Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Jun 12;21(12):4200.
doi: 10.3390/ijms21124200.

Role of Oxidative Stress in the Genesis of Ventricular Arrhythmias

Adriana Adameova  1 , Anureet K Shah  2 , Naranjan S Dhalla  3
Affiliations
Review

Role of Oxidative Stress in the Genesis of Ventricular Arrhythmias

Adriana Adameova et al. Int J Mol Sci. .

Abstract

Ventricular arrhythmias, mainly lethal arrhythmias, such as ventricular tachycardia and fibrillation, may lead to sudden cardiac death. These are triggered as a result of cardiac injury due to chronic ischemia, acute myocardial infarction and various stressful conditions associated with increased levels of circulating catecholamines and angiotensin II. Several mechanisms have been proposed to underlie electrical instability of the heart promoting ventricular arrhythmias; however, oxidative stress which adversely affects ion homeostasis due to changes in the ion channel structure and function, seems to play a critical role in eliciting different types of ventricular arrhythmias. Prevention or mitigation of the severity of ventricular arrhythmias due to antioxidants has been indicated as the fundamental contribution in the field of preventive cardiology; however, novel interventions have to be developed for greater effectiveness and specificity in attenuating the adverse effects of oxidative stress. In this review, we have attempted to discuss proarrhythmic effects of oxidative stress differing in time and concentration dependence and highlight a molecular and cellular concept how it alters cardiac cell automaticity and conduction velocity sensitizing the probability of ventricular arrhythmias with resultant sudden cardiac death due to ischemic heart disease and other stressful situations. It is concluded that pharmacological approaches targeting multiple mechanisms besides oxidative stress might be more effective in the treatment of ventricular arrhythmias than current antiarrhythmic therapy.

Keywords: angiotensin II; antioxidant therapy; catecholamines; ischemia-reperfusion injury; myocardial infarction; sudden cardiac death; ventricular arrhythmias.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Stress-promoted alterations in ion homeostasis of cardiac cells inducing a further production of reactive oxygen species, thereby highlighting the probability of ventricular arrhythmias as a result of such viscous cycle.
Figure 2
Figure 2
Events depicting the role of mitochondrial defects, reactive oxygen species (ROS)-released ROS and mitochondrial and sarcolemmal KATP channels in the generation of ventricular arrhythmias. ROS—reactive oxygen species; sarcKATP—sarcolemmal KATP channels and mitoKATP—mitochondrial KATP channels.
Figure 3
Figure 3
A scheme showing the role of high circulating levels of both angiotensin II and catecholamines in the generation of oxidative stress and subsequent events leading to the development of ventricular arrhythmias associated with acute myocardial infarction.
See this image and copyright information in PMC

References

    1. Silvia P.G., Blomström-Lundqvist C., Mazzanti† A., Blom N., Borggrefe M., Camm J., Elliott P.M., Fitzsimons D., Hatala R., Hindricks G., et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC) Eur. Hear. J. 2015;36:2793–2867. doi: 10.1093/eurheartj/ehv316. - DOI - PubMed
    1. Kirchhof P., Benussi S., Kotecha D., Ahlsson A., Atar D., Casadei B., Castellà M., Diener H.-C., Heidbuchel H., Hendriks J., et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. Hear. J. 2016;37:2893–2962. doi: 10.1093/eurheartj/ehw210. - DOI
    1. Al-Khatib S.M., Stevenson W.G., Ackerman M.J., Bryant W.J., Callans D.J., Curtis A.B., Deal B.J., Dickfeld T., Field M.E., Fonarow G.C., et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. Circulation. 2018;138:e272–e391. - PubMed
    1. January C.T., Wann L.S., Calkins H., Chen L.Y., Cigarroa J.E., Cleveland J.C., Ellinor P.T., Ezekowitz M.D., Field M.E., Furie K.L., et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation. 2019;140:e125–e151. doi: 10.1161/cir.0000000000000665. - DOI - PubMed
    1. Dhalla N.S., Elmoselhi A.B., Hata T., Makino N. Status of myocardial antioxidants in ischemia-reperfusion injury. Cardiovasc. Res. 2000;47:446–456. doi: 10.1016/S0008-6363(00)00078-X. - DOI - PubMed

MeSH terms