Holtz J
Institut für Pathophysiologie der Martin-Luther-Universität, Halle/Wittenberg.
Herz. 1993 Dec;18 Suppl 1:387-94.
Following myocardial infarction, there are structural changes in the surviving restmyocardium, including excentric hypertrophy. These changes are called "remodelling". It includes hypertrophy of the terminally differentiated cardiocytes and proliferation of other myocardial cells (e.g. connective tissue). In the hypertrophied cardiocytes, the pattern of gene expression is changing towards a perinatal-like phenotype. This phenotype change is called "dedifferentiation" and includes (among others) several critical alterations in myocyte Ca+(+)-homeostasis and electromechanical coupling: prolongation of the action potential and thereby augmented Ca+(+)-inflow into the cardiocyte during activation; reduced expression of sarcoplasmic reticulum Ca+(+)-ATPhase with retarded endsystolic Ca+(+)-reaccumulation into the sarcoplasmic reticulum; enhanced expression of the sarcolemmal Na(+)-Ca+(+)-exchanger with enhanced Ca+(+)-export via this rheogenic, asymmetrical exchanger, this export associated with depolarizing netto-inward current. Due to this phenotype constellation, high heart rates can induce cytosolic Ca+(+)-overload, relaxation abnormalities, depressed systolic force-frequency relations, and diastolic Ca+(+)-induced Ca+(+)-release leading to late afterdepolarizations and triggering ventricular tachyarrhythmias. While the poorly differentiated cardiocytes of newborns have a phenotype similar to that in hypertrophied dedifferentiated cardiocytes of overloaded myocardium (at least in some aspects of Ca+(+)-homeostasis), the neonatal heart is protected against arrhythmias by its high intercellular coupling (high density of "gap-junctions") and by its lower size. In contrast, the intercellular coupling in overloaded myocardium is often heterogeneous, the density of gap junctions is globally reduced, and the conductance of gap-junctions is functionally reduced by cytosolic Ca+(+)-overload. This enhances the susceptibility for arrhythmias due to "reentry" as well as due to focal depolarization of multiple origins.(ABSTRACT TRUNCATED AT 250 WORDS)
心肌梗死后,存活的残余心肌会发生结构变化,包括离心性肥大。这些变化被称为“重塑”。它包括终末分化心肌细胞的肥大以及其他心肌细胞(如结缔组织)的增殖。在肥大的心肌细胞中,基因表达模式正朝着类似围产期的表型转变。这种表型变化被称为“去分化”,其中包括(但不限于)心肌细胞钙稳态和机电偶联的若干关键改变:动作电位延长,从而在激活期间增加钙流入心肌细胞;肌浆网钙ATP酶表达减少,收缩末期钙重新积聚到肌浆网延迟;肌膜钠钙交换体表达增强,通过这种生电、不对称交换体增加钙外流,这种外流与去极化内向净电流相关。由于这种表型组合,高心率可诱发胞浆钙超载、舒张异常、收缩期力-频率关系降低以及舒张期钙诱导的钙释放,导致晚后去极化并引发室性快速心律失常。虽然新生儿未充分分化的心肌细胞具有与超负荷心肌肥大去分化心肌细胞类似的表型(至少在钙稳态的某些方面),但新生儿心脏因其高细胞间偶联(“缝隙连接”高密度)和较小的尺寸而受到心律失常的保护。相比之下,超负荷心肌中的细胞间偶联往往不均匀,缝隙连接的密度整体降低,并且缝隙连接的电导因胞浆钙超载而功能降低。这增加了因“折返”以及多个起源的局灶性去极化而导致心律失常的易感性。(摘要截断于250字)