钠/钙交换体和肌浆网在大鼠心脏高钾保护缺血再灌注功能障碍中的作用。

Participation of Na/Ca-exchanger and sarcoplasmic reticulum in the high [K]-protection against ischaemia-reperfusion dysfunction in rat hearts.

作者信息

Consolini A E, Quiroga P, Yuln G, Volonté M G

机构信息

Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP), La Plata, Argentina.

出版信息

Acta Physiol Scand. 2004 Oct;182(2):121-32. doi: 10.1111/j.1365-201X.2004.01342.x.

DOI:10.1111/j.1365-201X.2004.01342.x

PMID:15450108

Abstract

AIM

Na/Ca-exchanger (NCX) and sarcoplasmic reticulum (SR) roles during the protection by a cardioplegic solution (25 mm K and 0.5 mm Ca, CPG) against ischaemia-reperfusion was studied.

METHODS

Contractile performance (CP) and high energy phosphates contents (HEP) were evaluated in isolated ventricles from rats. They were pre-treated with Krebs (C) or CPG and submitted to no-flow ischaemia and reperfusion (I-R). KB-R7943 5 microm (inhibitor of NCX in reverse mode), 8 mm caffeine and ionic changes were used pre-ischaemically to evaluate each pathway role.

RESULTS

During R, CP recovered to 77 +/- 8% of basal in CPG-hearts vs. 55 +/- 8% (P < 0.05) in C-ones. CPG avoided the increases in end diastolic pressure (LVEDP) and in PCr/ATP ratio during I-R. Low [Na]o (78 mm) under both, CPG-2 mm Ca and C, increased further the LVEDP during I-R. LVEDP was also transiently increased by caffeine-CPG, but not modified by KB-R7943. The recovery of CP during reperfusion of CPG-hearts was decreased either, by caffeine (to approximately 75%), low [Na]o-2 mm Ca-CPG (to approximately 40%) and KB-R7943 (to approximately 16%).

CONCLUSIONS

CPG protected hearts from ischaemic contracture by attenuating the fall in ATP and removing diastolic Ca by means of NCX in forward mode. Moreover, CPG induces higher CP recovery during reperfusion by participation of SR and NCX in reverse mode. This work remarks the use of CPG based on the functional role of these Ca handling-mechanisms in a pathophysiological condition as ischaemia-reperfusion.

摘要

目的

研究在心脏停搏液（25 mmol/L K和0.5 mmol/L Ca，CPG）对缺血再灌注的保护过程中钠钙交换体（NCX）和肌浆网（SR）的作用。

方法

评估大鼠离体心室的收缩性能（CP）和高能磷酸盐含量（HEP）。它们先用Krebs液（C）或CPG预处理，然后进行无血流缺血和再灌注（I-R）。在缺血前使用5 μmol/L的KB-R7943（反向模式下NCX的抑制剂）、8 mmol/L咖啡因和离子变化来评估各途径的作用。

结果

在再灌注期间，CPG处理的心脏中CP恢复到基础值的77±8%，而C组心脏中为55±8%（P<0.05）。CPG避免了缺血再灌注期间舒张末期压力（LVEDP）和磷酸肌酸/三磷酸腺苷（PCr/ATP）比值的升高。在CPG-2 mmol/L Ca和C组中，低[Na⁺]o（78 mmol/L）在缺血再灌注期间进一步增加了LVEDP。咖啡因-CPG也使LVEDP短暂升高，但KB-R7943未使其改变。CPG处理的心脏再灌注期间CP的恢复也因咖啡因（降至约75%）、低[Na⁺]o-2 mmol/L Ca-CPG（降至约40%）和KB-R7943（降至约16%）而降低。