Novel method for induction of myocardial infarction in rats by ultrasound guided electrocoagulation of the left anterior descending artery

Abstract

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Minerva Imaging Background Murine models of acute myocardial infarction (MI) are commonly established through ligation of the left anterior descending artery (LAD). Despite inherent procedural challenges, including high mortality rates, limited improvements of the induction procedure have been made. Ultrasound-guided electrocoagulation of the LAD could be advantageous by improving animal welfare and decreasing procedural mortality. Purpose To investigate the feasibility of MI induction by ultrasound guided electrocoagulation in rats in comparison to traditional LAD ligation. Methods Thirty-eight female Sprague Dawley rats were randomized to MI by either of the two induction methods leading to 19 rats in each group. Infarct size and left ventricular ejection fraction (LVEF) were evaluated using positron emission tomography (PET) with [18F]fluorodeoxyglucose ([18F]FDG) 9 days post-MI. Myocardial infarct size was categorized as non-infarcted, mild, moderate, or severe based on [18F]FDG uptake. Animal welfare was assessed twice daily for the initial 48h post-surgery using a behavioural scoring system. Results There was no significant difference in the mortality rate of rats with MI induced by electrocoagulation compared to LAD ligation (16% vs 37%, P=0.27). Among the surviving animals both methods produced an equal number of myocardial infarcts (n=5). Electrocoagulation resulted in 1 mild, 2 moderate, and 2 severe MIs, while LAD ligation produced 1 mild, 0 moderate, and 4 severe MIs. Infarct size was similar in the electrocoagulation group compared to the LAD ligation group (mean±SD electrocoagulation: 15±5% vs ligation: 28±13%, P=0.13). The number of non-infarcted surviving rats in the electrocoagulation group was 11 compared to 7 in the LAD ligation group (P=0.33). The LVEF of infarcted rats showed no significant difference between groups (electrocoagulation: 47±8% vs ligation: 38±10%, P=0.14). The LVEF for non-infarcted rats was 53±5%. Post-surgical animal welfare appeared to be improved in the electrocoagulation group, however, the accumulated behavioural score did not reveal a significant difference (median [interquartile range] electrocoagulation: 0 [0-1] vs ligation 2 [0-2], P=0.19). Conclusion Induction of myocardial infarction by ultrasound-guided electrocoagulation is feasible in rats and should be considered as an alternative to LAD ligation. Further development is needed to improve the rate of success and consistency in infarct size.