Critical Care Research Group, The Prince Charles Hospital, Chermside, Brisbane, QLD, Australia.
Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
Sci Rep. 2021 Oct 14;11(1):20458. doi: 10.1038/s41598-021-00087-y.
Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Current animal models result in heterogenous cardiac injury and frequent episodes of refractory ventricular fibrillation. Thus, we aimed to develop an innovative, clinically relevant, and titratable model of severe cardiopulmonary failure. Six sheep (60 ± 6 kg) were anaesthetized and mechanically ventilated. VA-ECMO was commenced and CS was induced through intramyocardial injections of ethanol. Then, hypoxemic/hypercapnic pulmonary failure was achieved, through substantial decrease in ventilatory support. Echocardiography was used to compute left ventricular fractional area change (LVFAC) and cardiac Troponin I (cTnI) was quantified. After 5 h, the animals were euthanised and the heart was retrieved for histological evaluations. Ethanol (58 ± 23 mL) successfully induced CS in all animals. cTnI levels increased near 5000-fold. CS was confirmed by a drop in systolic blood pressure to 67 ± 14 mmHg, while lactate increased to 4.7 ± 0.9 mmol/L and LVFAC decreased to 16 ± 7%. Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. In conclusion, we present an innovative ovine model of severe cardiopulmonary failure in animals on VA-ECMO. This model could be essential to further characterize CS and develop future treatments.
难治性心原性休克（CS）常需要静脉-动脉体外膜肺氧合（VA-ECMO）来维持终末器官灌注。目前的动物模型导致心脏损伤不均一，频繁出现难治性心室颤动。因此，我们旨在开发一种创新的、与临床相关的、可滴定的严重心肺衰竭模型。六只绵羊（60±6kg）麻醉并机械通气。开始 VA-ECMO，通过心肌内注射乙醇诱导 CS。然后，通过大幅降低通气支持来实现低氧/高碳酸血症性肺衰竭。使用超声心动图计算左心室射血分数（LVFAC），并定量检测心肌肌钙蛋白 I（cTnI）。5 小时后，处死动物并取出心脏进行组织学评估。所有动物均成功接受乙醇（58±23mL）注射以诱导 CS。cTnI 水平增加近 5000 倍。CS 通过收缩压降至 67±14mmHg 来确认，同时乳酸增加到 4.7±0.9mmol/L，LVFAC 降至 16±7%。心肌样本证实存在广泛的细胞坏死和炎症浸润。总之，我们在接受 VA-ECMO 的动物中展示了一种新型的严重心肺衰竭绵羊模型。该模型对于进一步描述 CS 和开发未来治疗方法可能至关重要。
