The effect of K(atp)channel activation on myocardial cationic and energetic status during ischemia and reperfusion: role in cardioprotection.
The effect of K(atp)channel activation on myocardial cationic and energetic status during ischemia and reperfusion: role in cardioprotection.
复制标题
K（atp）通道激活对缺血和再灌注期间心肌阳离子和能量状态的影响：在心脏保护中的作用。
DOI：
10.1006/jmcc.2000.1328
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Pike,MM
中科院分区：
文献类型：
--
作者：
Fukuda,H;Luo,CS;Gu,X;Guo,L;Digerness,SB;Li,J;Pike,MM
阳离子和细胞能量稳态在ATP敏感性K+（KATP）通道诱导的心脏保护中的作用知之甚少。为了评估这一点，从暴露于尼可地尔或吡那地尔直接激活的Katp通道的离体大鼠心脏中获得快速衰减的23 Na和31 P NMR光谱。尼可地尔可减少ATP耗竭和细胞内Na+（Na+i）蓄积，延迟零流量缺血期间酸中毒的进展，并预防缺血性挛缩。KATP通道抑制剂5-羟基癸酸可阻断上述作用。吡那地尔在所用条件下不改变缺血期间的Na+蓄积、ATP耗竭或pH。两种激动剂都大大改善了缺血后的功能恢复。两种激动剂还显著改善了Na+i、PCr和ATP的再灌注恢复的速率和程度。Na+ i和PCr再灌注恢复率密切相关，表明存在因果关系。单独的原子吸收组织Ca 2+的测量结果显示，一个显着的再灌注Ca 2+的摄取，这是减少了两倍的吡那地尔。总之，这些结果清楚地表明，虽然KATP通道诱导的代谢改变可以变化，但这种形式的药理学预处理产生的功能性心脏保护不需要减轻缺血期间的酸中毒、细胞能量消耗或Na+蓄积。心脏保护过程可能涉及在再灌注期间快速恢复的能力，而不是在缺血期间保持阳离子/能量状态。提高再灌注Na+恢复可能是通过改善再灌注细胞能量状态实现的。这种加速的Na+ i恢复可能通过与再灌注组织Ca 2+摄取减少和由此产生的再灌注损伤的潜在因果关系而发挥重要的心脏保护作用。
The role of cation and cellular energy homeostasis in ATP-sensitive K+(KATP) channel-induced cardioprotection is poorly understood. To evaluate this, rapidly interleaved23Na and31P NMR spectra were acquired from isolated rat hearts exposed to direct KATPchannel activation from nicorandil or pinacidil. Nicorandil attenuated ATP depletion and intracellular Na+(Na+i) accumulation, delayed the progression of acidosis during zero-flow ischemia and prevented ischemic contracture. The KATPchannel inhibitor 5-hydroxydecanoate abolished these effects. Pinacidil did not alter Na+iaccumulation, ATP depletion or pH during ischemia under the conditions employed. Both agonists greatly improved the post-ischemic functional recovery. Both agonists also dramatically improved the rate and extent of the reperfusion recoveries of Na+i, PCr and ATP. The Na+iand PCr reperfusion recovery rates were tightly correlated, suggesting a causal relationship. Separate atomic absorption tissue Ca2+measurements revealed a marked reperfusion Ca2+uptake, which was reduced two-fold by pinacidil. In conclusion, these results clearly indicate that while KATPchannel-induced metabolic alterations can vary, the functional cardioprotection resulting from this form of pharmacological preconditioning does not require attenuation of acidosis, cellular energy depletion, or Na+iaccumulation during ischemia. Rather than preservation of cationic/energetic status during ischemia, the cardioprotective processes may involve a preserved capability for its rapid restoration during reperfusion. The enhanced reperfusion Na+irecovery may be enabled by the improved reperfusion cellular energy state. This accelerated Na+irecovery could play an important cardioprotective role via a potential causal relationship with the reduction of reperfusion tissue Ca2+uptake and resultant reperfusion injury.