Hasin Y, Eilam Y, Hassin D, Fixler R
Cardiology Department, Hadassah Medical Organization, Jerusalem, Israel.
Adv Exp Med Biol. 1995;382:229-38. doi: 10.1007/978-1-4615-1893-8_23.
Cytotoxic T lymphocytes are important in the pathogenesis of several disease states, yet the pathophysiology of the lymphocyte-myocyte interaction is not well known. We have developed in vitro viral and autoimmune models to study the physiological phenomena associated with this interaction. To produce these models, lymphocytes were obtained from adult rats injected either with mengo virus or autologous cardiac myocytes. Cardiac myocytes from neonatal rats were then exposed to these lymphocytes. In both models, reversible physiologic changes in myocytes preceded irreversible cell damage. The physiologic changes included reduced amplitude of myocyte contraction, impairment of relaxation and prolongation of the duration of contraction and action potential. In addition, oscillations were noted in the plateau phase of the action potentials. These physiologic changes were accompanied by an early elevation in the cytosolic free calcium concentration, a late elevation in the total exchangeable calcium pool, and attenuation of the [Ca2+]i transient signals. Verapamil inhibited the late elevation in the total exchangeable calcium pool, but failed to inhibit the early elevation in the cytosolic free calcium concentration. These phenomena may explain transient cardiac functional abnormalities that may appear during myocarditis prior to cell destruction.
细胞毒性T淋巴细胞在多种疾病状态的发病机制中起着重要作用，然而淋巴细胞与心肌细胞相互作用的病理生理学尚不清楚。我们建立了体外病毒和自身免疫模型来研究与这种相互作用相关的生理现象。为了构建这些模型，从注射了门戈病毒或自体心肌细胞的成年大鼠中获取淋巴细胞。然后将新生大鼠的心肌细胞暴露于这些淋巴细胞。在这两种模型中，心肌细胞的可逆生理变化先于不可逆的细胞损伤。生理变化包括心肌细胞收缩幅度降低、舒张功能受损以及收缩和动作电位持续时间延长。此外，在动作电位的平台期观察到振荡。这些生理变化伴随着胞质游离钙浓度早期升高、可交换钙总量后期升高以及[Ca2+]i瞬变信号减弱。维拉帕米抑制了可交换钙总量的后期升高，但未能抑制胞质游离钙浓度的早期升高。这些现象可能解释了在心肌炎细胞破坏之前可能出现的短暂心脏功能异常。
