格列本脲并不消除预处理对离体灌注大鼠心脏顿抑的保护作用。

Glibenclamide does not abolish the protective effect of preconditioning on stunning in the isolated perfused rat heart.

作者信息

Fralix T A, Steenbergen C, London R E, Murphy E

机构信息

Laboratory of Molecular Biophysics, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709.

出版信息

Cardiovasc Res. 1993 Apr;27(4):630-7. doi: 10.1093/cvr/27.4.630.

DOI:10.1093/cvr/27.4.630

PMID:8324797

Abstract

OBJECTIVE

The aim was to determine if the beneficial effects of preconditioning would be affected by inhibiting ATP sensitive potassium (KATP) channels in the isolated, perfused rat heart.

METHODS

The effects of inhibiting KATP channels with glibenclamide (10 microM) were evaluated on ionic alterations and recovery of function after 30 min ischaemia in non-preconditioned hearts and in hearts that had been preconditioned with four intermittent periods of 5 min ischaemia each separated by 5 min of reflow. [Ca2+]i, pHi, and high energy phosphate levels were measured using 19F and 31P nuclear magnetic resonance during the preconditioning periods of ischaemia, during 30 min of ischaemia, and during reflow, in the presence and absence of 10 microM glibenclamide.

RESULTS

High energy phosphate contents were decreased during the preconditioning period to a greater extent in glibenclamide treated hearts and the onset of contracture was hastened during the subsequent 30 min period of sustained ischaemia. However, glibenclamide (10 microM) did not abolish the protective effects of preconditioning on ion accumulation during ischaemia or on postischaemic recovery of contractile function. Recovery of left ventricular developed pressure (as % of initial value) following 30 min of ischaemia was 74(SEM 5)% in the preconditioned hearts without drug and 62(4)% in the preconditioned hearts with glibenclamide, while recovery was 25(5)% in the non-preconditioned hearts without drug and 19(2)% in the non-preconditioned hearts with drug. The alterations in [Ca2+]i and pHi during ischaemia were similar in the glibenclamide treated and untreated preconditioned hearts and in both cases were less marked than in the non-preconditioned untreated hearts.

CONCLUSIONS

Thus, although inhibition of KATP channels accelerates high energy phosphate depletion during the preconditioning period, this does not result in accentuation of the ionic derangements during a subsequent sustained period of ischaemia and does not abolish the protective effect of preconditioning on stunning in the isolated rat heart.

摘要

目的

旨在确定在离体灌注大鼠心脏中，抑制ATP敏感性钾（KATP）通道是否会影响预处理的有益作用。

方法

评估用格列本脲（10微摩尔）抑制KATP通道对未预处理心脏以及经四个5分钟缺血间歇期（每次缺血间歇期后有5分钟再灌注）预处理的心脏在30分钟缺血后离子变化和功能恢复的影响。在缺血预处理期、30分钟缺血期以及再灌注期，于有或无10微摩尔格列本脲存在的情况下，使用19F和31P核磁共振测量细胞内钙离子浓度（[Ca2+]i）、细胞内pH值（pHi）以及高能磷酸水平。

结果

在预处理期，格列本脲处理的心脏中高能磷酸含量下降幅度更大，且在随后持续30分钟的缺血期挛缩发作加快。然而，格列本脲（10微摩尔）并未消除预处理对缺血期间离子积聚或缺血后收缩功能恢复的保护作用。30分钟缺血后，未用药的预处理心脏左心室舒张末压恢复率（相对于初始值的百分比）为74（标准误5）%，使用格列本脲的预处理心脏为62（4）%，而未用药的未预处理心脏恢复率为25（5）%，使用药物的未预处理心脏为19（2）%。在格列本脲处理和未处理的预处理心脏中，缺血期间[Ca2+]i和pHi的变化相似，且在两种情况下均不如未预处理未处理的心脏明显。