ROLE OF INCREASED CYTOSOLIC-FREE CALCIUM-CONCENTRATION IN MYOCARDIAL ISCHEMIC-INJURY
ROLE OF INCREASED CYTOSOLIC-FREE CALCIUM-CONCENTRATION IN MYOCARDIAL ISCHEMIC-INJURY
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DOI：
10.1007/bf00795412
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发表时间：
1993-09-01
影响因子：
9.5
通讯作者：
MURPHY, E
中科院分区：
文献类型：
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作者：
STEENBERGEN, C;FRALIX, TA;MURPHY, E
细胞内游离钙浓度([Ca~(2+)]i)升高可能在心肌缺血损伤中起重要作用。如果在缺血损伤的可逆期对缺血心肌进行再灌流，则[Ca~(2+)]i升高的早期效应可能会损害缺血后的收缩功能；此外，如果[Ca~(2+)]i升高的时间延长，可能会引发一系列事件，最终导致致命性损伤。随着[Ca~(2+)]i测定方法的发展，直接评价[Ca~(2+)]i升高在心肌缺血损伤中的作用已成为可能。虽然已经有可能表明抑制导致早期[Ca~(2+)]i升高的转运过程可以同时减弱顿抑和[Ca~(2+)]_i升高，但如果[Ca~(2+)]_i升高在缺血性损伤中起重要作用，那么应该有可能表明改变缺血性损伤的时间进程的干预措施也以平行的方式改变[Ca~(2+)]_i升高的时间进程。最近，人们花了大量的精力来研究预适应现象的机制，即在持续的缺血期之前重复短暂的缺血期，以保护持续的缺血期的心肌免受损伤，这促使了更多的工作来理解腺苷作为预适应的媒介的可能参与以及腺苷的保护作用。用~(19)F核磁共振仪测量5FBAPTA负荷心脏的[Ca~(2+)]i表明，预适应可减弱缺血30分钟期间[Ca~(2+)]i的升高，并减少复流时的顿抑。腺苷预适应类似于预适应对[Ca~(2+)]i升高和顿抑的影响，但腺苷受体拮抗剂不能消除预适应的保护作用，尽管一些腺苷拮抗剂也阻断己糖转运，在这些条件下，预适应抑制[Ca~(2+)]i升高的能力被取消，预适应对顿抑的保护作用也相应丧失。尽管已有研究表明，格列本脲对心肌梗死面积的有利作用可被格列本脲所消除，但格列本脲不影响预适应对引起的[Ca~(2+)]i升高的减弱，也不影响顿抑。所有这些研究都表明，缺血期间[Ca~(2+)]i升高的幅度与再灌流期间的顿抑程度之间存在一致的关系。提示[Ca~(2+)]i升高在心肌缺血性损伤中起重要作用。
Increases in cytosolic free calcium concentration ([Ca2+]I) may play an important role in myocardial ischemic injury. An early effect of the rise in [Ca2+]I may be impaired postischemic contractile function if the ischemic myocardium is reperfused during the reversible phase of ischemic injury; furthermore, if the rise in [Ca2+]i is prolonged, a cascade of events may be initiated which ultimately results in lethal injury. With the development of methods for measuring [Ca2+]I, it has become possible to evaluate directly the role of increased [Ca2+]I in myocardial ischemic injury. Although it has been possible to show that inhibition of the transport processes which contribute to the early rise in [Ca2+]I attenuates stunning and the rise in [Ca2+]I concurrently, if increased [Ca2+]I plays an important role in ischemic injury, then it should be possible to show that interventions which alter the timecourse of ischemic injury also alter the timecourse of the rise in [Ca2+]I in a parallel manner. Recently, considerable effort has been expended to investigate the mechanisms underlying the preconditioning phenomenon, whereby repetitive brief periods of ischemia prior to a sustained period of ischemia protects the myocardium from injury during the sustained period of ischemia, and this has stimulated additional work to understand the possible involvement of adenosine as a mediator of preconditioning as well as to understand the protective effects of adenosine. Measurements of [Ca2+]I using 19F NMR of 5FBAPTA-loaded hearts have shown that preconditioning attenuates the rise in [Ca2+]I during 30 min of ischemia and reduces stunning during reflow. Adenosine pretreatment mimics the effects of preconditioning on the rise in [Ca2+]I and on stunning, but adenosine receptor antagonists do not eliminate the protective effects of preconditioning, although some adenosine antagonists also block hexose transport and under these conditions, the ability of preconditioning to attenuate the rise in [Ca2+]I is abolished and there is a corresponding loss of the protective effect of preconditioning on stunning. Although it has been suggested that the beneficial effect of preconditioning on infarct size can be eliminated by pretreatment with glibenclamide, in the isolated rat heart glibenclamide does not affect the attenuation of the rise in [Ca2+]I induced by preconditioning and does not affect stunning. All of these studies show a consistent relationship between the magnitude of the rise in [Ca2+]I during ischemia and the degree of stunning during reperfusion. The data suggest that increased [Ca2+]I plays a very important role in myocardial ischemic injury.