Cardiovascular and Thoracic Surgery Department, General Hospital of Athens "Evangelismos'', Greece.
3rd Cardiac Surgery Department, Onassis Cardiac Surgery Centre, Athens, Greece.
Semin Thorac Cardiovasc Surg. 2022 Spring;34(1):123-132. doi: 10.1053/j.semtcvs.2021.01.004. Epub 2021 Jan 15.
The impairment of intracellular calcium homeostasis plays an essential role during ischemia-reperfusion injury. Calcium release from sarcoplasmic reticulum which is triggered by myocardial ischemia is mainly mediated by ryanodine receptors. Dantrolene sodium is a ryanodine receptor antagonist. The objective of the present study was to evaluate the in-vivo impact of dantrolene sodium on myocardial ischemia-reperfusion injury in swine models. An in vivo, experimental trial comparing 10 experimental animals which received dantrolene sodium with 9 control swine models was conducted. Their left anterior descending coronary artery was temporarily occluded for 75 minutes via a vessel tourniquet, which was then released. Myocardial reperfusion was allowed for 24 hours. Dantrolene was administered at the onset of the reperfusion period and levels of troponin, creatine phosphokinase and creatine kinase myocardial band between the two groups were compared. Additionally, various other hemodynamic parameters and left ventricular morphology and function were examined. There were significantly lower values of troponin, creatine phosphokinase and creatine kinase myocardial band in the dantrolene group indicating less ischemia-reperfusion injury. Moreover, the postischemic cardiac index was also greater in the dantrolene group, whereas viable myocardium was also better preserved. In conclusion, the in vivo cardioprotective role of dantrolene sodium against ischemia-reperfusion injury in swine models was indicated in this study. Therefore, dantrolene sodium administration could be a promising treatment against ischemia-reperfusion injury in humans. However, large randomized clinical studies should be firstly carried out to prove this hypothesis.
细胞内钙稳态的损伤在缺血再灌注损伤中起着至关重要的作用。心肌缺血触发的肌浆网钙释放主要由兰尼碱受体介导。丹曲林钠是一种兰尼碱受体拮抗剂。本研究的目的是评估丹曲林钠对猪模型心肌缺血再灌注损伤的体内影响。这是一项体内、实验性试验，比较了 10 只接受丹曲林钠的实验动物和 9 只对照猪模型。通过血管止血带暂时阻断它们的左前降支冠状动脉 75 分钟，然后释放。允许心肌再灌注 24 小时。在再灌注期开始时给予丹曲林钠，并比较两组之间肌钙蛋白、肌酸磷酸激酶和肌酸激酶同工酶的水平。此外，还检查了各种其他血流动力学参数以及左心室形态和功能。丹曲林钠组的肌钙蛋白、肌酸磷酸激酶和肌酸激酶同工酶水平明显较低，表明缺血再灌注损伤较少。此外，丹曲林钠组的缺血后心脏指数也较大，而存活心肌也得到了更好的保存。总之，本研究表明丹曲林钠对猪模型缺血再灌注损伤具有体内心脏保护作用。因此，丹曲林钠的给药可能是一种有前途的针对人类缺血再灌注损伤的治疗方法。然而，首先应该进行大规模的随机临床试验来证明这一假设。
