A common mechanism in the protective effects of preconditioning, cardiac pacing and physical exercise against ischemia and reperfusion-induced arrhythmias

Ischemic preconditioning results not only in a reduction in myocardial ischemic damage, but also in a marked suppression of those ventricular arrhythmias that result from a more prolonged period of ischemia and reperfusion insult. This protection is time-dependent and occurs in two distinct phases. There is an ‘early phase’ which is apparent immediately after the preconditioning stimulus but fades quickly (within 1 h to 2 h), and a ‘delayed protection phase’ in which the antiarrhythmic protection reappears 20 h to 24 h later. In both phases, the intensity of protection largely depends on the nature of the preconditioning stimulus. This can be ischemia resulting from brief coronary artery occlusions, cardiac pacing or vigorous physical exercise. Both cardiac pacing and exercise results in a marked reduction in the incidence and severity of ischemia and reperfusion-induced ventricular arrhythmias 24 h later. Although the precise mechanisms of the delayed protection that results from cardiac pacing and exercise are not yet fully understood, there is some evidence that similar endogenous protective substances (such as bradykinin, prostanoids and nitric oxide), as with ischemic preconditioning, play a pivotal trigger and mediator role in this anti-arrhythmic protection.     

丙泊酚对异氟醚心肌预处理效应的影响

目的 评价在心脏直视手术中异氟醚是否具有处理效应及丙泊酚对异氟醚预处理效应的影响。方法 将30例择期行心脏直视手术的室间隔缺损（VSD）患者分为三组：异氟醚吸入组（Ⅰ组）、异氟醚吸入加丙泊酚输注组（Ⅱ组）和对照组（Ⅲ组）。分别于麻醉诱导平稳后（T1）、主动脉阻断时（T2）、主动脉阻断开放后30min（T3）采血检测超氧化物歧化酶（SOD）、丙二醛（MDA）；分别于T2、T3、再灌注后3h（T4）及12h（T5）采血检测肌酸激酶同功酶（CK-MB）和乳酸脱氢酶（LDH）。结果 在T2时，与同期Ⅲ组比较，Ⅰ组SOD活性降低（P〈0．05），MDA含量升高（P〈0．05），Ⅱ组SOD活性升高（P〈0．05）。T3时Ⅰ组SOD活性和MDA含量均低于Ⅱ组和Ⅲ组（P〈0．05）。主动脉开放后的各个时点（T3、T4、T5），三组的血清LDH活性和CK-MB活性均较T2时显著升高（P〈0．05）；Ⅰ组的LDH活性和CK-MB活性在T3、T4、T5时较Ⅱ组和Ⅲ组低（P〈0．05）。结论 心脏直视手术中缺血前吸入异氟醚对再灌注心肌具有一定保护作用。缺血前吸入异氟醚同时输注丙泊酚可能会减弱异氟醚对心肌的保护作用。     

Preconditioning and its clinical potential

Preconditioning is emerging as a simple, safe and highly effective means of attenuating local and systemic effects of medical and surgical insult. Its enormous potential has not yet been harnessed and ongoing work will continue to bring it to the fore. This article covers the history, development and future clinical potential of preconditioning with particular regard to surgical insult.     

Preconditioning during warm blood cardioplegia

Objective: Preconditioning describes the cardioprotective effects of multiple brief episodes of warm ischemia. The purpose of the study was to determine whether warm ischemia, during the intermittent delivery of warm blood cardioplegia, would induce preconditioning during cardioplegia arrest. Methods: Dogs, 15, were randomized to a preconditioning protocol or to serve as controls. The control group received 60 min of continuous warm blood cardioplegia (WBC) followed by 30 min of warm arrested ischemia. The preconditioned group were arrested with WBC and then underwent three consecutive cycles consisting of 10 min of warm ischemia followed by 10 min of reperfusion. Reperfusion was provided by a continuous infusion of WBC. The preconditioning protocol was followed by 30 min of warm arrested ischemia. Myocardial functional recovery was assessed before cardiopulmonary bypass and cardioplegia arrest and again 30, 60 and 90 min after the arrest. Pressure-volume loops were used to measure the maximum elastance of the left ventricle (E_max), diastolic compliance, and used to calculate preload recruitable stroke work area. Results: Myocardial functional recovery was better preserved after 30 min of warm arrested ischemia in those animals that had been preconditioned. Conclusion: Preconditioning may be induced when warm blood cardioplegia is delivered intermittently during cardioplegia arrest.     

Criteria for a mediator or effector of myocardial preconditioning: Do KATP channels meet the requirements?

Conclusions A set of criteria have been presented which we feel need to be met before one can assign an important role for a particular endogenous mediator, ion channel or enzyme as an important component of ischemic PC and evidence has been presented to suggest that the KATP channel meets most of the criteria listed. Obviously, this list is not all conclusive and other important factors will evolve as we increase our understanding of this fascinating phenomenon of ischemic PC.     

Preconditioning ischemia attenuates increased neurexin-neuroligin1-PSD-95 interaction after transient cerebral ischemia in rat hippocampus

In this study, we investigated the interactions between synapse adhesion molecules neurexin, neuroligin1, neuroligin2 and postsynaptic density protein 95 (PSD-95) in transient cerebral ischemia and possible regulatory mechanism of these interactions. Our data show that preconditioning ischemia can down-regulate the increased neurexin-neuroligin1-PSD-95 interaction induced by ischemia injury and exerts a neuroprotective effect. Pre-treatment of N-methyl-D-aspartate (NMDA) receptor antagonist ketamine can demolish this neuroprotective effect of preconditioning by increasing neurexin-neuroligin1-PSD-95 interaction. These results indicate that the neurexin-neuroligin1-PSD-95 is an important signalling module in ischemic injury and a novel possible target in therapeutics of brain ischemia.     

核转录因子NF-κＢ参与单磷酰脂A预处理的延迟保护作用

目的：探讨核转录因子NF-κB在单磷酰脂A预处理的延迟阶段的作用。 方法： 建立大鼠心肌缺血/再灌注（I/R）损伤模型。分别应用单磷酰脂A（MLA）、NF-κB的特异性抑制剂DDTC加MLA预处理心脏, 24 h对心脏进行较长时间缺血再灌注，检测心肌梗死范围、LDH释放及心肌细胞凋亡率。另外分组检测MLA预处理0 min、15 min、30 min、60 min、NF-κB抑制剂DDTC加MLA预处理后30 min时NF-κB活性。 结果: MLA预处理减小再灌注心肌梗死范围、降低血浆LDH活性、减少细胞凋亡(P<0.05 vs I/R)。同MLA预处理组相比， DDTC+MLA组心肌梗死范围增大、LDH活性增高, 细胞凋亡增加(P<0.05)。与预处理前相比，NF-κB活性在预处理后15 min明显升高、30 min达到高峰、60 min下降(P<0.01)。与MLA预处理后15 min、30 min、60 min相比， DDTC加MLA预处理后30 min时,NF-κB活性明显降低(P<0.01)，而与MLA预处理0 min无显著差别(P＞0.05)。 结论: (1) MLA预处理对24 h后缺血/再灌注心肌有保护作用。(2) 核转录因子NF-κB参与心肌预处理后的延迟保护作用，MLA预处理后NF-κB快速的核转移并激活可能是药物预处理延迟保护作用的重要机制之一。     

心肌缺血/再灌注前处置时血浆一氧化氮的变化及意义

目的：在兔心肌缺血／再灌注前处置模型的基础上，了解NO在心肌缺血前处置中所起的作用及意义。方法：采用免麻醉后开胸结扎左冠状动脉降支，反复结扎（缺血）10分钟，放开（再灌）5分钟，最后结扎30分钟再灌20分钟造成缺血／再灌注前处置模型后，对比观察了各组动物血浆中NO、TXB2、6－K－PGF1α、SOD和MDA浓度的变化，以及各组动物球结膜微循环及心肌病理学的变化。结果：前处置组血浆NO、6－K－PGF1α、SOD浓度显著高于缺血／再灌注组，而MDA、TXB2浓度明显低于缺血／再灌注组。前处置组心肌超微结构损伤明显轻于缺血／再灌注组，球结膜微循环基本正常。结论：心肌缺血前处置可增加心血管内皮细胞合成NO，而NO具有减轻心肌缺血／再灌注损伤、改善微循环障碍的作用。