Development of Electrocardiography Standards for Evaluating Myocardial Infarction and Ischemia–Reperfusion Injury in Mice

Figures

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  Figure 1. STE >0.1 mV in lead II as a criterion for validating murine MI model success. A, TTC staining at 24 hours after surgery revealed the infarct area in a representative mouse heart. White demarcations indicate the ischemic tissues. Scale bar, 2 mm. B, ECG recordings showed STE in lead II at 60 minutes after surgery, demonstrating a classic pattern of myocardial ischemia. C, Echocardiography performed 1 week after surgery revealed damaged cardiac function with regional contractile impairment in the mice represented in (B). D, EF in the sham group (n=7), failed MI model group (n=7), and successful MI model group (n=20). E, Fractional shortening in the sham group (n=7), failed MI model group (n=7), and successful MI model group (n=20). Statistical significance was evaluated via permutation 1‐way ANOVA followed by permutation t tests with maxT correction (D and E). EF indicates ejection fraction; MI, myocardial infarction; STE, ST‐segment elevation; and TTC, 2,3,5‐triphenyltetrazolium chloride.

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  Figure 2. QTc interval prolongation in lead II as a biomarker of murine MI model success. A, Mice that exhibited STE without QTc interval prolongation in lead II represent unsuccessful MI models. B, TTC staining at 24 hours after surgery showed no infarct area in mice from the group represented in (A). Red demarcations indicate the viable myocardium. Scale bar, 2 mm. C, Mice exhibited both significant STE and QTc interval prolongation in postoperative ECGs compared with baseline. D, TTC staining at 24 hours after surgery revealed the infarct area in mice represented in (C). White demarcations indicate ischemic areas. Scale bar, 2 mm. (E) Successful MI models (n=9) exhibited QTc prolongation vs failed (n=3) and sham models (n=9). F, Echocardiography performed 1 week after surgery in mice, as shown in (A) revealed preserved ventricular function. Statistical significance was evaluated via permutation 1‐way ANOVA followed by permutation t tests with maxT correction (E). MI, myocardial infarction; QTc, corrected QT; STE, ST‐segment elevation; and TTC, 2,3,5‐triphenyltetrazolium chloride.

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  Figure 3. Changes in postoperative ECG at 30 minutes as a time window for diagnosis. A, Acute STE developed in lead II immediately after LAD ligation but resolved spontaneously within 60 minutes. B, TTC staining at 24 hours after surgery showed no evident ischemic regions in mice, as shown in (A). Scale bar, 2 mm. C, Echocardiography at 1 week after surgery in mice, as shown in (A), revealed preserved ventricular function. D, STE was not observed until 30 minutes after surgery. E, TTC staining at 24 hours after surgery showed evident ischemic regions in mice, as shown in (D). Scale bar, 2 mm. LAD indicates left anterior descending; STE, ST‐segment elevation; and TTC, 2,3,5‐triphenyltetrazolium chloride.

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  Figure 4. The relationship among the magnitude of STE, location of LAD coronary artery ligation, and EF. A, Macroscopic analysis showing the ligation sites on the LAD coronary artery in mice with high and low STE, examined 1 day after surgery. B, ECGs at 30 minutes after ligation from mice in the high‐STE (STE >0.2 mV) and low‐STE (STE <0.2 mV) groups. C, Correlation between the magnitude of lead II STE at 30 minutes after surgery and the distance from the cardiac apex. D, TTC staining of hearts from mice with high STE or low STE in lead II at 24 hours after surgery. Ischemic areas are white. Scale bar, 2 mm. E, Echocardiography was performed 1 week after surgery in mice with high STE or low STE in lead II. F, Correlation between the magnitude of lead II STE at 30 minutes after surgery and EF. G, Gross morphology at 4 weeks after surgery, showing differences in ventricular remodeling between mice with high STE or low STE in lead II. H, The EF and fractional shortening were measured in mice with lead II STE greater than (n=6) or less than (n=7) 0.2 mV at 7 days after surgery. Statistical significance was evaluated using linear regression (C and F) and 2‐tailed permutation t test (H). EF…

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  Figure 5. Validation of ECG‐based diagnostic criteria for assessing the mouse IRI model. A, Representative lead II ECG traces showing STE resolution within 3 minutes after reperfusion. Red arrow, QRS wave; black arrow, T wave. B, Representative lead II ECG traces showing delayed STE resolution at 10 minutes after reperfusion. C, TTC staining at 24 hours after surgery confirmed anterolateral infarction, as shown in (A). White demarcations indicate ischemic myocardium. Scale bar, 2 mm. I indicates ischemia; IRI, ischemia–reperfusion injury; R, reperfusion; STE, ST‐segment elevation; and TTC, 2,3,5‐triphenyltetrazolium chloride.