AUGMENTED SPONTANEOUS CA2+ RELEASE IN SENESCENT HEART

伴随着兴奋-收缩机制的特征变化 慢性动脉压引起的心肌细胞肥大 装满了啮齿动物。这些变化：跨膜延长 兴奋后动作电位和胞内钙瞬变； 肌浆网钙摄取速度减慢可能 被认为是适应性的。它们允许更长的承重时间 励磁后的容量。然而，在钙离子的条件下， 应激，例如在快速起搏或高位沐浴[钙](CaO)后， 细胞内钙超载发生的可能性增加。 心肌细胞肥大与兴奋收缩模式 与年轻啮齿动物的压力超负荷相同的适应发生在 血压正常的啮齿动物的高龄。本研究调查是否， 就像在压力肥大的心肌中一样，一种隐藏的钙离子 老年心肌存在不耐受现象。在施加钙离子后 应激时，钙超载的表现更容易发生在 较老的心脏与较年轻的心脏。为了确定心肌细胞是否存在钙不耐受， 在收缩(AC)或心室收缩后表现为钙依赖 房颤(VF)不同于高龄、孤立、等容房室传导阻滞 24-26mo(0)和5-7mo(Y)雄性大鼠(n=8)的心脏被灌流 恒流(HEPES，37xC)，[Ca~(2+)]为1.5~10 mM。这个 两种交流所需的[Ca2+]，通过以下压力记录测量 在2.0赫兹停止起搏，并通过体表记录VF 在起搏过程中自发发生的电信号，减少到0。 室性心动过速无一例发生，80例心脏中6例发生室颤。结果表明， 钙依赖异常发生的可能性增加 随着成年人年龄的增长，心脏细胞功能也会发生变化。衰老(24-26个月) 大鼠心脏表现为心肌和细胞内钙离子耐量增加 与其年轻的成年同类相比。明显的钙不耐受 因为较小的收缩压增加加上夸张的 静息压力的增加和更大的可能性 当灌流液[Ca]增加时，会出现后收缩和室颤。 直接在细胞内观察到或表现为自发的钙振荡 间接地在灌流的心脏中是细胞基础 依赖钙离子的静息压、后收缩和 可能是VF的。

Characteristic changes in excitation-contraction mechanisms accompany cardiac cellular hypertrophy in response to chronic arterial pressure loading in rodents. These changes: prolongation of the transmembrane action potential and cytosolic calcium transient following excitation; reduction of the velocity of Ca2+ uptake into sarcoplasmic reticulum may be considered adaptive. They permit an extended duration of load bearing capacity following excitation. However, under conditions of a Ca2+ stress, e.g. following rapid pacing or elevated bathing [Ca2+](Cao), there is an increased likelihood for cellular Ca2+ overload to occur. Myocardial cellular hypertrophy and a pattern of excitation-contraction adaptations identical to pressure overload in younger rodents occur with advanced age in normotensive rodents. The present study examines whether, as in the pressure hypertrophied myocardium, an occult form of Ca2+ intolerance exists in aged myocardium. Following the imposition of Ca2+ stress, the manifestations of Ca2+ overload are more likely to occur in older vs younger heart. To determine whether myocardial Ca2+ intolerance, manifest as Ca2+ dependence after contractions (AC) or ventricular fibrillation (VF) differ in advanced age, isolated, isovolumic AV-blocked hearts from 24-26 mo (0) and 5-7 mo male rats (Y) (n=8 each) were perfused at constant flow (HEPES, 37xC) with [Ca2+] varied from 1.5 to 10 mM. The [Ca2+] required for both AC, measured from pressure recording following cessation of pacing at 2.0 Hz, and for VF, recorded via surface electrogram and occurring spontaneously during pacing, is reduced in 0. VF occurred in no Y but in 6 of 8 0 hearts. The results indicate an enhanced likelihood for occurrence of Ca2+ dependent abnormalities of cardiac cell function occurs with adult aging. The senescent (24-26 mo) rat heart exhibits exaggerated myocardial and cellular Ca2+ intolerance compared to its younger adult counterpart. Ca2+ intolerance is manifest as a lesser increase in systolic pressure coupled with an exaggerated increase in resting pressure and a greater likelihood for aftercontractions and VF to occur as perfusate [Ca] is increased. Spontaneous Ca2+ oscillations observed directly in cells, or manifest indirectly as SLIF in the perfused heart are the cellular basis for the Ca2+ dependent increase in resting pressure, aftercontractions and possibly for VF.