Mizutani Shinichi, Al-Dadah Ashraf S, Bloch Jeffrey B, Prasad Sandip M, Diodato Michael D, Schuessler Richard B, Damiano Ralph J, Lawton Jennifer S
Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110-1013, USA.
Ann Thorac Surg. 2006 Jan;81(1):154-9. doi: 10.1016/j.athoracsur.2005.06.057.
Hyperkalemic cardioplegia (9 degrees C) results in significant myocyte swelling and reduced contractility, representing a possible mechanism of myocardial stunning. Adenosine triphosphate-sensitive potassium channel (KATP) openers have been shown to ameliorate stunning. This study evaluated the hypothesis that a KATP opener would prevent hyperkalemic cardioplegia-induced myocyte swelling and reduced contractility.
Isolated rabbit myocytes were perfused with 37 degrees C Tyrode's solution for 20 minutes, followed by test solution (9 degrees C or 37 degrees C) including control Tyrode's, Tyrode's + 100 micromol/L diazoxide (KATP opener), St. Thomas's solution; or 9 degrees C St. Thomas's + 100 micromol/L diazoxide or St. Thomas's + 100 micromol/L diazoxide + 20 micromol/L HMR1098 or 50 micromol/L 5-hydroxydeconoate (KATP blockers) for 20 minutes (n = 8 per group). Myocytes were then reexposed to 37 degrees C Tyrode's solution for 20 minutes. Volume and contractility were measured by videomicroscopy and video-based edge detection, respectively.
St. Thomas's solution (9 degrees C) caused significant myocyte swelling and associated reduced contractility (p < 0.05). The addition of diazoxide abolished myocyte swelling (p < 0.0001), and eliminated the associated reduced contractility (p < 0.05). Findings were unchanged by the addition of HMR 1098 and 5-hydroxydeconoate.
Diazoxide prevented myocyte swelling and reduced contractility secondary to hyperkalemic cardioplegia, and this was unchanged by the addition of either KATP channel blocker. Prevention of myocyte swelling was associated with improved contractility, consistent with the hypothesis that myocyte swelling may be a mechanism of myocardial stunning. Diazoxide may play a role in myocyte volume homeostasis by means of a mechanism separate from opening the KATP channel.
高钾停搏液（9℃）可导致明显的心肌细胞肿胀和收缩力降低，这可能是心肌顿抑的一种机制。已证明三磷酸腺苷敏感性钾通道（KATP）开放剂可改善心肌顿抑。本研究评估了KATP开放剂可预防高钾停搏液诱导的心肌细胞肿胀和收缩力降低这一假说。
将分离的兔心肌细胞用37℃的台氏液灌注20分钟，然后用测试液（9℃或37℃）灌注20分钟，测试液包括对照台氏液、台氏液+100μmol/L二氮嗪（KATP开放剂）、圣托马斯液；或9℃圣托马斯液+100μmol/L二氮嗪或圣托马斯液+100μmol/L二氮嗪+20μmol/L HMR1098或50μmol/L 5-羟基癸酸（KATP阻滞剂）（每组n = 8）。然后将心肌细胞重新暴露于37℃的台氏液中20分钟。分别通过视频显微镜和基于视频的边缘检测测量细胞体积和收缩力。
圣托马斯液（9℃）导致明显的心肌细胞肿胀和相关的收缩力降低（p < 0.05）。加入二氮嗪可消除心肌细胞肿胀（p < 0.0001），并消除相关的收缩力降低（p < 0.05）。加入HMR1098和5-羟基癸酸后结果不变。
二氮嗪可预防高钾停搏液引起的心肌细胞肿胀和收缩力降低，加入任何一种KATP通道阻滞剂后这一作用均未改变。预防心肌细胞肿胀与收缩力改善相关，这与心肌细胞肿胀可能是心肌顿抑机制的假说一致。二氮嗪可能通过与开放KATP通道不同的机制在心肌细胞体积稳态中发挥作用。
