AUGMENTED CA2+ RELEASE AND ARRHYTHMOGENESIS IN CA2+ STRESS IN AGING 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。但在Ca~(2+)胁迫下， 例如，在快速起搏或高位沐浴[Ca~(2+)](CaO)后，有一种 细胞内钙超载发生的可能性增加。心肌 细胞肥大与兴奋-收缩适应模式 与年轻啮齿动物的压力超负荷相同，随着年龄的增长，压力超负荷也会发生 在血压正常的啮齿动物身上。本研究审查了是否如在 高压性肥厚心肌--一种隐匿性的钙耐量异常 存在于老年心肌中。在施加钙胁迫后， 钙超载的表现更有可能发生在老年人和老年人。 年轻的心脏。以确定心肌钙耐量异常，是否表现为 作为收缩(AC)或室颤后的钙依赖 (VF)高龄、隔离、等容量房室传导阻滞的心脏与 24-26mo(O)和5-7mo(Y)雄性大鼠(n=8)恒定灌流 流量(HEPES，37摄氏度)，[Ca~(2+)]从1.5到10 mm不等。 通过压力记录测量两种AC所需的[Ca~(2+)] 在2.0赫兹起搏停止后，对于VF，通过体表记录 起搏时自发的心电信号，在OVF中减少 发生在8颗心脏中6颗，而不是Y。结果表明， 心肌细胞钙依赖性异常发生的可能性 随着成人年龄的增长，这种功能也会发生。衰老(24-26个月)大鼠心脏 表现出夸大的心肌和细胞钙耐量 它是年轻的成年对应物。钙离子不耐受表现为较轻的 收缩压的增加，加上心脏收缩压的夸大增加 静息压力和更大的可能性后收缩和 当灌流液[Ca]增加时，就会发生室颤。 直接在细胞内观察到或表现为自发的钙振荡 心脏灌流中间接AS是心肌梗死的细胞基础 静息压、后收缩和可能的2+依赖性增加 用于治疗室颤。

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 Ca 2+ uptake into sarcoplasmic reticulum may be considered adaptive. They permit an extended duration of load bearing capacity following excitation. However, under conditions of Ca 2+ stress, e.g. following rapid pacing or elevated bathing [Ca 2+](Ca O), there is an increased likelihood for cellular Ca 2+ 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 Ca 2+ intolerance exists in aged myocardium. Following the imposition of Ca 2+ stress, the manifestations of Ca 2+ overload are more likely to occur in older vs. younger heart. To determine whether myocardial Ca 2+ intolerance, manifest as Ca 2+ dependence after contractions (AC) or ventricular fibrillation (VF) differ in advanced age, isolated, isovolumic AV-blocked hearts from 24-26 mo (O) and 5-7 mo male rats (Y) (n=8 each) were perfused at constant flow (HEPES, 37 degrees Celsius) with [Ca 2+] varied from 1.5 to 10 mM. The [Ca 2+] 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 O. VF occurred in no Y but in 6 of 8 O hearts. The results indicate an enhanced likelihood for occurrence of Ca 2+ dependent abnormalities of cardiac cell function occurs with adult aging. The senescent (24-26 mo) rat heart exhibits exaggerated myocardial and cellular Ca 2+ intolerance compared to its younger adult counterpart. Ca 2+ 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 ventricular fibrillation to occur as perfusate [Ca] is increased. Spontaneous Ca 2+ oscillations observed directly in cells, or manifest indirectly as SLIF in the perfused heart are the cellular basis for the Ca 2+ dependent increase in resting pressure, aftercontractions and possibly for ventricular fibrillation.