Effects of K+ channel openers on ischemic dysfunction and metabolic disturbance in isolated perfused rat heart.
The effects of two structurally different K+ channel openers, KRN2391 and cromakalim, on cardiac mechanisms during ischemia and reperfusion were studied in isolated perfused rat hearts. Isolated buffer-perfused rat hearts pretreated with KRN2391, cromakalim and vehicle were subjected to 25 min of ischemia followed by 30 min of reperfusion. Before ischemia, KRN2391 (1-10 microM) and cromakalim (1-10 microM) increased coronary flow, but did not modify cardiac function or biochemical parameters (adenine nucleotides, energy charge potential: ECP, lactate). During ischemia, KRN2391 (3, 10 microM) and cromakalim (10 microM) significantly accelerated the reduction in cardiac function and attenuated the decreased levels of ATP and ECP, but did not change the lactate content. After 30 min of reperfusion, pretreatment with KRN2391 and cromakalim resulted in a significant improvement in cardiac function, ischemic contracture and biochemical parameters. Thus, both KRN2391 and cromakalim have beneficial effects on biochemical parameters during ischemia and reperfusion, effects which may be related to cardiodepression during ischemia.
Ohta
H
H
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd., Gunma, Japan.
Nakazawa
H
H
Jinno
Y
Y
Harada
K
K
Ogawa
N
N
Miwa
A
A
Nishikori
K
K
D000818:Animals; D001578:Benzopyrans / Q000627:therapeutic use*; D019806:Cromakalim; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D015425:Myocardial Reperfusion; D011725:Pyridines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000627:therapeutic use*
D001578:Benzopyrans; D011725:Pyridines; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate