Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis

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Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis. / Axelsen, Lene Nygaard; Callø, Kirstine; Braunstein, Thomas Hartig; Riemann, Mads; Hofgaard, Johannes Pauli; Liang, Bo; Jensen, Christa Funch; Olsen, Kristine Boisen; Bartels, Emil Daniel; Baandrup, Ulrik; Jespersen, Thomas; Nielsen, Lars Bo; von Holstein-Rathlou, Niels-Henrik; Nielsen, Morten Schak.

In: Cardiovascular Diabetology, Vol. 14, 87, 14.07.2015.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Axelsen, LN, Callø, K, Braunstein, TH, Riemann, M, Hofgaard, JP, Liang, B, Jensen, CF, Olsen, KB, Bartels, ED, Baandrup, U, Jespersen, T, Nielsen, LB, von Holstein-Rathlou, N-H & Nielsen, MS 2015, 'Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis' Cardiovascular Diabetology, vol. 14, 87. https://doi.org/10.1186/s12933-015-0246-8

APA

Axelsen, L. N., Callø, K., Braunstein, T. H., Riemann, M., Hofgaard, J. P., Liang, B., ... Nielsen, M. S. (2015). Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis. Cardiovascular Diabetology, 14, [87]. https://doi.org/10.1186/s12933-015-0246-8

Vancouver

Axelsen LN, Callø K, Braunstein TH, Riemann M, Hofgaard JP, Liang B et al. Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis. Cardiovascular Diabetology. 2015 Jul 14;14. 87. https://doi.org/10.1186/s12933-015-0246-8

Author

Axelsen, Lene Nygaard ; Callø, Kirstine ; Braunstein, Thomas Hartig ; Riemann, Mads ; Hofgaard, Johannes Pauli ; Liang, Bo ; Jensen, Christa Funch ; Olsen, Kristine Boisen ; Bartels, Emil Daniel ; Baandrup, Ulrik ; Jespersen, Thomas ; Nielsen, Lars Bo ; von Holstein-Rathlou, Niels-Henrik ; Nielsen, Morten Schak. / Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis. In: Cardiovascular Diabetology. 2015 ; Vol. 14.

Bibtex

@article{e726a1fcf2564535964d445a5c6785f0,
title = "Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis",
abstract = "BACKGROUND: Type 2 diabetes is associated with abnormal electrical conduction and sudden cardiac death, but the pathogenic mechanism remains unknown. This study describes electrophysiological alterations in a diet-induced pre-diabetic rat model and examines the underlying mechanism.METHODS: Sprague-Dawley rats were fed either high-fat diet and fructose water or normal chow and water for 6 weeks. The electrophysiological properties of the whole heart was analyzed by in vivo surface ECG recordings, as wells as ex vivo in Langendorff perfused hearts during baseline, ischemia and reperfussion. Conduction velocity was examined in isolated tissue strips. Ion channel and gap junction conductances were analyzed by patch-clamp studies in isolated cardiomyocytes. Fibrosis was examined by Masson's Trichrome staining and thin-layer chromatography was used to analyze cardiac lipid content. Connexin43 (Cx43) expression and distribution was examined by western blotting and immunofluorescence respectively.RESULTS: Following 6 weeks of feeding, fructose-fat fed rats (FFFRs) showed QRS prolongation compared to controls (16.1 ± 0.51 (n = 6) vs. 14.7 ± 0.32 ms (n = 4), p < 0.05). Conduction velocity was slowed in FFFRs vs. controls (0.62 ± 0.02 (n = 13) vs. 0.79 ± 0.06 m/s (n = 11), p < 0.05) and Langendorff perfused FFFR hearts were more prone to ventricular fibrillation during reperfusion following ischemia (p < 0.05). The patch-clamp studies revealed no changes in Na(+) or K(+) currents, cell capacitance or gap junctional coupling. Cx43 expression was also unaltered in FFFRs, but immunofluorescence demonstrated an increased fraction of Cx43 localized at the intercalated discs in FFFRs compared to controls (78 ± 3.3 (n = 5) vs. 60 ± 4.2 {\%} (n = 6), p < 0.01). No fibrosis was detected but FFFRs showed a significant increase in cardiac triglyceride content (1.93 ± 0.19 (n = 12) vs. 0.77 ± 0.13 nmol/mg (n = 12), p < 0.0001).CONCLUSION: Six weeks on a high fructose-fat diet cause electrophysiological changes, which leads to QRS prolongation, decreased conduction velocity and increased arrhythmogenesis during reperfusion. These alterations are not explained by altered gap junctional coupling, Na(+), or K(+) currents, differences in cell size or fibrosis.",
author = "Axelsen, {Lene Nygaard} and Kirstine Call{\o} and Braunstein, {Thomas Hartig} and Mads Riemann and Hofgaard, {Johannes Pauli} and Bo Liang and Jensen, {Christa Funch} and Olsen, {Kristine Boisen} and Bartels, {Emil Daniel} and Ulrik Baandrup and Thomas Jespersen and Nielsen, {Lars Bo} and {von Holstein-Rathlou}, Niels-Henrik and Nielsen, {Morten Schak}",
year = "2015",
month = "7",
day = "14",
doi = "10.1186/s12933-015-0246-8",
language = "English",
volume = "14",
journal = "Cardiovascular Diabetology",
issn = "1475-2840",
publisher = "BioMed Central Ltd.",

}

RIS

TY - JOUR

T1 - Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis

AU - Axelsen, Lene Nygaard

AU - Callø, Kirstine

AU - Braunstein, Thomas Hartig

AU - Riemann, Mads

AU - Hofgaard, Johannes Pauli

AU - Liang, Bo

AU - Jensen, Christa Funch

AU - Olsen, Kristine Boisen

AU - Bartels, Emil Daniel

AU - Baandrup, Ulrik

AU - Jespersen, Thomas

AU - Nielsen, Lars Bo

AU - von Holstein-Rathlou, Niels-Henrik

AU - Nielsen, Morten Schak

PY - 2015/7/14

Y1 - 2015/7/14

N2 - BACKGROUND: Type 2 diabetes is associated with abnormal electrical conduction and sudden cardiac death, but the pathogenic mechanism remains unknown. This study describes electrophysiological alterations in a diet-induced pre-diabetic rat model and examines the underlying mechanism.METHODS: Sprague-Dawley rats were fed either high-fat diet and fructose water or normal chow and water for 6 weeks. The electrophysiological properties of the whole heart was analyzed by in vivo surface ECG recordings, as wells as ex vivo in Langendorff perfused hearts during baseline, ischemia and reperfussion. Conduction velocity was examined in isolated tissue strips. Ion channel and gap junction conductances were analyzed by patch-clamp studies in isolated cardiomyocytes. Fibrosis was examined by Masson's Trichrome staining and thin-layer chromatography was used to analyze cardiac lipid content. Connexin43 (Cx43) expression and distribution was examined by western blotting and immunofluorescence respectively.RESULTS: Following 6 weeks of feeding, fructose-fat fed rats (FFFRs) showed QRS prolongation compared to controls (16.1 ± 0.51 (n = 6) vs. 14.7 ± 0.32 ms (n = 4), p < 0.05). Conduction velocity was slowed in FFFRs vs. controls (0.62 ± 0.02 (n = 13) vs. 0.79 ± 0.06 m/s (n = 11), p < 0.05) and Langendorff perfused FFFR hearts were more prone to ventricular fibrillation during reperfusion following ischemia (p < 0.05). The patch-clamp studies revealed no changes in Na(+) or K(+) currents, cell capacitance or gap junctional coupling. Cx43 expression was also unaltered in FFFRs, but immunofluorescence demonstrated an increased fraction of Cx43 localized at the intercalated discs in FFFRs compared to controls (78 ± 3.3 (n = 5) vs. 60 ± 4.2 % (n = 6), p < 0.01). No fibrosis was detected but FFFRs showed a significant increase in cardiac triglyceride content (1.93 ± 0.19 (n = 12) vs. 0.77 ± 0.13 nmol/mg (n = 12), p < 0.0001).CONCLUSION: Six weeks on a high fructose-fat diet cause electrophysiological changes, which leads to QRS prolongation, decreased conduction velocity and increased arrhythmogenesis during reperfusion. These alterations are not explained by altered gap junctional coupling, Na(+), or K(+) currents, differences in cell size or fibrosis.

AB - BACKGROUND: Type 2 diabetes is associated with abnormal electrical conduction and sudden cardiac death, but the pathogenic mechanism remains unknown. This study describes electrophysiological alterations in a diet-induced pre-diabetic rat model and examines the underlying mechanism.METHODS: Sprague-Dawley rats were fed either high-fat diet and fructose water or normal chow and water for 6 weeks. The electrophysiological properties of the whole heart was analyzed by in vivo surface ECG recordings, as wells as ex vivo in Langendorff perfused hearts during baseline, ischemia and reperfussion. Conduction velocity was examined in isolated tissue strips. Ion channel and gap junction conductances were analyzed by patch-clamp studies in isolated cardiomyocytes. Fibrosis was examined by Masson's Trichrome staining and thin-layer chromatography was used to analyze cardiac lipid content. Connexin43 (Cx43) expression and distribution was examined by western blotting and immunofluorescence respectively.RESULTS: Following 6 weeks of feeding, fructose-fat fed rats (FFFRs) showed QRS prolongation compared to controls (16.1 ± 0.51 (n = 6) vs. 14.7 ± 0.32 ms (n = 4), p < 0.05). Conduction velocity was slowed in FFFRs vs. controls (0.62 ± 0.02 (n = 13) vs. 0.79 ± 0.06 m/s (n = 11), p < 0.05) and Langendorff perfused FFFR hearts were more prone to ventricular fibrillation during reperfusion following ischemia (p < 0.05). The patch-clamp studies revealed no changes in Na(+) or K(+) currents, cell capacitance or gap junctional coupling. Cx43 expression was also unaltered in FFFRs, but immunofluorescence demonstrated an increased fraction of Cx43 localized at the intercalated discs in FFFRs compared to controls (78 ± 3.3 (n = 5) vs. 60 ± 4.2 % (n = 6), p < 0.01). No fibrosis was detected but FFFRs showed a significant increase in cardiac triglyceride content (1.93 ± 0.19 (n = 12) vs. 0.77 ± 0.13 nmol/mg (n = 12), p < 0.0001).CONCLUSION: Six weeks on a high fructose-fat diet cause electrophysiological changes, which leads to QRS prolongation, decreased conduction velocity and increased arrhythmogenesis during reperfusion. These alterations are not explained by altered gap junctional coupling, Na(+), or K(+) currents, differences in cell size or fibrosis.

U2 - 10.1186/s12933-015-0246-8

DO - 10.1186/s12933-015-0246-8

M3 - Journal article

VL - 14

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

SN - 1475-2840

M1 - 87

ER -

ID: 142171196