Si Daoyuan, Chakraborty Praloy, Azam Mohammed Ali, Nair Madhav Krishna Kumar, Massé Stéphane, Lai Patrick F H, Labos Christopher, Riazi Sheila, Nanthakumar Kumaraswamy
The Hull Family Cardiac Fibrillation Management Laboratory, Toronto General Hospital, University Health Network, Toronto, Canada.
Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
Heart Rhythm O2. 2022 Jun 15;3(5):568-576. doi: 10.1016/j.hroo.2022.06.001. eCollection 2022 Oct.
Post-defibrillation myocardial contractile dysfunction adversely affects the survival of patients after cardiac arrest. Attenuation of diastolic calcium (Ca) overload by stabilization of the cardiac ryanodine receptor (RyR2) is found to reduce refibrillation after long-duration ventricular fibrillation (LDVF).
In the present study, we explored the effects of RyR2 stabilization by azumolene on systolic Ca release synchrony and myocardial contractility.
After completion of baseline optical mapping, Langendorff-perfused rabbit hearts were subjected to global ischemia followed by reperfusion with azumolene or deionized distilled water (vehicle). Following reperfusion, LDVF was induced with burst pacing. In the first series of experiments (n = 16), epicardial Ca transient was analyzed for Ca transient amplitude alternans and dispersion of Ca transient amplitude alternans index (CAAI). In the second series of experiments following the same protocol (n = 12), ventricular contractility was assessed by measuring the left ventricular pressure.
Ischemic LDVF led to greater CAAI (0.06 ± 0.02 at baseline vs 0.12 ± 0.02 post-LDVF, < .01) and magnitude of dispersion of CAAI (0.04 ± 0.01 vs 0.09 ± 0.01, < .01) in control hearts. In azumolene-treated hearts, no significant changes in CAAI (0.05 ± 0.01 vs 0.05 ± 0.01, = .84) and dispersion of CAAI (0.04 ± 0.01 vs 0.04 ± 0.01, = .99) were noted following ischemic LDVF. Ischemic LDVF was associated with reduction in left ventricular developed pressure (100% vs 36.8% ± 6.1%, = .002) and dP/dt (100% vs 45.3% ± 6.5%, = .003) in control hearts, but these reductions were mitigated (left ventricular developed pressure: 100% vs 74.0% ± 8.1%, = .052, dP/dt: 100% vs 80.8% ± 7.9%, = .09) in azumolene-treated hearts.
Treatment with azumolene is associated with improvement of systolic Ca release synchrony and myocardial contractility following ischemic LDVF.
除颤后心肌收缩功能障碍对心脏骤停后患者的生存产生不利影响。研究发现，通过稳定心肌兰尼碱受体（RyR2）减轻舒张期钙（Ca）超载可减少长时间室颤（LDVF）后的再发室颤。
在本研究中，我们探讨了阿祖莫林稳定RyR2对收缩期Ca释放同步性和心肌收缩力的影响。
在完成基线光学映射后，对Langendorff灌注的兔心脏进行全心缺血，然后用阿祖莫林或去离子蒸馏水（溶剂）进行再灌注。再灌注后，通过猝发起搏诱导LDVF。在第一系列实验（n = 16）中，分析心外膜Ca瞬变的Ca瞬变幅度交替和Ca瞬变幅度交替指数（CAAI）的离散度。在遵循相同方案的第二系列实验（n = 12）中，通过测量左心室压力评估心室收缩力。
缺血性LDVF导致对照心脏的CAAI更大（基线时为0.06±0.02，LDVF后为0.12±0.02，P<0.01）和CAAI离散度幅度更大（0.04±0.01对0.09±0.01，P<0.01）。在阿祖莫林治疗的心脏中，缺血性LDVF后CAAI（0.05±0.01对0.05±0.01，P = 0.84）和CAAI离散度（0.04±0.01对0.04±0.01，P = 0.99）无显著变化。缺血性LDVF与对照心脏左心室舒张末压降低（100%对36.8%±6.1%，P = 0.002）和dP/dt降低（100%对45.3%±6.5%，P = 0.003）相关，但在阿祖莫林治疗的心脏中这些降低得到缓解（左心室舒张末压：100%对74.0%±8.1%，P = 0.052，dP/dt：100%对80.8%±7.9%，P = 0.09）。
阿祖莫林治疗与缺血性LDVF后收缩期Ca释放同步性和心肌收缩力的改善相关。
