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.

中文翻译：

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超声引导左前降支电凝诱发大鼠心肌梗死的新方法


资金致谢 资金来源类型：私人公司。主要资金来源：Minerva Imaging 背景 小鼠急性心肌梗死 (MI) 模型通常通过结扎左前降支 (LAD) 建立。尽管存在固有的程序挑战，包括高死亡率，但诱导程序的改进有限。超声引导下的 LAD 电凝可以改善动物福利并降低手术死亡率。目的 与传统 LAD 结扎相比，探讨超声引导电凝诱导大鼠心肌梗死的可行性。方法 将 38 只雌性 Sprague Dawley 大鼠通过两种诱导方法中的任一种随机分配至 MI，每组 19 只。 MI后9天使用正电子发射断层扫描(PET)和[18F]氟脱氧葡萄糖([18F]FDG)评估梗塞面积和左心室射血分数(LVEF)。根据 [18F]FDG 摄取情况，心肌梗塞大小分为非梗塞、轻度、中度或重度。术后最初 48 小时内，使用行为评分系统每天评估动物福利两次。结果 电凝致心肌梗死大鼠的死亡率与LAD结扎大鼠的死亡率差异无统计学意义（16% vs 37%，P=0.27）。在幸存的动物中，两种方法产生相同数量的心肌梗塞（n=5）。电凝导致 1 例轻度、2 例中度和 2 例重度 MI，而 LAD 结扎产生 1 例轻度、0 例中度和 4 例重度 MI。与LAD结扎组相比，电凝组的梗塞面积相似（平均值±SD电凝：15±5% vs 结扎：28±13%，P=0.13）。 电凝组中未梗死的存活大鼠数量为11只，而LAD结扎组中存活的大鼠数量为7只（P=0.33）。梗死大鼠的 LVEF 组间无显着差异（电凝：47±8% vs 结扎：38±10%，P=0.14）。非梗塞大鼠的 LVEF 为 53±5%。电凝组的术后动物福利似乎有所改善，但是，累积的行为评分并未显示出显着差异（中位[四分位距]电凝：0 [0-1] vs 结扎 2 [0-2]，P =0.19）。结论 超声引导下电凝诱导大鼠心肌梗死是可行的，应考虑作为 LAD 结扎的替代方法。需要进一步开发以提高梗塞面积的成功率和一致性。