Department of Anesthesiology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
J Anesth. 2011 Dec;25(6):831-8. doi: 10.1007/s00540-011-1234-0. Epub 2011 Oct 8.
Release of calcium (Ca(2+)) from the sarcoplasmic reticulum (SR) induced by Ca(2+) influx through voltage-dependent sarcolemmal L-type Ca(2+) channels (CICR) in cardiac muscle cells has been implicated as a potential target contributing to anesthetic-induced myocardial depression. In an earlier study, we found that (1) a half-logistic (h-L) function, which represents a half-curve of a sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phases of the isometric myocardial tension and isovolumic left ventricular (LV) pressure waveforms better than a mono-exponential (m-E) function and (2) the h-L time constants are useful as inotropic indices. We report here our investigation of the potential application of an h-L function to the analysis of the first half of the ascending phase of the Ca(2+) transient curve (faCaT) that precedes and initiates myocardial contraction and the increase in LV pressure.
Ca(2+) transients (CaT) were measured using the Ca(2+)-sensitive photoprotein aequorin, which was microinjected into seven isolated rabbit right ventricular and 15 isolated mouse LV papillary muscles. The faCaT data from the beginning of twitch stimulation to the maximum of the first-order time derivative of Ca(2+) concentration (dCa/dt(max)) was curve-fitted by the least-squares method using h-L and m-E function equations.
The mean correlation coefficient (r) values of the h-L and m-E curve-fits for the faCaTs were 0.9740 and 0.9654 (P < 0.05) in the rabbit and 0.9895 and 0.9812 (P < 0.0001) in the mouse.
The h-L curves tracked the amplitudes and time courses of the faCaTs in cardiac muscles more accurately than m-E functions. Based on this result, we suggest that the h-L time constant may be a more reliable index than the m-E time constant for evaluating the rate of CICR from the SR in myocardial Ca(2+) handling. The h-L approach may provide a more useful model for the study of CICR during the contraction process induced by anesthetic agents.
通过电压依赖性肌浆网 L 型钙通道（CICR）介导的钙内流，从肌浆网（SR）中释放钙（Ca（2+）），这被认为是导致麻醉诱导心肌抑制的潜在靶点之一。在早期的研究中，我们发现：（1）半对数（h-L）函数，它代表了 sigmoid 逻辑函数的一半曲线，在拐点处有一个边界，比单指数（m-E）函数更能拟合等长心肌张力和等容左心室（LV）压力波形的上升相的前半部分；（2）h-L 时间常数可用作变力指数。我们在此报告我们对 h-L 函数的潜在应用的研究，该函数用于分析 Ca（2+）瞬变曲线（faCaT）的上升相的前半部分，该曲线先于并引发心肌收缩和 LV 压力增加。
使用钙敏感的发光蛋白虫荧光素（aequorin）测量 Ca（2+）瞬变（CaT），将其微注射到 7 个分离的兔右心室和 15 个分离的小鼠 LV 乳头肌中。通过最小二乘法，使用 h-L 和 m-E 函数方程，对从收缩刺激开始到 Ca（2+）浓度一阶导数最大值（dCa/dt（max））的 faCaT 数据进行曲线拟合。
兔的 h-L 和 m-E 曲线拟合的平均相关系数（r）值分别为 0.9740 和 0.9654（P < 0.05），而小鼠的 r 值分别为 0.9895 和 0.9812（P < 0.0001）。
h-L 曲线比 m-E 函数更准确地跟踪心肌中 faCaT 的幅度和时程。基于这一结果，我们认为 h-L 时间常数可能比 m-E 时间常数更能可靠地评估心肌 Ca（2+）处理中从 SR 释放的 CICR 速率。h-L 方法可能为研究麻醉剂诱导的收缩过程中的 CICR 提供更有用的模型。
