Dataset Information

Atrial Anti-Arrhythmic Effects of Heptanol in Langendorff-Perfused Mouse Hearts.

ABSTRACT: Acute effects of heptanol (0.1 to 2 mM) on atrial electrophysiology were explored in Langendorff-perfused mouse hearts. Left atrial bipolar electrogram or monophasic action potential recordings were obtained during right atrial stimulation. Regular pacing at 8 Hz elicited atrial activity in 11 out of 11 hearts without inducing atrial arrhythmias. Programmed electrical stimulation using a S1S2 protocol provoked atrial tachy-arrhythmias in 9 of 17 hearts. In the initially arrhythmic group, 2 mM heptanol exerted anti-arrhythmic effects (Fisher's exact test, P < 0.05) and increased atrial effective refractory period (ERP) from 26.0 ± 1.9 to 57.1 ± 2.5 ms (ANOVA, P < 0.001) despite increasing activation latency from 18.7 ± 1.1 to 28.9 ± 2.1 ms (P < 0.001) and leaving action potential duration at 90% repolarization (APD90) unaltered (25.6 ± 1.2 vs. 27.2 ± 1.2 ms; P > 0.05), which led to increases in ERP/latency ratio from 1.4 ± 0.1 to 2.1 ± 0.2 and ERP/APD90 ratio from 1.0 ± 0.1 to 2.1 ± 0.2 (P < 0.001). In contrast, in the initially non-arrhythmic group, heptanol did not alter arrhythmogenicity, increased AERP from 47.3 ± 5.3 to 54.5 ± 3.1 ms (P < 0.05) and activation latency from 23.7 ± 2.2 to 31.3 ± 2.5 ms and did not alter APD90 (24.1 ± 1.2 vs. 25.0 ± 2.3 ms; P > 0.05), leaving both AERP/latency ratio (2.1 ± 0.3 vs. 1.9 ± 0.2; P > 0.05) and ERP/APD90 ratio (2.0 ± 0.2 vs. 2.1 ± 0.1; P > 0.05) unaltered. Lower heptanol concentrations (0.1, 0.5 and 1 mM) did not alter arrhythmogenicity or the above parameters. The present findings contrast with known ventricular pro-arrhythmic effects of heptanol associated with decreased ERP/latency ratio, despite increased ERP/APD ratio observed in both the atria and ventricles.

SUBMITTER: Tse G

PROVIDER: S-EPMC4752503 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Atrial Anti-Arrhythmic Effects of Heptanol in Langendorff-Perfused Mouse Hearts.

Tse Gary G Tse Vivian V Yeo Jie Ming JM Sun Bing B

PloS one 20160212 2

Acute effects of heptanol (0.1 to 2 mM) on atrial electrophysiology were explored in Langendorff-perfused mouse hearts. Left atrial bipolar electrogram or monophasic action potential recordings were obtained during right atrial stimulation. Regular pacing at 8 Hz elicited atrial activity in 11 out of 11 hearts without inducing atrial arrhythmias. Programmed electrical stimulation using a S1S2 protocol provoked atrial tachy-arrhythmias in 9 of 17 hearts. In the initially arrhythmic group, 2 mM he ...[more]

PMID: 26872148

Similar Datasets

Project description:BackgroundTime-domain and non-linear methods can be used to quantify beat-to-beat repolarization variability but whether measures of repolarization variability can predict ventricular arrhythmogenesis in mice have never been explored.MethodsLeft ventricular monophasic action potentials (MAPs) were recorded during constant right ventricular 8 Hz pacing in Langendorff-perfused mouse hearts, in the presence or absence of the gap junction and sodium channel inhibitor heptanol (0.1, 0.5, 1 or 2 mM).ResultsUnder control conditions, mean action potential duration (APD) was 39.4 ± 8.1 ms. Standard deviation (SD) of APDs was 0.3 ± 0.2 ms, coefficient of variation was 0.9 ± 0.8% and the root mean square (RMS) of successive differences in APDs was 0.15 ± 0.14 ms. Poincaré plots of APDn+1 against APDn revealed ellipsoid morphologies with a SD along the line-of-identity (SD2) to SD perpendicular to the line-of-identity (SD1) ratio of 4.6 ± 2.1. Approximate and sample entropy were 0.61 ± 0.12 and 0.76 ± 0.26, respectively. Detrended fluctuation analysis revealed short- and long-term fluctuation slopes of 1.49 ± 0.27 and 0.81 ± 0.36, respectively. Heptanol at 2 mM induced ventricular tachycardia in five out of six hearts. None of the above parameters were altered by heptanol during which reproducible electrical activity was observed (KW-ANOVA, P > 0.05). Contrastingly, SD2/SD1 decreased to 2.03 ± 0.41, approximate and sample entropy increased to 0.82 ± 0.12 and 1.45 ± 0.34, and short-term fluctuation slope decreased to 0.82 ± 0.19 during the 20-s period preceding spontaneous ventricular tachy-arrhythmias (n = 6, KW-ANOVA, P < 0.05).ConclusionMeasures of repolarization variability, such as SD2/SD1, entropy, and fluctuation slope are altered preceding the occurrence of ventricular arrhythmogenesis in mouse hearts. Changes in these variables may allow detection of impending arrhythmias for early intervention.

Project description:The clinical effects of hypokalemia including action potential prolongation and arrhythmogenicity suppressible by lidocaine were reproduced in hypokalemic (3.0 mM K(+)) Langendorff-perfused murine hearts before and after exposure to lidocaine (10 muM). Novel limiting criteria for local and transmural, epicardial, and endocardial re-excitation involving action potential duration (at 90% repolarization, APD(90)), ventricular effective refractory period (VERP), and transmural conduction time (Deltalatency), where appropriate, were applied to normokalemic (5.2 mM K(+)) and hypokalemic hearts. Hypokalemia increased epicardial APD(90) from 46.6 +/- 1.2 to 53.1 +/- 0.7 ms yet decreased epicardial VERP from 41 +/- 4 to 29 +/- 1 ms, left endocardial APD(90) unchanged (58.2 +/- 3.7 to 56.9 +/- 4.0 ms) yet decreased endocardial VERP from 48 +/- 4 to 29 +/- 2 ms, and left Deltalatency unchanged (1.6 +/- 1.4 to 1.1 +/- 1.1 ms; eight normokalemic and five hypokalemic hearts). These findings precisely matched computational predictions based on previous reports of altered ion channel gating and membrane hyperpolarization. Hypokalemia thus shifted all re-excitation criteria in the positive direction. In contrast, hypokalemia spared epicardial APD(90) (54.8 +/- 2.7 to 60.6 +/- 2.7 ms), epicardial VERP (84 +/- 5 to 81 +/- 7 ms), endocardial APD(90) (56.6 +/- 4.2 to 63.7 +/- 6.4 ms), endocardial VERP (80 +/- 2 to 84 +/- 4 ms), and Deltalatency (12.5 +/- 6.2 to 7.6 +/- 3.4 ms; five hearts in each case) in lidocaine-treated hearts. Exposure to lidocaine thus consistently shifted all re-excitation criteria in the negative direction, again precisely agreeing with the arrhythmogenic findings. In contrast, established analyses invoking transmural dispersion of repolarization failed to account for any of these findings. We thus establish novel, more general, criteria predictive of arrhythmogenicity that may be particularly useful where APD(90) might diverge sharply from VERP.

Project description:Insulin exerts positive inotropic effects on cardiac muscle; however, the relationship between cardiac contractility and phosphoinositol-3-kinase/Akt (PI3K/Akt) activation remains unclear. We hypothesized that the positive inotropic effects of insulin are dose-dependent and mediated via the PI3K/Akt pathway in isolated normal rat hearts. The Institutional Animal Investigation Committee approved the use of hearts excised from rats under pentobarbital anesthesia. The hearts were perfused at a constant pressure using the Langendorff technique. After stabilization (baseline), the hearts were randomly divided into the following four insulin (Ins) groups: 1) Ins0 (0 IU/L), 2) Ins0.5 (0.5 IU/L), 3) Ins5 (5 IU/L), and 4) Ins50 (50 IU/L) (n = 8 in each group). To clarify the role of the PI3K/Akt pathway in insulin-dependent inotropic effects, we also treated the insulin groups with the PI3K inhibitor wortmannin (InsW): 5) InsW0 (0 IU/L), 6) InsW0.5 (0.5 IU/L), 7) InsW5 (5 IU/L), and 8) InsW50 (50 IU/L). Hearts were perfused with Krebs–Henseleit buffer solution with or without wortmannin for 10 min, followed by 20 min perfusion with the solution containing each concentration of insulin. The data were recorded as the maximum left ventricular derivative of pressure development (LV dP/dt max). Myocardial p-Akt levels were measured at 3 min, 5 min, and at the end of the perfusion. In the Ins groups, LV dP/dt max in Ins5 and Ins50 increased by 14% and 48%, respectively, 3 min after insulin perfusion compared with the baseline. Tachyphylaxis was observed after 10 min in the Ins5 and Ins50 treatment groups. Wortmannin partially inhibited the positive inotropic effect of insulin; although insulin enhanced p-Akt levels at all time points compared with the control group, this increase was suppressed in the presence of wortmannin. The positive inotropic effect of insulin is dose-dependent and consistent with Akt activation. This effect mediated by high doses of insulin on cardiac tissue was temporary and caused tachyphylaxis, potentially triggered by Akt overactivation, which leads beta 1 deactivation.

Dataset Information

Atrial Anti-Arrhythmic Effects of Heptanol in Langendorff-Perfused Mouse Hearts.

Publications

Atrial Anti-Arrhythmic Effects of Heptanol in Langendorff-Perfused Mouse Hearts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets