Ischemic preconditioning in chronically hypoxic neonatal rat heart.
Rat hearts isolated on d 1, 4, 7, and 10 of postnatal life were perfused (in Langendorff mode) with Krebs-Henseleit solution at constant pressure, temperature, and stimulation rate. Recovery of the contractile function after global ischemia was measured by an isometric force transducer and analyzed using an online computer. Ischemic preconditioning (IP) was induced by three 3-min periods of global ischemia, each separated by a 5-min period of reperfusion. Prenatal hypoxia was induced by exposure of pregnant mothers to intermittent high altitude (IHA), simulated in a barochamber (8 h/d, 5000 m) from d 15 to 20 of pregnancy. Postnatal hypoxia was simulated by the identical procedure from postnatal d 1 to 6 and 9. Prenatal exposure to IHA failed to improve ischemic tolerance on d 1, but postnatal exposure to IHA improved recovery of the developed force after ischemia on d 7 (33 +/- 3% versus 43 +/- 4%) and 10 (39 +/- 2% versus 54 +/- 2%). Combination of IHA and IP induced higher protective effects in all age groups, including postnatal d 1 (48 +/- 2% versus 56 +/- 3%), whereas IHA and IP applied separately failed to improve ischemic tolerance. Neither the mitochondrial K(ATP) channel blocker 5-hydroxydecanoate nor the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester abolished protection by IP in normoxic animals, but they decreased significantly protection by IHA hypoxia. The final recovery was even lower than the corresponding normoxic values. It seems likely that mitochondrial K(ATP) channels and nitric oxide may be involved in the protective mechanisms of adaptation to chronic hypoxia but not to that of IP, at least in neonates.
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D003652:Decanoic Acids / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006400:Hematocrit; D006880:Hydroxy Acids / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar
D003652:Decanoic Acids; D006880:Hydroxy Acids; C052853:5-hydroxydecanoic acid; D019331:NG-Nitroarginine Methyl Ester