From The Hull Family Cardiac Fibrillation Management Laboratory, University Health Network, University of Toronto, Toronto, ON, Canada (A.M., N.Z., S.M., M.K., M.A.A, P.F.H.L., M.B.W., K.N.); Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada (A.R., X.H., A.A.-H., P.D.); Institute of Medical Science, University of Toronto, Toronto, ON, Canada (N.Z.); Department of Physiology, University of Toronto, Toronto, ON, Canada (J.L., P.B.); Institute LIRYC, Université Bordeaux 1, Bordeaux, France (E.J.V.); Institute for Computational Medicine, Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD (P.M.B.); and Department of Electrical Engineering, University of Calgary, Calgary, AB, Canada (E.B.).
Circulation. 2014 Feb 25;129(8):875-85. doi: 10.1161/CIRCULATIONAHA.113.005443. Epub 2014 Jan 8.
Resistant ventricular fibrillation, refibrillation. and diminished myocardial contractility are important factors leading to poor survival after cardiac arrest. We hypothesized that dantrolene improves survival after ventricular fibrillation (VF) by rectifying the calcium dysregulation caused by VF.
VF was induced in 26 Yorkshire pigs for 4 minutes. Cardiopulmonary resuscitation was then commenced for 3 minutes, and dantrolene or isotonic saline was infused at the onset of cardiopulmonary resuscitation. Animals were defibrillated and observed for 30 minutes. To study the effect of VF on calcium handling and its modulation by dantrolene, hearts from 14 New Zealand rabbits were Langendorff-perfused. The inducibility of VF after dantrolene administration was documented. Optical mapping was performed to evaluate diastolic spontaneous calcium elevations as a measure of cytosolic calcium leak. The sustained return of spontaneous circulation (systolic blood pressure ≥60 mm Hg) was achieved in 85% of the dantrolene group in comparison with 39% of controls (P=0.02). return of spontaneous circulation was achieved earlier in dantrolene-treated pigs after successful defibrillation (21 ± 6 s versus 181 ± 57 s in controls, P=0.005). The median number of refibrillation episodes was lower in the dantrolene group (0 versus 1, P=0.04). In isolated rabbit hearts, the successful induction of VF was achieved in 83% of attempts in controls versus 41% in dantrolene-treated hearts (P=0.007). VF caused diastolic calcium leaks in the form of spontaneous calcium elevations. Administration of 20 μmol/L dantrolene significantly decreased spontaneous calcium elevation amplitude versus controls. (0.024 ± 0.013 versus 0.12 ± 0.02 arbitrary unit [200-ms cycle length], P=0.001).
Dantrolene infusion during cardiopulmonary resuscitation facilitates successful defibrillation, improves hemodynamics postdefibrillation, decreases refibrillation, and thus improves survival after cardiac arrest. The effects are mediated through normalizing VF-induced dysfunctional calcium cycling.
心室颤动（VF）的复律、再颤动和心肌收缩力降低是导致心搏骤停后存活率低的重要因素。我们假设丹曲林钠可通过纠正 VF 引起的钙代谢紊乱来提高 VF 后的存活率。
26 头约克夏猪发生 4 分钟的 VF。随后进行心肺复苏（CPR）3 分钟，在 CPR 开始时输注丹曲林钠或等渗盐水。动物进行除颤并观察 30 分钟。为了研究 VF 对钙处理的影响及其被丹曲林钠的调节作用，14 只新西兰兔的心脏进行 Langendorff 灌流。记录丹曲林钠给药后 VF 的可诱导性。光学映射用于评估作为胞质钙渗漏的指标的舒张自发性钙升高。与对照组（39%）相比，丹曲林钠组中有 85%（n=8/9）可持续恢复自主循环（收缩压≥60mmHg）（P=0.02）。在成功除颤后，丹曲林钠治疗猪更早地恢复自主循环（21±6s 与对照组 181±57s，P=0.005）。丹曲林钠组的复律发作次数中位数较低（0 次与 1 次，P=0.04）。在离体兔心，在对照组中 83%（n=16/19）的尝试中成功诱导 VF，而在丹曲林钠治疗组中为 41%（n=8/19）（P=0.007）。VF 以自发性钙升高的形式引起舒张期钙渗漏。与对照组相比，20μmol/L 丹曲林钠显著降低自发性钙升高幅度（0.024±0.013 与 0.12±0.02 任意单位[200ms 心动周期长度]，P=0.001）。
CPR 期间输注丹曲林钠有助于成功除颤，改善除颤后血液动力学，减少复律，从而提高心搏骤停后的存活率。这些作用是通过使 VF 引起的功能失调的钙循环正常化来介导的。
