline and after 30 min mechanical ventilation. Isolated hearts were subsequently subjected to 30 min ischaemia and 120 min reperfusion. Infarct size and left ventricular end-diastolic pressure (LVEDP), developed pressure (LVDP) and coronary flow (CF) were measured. In order to investigate the role of ROS and KATP channels within the mechanism leading to cardioprotection, the free radical scavenger N-acetylcysteine (NAC; 150 mg/kg) was infused in mechanically ventilated rats and the KATP channel blockers glibenclamide (200 mmol/L) or 5-hydroxydecanoate (10 mmol/L) were infused in isolated hearts immediately before ischaemia. 3. No differences were detected in P CO2, pH, heart rate, airway and blood pressure between the groups. However, the PO2 in hyperoxic groups was significantly higher compared with that in normoxic groups (P < 0.01). After 30 min ischaemia, we found that hyperoxic preconditioning significantly improved CF (P < 0.01), LVDP (P < 0.01) and LVEDP (P < 0.01) and reduced the extent of infarct size in the reperfused heart compared with the normoxic group (P < 0.01). When rats were pretreated either with NAC before hyperoxic ventilation or with K(ATP) channel blockers before ischaemia, myocardial protection was abolished. 4. Hyperoxic mechanical ventilation, prior to ischaemia, reduces myocardial reperfusion injury. This is likely to occur through the induction of oxidative stress, which leads to myocyte mitoKATP channel opening.
Department of Emergency and Transplants, Section of Anaesthesia and Critical Care, University of Bari, Bari, Italy.
Giuseppe
G
Colantuono
Edy Altea
EA
Tiravanti
Nicola
N
Di Venosa
Antonia
A
Cazzato
Raffaella
R
Rastaldo
Raffaele
R
Cagiano
Donato
D
D'Agostino
Antonio
A
Federici
Tommaso
T
Fiore
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D003326:Coronary Circulation; D003652:Decanoic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate; D006880:Hydroxy Acids / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012121:Respiration, Artificial; D013997:Time Factors; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
D003652:Decanoic Acids; D016166:Free Radical Scavengers; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D017382:Reactive Oxygen Species; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; D005905:Glyburide; D000111:Acetylcysteine