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Anti-arrhythmic effects of hypercalcemia in hyperkalemic, Langendorff-perfused mouse hearts

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ABSTRACT

The present study examined the ventricular arrhythmic and electrophysiological properties during hyperkalemia (6.3 mM [K+] vs. 4 mM in normokalemia) and anti-arrhythmic effects of hypercalcemia (2.2 mM [Ca2+]) in Langendorff-perfused mouse hearts. Monophasic action potential recordings were obtained from the left ventricle during right ventricular pacing. Hyperkalemia increased the proportion of hearts showing provoked ventricular tachycardia (VT) from 0 to 6 of 7 hearts during programmed electrical stimulation (Fisher's exact test, P<0.05). It shortened the epicardial action potential durations (APDx) at 90, 70, 50 and 30% repolarization and ventricular effective refractory periods (VERPs) (analysis of variance, P<0.05) without altering activation latencies. Endocardial APDx and VERPs were unaltered. Consequently, ∆APDx (endocardial APDx-epicardial APDx) was increased, VERP/latency ratio was decreased and critical intervals for reexcitation (APD90-VERP) were unchanged. Hypercalcemia treatment exerted anti-arrhythmic effects during hyperkalemia, reducing the proportion of hearts showing VT to 1 of 7 hearts. It increased epicardial VERPs without further altering the remaining parameters, returning VERP/latency ratio to normokalemic values and also decreased the critical intervals. In conclusion, hyperkalemia exerted pro-arrhythmic effects by shortening APDs and VERPs. Hypercalcemia exerted anti-arrhythmic effects by reversing VERP changes, which scaled the VERP/latency ratio and critical intervals.

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Epicardial action potential durations (APDx) at x=(A) 90, (B) 70, (C) 50 and (D) 30% repolarization (msec) (mean ± SEM) (C) under control conditions, hyperkalemia alone or following hypercalcemia treatment during 8 Hz pacing (n=7). All APDx values were shortened by hyperkalemia (ANOVA, ***P<0.001, ***P<0.001, **P<0.01, *P<0.05, respectively), which were not further altered by hypercalcemia treatment (ANOVA, P>0.05). Endocardial APDx at x=(E) 90, (F) 70, (G) 50 and (H) 30% repolarization (msec) (mean ± SEM) obtained under the same experimental conditions. None of these values was altered by hyperkalemia alone or following hypercalcemia treatment (ANOVA, P>0.05). APD, action potential duration; SEM, standard error of the mean; ANOVA, analysis of variance.
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f3-br-0-0-735: Epicardial action potential durations (APDx) at x=(A) 90, (B) 70, (C) 50 and (D) 30% repolarization (msec) (mean ± SEM) (C) under control conditions, hyperkalemia alone or following hypercalcemia treatment during 8 Hz pacing (n=7). All APDx values were shortened by hyperkalemia (ANOVA, ***P<0.001, ***P<0.001, **P<0.01, *P<0.05, respectively), which were not further altered by hypercalcemia treatment (ANOVA, P>0.05). Endocardial APDx at x=(E) 90, (F) 70, (G) 50 and (H) 30% repolarization (msec) (mean ± SEM) obtained under the same experimental conditions. None of these values was altered by hyperkalemia alone or following hypercalcemia treatment (ANOVA, P>0.05). APD, action potential duration; SEM, standard error of the mean; ANOVA, analysis of variance.

Mentions: Shortenings in the QT interval were observed in electrocardiograms (ECGs) obtained from patients suffering from hyperkalemia (6). This may reflect alterations in APD either locally or transmurally across the myocardial wall. APDs at x=30, 50, 70 and 90% repolarization (APDx) were therefore assessed in the epicardium and endocardium, allowing calculation of ∆APD90 given by endocardial APD90-epicardial APD90, thereby providing an indication of the transmural repolarization gradient. Epicardial APD90 was decreased from 42.2±2.6 to 24.5±1.6 msec by hyperkalemia (P<0.001; Fig. 3A), as were APD70 (P<0.001; Fig. 3B), APD50 (P<0.01; Fig. 3C) and APD30 (P<0.05; Fig. 3D). However, the corresponding endocardial APDx values were not altered (P>0.05; Fig. 3E-H). These changes corresponded to increases in ΔAPD90 (Student's t-test, P<0.05; Fig. 4A), ΔAPD70 (P<0.01; Fig. 4B), ΔAPD50 (P<0.01; Fig. 4C) and ΔAPD30 (P<0.05; Fig. 4D). None of the epicardial or endocardial APDx and ΔAPDx values were further altered upon hypercalcemia treatment (P>0.05 in all cases).


Anti-arrhythmic effects of hypercalcemia in hyperkalemic, Langendorff-perfused mouse hearts
Epicardial action potential durations (APDx) at x=(A) 90, (B) 70, (C) 50 and (D) 30% repolarization (msec) (mean ± SEM) (C) under control conditions, hyperkalemia alone or following hypercalcemia treatment during 8 Hz pacing (n=7). All APDx values were shortened by hyperkalemia (ANOVA, ***P<0.001, ***P<0.001, **P<0.01, *P<0.05, respectively), which were not further altered by hypercalcemia treatment (ANOVA, P>0.05). Endocardial APDx at x=(E) 90, (F) 70, (G) 50 and (H) 30% repolarization (msec) (mean ± SEM) obtained under the same experimental conditions. None of these values was altered by hyperkalemia alone or following hypercalcemia treatment (ANOVA, P>0.05). APD, action potential duration; SEM, standard error of the mean; ANOVA, analysis of variance.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4998139&req=5

f3-br-0-0-735: Epicardial action potential durations (APDx) at x=(A) 90, (B) 70, (C) 50 and (D) 30% repolarization (msec) (mean ± SEM) (C) under control conditions, hyperkalemia alone or following hypercalcemia treatment during 8 Hz pacing (n=7). All APDx values were shortened by hyperkalemia (ANOVA, ***P<0.001, ***P<0.001, **P<0.01, *P<0.05, respectively), which were not further altered by hypercalcemia treatment (ANOVA, P>0.05). Endocardial APDx at x=(E) 90, (F) 70, (G) 50 and (H) 30% repolarization (msec) (mean ± SEM) obtained under the same experimental conditions. None of these values was altered by hyperkalemia alone or following hypercalcemia treatment (ANOVA, P>0.05). APD, action potential duration; SEM, standard error of the mean; ANOVA, analysis of variance.
Mentions: Shortenings in the QT interval were observed in electrocardiograms (ECGs) obtained from patients suffering from hyperkalemia (6). This may reflect alterations in APD either locally or transmurally across the myocardial wall. APDs at x=30, 50, 70 and 90% repolarization (APDx) were therefore assessed in the epicardium and endocardium, allowing calculation of ∆APD90 given by endocardial APD90-epicardial APD90, thereby providing an indication of the transmural repolarization gradient. Epicardial APD90 was decreased from 42.2±2.6 to 24.5±1.6 msec by hyperkalemia (P<0.001; Fig. 3A), as were APD70 (P<0.001; Fig. 3B), APD50 (P<0.01; Fig. 3C) and APD30 (P<0.05; Fig. 3D). However, the corresponding endocardial APDx values were not altered (P>0.05; Fig. 3E-H). These changes corresponded to increases in ΔAPD90 (Student's t-test, P<0.05; Fig. 4A), ΔAPD70 (P<0.01; Fig. 4B), ΔAPD50 (P<0.01; Fig. 4C) and ΔAPD30 (P<0.05; Fig. 4D). None of the epicardial or endocardial APDx and ΔAPDx values were further altered upon hypercalcemia treatment (P>0.05 in all cases).

View Article: PubMed Central - PubMed

ABSTRACT

The present study examined the ventricular arrhythmic and electrophysiological properties during hyperkalemia (6.3 mM [K+] vs. 4 mM in normokalemia) and anti-arrhythmic effects of hypercalcemia (2.2 mM [Ca2+]) in Langendorff-perfused mouse hearts. Monophasic action potential recordings were obtained from the left ventricle during right ventricular pacing. Hyperkalemia increased the proportion of hearts showing provoked ventricular tachycardia (VT) from 0 to 6 of 7 hearts during programmed electrical stimulation (Fisher's exact test, P&lt;0.05). It shortened the epicardial action potential durations (APDx) at 90, 70, 50 and 30% repolarization and ventricular effective refractory periods (VERPs) (analysis of variance, P&lt;0.05) without altering activation latencies. Endocardial APDx and VERPs were unaltered. Consequently, &#8710;APDx (endocardial APDx-epicardial APDx) was increased, VERP/latency ratio was decreased and critical intervals for reexcitation (APD90-VERP) were unchanged. Hypercalcemia treatment exerted anti-arrhythmic effects during hyperkalemia, reducing the proportion of hearts showing VT to 1 of 7 hearts. It increased epicardial VERPs without further altering the remaining parameters, returning VERP/latency ratio to normokalemic values and also decreased the critical intervals. In conclusion, hyperkalemia exerted pro-arrhythmic effects by shortening APDs and VERPs. Hypercalcemia exerted anti-arrhythmic effects by reversing VERP changes, which scaled the VERP/latency ratio and critical intervals.

No MeSH data available.


Related in: MedlinePlus