严重受损心脏的血液心脏停搏保护：预处理或控制性再灌注补充期间钠氢交换抑制的作用。

Blood cardioplegic protection in profoundly damaged hearts: role of Na+-H+ exchange inhibition during pretreatment or during controlled reperfusion supplementation.

作者信息

Castellá Manuel, Buckberg Gerald D, Tan Zhongtuo

机构信息

Department of Surgery, Division of Cardiothoracic Surgery, University of California, Los Angeles, School of Medicine, Los Angeles, California, USA.

出版信息

Ann Thorac Surg. 2003 Apr;75(4):1238-45. doi: 10.1016/s0003-4975(02)04499-5.

DOI:10.1016/s0003-4975(02)04499-5

PMID:12683570

Abstract

BACKGROUND

Inhibition of the Na+/H+ exchanger before ischemia protects against ischemia-reperfusion injury, but use as pretreatment before blood cardioplegic protection or as a supplement to controlled blood cardioplegic reperfusion was not previously tested in jeopardized hearts.

METHODS

Control studies tested the safety of glutamate-aspartate-enriched blood cardioplegic solution in 4 Yorkshire-Duroc pigs undergoing 30 minutes of aortic clamping without prior unprotected ischemia. Twenty-four pigs underwent 30 minutes of unprotected normothermic global ischemia to create a jeopardized heart. Six of these hearts received normal blood reperfusion, and the other 18 jeopardized hearts underwent 30 more minutes of aortic clamping with cardioplegic protection. In 12 of these, the Na+/H+ exchanger inhibitor cariporide was used as intravenous pretreatment (n = 6) or added to the cardioplegic reperfusate (n = 6).

RESULTS

Complete functional, biochemical, and endothelial recovery occurred after 30 minutes of blood cardioplegic arrest without preceding unprotected ischemia. Thirty minutes of normothermic ischemia and normal blood reperfusion produced 33% mortality and severe left ventricular dysfunction in survivors (preload recruitable stroke work, 23% +/- 6% of baseline levels), with raised creatine kinase MB, conjugated dienes, endothelin-1, myeloperoxidase activity, and extensive myocardial edema. Blood cardioplegia was functionally protective, despite adding 30 more minutes of ischemia; there was no mortality, and left ventricular function improved (preload recruitable stroke work, 58% +/- 21%, p < 0.05 versus normal blood reperfusion), but adverse biochemical and endothelial variables did not change. In contrast, Na+/H+ exchanger inhibition as either pretreatment or added during cardioplegic reperfusion improved myocardial recovery (preload recruitable stroke work, 88% +/- 9% and 80% +/- 7%, respectively, p < 0.05 versus without cariporide) and comparably restored injury variables.

CONCLUSIONS

Na+/H+ exchanger blockage as either pretreatment or during blood cardioplegic reperfusion comparably delays functional, biochemical, and endothelial injury in jeopardized hearts.

摘要

背景

在缺血前抑制钠氢交换体可预防缺血再灌注损伤，但此前未在濒危心脏中测试其作为血液停搏液保护前的预处理或作为控制性血液停搏液再灌注补充剂的用途。

方法

对照研究在4只约克夏-杜洛克猪身上测试了富含谷氨酸-天冬氨酸的血液停搏液的安全性，这些猪在未经历先前无保护缺血的情况下接受了30分钟的主动脉阻断。24只猪经历了30分钟的无保护常温全心缺血以制造濒危心脏。其中6只心脏接受正常血液再灌注，另外18只濒危心脏在心脏停搏液保护下又接受了30分钟的主动脉阻断。在这18只心脏中，12只使用钠氢交换体抑制剂卡立泊来德作为静脉预处理（n = 6）或添加到心脏停搏液再灌注液中（n = 6）。

结果

在未经历先前无保护缺血的情况下，血液心脏停搏30分钟后实现了完全的功能、生化和内皮恢复。30分钟的常温缺血和正常血液再灌注导致33%的死亡率，幸存者出现严重的左心室功能障碍（预负荷可募集搏功，为基线水平的23%±6%），肌酸激酶MB、共轭二烯、内皮素-1、髓过氧化物酶活性升高，且有广泛的心肌水肿。尽管又增加了30分钟的缺血时间，但血液心脏停搏具有功能保护作用；无死亡发生，左心室功能改善（预负荷可募集搏功，为58%±21%，与正常血液再灌注相比p < 0.05），但不良生化和内皮变量未改变。相比之下，无论是作为预处理还是在心脏停搏液再灌注期间添加钠氢交换体抑制剂，均可改善心肌恢复（预负荷可募集搏功分别为88%±9%和80%±7%，与未使用卡立泊来德相比p < 0.05），并同等程度地恢复损伤变量。