MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Protektivní faktory a podpůrné možnosti

Apocynin

  • As an antioxidant, could pre-emptively prevent ROS formation and markedly block the induction and duration of AF
    • By regulating the expression of oxidative stress-related proteins
    • By inhibiting the increased Ca2+ release in sarcoplasmic reticulum to attenuate atrial electrical remodeling
  • edepot.wur.nl/545957






Arnebiae Radix

  • Prevents atrial fibrillation in rats
    • By ameliorating atrial remodeling and cardiac function
Qian Zhou 1, Bin Chen 2, Xiaodong Chen 1, Yue Wang 1, Jiawen Ji 1, Murat Kizaibek 3, Xindong Wang 1, Lixing Wu 1, Zhengli Hu 1, Xin Gao 1, Na Wu 1, Dan Huang 1, Xiaojin Xu 1, Wuguang Lu 1, Xueting Cai 1, Yang Yang 1, Juan Ye 1, Qingyun Wei 1, Jianping Shen 4, Peng Cao 5
PMID: 31629862 DOI: 10.1016/j.jep.2019.112317

Rats: acetylcholine (Ach) + CaCl2 used to induce atrial fibrillation

  • Arnebiae Radix on Ach-CaCl2 induced AF X amiodarone
  • Arnebiae Radix (0.18 g/mL) one week before or concurrently with the establishment of the AF model
  • At the end of the experimental period, the induction, duration and timing of AF were monitored using electrocardiogram recordings.
  • Arnebiae Radix decreased
    • AF induction,
    • Duration and susceptibility to AF
    • Atrial fibrosis
    • Inhibited atrial enlargement induced by Ach-CaCl2
  • There was an apparent improvement in cardiac function in the Arnebiae Radix-treated group.
  • Our findings indicate that Arnebiae Radix treatment can
    • Attenuate Ach-CaCl2-induced atrial injury
    • Serve as an effective therapeutic strategy for the treatment of AF in the future.
  • pubmed.ncbi.nlm.nih.gov/31629862/

Canagliflozin


Dapagliflozin

  • A reduced burden of ventricular arrhythmias following ischemia-reperfusion
    • Could also be observed in rats treated with dapagliflozin
  • Suppress prolonged ventricular repolarization in rats with metabolic syndrome induced by a high carbohydrate diet
    • Animals were all non-diabetic
  • Dapagliflozin treatment
    • Reduce epicardial fat volume in human patients with diabetes mellitus
    • Framingham Heart Study, epicardial fat volume is directly associated with prevalent atrial fibrillation via adipokines
  • Dapagliflozin in patients with diabetes for 6 months resulted in significantly decreased:
    • P-wave dispersion,
    • P-wave variation changes,
      • Higher values of these P-wave indices are considered to be risk factors for atrial fibrillation
    • Epicardial fat volume compared to the control group
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC8835896/
  • Dapagliflozin reduced inflammation
    • By attenuation of NOD-like receptor 3 (NLRP3),IL-1b, IL-6
      • Through the activation of AMP-activated protein kinase (AMPK) pathways
  • Ability to activate the mTOR pathway
    • Slowing the progression of dilated cardiomyopathy (DCM) as a result

Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure Trial (DAPA-HF trial)

  • (ClinicalTrials.gov number, NCT03036124)
  • Treatment with dapagliflozin definitively reduced the risk of precipitated HF or death from cardiovascular causes in patients with HF.
  • A risk association for AF was observed in the study of Shao et al. between dapagliflozin and empagliflozin
  • www.frontiersin.org/articles/10.3389/fcvm.2022.1011429/full



Empagliflozin

  • Treatment significantly ameliorates sotalol-induced prolongation of the QTc interval
  • In an ex vivo model of global ischemia-reperfusion
    • Empagliflozin reduced ventricular arrhythmia vulnerability in rabbit hearts via SGLT2-independent mechanisms
  • Experimental series in male Sprague Dawley rats
    • Empagliflozin pretreatment could completely avoid the occurrence of lethal ventricular arrhythmias
      • After ligation of the left main coronary artery for five minutes followed by a reperfusion of 20 min
    • Control group, 69% of all rats died due to ventricular tachycardia
  • An inhibitor of the ERK1/2 pathway
    • Abolished the effect of empagliflozin
      • Pathway a potential downstream target
  • Empagliflozin seems to target the epicardial fat tissue as well
    • Adipocytes located in the epicardial region secrete adipokines
      • Exert effects on the expression levels of ion channels in cardiomyocytes
    • Mice with metabolic syndrome -adipokines induced:
      • A decrease in the expression level of potassium channels
      • Increase in the expression levels of calcium channels
    • Empagliflozin pretreatment could attenuate this effect in mice with metabolic syndrome
      • Reducing the risk of arrhythmias due to a disturbed ion homeostasis
  • Mice with induced diabetes were treated with empagliflozin or placebo
    • Empagliflozin successfully ameliorated atrial structural and electrical remodeling expressed by
      • Reduced left atrial diameter,
      • Reduced interstitial fibrosis,
      • Reduced incidence of atrial fibrillation
    • Broad analysis of potentially involved proteins depicted a PGC-1a/NRF-1/Tfam pathway causing these beneficial effects
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC8835896/
  • Empagliflozin could reverse 59% of all known protein alterations in heart failure with preserved ejection fraction (HFpEF)
    • With a predominance of the effect via the sodium hydrogen antiporter 1 (NHE1) receptor
  • Impact on
    • Oxidative stress modulation
    • Myocardial stiffness,
    • Myocardial extracellular matrix remodeling
    • Systemic inflammation
  • Involves
    • Upregulations of the JAK/STAT3
    • The ERK 1/2
    • CGCH1-BH4/NO
    • B-cell lymphoma 2 gene
    • AMPK pathways
  • A modification of adipokines from epicardial fat may play a role as well
  • Improvement of the myocardial function will likely prevent the development of ventricular arrhythmias in the long term
  • PGC-1a/NRF-1/Tfam pathway
  • Modifications of the sodium-calcium exchanger (NCX) protein after SGLT2 inhibitor treatment
  • Multifactorial mechanism of action seems currently the most obvious explanation
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC8835896/
  • Empagliflozin in mice
    • Protective effect on diastolic function
    • Protective on cardiac hypertrophy
  • Rat model with DM
    • Empagliflozin attenuated cardiac inflammation
      • By activating AMPK signaling pathway
      • Promoting autophagy in cardiomyocytes
  • Empagliflozin ameliorated LV diastolic function in a DCM model
    • By suppressing calcium/calmodulin-dependent protein kinase II (CaMKII) Thr286,
      • A protein kinase which can retard the phosphorylation of ryanodine receptors
  • Diabetic mouse model, empagliflozin
    • Stimulated sarcoplasmic ATPase2a (SERCA2a) function
      • Thus enabling the Ca2 + homeostasis required to improve diastolic function

Matrine

  • Could prevent atrial fibrillation (AF) after myocardial infarction
    • By reducing left atrial fibrosis,
  • Five weeks after MI, matrine-treated rats
    • Had lower rates of AF inducibility
    • Shorter AF duration than MI rats
  • Matrine improved the left atrial conduction velocity and homogeneity.
  • Matrine decreased the fibrosis positive areas and the protein levels of type I collagen and type III collagen in the left atrium.
  • Matrine inhibited CFs differentiation to myofibroblasts and the expression of transforming growth factor-beta 1 and matrix metalloproteinase 9
  • In vitro,
    • Matrine inhibited the CFs proliferation, migration, differentiation, and secretion ability.
  • Matrine has the potential to reduce susceptibility to AF after MI due, at least in part, to reduced atrial fibrosis via inhibiting CFs proliferation, migration, differentiation, and secretion ability.
  • pubmed.ncbi.nlm.nih.gov/29377366/

Melatonin

  • As an antioxidant, melatonin can directly carry out its oxidationresisted capacity via protecting Tom70, a mitochondrial translocase, which is considered
as a repressor of oxidative stress [204]. On the other hand, melatonin is also involved inthe c-Jun N-terminal kinase pathway, downregulating c-Jun N-terminal kinase expression,thus lowering the stimulation of oxidative stress [205]. Collectively, these antioxidants willenable potentially therapeutic treatments for IRI and related complications by targeting

MitoTEMPO



NAD ribosid

  • The HF-AF ENERGY Trial: Nicotinamide Riboside for the Treatment of Atrial Fibrillation in Heart Failure Patients
  • Lisa Pool, Paul Knops, Olivier C. Manintveld, Jasper J. Brugts, Dominic A. M. J. Theuns, Bianca J. J. M. Brundel, Natasja M. S. de Groot
  • nicotinamide-riboside-for-the-treatment-of">researchinformation.amsterdamumc.org/en/publications/the-hf-af-energy-trial-nicotinamide-riboside-for-the-treatment-of


ABT-888, Olaparib and nicotinamide (NAM) - PARP1 inhibition

  • AF was associated with excessive PARP1
  • Activation precipitated by oxidative DNA damage
  • Activated PARP1 in turn consumed NAD+
    • Resulting in contractile dysfunction in tachypaced cardiomyocytes and persistent AF patients
  • This uncovered PARP1 as a potential oxidative DNA damage and repair mechanism-based therapeutic target for preventing AF.
  • It was revealed that pharmacological PARP1 inhibitors, including ABT-888, Olaparib and nicotinamide (NAM)
    • Counteracted NAD+ depletion
    • Precluded oxidative DNA damage
    • Preserved atrial contractile dysfunction in experimental AF
  • Potential of therapeutic targeting of the oxidative DNA damage-induced PARP1 activation pathway in clinical AF.
  • edepot.wur.nl/545957


Pinocembrin (5,7-dihydroxyflavanone)

  • Reduces cardiac arrhythmia and infarct size in rats subjected to acute myocardial ischemia/reperfusion
  • Flavonoid found in propolis
  • In rhizomes of fingerroot (Boesenbergia pandurata)
    • Antimicrobial, antioxidant, and anti-inflammatory

Kardioprotective effects of pinocembrin in an I/R Male Wistar rats (n = 20)

  • 2 groups to receive either pinocembrin (30 mg/kg body weight) or the vehicle intravenously
  • Thirty minutes later, the left anterior descending coronary artery of each rat was ligated for 30 min, and then reperfusion was allowed for 120 min.
  • Cardiac function improved in the pinocembrin-treated group
    • The time to first ventricular fibrillation (VF) was significantly longer in the treated group (550 ± 54 s) than in the vehicle-only control group (330 ± 27 s) (p < 0.05).
    • VF incidence and arrhythmia score were lower
    • Infarcts were 49% smaller in the pinocembrin-treated group
  • Pinocembrin exhibited cardioprotective effects during I/R
    • Evidenced by improved cardiac function,
    • Fewer arrhythmias,
    • Smaller infarcts in treated hearts than in controls
  • Pinocembrin’s antiapoptotic and anti-oxidative stress effects
  • Increase the phosphorylation of Cx43 in ischemic myocardium.
  • cdnsciencepub.com/doi/abs/10.1139/apnm-2015-0108
  • Pinocembrin enriched fraction of Elytranthe parasitica (L.) Danser
    • Induces apoptosis in HCT 116 colorectal cancer cells.
    • Chemical profiling, in vitro antibacterial, and cytotoxic properties of Elytranthe parasitica (L.) Danser – A hemiparasitic Indian mistletoe
  • Pinocembrin Inhibits the Proliferation and Metastasis of Breast Cancer via Suppression of the PI3K/AKT Signaling Pathway

Polyphenols


Quercetin (Que)

  • Used to treat cardiovascular diseases such as arrhythmias

Study - action of Que in AF

  • Using network pharmacology and molecular docking
  • Top targets were IL6, VEGFA, JUN, MMP9 and EGFR
  • And Que for AF treatment might involve the role of
    • AGE-RAGE signaling pathway in diabetic complications
    • MAPK signaling pathway
    • IL-17 signaling pathway
  • Molecular docking showed that Que binds strongly to key targets
    • Is differentially expressed in AF

In vivo results

  • Que significantly reduced the duration of AF fibrillation
  • Improved atrial remodeling,
  • Reduced p-MAPK protein expression,
  • Inhibited the progression of AF
  • Combining network pharmacology and molecular docking approaches with in vivo studies
    • Advance our understanding of the intensive mechanisms of Quercetin,
    • Provide the targeted basis for clinical Atrial fibrillation treatment.
  • pubmed.ncbi.nlm.nih.gov/35697725/

Resveratrol

  • May effectively treat AF and ventricular arrhythmias caused by ischaemia–reperfusion injury.
  • It reduces the mortality associated with life-threatening ventricular arrhythmias
  • Can be used to prevent myocardial remodelling.
  • www.mdpi.com/2076-3921/11/6/1109

Rhodiola

  • Inhibits Atrial Arrhythmogenesis in a Heart Failure Model
Shuen-Hsin Liu 1, Ya-Wen Hsiao 2, Eric Chong 3, Rahul Singhal 4, Man-Cai Fong 5, Yung-Nan Tsai 2 6, Chiao-Po Hsu 6 7, Yao-Chang Chen 8, Yi-Jen Chen 9 10, Chuen-Wang Chiou 2 6, Shuo-Ju Chiang 11, Shih-Lin Chang 12 13, Shih-Ann Chen 2 6
PMID: 27255210 DOI: 10.1111/jce.13026
  • Rhodiola, a popular plant in Tibet
  • Has been proven to decrease arrhythmia

3 groups of rabbits

  • 1 - control,
  • 2 - rabbits with HF created by coronary ligation + 2 weeks of water as a placebo (n = 5)
  • 3 - rabbits with HF + 2 weeks of a rhodiola 270 mg/kg/day treatment orally (n = 5)
  • Rhodiola group had
    • Attenuated atrial fibrosis (35.4 ± 17.4% vs. 16.9 ± 8.4%, P = 0.05)
    • Improved left ventricular (LV) ejection fraction (51.6 ± 3.4% vs. 68.0 ± 0.5%, P = 0.001)
    • Shorter ERP (85.3 ± 6.8 vs. 94.3 ± 1.2, P = 0.002), APD90 (89.3 ± 1.5 vs. 112.7 ± 0.7, P < 0.001) in the left atrium (LA)
    • Decreased AF inducibility (0.90 ± 0.04 vs. 0.42 ± 0.04, P < 0.001)
  • Compared with the HF group
  • MRNA expressions of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, and SERCA2a in the HF LA were up-regulated after rhodiola treatment.
  • The rhodiola-treated HF LA demonstrated higher mRNA expression of PI3K-AKT compared with the HF group.
  • Rhodiola
    • Reversed LA electrical remodeling,
    • Attenuated atrial fibrosis
    • Suppressed AF in rabbits with HF.
  • The beneficial electrophysiological effect of rhodiola may be related to
    • Upregulation of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, SERCA2a,
    • Activation of PI3K/AKT signaling
  • pubmed.ncbi.nlm.nih.gov/27255210/

  • Rhodiola rosea
  • Is a kind of traditional Chinese medicine
  • Antimyocardial ischemia-reperfusion injury, lowering blood fat, antithrombosis, and antiarrhythmia
  • Article reviews the research on the pharmacological effects of Rhodiola rosea on cardiovascular diseases
  • References for the clinical treatment of cardiovascular diseases.
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC8898776/

Rikkunshito

  • Prevents angiotensin II-Induced atrial fibrosis and fibrillation
Yinge Zhan 1, Ichitaro Abe 2, Mikiko Nakagawa 3, Yumi Ishii 4, Shintaro Kira 4, Miho Miyoshi 4, Takahiro Oniki 4, Hidekazu Kondo 4, Yasushi Teshima 4, Kunio Yufu 4, Motoki Arakane 5, Tsutomu Daa 5, Naohiko Takahashi 4
PMID: 32682626 DOI: 10.1016/j.jjcc.2020.07.001
  • Rikkunshito (RKT), a traditional herbal medicine
  • Anti-inflammatory, anti-apoptotic, and anti-fibrotic effects in several organs

Eight-week-old male C57BL/6 mice

  • Infused with either vehicle or AngII (2.0 mg/kg/day) for 2 weeks
  • Water or RKT at a dose of 1000 mg/kg/day were orally administered once daily for 2 weeks
  • AF was induced either by transesophageal burst pacing in vivo or by burst/extrastimuli in isolated perfused hearts using a Langendorff apparatus.
  • RKT at a dose of 1000 mg/kg/day for 2 weeks
    • Attenuated atrial interstitial fibrosis and profibrotic and proinflammatory signals induced by continuous infusion of AngII
  • RKT attenuated AngII-induced enhanced vulnerability to AF in in vivo experiments and in isolated perfused hearts
  • Atractylodin
    • An active component of RKT
    • Exhibited antifibrotic activity comparable to that of RKT
  • RKT reversed AngII-induced suppression of sirtuin 1 (Sirt1) translocation to the nuclei
  • RKT suppressed
    • AngII-induced phosphorylation of I?B
    • Overexpression of p53
    • Cellular apoptotic signals and apoptosis
  • All of the antagonizing effects of RKT against AngII were attenuated by
    • A concomitant treatment with a growth hormone secretagogue receptor (GHSR)-inhibitor.
  • RKT prevented atrial fibrosis and attenuated enhanced vulnerability to AF induced by AngII.
  • The results also suggested that potentiating the GHSR-Sirt1 pathway is involved in these processes.
  • pubmed.ncbi.nlm.nih.gov/32682626/

SGLT2 inhibitors

  • Impact on mitochondrial dysfunction in atrial remodeling
    • Independent of the presence of diabetes
    • Mitochondria-protective effects of SGLT2 inhibitors could thus provide benefits in patients with and without diabetes

Analysis of the large FDA adverse event reporting system

  • 700,000+ adverse events revealed a lower incidence of atrial fibrillation in diabetic patients treated with SGLT2 inhibitors
    • Compared to other glucose-lowering drugs
    • After excluding reports on used antiarrhythmic drugs, renal disease and/or other cardiovascular disease
  • Robust antiarrhythmic effect

Meta-analysis including all clinical trials that investigated SGLT2 inhibitors until December 2020

  • Reports a significant reduction of the incidence of atrial arrhythmias
  • Overall prevalence of approximately 1% of the study population

Pooled analysis of 31 randomized clinical trials including more than 75,000 patients

  • SGLT2 inhibitor use is associated with a lower incidence and recurrence of atrial fibrillation
  • With a reduced rate of cardiovascular outcomes
  • Could not be retraced in another meta-analysis dealing with a similar yet older database based on reported trial data until October 2019

Post hoc analysis from the DECLARE-TIMI 58

  • Incidence of the first episode and total episodes of atrial arrhythmias in 17,160 patients
    • With type 2 diabetes
    • Treated with dapagliflozin or placebo
  • Dapagliflozin decreased the incidence of atrial arrhythmias with RR of 19%
    • Independent of a prior known atrial arrhythmia
  • Absolute number of 589 events (= 3.4% in relation to the total study population)
    • Over an observation period of 4 years seems pretty low

Taiwanese multi-center healthcare provider reports

  • Lower incidence rate of atrial fibrillation after SGLT2 inhibitor treatment
    • Compared to dipeptidyl peptidase 4 (DPP4) inhibitor treatment
  • In more than 25,000 patients
  • Study design was retrospective and must be interpreted with caution
  • Nearly all clinical trials dealing with antidiabetic medications do not routinely report atrial arrhythmias in their primary analysis
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC8835896/
  • Focus on the role of SGLT2 inhibitors in Na+ and Ca2 + homeostasis
    • Transients of Na+ and Ca2 +
  • Protective role of SGLT2 inhibitors in
    • Structural remodeling from the perspective of fibrosis,
    • Inflammation, oxidative stress, and apoptosis.
  • SGLT2 inhibitors have significant benefits on cardiovascular diseases such as HF, myocardial hypertrophy and myocardial infarction
    • Can be expected that SGLT2 inhibitors can reduce the risk of arrhythmia
  • www.frontiersin.org/articles/10.3389/fcvm.2022.1011429/full

SGLT2 inhibitor - Inhibition of NHE-1 by

  • Might restore the Ca2+ and Na+ homeostasis within atrial cardiomyocytes
  • Attenuate the triggered activity induced by Ca2+ or Na+ overload
  • Normalize the inflammasome activity
    • Attenuating the atrial arrhythmogenicity
  • SGLT2-independent activation of adenosine monophosphate kinase (AMPK)
    • By increasing the phosphorylation of AMPK (p-APMK)
    • By dapagliflozin have been described in vitro
    • P-AMPK improves the metabolic function of the mitochondria
      • Attenuates mitochondrial dysfunction during atrial fibrillation

Sestrins

  • Are stress-related proteins, accumulate when cells are exposed to detrimental environments, such as hypoxia, oxidative stress and DNA damage
  • The upregulation of sestrins against ROS accumulation and Ca2+ overload
    • Was revealed for the first time by Dong et al. to protect atria against oxidative damage and fibrosis in both experimental and clinical AF
  • Although the physiological mechanisms of sestrin function still remain poorly understood, this type of antioxidant may have potential as an endogenous protective target in clinical management of AF.
  • edepot.wur.nl/545957

Sotagliflozin

  • SGLT1/SGLT2 inhibitor
  • Counteracted left atrial enlargement in vivo
  • Reduced spontaneous calcium release events in vitro
    • Typically observed in conditions of atrial fibrillation

Statins



Taurine and l-arginine

  • Deficiencies in people with very frequent arrhythmias

10-20g taurine per day

  • Reduced PACs by 50%
  • Prevented all PVCs
  • But did not prevent pauses

Adding 4-6g of l-arginine

  • Immediately terminated essentially all remaining pauses and PACs
  • Maintaining normal cardiac rhythm with continued treatment

Taurine

  • Effects of taurine useful in preventing arrhythmias include
    • Regulating potassium, calcium and sodium levels in the blood and tissues
    • Regulating excitability of the myocardium,
    • Protecting against free radicals damage
  • Taurine
    • Restored energy and endurance in one of the cases from a debilitated status to normal
  • Arrhythmias may also respond to taurine
    • Because it dampens activity of the sympathetic nervous system
    • Dampens epinephrine release

L-arginine

  • May have anti-arrhythmic properties
  • Resulting from its role as a nitric oxide (NO) precursor
    • From its ability to restore sinus rhythm spontaneously
  • Endogenous production of taurine and l-arginine
    • May decline in aging perturbing cardiac rhythm
    • These "conditional" essential nutrients therefore become "essential"
  • Hypothesized to prevent cardiac arrhythmias by NO stabilization of the sinus node
  • pubmed.ncbi.nlm.nih.gov/16797868/

Taurine

  • Prevents the Electrical Remodeling in Ach-CaCl2 Induced Atrial Fibrillation in Rats
Qunhui Yang # 1, Qiufeng Lv 1, Man Feng 1, Mei Liu 1, Ying Feng 1, Shumei Lin # 1, Jiancheng Yang 1, Jianmin Hu 2
PMID: 28849502 DOI: 10.1007/978-94-024-1079-2_64

Male Wistar rats

  • Injected with the mixture of acetylcholine (Ach) (66 µg/mL)-CaCl2 (10 mg/mL) (i.v.) for 7 days to establish AF model
  • Taurine was administered in drinking water 1 week before or at the same time of AF model establishment
  • The duration of AF was monitored by recording ECG of rats during the model establishment.
  • Taurine administration
    • Effectively shortened the AF duration of rats
    • Prolonged atrial ERP than the model and taurine depleted rats
    • Atrial K+ level in taurine treated groups was significantly reduced nearly to the normal level
    • MRNA expression levels of Kir3.4 and Kv1.5 were significantly increased in the taurine preventive treated groups.
  • Conclusions:
    • Taurine can prevent the atrial electrical remodeling
    • Decrease the duration of AF in rats
      • By reducing the atrial K+ concentration
      • Up-regulating mRNA expression levels of Kir3.4 and Kv1.5.
  • pubmed.ncbi.nlm.nih.gov/28849502/

Forms of B3 vitamin

Nicotinic acid (NA), NAM, nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN)

  • NA, NMN, or NR as an effective strategy for boosting NAD+ levels in mouse models of
    • Aging
    • , vascular diseases
    • Diabetes
  • High dose NA supplementation can cause side effects, such as flushing
  • High dose NR supplementation has shown effectiveness in some disease models
    • Obesity
    • Diabetic neuropathy
    • Dilated cardiomyopathy
  • edepot.wur.nl/545957

Fekální transplantace

  • Zhang et al. showed that transplantation of young faecal microbiota into AF-susceptible aged rats
    • Led to a reduction in LPS concentration
    • Suppression of NLRP3 activity
    • Decreased atrial fibrosis and AF inducibility
  • Several studies have shown promise towards managing AF risk factors
  • Probiotics rich in Lactobacillus spp. and Bifidobacterium spp.
    • Have been shown to be effective in the management of AF risk factors
      • Atherosclerosis, dyslipidaemia and hypertension
  • Supplementation with SCFAs (propionate)
    • Associated with improved insulin sensitivity and blood pressure control

Reduced blood pressure



Nitric oxide synthase inhibitors


NR

High fat diet

  • A research team from the University of Tsukuba in Japan
  • Article in the International Journal of Molecular Sciences

Mice fed high fat diets to model obesity

  • Nampt levels decreased
  • Atrial fibrillation susceptibility and duration increased significantly

Treatment with nicotinamide riboside (NR)

  • Which can rescue NAD+ levels
  • Partially restored the atrial fibrillation perpetuation in mice fed high fat diets
  • Nampt/NAD+ axis may be a potent therapeutic target for atrial fibrillation.
  • NAD+ and Nampt are found in every cell in your body
  • Levels decrease with aging and obesity
  • Nampt/NAD+ axis
    • Protective roles against aging and obesity-related disorders
    • Diminish in obesity and aging
  • Levels of Nampt were cut in half in atrial tissues in mice fed high fat diets
    • Compared to mice fed normal diets
  • Genetically modified mice with decreased Nampt were fed high fat diets
    • Had even lower levels of Nampt compared to mice fed normal diets in atrial tissues
  • Diet affects the Nampt/NAD+ axis in mouse atria.
  • Mice with decreased levels of Nampt
    • Had increased susceptibility and prolonged duration of atrial fibrillation without significant structural abnormalities in the heart
  • NAD+ precursor NR
    • Increases Nampt amount
    • Decreases atrial fibrillation duration
  • Treatment with NR
    • Restored atrial fibrillation susceptibility and duration in mice fed high fat diets

NR supplementation

  • Significantly increased Nampt and NAD levels in high fat diet fed mice
    • Atrial fibrillation duration …significantly recovered by NR supplementation
  • NR may be a promising therapeutic agent for cardiovascular diseases
    • Including atrial fibrillation
Feng D, Xu D, Murakoshi N, et al. Nicotinamide Phosphoribosyltransferase (Nampt)/Nicotinamide Adenine Dinucleotide (NAD) Axis Suppresses Atrial Fibrillation by Modulating the Calcium Handling Pathway. Int J Mol Sci. 2020;21(13):4655. doi:10.3390/ijms21134655


Vitamins C and E

  • Can reduce the recurrence of atrial fibrillation (AF)
    • After successful electrical cardioversion
    • Protect against AF after cardiac surgery
  • But do not affect the incidence of atrial arrhythmias in critically ill patients with trauma
  • www.mdpi.com/2076-3921/11/6/1109
  • 203 patients with post-operative AF (POAF) in a randomised, double-blind placebo-controlled trial
    • Two days before cardiac surgery
    • 1 g/day of vitamin C,
    • 400 IU/day of vitamin E
    • 2 g/day of n - 3 polyunsaturated fatty acids (PUFAs)
  • As a result, 32% of patients in the placebo group
    • Only 9.7% in the treatment group developed AF
  • The placebo group
    • Had a 3.62 times higher risk of POAF on any day by comparison with supplemented patients
  • 66% reduction in atrial tissue susceptibility to arrhythmia was demonstrated
    • Provided a significant risk reduction of POAF by over 20%
      • By increasing the activity of antioxidant enzymes in the heart
  • Antioxidants can reduce OS in inflammation or cardiac ischaemia after surgery
  • Mirhoseini et al. presented antioxidant supplementation and atrial arrhythmias in critically ill trauma patients
    • Representing a very diverse group
  • AF is the most common arrhythmia and is independently associated with higher mortality in trauma patients
  • Vitamin C—1000 mg orally, per tube or intravenously every 8 h
  • Vitamin E—1000 units orally or per tube every 8 h
  • Selenium—200 mcg orally, per tube or intravenously,
  • Daily for 7 days in total during a two-week hospitalisation or before discharge,
  • No differences were found in the hospital mortality rates
  • Use of antioxidants was associated with a
    • Longer expected survival time
  • Vitamin C
    • Decreases the spontaneous activity of the pulmonary vein
    • Attenuates the arrhythmogenic effects of H2O2 in rabbits
      • Due to the intensification of ectopic beats
      • Related to the increase in Ca2+ release
      • Can be important when performing ablation procedures
  • Meta-analysis of 15 clinical trials with 1738 subjects
  • Reduced POAF (21% vs. 34% in the control group) incidence after coronary artery bypass grafting (CABG) or valve replacement
  • A meta-analysis of 11 randomised controlled trials with 3137 patients
    • N-3 PUFA without antioxidants did not reduce the incidence of POAF compared with the control group
    • Combination therapy with vitamins C and E decreased the incidence of POAF by 68%
  • www.mdpi.com/2076-3921/11/6/1109


Vitamin C (VitC)

Meta-analysis that included a total of 2050 high-risk AF patients from different countries,

  • Administration of VitC on average lowered the incidence of poAF by more than 25%
  • Cases in developing countries showed a much higher efficacy x well-developed countries
    • Possibly due to differences in nutritional status

Another study found an unremarkable benefit

  • Of long term oral VitC administration on prevention of AF
    • Especially for middle-aged and older people
  • Additional dose of VitC, beyond daily requirement, does not provide any additive effect on AF prevention
  • edepot.wur.nl/545957
Takže hlavně nemít deficit


Vitamin C

  • Administration of vitamin C before and after successful electrical cardioversion of AF
    • Reduces early recurrence rates from 36.3% in the control group to only 4.5% in patients who received vitamin C
  • In patients with implanted cardiac resynchronisation therapy defibrillators (CRT-D) or ICDs
    • In order to increase treatment effectiveness
  • www.mdpi.com/2076-3921/11/6/1109


Vitamin E

  • Alpha-tocopherol inhibited the arrhythmogenic effects of CaCl2, vasopressin and epinephrine in rats [36]. It was found that the administration of 50 mg/100 g i.p. vitamin E for five days limits the development of arrhythmias. Animals treated with tocopherol had significantly lower incidence rate of sinus arrhythmia (16.6% vs. 75% in control group), wandering pacemaker (16.6% vs. 58.3%), ventricular extrasystoles (41.6% vs. 100%) and paroxysmal tachycardia (0% vs. 33.3%) [36]. Another experiment showed that rats in the tocopherol group with epinephrine-induced arrhythmia had significantly lower glutathione reductase activity and higher total content of SH-groups [36]. Therefore, vitamin E exerts important antiarrhythmic, antioxidant and cardioprotective effects by inhibiting epinephrine-induced lipid peroxidation. This observation may be of particular importance in patients treated in intensive care units with high doses of catecholamines, or in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT).
  • www.mdpi.com/2076-3921/11/6/1109


Reduced body weight



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Poslední aktualizace: 24. 4. 2024 2:24:47