钾通道开放剂增强型心脏停搏液：对慢性左心室功能障碍患者心肌收缩力的保护作用

Potassium channel opener-augmented cardioplegia: protection of myocyte contractility with chronic left ventricular dysfunction.

作者信息

Dorman B H, Hebbar L, Clair M J, Hinton R B, Roy R C, Spinale F G

机构信息

Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston 29425-2207, USA.

出版信息

Circulation. 1997 Nov 4;96(9 Suppl):II-253-9.

PMID:9386107

Abstract

BACKGROUND

An increased number of patients with preexisting left ventricular (LV) dysfunction and congestive heart failure (CHF) are undergoing cardiac surgery with a higher risk for decreased LV contractility after hyperkalemic cardioplegic arrest. Activation of adenosine triphosphate-sensitive potassium channels by potassium channel openers (PCO) within the myocyte appears to confer a protective effect in the setting of ischemia. Accordingly, the present study was designed to determine whether PCO supplementation during hyperkalemic cardioplegic arrest would provide protective effects on myocyte contractile function, particularly in the setting of CHF.

METHODS AND RESULTS

LV myocytes were isolated from control pigs (n=7) and pigs with CHF (rapid pacing, 240 beats per minute; n=7) and then assigned to the following treatment groups: normothermia (cell culture media, 2 hours, 37 degrees C); cardioplegia (24 mEq/L K+, 2 hours, 4 degrees C; then 10 minutes of reperfusion); or PCO/cardioplegia (cardioplegia supplemented with 100 micromol/L of the PCO aprikalim). Myocyte velocity of shortening was reduced in both control (66+/-2 versus 33+/-1 microm/s) and CHFmyocytes (32+/-1 versus 22+/-1 microm/s) after hyperkalemic cardioplegic arrest (P<.05). Contractility after PCO cardioplegia was similar to normothermic values in control (57+/-2 microm/s) and CHF (33+/-1 microm/s) myocytes (P<.05). Intracellular free Ca2+ increased from normothermia during hyperkalemic cardioplegia in control (81+/-4 to 145+/-7 nmol/L) and CHF (262+/-30 to 823+/-55 nmol/L) myocytes (P<.05). PCO cardioplegia attenuated the intracellular increase in free Ca2+ during the cardioplegic interval in control (110+/-6 nmol/L) and CHF (383+22 nmol/L) myocytes (P<.05).

CONCLUSIONS

PCO-augmented cardioplegic arrest preserved myocyte contractility and reduced the intracellular free Ca2+ release, which therefore may be of particular benefit in the setting of preexisting LV dysfunction.

摘要

背景

越来越多患有既往左心室（LV）功能障碍和充血性心力衰竭（CHF）的患者正在接受心脏手术，在高钾停搏后左心室收缩力下降的风险更高。心肌细胞内的钾通道开放剂（PCO）激活三磷酸腺苷敏感性钾通道似乎在缺血情况下具有保护作用。因此，本研究旨在确定在高钾停搏期间补充PCO是否会对心肌细胞收缩功能提供保护作用，特别是在CHF的情况下。

方法和结果

从对照猪（n = 7）和CHF猪（快速起搏，每分钟240次搏动；n = 7）中分离出LV心肌细胞，然后将其分配到以下治疗组：正常体温（细胞培养基，2小时，37℃）；心脏停搏（24 mEq/L K +，2小时，4℃；然后再灌注10分钟）；或PCO/心脏停搏（心脏停搏液中补充100 μmol/L的PCO阿普卡林）。高钾停搏后，对照心肌细胞（66±2对33±1μm/s）和CHF心肌细胞（32±1对22±1μm/s）的心肌细胞缩短速度均降低（P<0.05）。PCO心脏停搏后的收缩力与对照（57±2μm/s）和CHF（33±1μm/s）心肌细胞的正常体温值相似（P<0.05）。在对照心肌细胞（81±4至145±7 nmol/L）和CHF心肌细胞（262±30至823±55 nmol/L）中，高钾心脏停搏期间细胞内游离Ca2+从正常体温时增加（P<0.05）。PCO心脏停搏减弱了对照心肌细胞（110±6 nmol/L）和CHF心肌细胞（383 + 22 nmol/L）在心脏停搏期间细胞内游离Ca2+的增加（P<0.05）。