The effect of K-ATP channel activation on myocardial cationic and energetic status during ischemia and reperfusion: Role in cardioprotection

The role of cation and cellular energy homeostasis in ATP-sensitive K-1 (K- APP) channel-induced cardioprotection is poorly understood. To evaluate thi s, rapidly interleaved Na-23 and P-31 NMR spectra were acquired from isolat ed rat hearts exposed to direct Na-i(+) channel activation from nicorandil or pinacidil. Nicorandil attenuated ATP depiction and intracellular Na+ (Na -i(+)) accumulation, delayed the progression of acidosis during zero-flow i schemia and prevented ischemic contracture. The Na-i(+) channel inhibitor 5 -hydroxydecanoate abolished these effects. Pinacidil did not alter Na-i(+), accumulation, ATF depletion or pH during ischemia under the conditions emp loyed. Both agonists greatly improved the post-ischemic functional recovery . Both agonists also dramatically improved tl-re rate and extent of the rep erfusion recoveries of Na-i(+) PCr and ATP. The Na-i(+) and PCr reperfusion recovery rates were tightly correlated, suggesting a causal relationship. Separate atomic absorption tissue Ca2+ measurements revealed a marked reper fusion Ca2+ uptake, which was reduced two-fold by pinacidil. In conclusion, these results clearly indicate that while K-ATP channel-induced metabolic alterations carl vary the functional cardioprotection resulting from this f orm of pharmacological preconditioning does not require atenuation of acido sis, cellular energy depletion, or Na-i(+) accumulation during ischemia. Ra ther than preservation of cationic/energetic status during ischemia, the ca rdioprotective processes may involve a preserved capability for its rapid r estoration during reperfusion. The enhanced reperfusion Na-i(+) recovery ma p be enabled by the improved reperfusion cellular energy state. This accele rated Na-i(+) recovery could play an important cardioprotective role via a potential causal relationship with the reduction of reperfusion tissue Ca2 uptake and resultant reperfusion injury. (C) 2001 Academic Press.