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.