Development and characterisation of a porcine closed chest model of acute myocardial infarction for cells, drugs, and tissue engineering applications.

Abstract

Background: Myocardial infarction (MI) is a major cause of death and disability worldwide with 20% and 45% mortality at 1- and at 5-year respectively. Following MI several detrimental changes are known to occur in the myocardium and a better understanding of these changes would be beneficial for the prevention and treatment of the disease. The aim of this research project was to develop and characterise a large animal model of closed-chest balloon MI with ischaemia reperfusion injury for diagnostic and therapeutic purposes.
Methods: From November 2016 to March 2018, a closed-chest MI model using percutaneous coronary occlusion was performed in 65 Yorkshire swine. This thesis reports the clinical, haemodynamic, and biochemical parameters related to the model. In addition, this thesis reports the findings cardiac magnetic resonance (CMR) studies performed in the acute and chronic phase after MI.
Results: In total, 65 experiments were performed. Overall experiment-related mortality was 6.1% with 40% of the animals demonstrating malignant arrhythmia during the induction of MI. Longer periods of coronary occlusion (90 minutes vs 60 minutes) resulted in a higher incidence of complications and mortality rate. The average scar size by CMR in the acute phase was 20.70±7.24 grams (as percentage of LV mass = 21.61±7.58 %) at early CMR, and at chronic time point was
8.38±3.5 grams (as percentage of LV mass = 7.93±3.36 %). The left ventricular function (LVEF) decreased significantly at early CMR with a mean value of 43.21±8.62 %. The mean value of cardiac troponin I four hours after MI was 87.47 ± 48.62 ng/ml.
Conclusion: With this work we have been able to develop a reliable and highly reproducible model of acute MI in large animal. The model is affected by a very low failure rate, produces a consistent myocardial scar, and can be used for multiple therapeutic and diagnostic purposes in MI.

Date of Award	11 May 2021
Original language	English
Awarding Institution	The University of Bristol
Supervisor	Raimondo Ascione (Supervisor), Thomas W Johnson (Supervisor) & M.Saadeh Suleiman (Supervisor)