Premium
HYPEROXIA CONFERS MYOCARDIAL PROTECTION IN MECHANICALLY VENTILATED RATS THROUGH THE GENERATION OF FREE RADICALS AND OPENING OF MITOCHONDRIAL ATP‐SENSITIVE POTASSIUM CHANNELS
Author(s) -
Colantuono Giuseppe,
Tiravanti Edy Altea,
Di Venosa Nicola,
Cazzato Antonia,
Rastaldo Raffaella,
Cagiano Raffaele,
D’Agostino Donato,
Federici Antonio,
Fiore Tommaso
Publication year - 2008
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04745.x
Subject(s) - hyperoxia , preload , free radical scavenger , cardioprotection , ventilation (architecture) , anesthesia , ischemia , medicine , chemistry , cardiology , hemodynamics , oxidative stress , lung , mechanical engineering , engineering
SUMMARY1 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 (F i o 2 = 0.3) or hyperoxia (F i o 2 = 1.0) for 30 min and pH, P co 2 , P o 2 , 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 K ATP 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 K ATP 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 co 2 , pH, heart rate, airway and blood pressure between the groups. However, the P o 2 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 mitoK ATP channel opening.