Effects of potassium channel modulation during global ischaemia in isolated rat heart with and without cardioplegia.
Effects of potassium channel modulation during global ischaemia in isolated rat heart with and without cardioplegia.
复制标题
钾通道调节对离体大鼠心脏整体缺血期间有或没有心脏停搏的影响。
DOI：
10.1093/cvr/26.11.1063
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发表时间：
1992
影响因子：
10.8
通讯作者：
Hearse,DJ
中科院分区：
文献类型：
--
作者：
Galiñanes,M;Shattock,MJ;Hearse,DJ
目的：局部缺血时钾（K+）通道的打开可能是一种内在的能量节约机制，通过诱发快速收缩骤停。因此，K+通道开放剂（例如lemakalim）具有显著的抗缺血作用，而格列本脲会加剧缺血挛缩并限制缺血后功能恢复。该研究的目的是研究这些化合物在单独使用或与高K+心脏骤停溶液联合使用时影响缺血性损伤的能力。方法：采用脑内球囊法评价Langendorff灌注大鼠离体心脏的收缩功能。使用或不使用格列本脲或莱马卡林时，心脏遭受常温全局缺血（20分钟）或心搏骤停（35分钟）。在缺血发作前立即给予Lemakalim （10 μmol·l - 1）或glibenclamide (10 μmol·l - 1)，无论是否存在心脏骤停。测量缺血致收缩衰竭的发生率、缺血挛缩的严重程度和缺血后功能恢复的程度。结果：在没有心脏骤停的情况下，对照心脏的收缩骤停时间为133 (SEM 4) s，格列本脲组将其延长至145(6)s，左马卡林组将其缩短至112(6)s。到缺血性挛缩发生的时间[8(1)min]，格列本脲组加速[4(1)min]，左马卡林组延迟[14(1)min]。Lemakalim显著改善左心室发育压的恢复，从对照组的49.7%提高到65.3%，左心室舒张末期压从41.3%提高到21.4%。用格列本脲预处理的心脏恢复情况与对照组相似。在再灌注过程中，来马卡林发挥短暂的血管扩张作用，而格列苯脲则引起短暂的血管收缩。当将格列本脲或来马卡林加入高K+心脏麻痹溶液中，心脏缺血35分钟时，这两种化合物影响缺血挛缩和缺血后功能恢复的能力丧失。在另外的研究中，利马卡林对缺血引起的机械故障和电骤停的相对时间的影响进行了评估。对照组心脏到收缩衰竭的时间为128(5)秒，到电骤停的时间为241（30）秒，而lemakalim处理心脏的时间分别为103(2)秒和509（161）秒。左马卡林组所有心脏均出现持续性室性心律失常；对照组无一例心律失常。结论：乐玛卡林单用具有明显的抗缺血作用。当它与高K+心脏截止剂联合使用时，这种效果就会消失。因此，lemakalim的抗缺血特性可能仅限于其加速收缩停止的能力。心血管Research1992;26:1063 - 1068
Objective:The opening of potassium (K+) channels during regional ischaemia may, by inducing rapid contractile arrest, be an intrinsic energy sparing mechanism. Thus K+channel openers (for example, lemakalim) exert significant anti-ischaemic effects, whereas glibenclamide exacerbates ischaemic contracture and limits postischaemic functional recovery. The aim of the study was to investigate the ability of these compounds to influence ischaemic injury when used either alone or in combination with rapid arrest induced by a high K+cardioplegic solution.Methods:Contractile function of isolated Langendorff perfused rat hearts was assessed using an intraventricular balloon. Hearts were subjected to normothermic global ischaemia (20 min) or cardioplegic arrest (35 min) with and without glibenclamide or lemakalim. Lemakalim (10 μmol·litre−1) or glibenclamide (10 μmol·litre−1) was given, in the presence or absence of cardioplegia, for 2 min immediately prior to the onset of ischaemia. The rate of ischaemia induced contractile failure, the severity of ischaemic contracture, and the degree of postischaemic functional recovery were all measured.Results:In the absence of cardioplegia, the time to contractile arrest in control hearts was 133 (SEM 4) s. This was increased by glibenclamide, to 145(6) s, and decreased by lemakalim, to 112(6) s. The time to onset of ischaemic contracture [8(1) min] was accelerated by glibenclamide [4(1) min] and delayed by lemakalim [14(1) min]. Lemakalim significantly improved the recovery of left ventricular developed pressure from 49(7)% in control hearts to 65(3)%, and left ventricular end diastolic pressure from 41(3) to 21(4) mm Hg. Hearts pretreated with glibenclamide showed similar recoveries to control hearts. During reperfusion, lemakalim exerted a transient vasodilator effect whereas glibenclamide caused a transient vasoconstriction. When either glibenclamide or lemakalim was added to a high K+cardioplegic solution and hearts rendered ischaemic for 35 min, the ability of both compounds to influence ischaemic contracture and postischaemic functional recovery was lost. In additional studies the effect of lemakalim on the relative times to ischaemia induced mechanical failure and electrical arrest was assessed. In control hearts the time to contractile failure was 128(5) s and the time to electrical arrest was 241(30) s, while in the lemakalim treated hearts the values were 103(2) s and 509 (161) s, respectively. In the lemakalim group all the hearts showed sustained ventricular arrhythmias; in the control group there were no arrhythmias.Conclusions:Lemakalim can exert a significant anti-ischaemic effect when given alone. This effect is lost when it is used in combination with high K+cardioplegia. The anti-ischaemic properties of lemakalim may thus be limited to its ability to accelerate contractile arrest.Cardiovascular Research1992;26:1063-1068