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.
Tawa
Masashi
M
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
Fukumoto
Taiki
T
Yamashita
Naoto
N
Ohkita
Mamoru
M
Ayajiki
Kazuhide
K
Okamura
Tomio
T
Matsumura
Yasuo
Y
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