Increased Afterload Following Myocardial Infarction Promotes Conduction-Dependent Arrhythmias That Are Unmasked by Hypokalemia

Figures

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  Figure 1. Porcine Model of MI/iAL (A) Schematic representation and image of the arterially perfused porcine wedge preparation. (B) Representative transmural optical action potentials measured from across the ventricular wall of the wedge preparation. (C) Quantification of scar size using triphenyl-tetrazolium chloride staining. (D) Images of picrosirius red (fibrosis) (top) and wheat-germ agglutinin (hypertrophy) (bottom) staining showing advanced structural remodeling in hearts from the myocardial infarction model with increased afterload (MI/iAL). (E) Bar graphs show quantitation of interstitial collagenous tissue area against the cardiomyocyte area highlighting pronounced fibrotic remodeling in MI/iAL. (F) Cx43 messenger ribonucleic acid (mRNA) expression in naive control animals (Ctrl), MI/iAL, and MI animals was not different. (G) Quantitation of fibrosis-related gene expression at the mRNA level. Connective tissue growth factor (CTGF), transforming growth factor (TGF)-β, COL1A1, and COL3A1 but not SMAD3 ere markedly up-regulated in MI/iAL hearts compared with MI and Ctrl hearts. Three pig hearts for each group were used for the reverse transcription polymerase chain reaction…

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  Figure 2. Arrhythmia Incidence (A) Representative electrogram recordings from Ctrl and MI/iAL preparations during normokalemia and hypokalemia. Arterially perfused wedges from MI/iAL animals but not Ctrl animals were prone to ventricular tachycardia/ventricular fibrillation (VT/VF) during challenge with rapid pacing under conditions of hypokalemia. (B) Incidence of VT/VF in Ctrl (n = 7), MI (n = 5), and MI/iAL (n = 7) hearts during hypokalemia. Abbreviations as in Figure 1.

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  Figure 3. Loss of 1:1 Pacing Capture During Hypokalemia (A) Representative optical action potentials recorded at progressively faster pacing rates (1.0 to 6.0 Hz) from the Ctrl, MI, and MI/iAL wedges during hypokalemia. (B) Incidence of pacing-induced loss of 1:1 capture in the Ctrl (n = 7), MI (n = 5), and MI/iAL (n = 7) preparations. Abbreviations as in Figure 1.

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  Figure 4. Basal and Critical Conduction Velocities (A) Representative depolarization isochrone maps from Ctrl and MI/iAL preparations at baseline (normokalemia, pacing cycle length 1,000 ms). Comparison of basal conduction velocity (CVb) in the Ctrl, MI, and MI/iAL preparations (Ctrl: n = 11; MI: n = 9; and MI/iAL: n = 10). No significant differences in CVb were found between the MI or MI/iAL preparations compared with the Ctrl preparations. (B) Representative electrogram tracings recorded at a wide range of pacing rates in the Ctrl, MI, and MI/iAL preparations during hypokalemia challenge. (C) Comparison of average critical conduction velocity (CVc) (Ctrl: n = 7; MI: n = 4; and MI/iAL: n = 7) indicating significantly decreased levels in the MI/iAL group. Abbreviations as in Figures 1 and 3.

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  Figure 5. Individual Values of CVc for VT/VF (+) Versus VT/VF (−) Preparations VT/VF (+) = preparations that exhibited sustained VT/VF; VT/VF (−) = preparations that did not exhibit VT/VF. Abbreviations as in Figures 2 and 4.

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  Figure 6. Rate-Dependence of Conduction Slowing (A) Rate-dependent conduction slowing during hypokalemia in wedges from Ctrl (n = 6) and MI/iAL (n = 5) animals. CV at each rate is normalized to CVb. (B) Corresponding average linear slope of normalized CV restitution curves in Ctrl and MI/iAL wedges during hypokalemia at a pacing cycle length (PCL) <250 ms. (C) Representative depolarization isochrone maps from Ctrl and MI/iAL wedges. Abbreviations as in Figures 1 and 4.

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  Supplemental Video 1 Activation Wavefronts Underlying VT/VF During Hypokalemia in a MI/iAL Preparation Video reveals reentry with a figure-of-8 pattern. MI/iAL = myocardial infarction model with increased afterload; VT/VF = ventricular tachycardia/ventricular fibrillation.