Atrial Fibrillation Risk Factors Notes Jorma Jyrkkanen Researcher 2024-05-03

Are mRNA jabs a risk factor?

SITREP

Abstract

Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with severe consequences, including symptoms, hemodynamic instability, increased cardiovascular mortality, and stroke. While other arrhythmias such as torsades de pointes and sinus bradycardia are more typically thought of as drug-induced, AF may also be precipitated by drug therapy, although ascribing causality to drug-associated AF is more difficult than with other drug-induced arrhythmias. Drug-induced AF is more likely to occur in patients with risk factors and comorbidities that commonly coexist with AF, such as advanced age, alcohol consumption, family history of AF, hypertension, thyroid dysfunction, sleep apnea, and heart disease. New-onset AF has been associated with cardiovascular drugs such as adenosine, dobutamine, and milrinone. In addition, medications such as corticosteroids, ondansetron, and antineoplastic agents such as paclitaxel, mitoxantrone, and anthracyclines have been reported to induce AF. Whether bisphosphonate drugs are associated with new onset AF remains controversial and requires further study. The potential contribution of specific drug therapy should be considered when patients present with new onset AF.

http://Kaakeh Y, Overholser BR, Lopshire JC, Tisdale JE. Drug-induced atrial fibrillation. Drugs. 2012 Aug 20;72(12):1617-30. doi: 10.2165/11633140-000000000-00000. PMID: 22834678; PMCID: PMC5531271.

Abstract

Cancer therapy has made major progress in the past several decades, but treatments are often accompanied by significant side effects. Arrhythmias are a widespread complication of some antineoplastic drugs, with atrial fibrillation (AF) being the most often encountered drug-associated arrhythmia. Preexisting AF risk factors are commonly present in cancer patients who develop drug-associated AF, and active cancer itself may cause or promote AF. Although anticancer drugs may induce AF in cancer patients without AF risk factors, it appears that most drug-associated AF develop when cancer drugs add or aggravate precancer-existing and/or cancer-related pro-AF factors/alterations, additively or synergistically producing AF. Abnormalities in intracellular calcium activity seem to be involved in the generation of anticancer drug-induced AF. In cancer survivors with cancer therapy-induced cardiomyopathy, AF often occurs, with most of the arrhythmias likely to develop secondary to the cardiomyopathy. AF may lead to modification or even cessation of cancer therapy. The management of AF in patients with cancer is currently conducted largely based on pragmatic assumptions. This review briefly discusses AF caused by anticancer drugs and the underlying mechanisms.

Abstract

Oxidative stress has been suggested to play a role in the pathogenesis of atrial fibrillation (AF). Indeed, the prevalence of AF increases with age as does oxidative stress. However, the mechanisms linking redox state to AF are not well understood. In this study we identify a link between oxidative stress and aberrant intracellular Ca(2+) release via the type 2 ryanodine receptor (RyR2) that promotes AF. We show that RyR2 are oxidized in the atria of patients with chronic AF compared with individuals in sinus rhythm. To dissect the molecular mechanism linking RyR2 oxidation to AF we used two murine models harboring RyR2 mutations that cause intracellular Ca(2+) leak. Mice with intracellular Ca(2+) leak exhibited increased atrial RyR2 oxidation, mitochondrial dysfunction, reactive oxygen species (ROS) production and AF susceptibility. Both genetic inhibition of mitochondrial ROS production and pharmacological treatment of RyR2 leakage prevented AF. Collectively, our results indicate that alterations of RyR2 and mitochondrial ROS generation form a vicious cycle in the development of AF. Targeting this previously unrecognized mechanism could be useful in developing effective interventions to prevent and treat AF.

http://Xie W, Santulli G, Reiken SR, Yuan Q, Osborne BW, Chen BX, Marks AR. Mitochondrial oxidative stress promotes atrial fibrillation. Sci Rep. 2015 Jul 14;5:11427. doi: 10.1038/srep11427. PMID: 26169582; PMCID: PMC4501003.

Moreover, accumulating evidence suggests that oxidative stress coupled with the cytokine storm contribute to COVID-19 pathogenesis and immunopathogenesis by causing endotheliitis and endothelial cell dysfunction and by activating the blood clotting cascade that results in blood coagulation and microvascular thrombosis

Alam MS, Czajkowsky DM. SARS-CoV-2 infection and oxidative stress: Pathophysiological insight into thrombosis and therapeutic opportunities. Cytokine Growth Factor Rev. 2022 Feb;63:44-57. doi: 10.1016/j.cytogfr.2021.11.001. Epub 2021 Nov 15. PMID: 34836751; PMCID: PMC8591899.

Uversky VN, Redwan EM, Makis W, Rubio-Casillas A. IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein. Vaccines (Basel). 2023 May 17;11(5):991. doi: 10.3390/vaccines11050991. PMID: 37243095; PMCID: PMC10222767.

https://twitter.com/i/status/1674789371810312195

What leaps out at me is the link between oxidative stress and atrial fibrillation. It has been of found that damage to mitochondria can be caused by spike and this can induce oxidative stress ergo potentially AFib. Repeated vaccination may induce autoimmune mycarditis. The inflammatory cascade induces fibrotic changes in the myocardium, an arrhythmogenic process that stimulates further inflammation. I have seen slides of mitochondrial damage induced by spike protein. Mitochondrial damage has been linked to heart disease and immune dysfunction.

SYNOPSIS

Impacts of Antibiotics on Heart Diseases

Jorma Jyrkkanen, 2021-03-19, jjyrkkanen76@outlook.com ph: 1-250-859-5330

Background

After reviewing the work of Sameer Calghatgi et al 2013 it became clear to me that the antibiotic production of ROS and Lipid Peroxide were the byproducts of antibiotics on mitochondria with potential CARDIOLOGY outcomes. From only a preliminary cursory examination of a few of the thousands of genes involved in heart function that are potentially impacted by ROS and LP I found the following potential routes for their impacts on heart and coronary artery diseases which need detailed and close examination with each and every antibiotic in use. I based the cardiology impacts on predictions arising from this work. https://www.heighpubs.org/jccm/pdf/jccm-aid1104.pdf

1. Oxidative damage to DNA, membranes, lipids and proteins, alteration of gene expression

2. Lipid Peroxide

3. Rupture of mitochondria

4. Mutations in mitochondrial proteins and peptides

5. Mutation of heart function genes and probable epigenetic alteration of genes

6. Loss or damage to mitochondria integrity and reproduction essential for heart energy supply

7. Dysbiosis linked issues of pathogenic substances and signalling

8. Inflammation and athersclerosis

9. Damage associated molecular pattern molecules (DAMPs) that are released during condition of oxidative stress.

10. Redox stress leading to release of DAMPs triggering TLR4-mediated inflammation and organ injury.

11. Cardiovascular diseases associated with increases in IL-6, such as atherosclerosis and hypertension, are also associated with oxidative stress, particularly increases in vascular superoxide, suggesting a potential relationship between superoxide, IL-6 and arterial pressure.

12. Interleukin-6 (IL-6) has been emphasized by reports of elevated circulating as well as intracardiac IL-6 levels in patients with congestive heart failure (CHF). IL-6 may contribute to the progression of myocardial damage and dysfunction in chronic heart failure syndrome resulting from different causes

13. ROS at low concentrations have important functions in regulating pathways such as TNFR1 signaling, but high ROS concentrations ultimately lead to DNA damage and cell death. TNF modulates both cardiac contractility and peripheral resistance, the two most important haemodynamic determinants of cardiac function

14. DNA Damage Response/TP53 Pathway Is Activated and Contributes to the Pathogenesis of Dilated Cardiomyopathy Associated With LMNA (Lamin A/C) Mutations

15. Increased ROS generation and reduction in ATP level, contributing to ATP-producing disorders and oxidative stress, which may further accelerate development or vulnerability of atherosclerosis and myocardial ischemic injury

16. Dysregulated ROS production and oxidative stress have been implicated in a host of cardiac diseases, including cardiac hypertrophy, heart failure (HF), cardiac ischemia–reperfusion injury (IRI), and diabetic cardiomyopathy

17. HNE a breakdown product of LP can trigger cardiovascular pathology by inflammation. LP linked to atherogenesis.

18. Dysbiosis triggers immune depression opening door to pathogenic viruses, bacteria, microbial toxins which may also pose a risk to neurological intereference in vagal nerve signalling.

19. Depression of TP53 TSG function affects OP and ATP, antioxidant regulation and stability, programmed senescence

20. Epigenetic effects on cardiology important genes undetermined. Ex; Silencing, turning on when not supposed to, over expression

Reference

Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells

By Sameer Kalghatgi, Catherine S. Spina, James C. Costello, Marc Liesa, J. Ruben Morones-Ramirez, Shimyn Slomovic, Anthony Molina, Orian S. Shirihai, James J. Collins. Science Translational Medicine03 Jul 2013 : 192ra85. Mitochondrial dysfunction and oxidative damage induced by bactericidal antibiotics in mammalian cells may be alleviated by an antioxidant or prevented by preferential use of bacteriostatic antibiotics.

 

A hypothesis on the mechanism of antibiotic carcinogenesis. 11 March 2019