An innovative ovine model of severe cardiopulmonary failure supported by veno-arterial extracorporeal membrane oxygenation

Silver Heinsar,Sebastiano Maria Colombo,Carmen Ainola,Indrek Rätsep,Margaret Passmore,Gabriella Abbate,Xiaomeng Wang,Jacky Y Suen,Chiara Palmieri,Wayne B Dyer ,Emily Wilson ,Jae‐Seung Jung ,Roberto Lorusso,Noriko Sato,Samantha Livingstone ,Mahè Bouquet ,Leticia Pretti Pimenta,Bruno Vidal,Sacha Rozencwajg,Haris M Haqqani,Kei Sato,Daniel Mcguire,Karin Wildi,Nicole Bartnikowski,Gianluigi Li Bassi,J Reid ,John F Fraser

doi:10.1038/s41598-021-00087-y

Abstract

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.

Highlights

Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion
We present our study methods and results in accordance with the ARRIVE Guidelines for reporting in vivo research and according to recommendations provided by the European Extracorporeal Life Support Organisation Innovations Workgroup[22,23]
This study was approved by the University Animal Ethics Committee (UAEC) of Queensland University of Technology (QUT) (Approval no. 1800000337) and adhered to the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes of the National Health and Medical Research Council (NHMRC)[24]

Summary

Introduction

Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Management of CS patients includes treatment of the cause (e.g. coronary reperfusion in AMI) and restoration of adequate end-organ perfusion The latter can be achieved with medications, ie vasopressors and inotropes, mechanical circulatory support (MCS), or both. Reproducing a stable cardiogenic shock model by ligating major coronary arteries often resulted in refractory and life-threatening ventricular a rrhythmias[16,17,18,19] Other methods, such as carbon monoxide poisoning or drug-induced CS (beta-blockers), have resulted in heterogeneous outcomes and cause a global decrease in ventricular contractility, different to regional wall motion abnormalities usually seen in myocardial infarction[20,21]. We aimed to develop a model with high level of reproducibility, and reduced risk of refractory arrhythmias that could be reliably applied to assess novel therapeutic strategies and devices that could improve patients outcomes

Objectives

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Discussion

Conclusion