Cardiac ischemia and reperfusion in mice: a comprehensive hemodynamic, electrocardiographic and electrophysiological characterization

Figures

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  Figure 1. Alterations in surface electrogram after I/R in mice. (A) Gomoris trichrome staining of transverse sections at the mid-cavity level of the left ventricle from a mouse 7 days after I/R yielding an infarction size of 33% (upper panel) and a sham control mouse (lower panel). (B) Representative telemetric electrogram recordings from a mouse after I/R (upper panel) and after sham operation. Duration of indicated intervals is given in ms. Note a marked shortening of the RR interval and prolongation of the QRS and QT interval 7 days after I/R. QRS morphology often presented with negatively deflected fragmentation after I/R.

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  Figure 2. The susceptibility for spontaneous VA increases in the subacute stage after I/R. The herein applied arrhythmia score rates both number and severity of VA (see “Methods” section). VA score values of one hour are averaged at each given time interval. Data are given as geometric mean and 95% confidence interval (BL, p = 0.393; 0–6 h; ***p < 0.001; 6–24 h; ***p < 0.001; 1–2 days; ***p < 0.001; 3–4 days; **p = 0.003; 6–7 days; **p = 0.004; sham n = 6, I/R n = 10, non-parametric Mann Whitney U-test).

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  Figure 3. I/R raises the electrical ventricular vulnerability. (A) EPS reveals a similar burden of VA at 2 days after I/R compared to sham operated controls (p = 0.731, n = 6, unpaired two-sided t-test). (B) The number of VA inductions increases significantly 7 days after I/R over sham controls (p = 0.038, n = 10, unpaired two-sided t-test). (C) The severity of VA at 2 days is indifferent between groups independent of the used PES protocol (two-way ANOVA (Sidak); S2–S4, p = 0.998; S4–S6, p = 0.999; S7–S11, p = 0.596; n = 6). (D) Application of multiple extrastimuli is most efficient to elicit VA at 7 days post I/R over sham control (MB S7–S11, *p = 0.018, n = 10, two-way ANOVA (Sidak); PES S2–S5, p = 0.544; MB S4–S6, p = 0.404). (E) The number of induced VA classified by type did not differ at 2 days (two-way ANOVA (Sidak); premature ventricular complex (PVC), p = 0.130; couplet, p = 0.969; triplet, p = 0.969; VT < 1 s, p = 0.982; VT > 1 s = 0.999; n = 6). (F) Predominantly, more PVC are induced in I/R mice compared to sham operated controls (***p < 0.001, n = 10, two-way ANOVA (Sidak); couplet, p = 0.531; triplet, p = 0.998; VT < 1 s, p = 0.884; VT > 1 s, p > 0.999). All data are given as…

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  Figure 4. Electrical ventricular vulnerability is associated with sympathetic activation after I/R. (A) The induction of VA at 7 days after I/R is associated with heart rate (HR) (linear regression; I/R (filled circles): y = 0.007719*x − 3.503, r2 = 0.5011, p = 0.020); sham (open circles): y = − 9.577e−006*x + 0.04268, r2 = 0.0001752, n.s.), (B) with the ventricular refractory period (VRP) at 90 ms (linear regression; I/R (filled circles): y = − 0.05940*x + 2.515, r2 = 0.4022, p 0.048; sham (open circles): y = 0.01225*x − 0.3459, r2 = 0.6677, p = 0.047), and (C) with the standard deviation of normals to normals (SDNN) (linear regression; I/R (filled circles), y = − 0.2074*x + 1.314, r2 = 0.5032, p = 0.043; sham (open circles): y = − 0.01721*x + 0.1585, r2 = 0.3475, p = 0.218). (D) The induction of VA tends to be increased in I/R mice exhibiting fragmentation of the QRS complex (fQRS (+)) compared to those without fQRS (-) (unpaired one-sided t-test (Mann–Whitney), p = 0.066). (E) The severity of VA induction as indicated by the VA score did not significantly correlate with increasing infarct size (linear regression, y = 0.02416*x − 0.3725, r2 = 0.07636, p = 0.439). Data are given as mean…

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  Figure 5. Baroreflex sensitivity is reduced after I/R. (A) Turbulence onset increases both at 2 days and 7 days after I/R as indicated (***p < 0.001 and *p = 0.046, respectively). (B) Turbulence slope is depressed at 2 days after I/R (*p = 0.034). The heart rate variability parameters turbulence onset and slope are surrogate markers for baroreflex sensitivity (see “Methods” section). Note that the results indicate a disturbed vagal nerve activity after I/R. Data are given as box and whiskers min to max (n = 6). Statistical significance of differences between I/R and sham control was assessed by a two-way ANOVA (Tukey’s multiple comparison).