Novel and Effective: ECG Utilization for MI Confirmation in Mouse Models

Abstract

Introduction Electrocardiography measures the electrical activity of the heart to generate an electrocardiogram (ECG) through a non‐invasive process that involves placing electrodes on strategic points on the body. When an MI occurs, the lack of contractility induces changes to the ECG, visualized by a prolonged QRS wave and amplification of the R wave. Previously, we identified the area under the QRS wave, 1 min after permanent ligation in a mouse model of myocardial infarction (MI) determined surgical success. The purpose of this study was to further demonstrate in a second cohort that the previous ECG parameters identified accurately confirmed that an MI has been administered by left anterior coronary artery ligation in real‐time. Methods and Results Permanent coronary artery ligation was performed on WT and CD8atmak1 (CD8‐/‐) mice (n=9/genotype); an ECG was recorded using a surgical monitoring platform and was analyzed on iWorkx LabScribe Data Acquisition and Analysis software. Previous analysis of the first dataset indicated no differences between sexes so both males and females were used in the second cohort. A receiver operating characteristic (ROC) curve was used to link changes in the QRS complex at the 1‐min mark with MI surgical success. By ROC analysis, the area under the QRS complex had an area under the curve (AUC) of 0.94 (p=0.01) indicating a strong association with MI success. To remove any potential effect of surgical platform variability, we normalized the 1 min data to pre‐MI values to determine fold‐change in the area under the QRS complex. ROC analysis of the normalized data also indicated a strong sensitivity and specificity for MI success with an AUC value of 0.90 (p=0.02). Mice in the second cohort were divided into two groups based on a cut‐off point for either the area under the QRS complex (≥0.003 mV/sec) or the normalized data (≥ 3.1 fold change in the QRS complex) to distinguish the two groups. Using the non‐normalized data alone, there was an 84% success rate with 2 false positives and 1 false negative. Analysis using the normalized data alone had an 74% success rate, with 2 false positives and 3 false negatives. None of these false positives or negatives were linked to genotype or sex. Conclusion Our data indicates that while changes in the QRS complex 1‐min after ligation may be useful for confirming MI surgical success, there are potential limitations that could skew the data. One possible explanation for the false positives could be variation between ECG boards. To remove this, we normalized post‐MI data to pre‐MI values but, this seemed to decrease effectiveness. It is also important to note that many of the false negatives were due to anomalies within the ECG such as the presence of R‐prime waves. For this reason, users must be consistent when analyzing the ECG data points to minimize variation. In summary, using the ECG data 1 min after ligation had a fairly strong prediction rate for MI surgical success.