Prognostic value of the metabolic syndrome in essential hypertension

Figures

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  Figure 1. Experimental setup and analysis A, schematic representation of the setup for the isolated heart high‐resolution optical mapping study. B, representative traces obtained during optical mapping. Optical mapping transients were obtained during stimulated rhythm at 4 Hz (top left), with the averaged action potential illustrating traditional action potential duration measurements (right). Optical mapping transients obtained during fibrillation are displayed in B (bottom left), showing single‐pixel traces of FV (modified from Arias‐Mutis, 2023). [Colour figure can be viewed at wileyonlinelibrary.com]

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  Figure 2. Modifications of standard ECG parameters produced by MetS diet A, sample ECG recording (top left) and superimposed ECG segmentation (right) from 15 min recordings [colour represents time from blue (earlier) to red (later) beats]. Average ECG for control and MetS animals at week 14 (wk‐14) and before ending the experimental protocol (wk‐28) are shown at the bottom of the panel. B, RR interval; C, PQ interval; D, QRS duration; E, QT interval; F, corrected QT interval (QTc); and G, T‐wave duration in control (n = 10) and MetS (n = 13) groups. * P < 0.05 vs. control; # P < 0.05 vs. pre‐diet. Data were analysed using a mixed‐model ANOVA. [Colour figure can be viewed at wileyonlinelibrary.com]

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  Figure 3. Plasmatic [Ca2+], [K+] and [Na+] Blood samples were taken from the auricular vein at weeks 16 and 32 in another set of rabbits fed with the same high‐fat and high‐sucrose diet. After 7 h fasting, samples were collected in lithium heparin and gel PST (BD Vacutainer, Plymouth, UK), stored on ice and centrifuged (1500 g, 15 min, 4°C). Then, plasma was obtained and stored in a −80°C refrigerator. Subsequently, 200 µL was used for analysis using the Diagnosis Plus Panel in the Skyla VB1 (SCIL Animal Care Company). We did not find differences in plasmatic [Ca2+], [K+] and [Na+] when comparing control vs. MetS animals or when comparisons were made, within groups, between weeks 16 and 32. Control (n = 11), MetS (n = 14). Data were analysed using a mixed‐model ANOVA. [Colour figure can be viewed at wileyonlinelibrary.com]

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  Figure 4. Modifications of optical APD produced in MetS A, representative optical APD90 maps of the LV and RV, respectively, in control and MetS at 250 ms pacing cycle length. Quantification of optical APD duration at different pacing cycle lengths in the LV and RV are shown below: APD30 (B), APD50 (C) and APD90 (D). Control (n = 11) and MetS (n = 12); * P < 0.05 vs. control. Data were analysed using a mixed‐model ANOVA. [Colour figure can be viewed at wileyonlinelibrary.com]

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  Figure 5. Differences in optical AP morphology in MetS A and B, representative triangulation coefficient (C tri) maps of the LV and RV, respectively, in control and MetS at 250 ms pacing cycle length (PCL). C, quantification of C tri at different PCL in the LV and RV. D, quantification velocity of depolarization (dV/dt) at different PCL in the LV and RV. Control (n = 11), MetS (n = 12); * P < 0.05 vs. control. Data were analysed using a mixed‐model ANOVA. [Colour figure can be viewed at wileyonlinelibrary.com]

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  Figure 6. Intrinsic changes in automatism, conduction and LV refractoriness A, RR interval; B, AV interval; C, LV effective refractory period (ERP); and D, LV functional refractory period (FRP) in isolated heart in control (n = 10) and MetS (n = 12) groups. Data were analysed using a mixed‐model ANOVA. [Colour figure can be viewed at wileyonlinelibrary.com]

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  Figure 7. Changes in conduction velocity and wavelength A and B, sample colour‐coded activation maps with isochrones and superimposed propagation direction for the LV and RV in both groups at 250 ms PCL (Control and MetS). C, quantification of CV in the LV and RV during steady‐state conditions in each frequency. D, we then computed wavelength as the product of optical APD90 × CV in the LV and RV. Control (n = 11) and MetS (n = 12); * P < 0.05 vs. Control; # P = 0.061 vs. control; ¥ P = 0.058 vs. control. Data were analysed using a mixed‐model ANOVA. [Colour figure can be viewed at wileyonlinelibrary.com]

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  Figure 8. Gene expression of the main ion channels which shape ventricular action potential mRNA levels of Nav1.5 coding for I Na (A), Kv4.2 and KChIP2 coding for I to (B and C), Cav1.2 coding for I Ca‐L (D), KvLQT1 coding for I Ks (E) and Kir2.1 coding for I K1 (F). G–I, gene expression for fibrosis markers (type I collagen, smooth muscle alpha‐2 actin) and connexin 43. Control (n = 8), MetS (n = 8). * P < 0.05 vs. control. Panels show median and interquartile range (error bars). Data were analysed using Mann–Whitney U test.

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  Figure 9. Restitution characteristics and emergence of alternans A, electrical restitution curves of activation recovery intervals obtained at increasing pacing frequencies for control and MetS (left) and regional restitution curves from optical data obtained at the LV and RV (right). B, representative optical transients obtained during the onset of alternance before induction for control (upper traces) and MetS (bottom traces). Blue‐shaded intervals represent 1 s. C, quantification of the maximum slope of the restitution curves between groups (control vs. MetS). D, quantification of the emergence and magnitude of alternans (alternance index). Control (n = 10), MetS (n = 12); * P < 0.05 vs. control. Data were analysed using a two‐way ANOVA. [Colour figure can be viewed at wileyonlinelibrary.com]

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  Figure 10. Characteristics of pacing‐induced VF A and B, representative mean dominant frequency (DF) maps for the LV (A) and RV (B), respectively, in controls and MetS. C, quantification of the mean DF of VF, where the time‐course evolution for the first 6 min (left) and the mean values (right) are shown for the RV and LV. D, the time‐course of the VV intervals during the 6 min of VF (left) and quantification of the mean VV of VF (right), for the LV and RV in control and MetS. Control (n = 9), MetS (n = 11); * P < 0.05 vs. control; # P < 0.05 vs. LV. Data were analysed using a two‐way ANOVA. [Colour figure can be viewed at wileyonlinelibrary.com]

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  Figure 11. Electrophysiological heterogeneity during VF A and B, representative mean regularity index (RI) maps for the LV (A) and RV (B), respectively, in control and MetS. C, quantification of the mean RI, where the time‐course evolution (left) and the mean values (right) are shown for the RV and LV. D, time‐course of the singularity points density (SPd) during the 6 min of VF (left) and quantification of the mean SPd of VF (right), for the LV and RV in control and MetS. Control (n = 9) and MetS (n = 11); # P < 0.05 vs. LV. Data were analysed using a two‐way ANOVA. [Colour figure can be viewed at wileyonlinelibrary.com]