Effect of cromakalim on ischemic and reperfused immature heart: experiments with isolated neonatal New Zealand white rabbit hearts.
To elucidate whether K+ channels are involved in the ischemia-reperfusion injury in immature heart, we examined the effect of cromakalim, a potent opener of ATP-sensitive K+ channel (KATP channel), on the ischemic and reperfused neonatal New Zealand white rabbit heart. The experiments were divided into control group and cromakalim pretreated group. When, the heart was loaded with 10 microM cromakalim preischemically, the recovery of heart rate and left ventricular developed pressure were significantly improved than those of the control group. Pretreatment with cromakalim also decreased lactate excretion in the coronary effluent. Measurements of cation contents with atomic absorption method revealed that intracellular K+ content was lower in cromakalim pretreated group at preischemia, end of ischemia and 20 min after ischemia. Intracellular accumulation of Na+ and Ca2+ at reperfusion period was inhibited by cromakalim pretreatment. From these results, it is assumed that cromakalim might act on KATP channels of plasma membrane and reduces the K+ content of the cardiomyocytes which in turn inhibits Na+ and Ca2+ accumulation during the reperfusion period. Prevention of Na+ and Ca2+ accumulation after ischemia might be a reason for cardioprotective effect of cromakalim on neonatal New Zealand white rabbit heart.
Shimoe
Y
Y
Department of Cardiovascular Surgery, School of Medicine, University of Tokushima, Japan.
Yoshizumi
M
M
Masuda
Y
Y
Kitagawa
T
T
Katoh
I
I
D000818:Animals; D000831:Animals, Newborn; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D012964:Sodium; D011188:Potassium