Unanesthetized Rodents Demonstrate Insensitivity of QT Interval and Ventricular Refractory Period to Pacing Cycle Length

Figures

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  FIGURE 1. Measured QT interval in unanesthetized rats show flat rate dependence. Analysis of the QT interval in rats following atrial pacing at various BCLs. RA pacing was performed with an implanted MBHE on the RA. (A) Example of ECG recordings at sinus rhythm and during atrial pacing at various BCLs (150, 120, and 90). Dots at the bottom indicate atrial pacing. (B) Left: QT interval measurements of individual rats as a function of BCL and during sinus rhythm (n = 10). Right: Averages of measured QT and calculated QTc plotted as a function of BCL. Statistical analysis did not reveal any significant changes in QT measurement as a function of BCL. For detailed data of individual rats see Supplementary Table S1.

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  FIGURE 2. Measured QT intervals in unanesthetized mice show flat rate dependence. Analysis of the QT interval in mice following atrial pacing at various BCLs. (A) Example of ECG recordings at sinus rhythm and during atrial pacing at various BCLs (120, 100, and 80). Dots at the bottom indicate atrial pacing. (B) Left: QT interval measurements of individual mice as a function of BCL (n = 9). Right: Averages of measured QT and calculated QTc plotted as a function of BCL. Statistical analysis did not reveal any significant changes in QT measurement as a function of BCL. For detailed data of individual mice see Supplementary Table S1.

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  FIGURE 3. Flat VERP rate dependence in unanesthetized rats. (A,B) Examples of VERP determination at a 160-ms BCL and 70-ms BCL, respectively. The upper traces denote ECG recording, and the lower traces mark the pacing through the ventricular electrode. Note the absence of VERP shortening in (B). (C) Left: VERP as a function of BCL for each individual rat (n = 10). Right: Average VERP measurements for all rats. Pooled data analysis showed slight but significant prolongation of the VERP as the BCL decreased Means ± SE are shown for the pooled data of BCL ≥ 130 ms, BCL between 120 and 100 ms and BCL < 100 ms. For detailed data of individual rats see Supplementary Table S1.

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  FIGURE 4. Flat VERP rate dependence in unanesthetized mice. (A,B) Examples of VERP determination at a 90-ms BCL and 40-ms BCL, respectively. The upper traces denote ECG recording, and the lower traces mark the pacing through the ventricular electrode. Note the absence of VERP shortening in (B). (C) Left: VERP as a function of BCL for each individual mouse (n = 9). Right: Averaged VERP measurements for all mice. Statistical analysis did not find any significant changes between the VERP measurements in the different BCLs with and without data grouping as in Figure 3. For detailed data of individual rats see Supplementary Table S1.

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  FIGURE 5. Dispersion between VERP and MAP recordings as a function of BCL in the isolated-perfused mouse hearts. (A) Example of simultaneous APD and VERP measurements using 10 beats S1S2 drive train. Left traces indicate the shortest BCLs for which S2 generates a response. Upper recordings: traces at 150 ms BCL indicating a VERP of 54 ms. Lower recordings: traces at 100 ms BCL indicating a VERP of 56 ms. This mild VERP prolongation (confirmed three times) occurred despite a sight shortening of the APD90. Note however, that the average VERP of all the preparations was not statistically different between the two BCLs as shown in (C) below. (B) Superimposed high magnification traces from (A), demonstrating the MAP recorded action potentials at 150 ms BCL (black) and 100 ms BCL (light gray). Arrow marks the APD90 difference. Note that VERP did not follow this slight shortening in the APD the even slightly increased to 56 ms. (C) Analysis of VERP and MAP rate-dependence in isolated-perfused mice hearts (n = 5). Comparison of parameters during 10 beats S1S2 drive train at 150 ms BCL vs. 100 ms. VERP measurements did not show any differences between the values in both BCLs. The APD and Peak AP…