Postconditioning improves postischemic cardiac dysfunction independently of norepinephrine overflow after reperfusion in rat hearts: comparison with preconditioning.
We investigated whether the cardioprotective effect of ischemic postconditioning (postC) against ischemia/reperfusion (I/R)-induced cardiac dysfunction is associated with the negative control of I/R-enhanced norepinephrine (NE) overflow, an aggravating factor of I/R injury, in comparison with the effects induced by ischemic preconditioning (preC). According to the Langendorff technique, isolated rat hearts were subjected to 40-minute global ischemia followed by 30-minute reperfusion. PostC, consisting of three cycles of 30-second reperfusion followed by 30-second ischemia at the end of the 40-minute ischemia, improved I/R-induced cardiac dysfunction. However, the potency of this postC-induced improvement was somewhat weaker than that produced by preC, consisting of three cycles of 5-minute ischemia followed by 5-minute reperfusion before 40-minute ischemia. The preC treatment markedly suppressed I/R-enhanced NE overflow, whereas postC had no apparent effect. A nonselective nitric oxide synthase inhibitor, N-nitro-L-arginine, almost completely abolished postC-induced cardiac protection without affecting NE overflow, whereas the effect of preC on I/R-induced cardiac dysfunction and NE overflow was only partially inhibited by N-nitro-L-arginine. These findings indicate that the beneficial effect of postC on I/R-induced cardiac dysfunction depends on nitric oxide and is irrelevant to NE overflow after reperfusion in contrast to the preC effect.
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
Masashi
M
Tawa
Taiki
T
Fukumoto
Naoto
N
Yamashita
Mamoru
M
Ohkita
Kazuhide
K
Ayajiki
Tomio
T
Okamura
Yasuo
Y
Matsumura
D000818:Animals; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019335:Nitroarginine; D009569:Nitric Oxide; D009638:Norepinephrine