Effects of KATP channel openers diazoxide and pinacidil in coronary-perfused atria and ventricles from failing and non-failing human hearts
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This study compared the effects of ATP-regulated potassium channel (K(ATP)) openers, diazoxide and pinacidil, on diseased and normal human atria and ventricles. We optically mapped the endocardium of coronary-perfused right (n=11) or left (n=2) posterior atrial-ventricular free wall preparations from human hearts with congestive heart failure (CHF, n=8) and non-failing human hearts without (NF, n=3) or with (INF, n=2) infarction. We also analyzed the mRNA expression of the K(ATP) targets K(ir)6.1, K(ir)6.2, SUR1, and SUR2 in the left atria and ventricles of NF (n=8) and CHF (n=4) hearts. In both CHF and INF hearts, diazoxide significantly decreased action potential durations (APDs) in atria (by -21±3% and -27±13%, p<0.01) and ventricles (by -28±7% and -28±4%, p<0.01). Diazoxide did not change APD (0±5%) in NF atria. Pinacidil significantly decreased APDs in both atria (-46 to -80%, p<0.01) and ventricles (-65 to -93%, p<0.01) in all hearts studied. The effect of pinacidil on APD was significantly higher than that of diazoxide in both atria and ventricles of all groups (p<0.05). During pinacidil perfusion, burst pacing induced flutter/fibrillation in all atrial and ventricular preparations with dominant frequencies of 14.4±6.1 Hz and 17.5±5.1 Hz, respectively. Glibenclamide (10 μM) terminated these arrhythmias and restored APDs to control values. Relative mRNA expression levels of K(ATP) targets were correlated to functional observations. Remodeling in response to CHF and/or previous infarct potentiated diazoxide-induced APD shortening. The activation of atrial and ventricular K(ATP) channels enhances arrhythmogenicity, suggesting that such activation may contribute to reentrant arrhythmias in ischemic hearts.
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At the same concentration, diazoxide decreased mouse atria APD but had no effect on human atria APD; in ventricles, it did not affect mouse ventricle APD but slightly decreased human ventricle APD.
“the same concentration of diazoxide decreased mouse atria APD while it had no effect on human atria APD. The opposite was observed in the ventricles; diazoxide did not affect mouse ventricle APD while it slightly decreased human ventricle APD”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Fedorov, et al., 2011
Diazoxide affects action potential duration of atria and ventricles differently in mouse and human.
“diazoxide, an ATP sensitive potassium (KATP) channel opener, affects action potential duration (APD) of atria and ventricles of mouse and humans differently.”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Fedorov, et al., 2011
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Small and large animal models in cardiac contraction research: advantages and disadvantages
Milani-Nejad, N., & Janssen, P. M. L. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.10.007 · Cited by 484 · see citing works
- Authors
- Fedorov, V. V., Glukhov, A. V., Ambrosi, C. M., Kostecki, G., Chang, R., Janks, D., Schuessler, R. B., Moazami, N., Nichols, C. G., & Efimov, I. R.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Efimov, Igor R.
- ORCID
- Venue
- Journal of Molecular and Cellular Cardiology
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 51
- Issue
- 2
- Pages
- 215-225
- ISSN
- 0022-2828 (ISSN-L)
- PMC
- PMC3124600
- OpenAlex
- W2056622908
- Cited by
- 111
- References
- 55
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 1 · 2023: 7 · 2022: 8 · 2021: 3 · 2020: 5 · 2019: 9 · 2018: 9 · 2017: 2 · 2016: 8 · 2015: 9 · 2014: 6 · 2013: 22 · 2012: 10
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Molecular and Cellular Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01 HL95010, R01HL085369, R01HL095010, R01HL114395)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Keywords
- KATP channel openers, diazoxide, pinacidil, congestive heart failure, myocardial infarction, action potential duration, atrial fibrillation, ventricular arrhythmias, glibenclamide, Kir6.1, Kir6.2, SUR1, SUR2, cardiac remodeling, reentrant arrhythmias
- MeSH terms
- Action Potentials, Adolescent, Adult, Arrhythmias, Cardiac, Coronary Vessels, Diazoxide, Female, Gene Expression Regulation, Heart Atria, Heart Failure, Heart Ventricles, Humans, Male, Middle Aged, RNA, Messenger, Vasodilator Agents, Myocardial Ischemia, Pinacidil, KATP Channels, Young Adult
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