Botulinum toxin – a new method in long-term prevention of recurring atrial fibrillation

iStock_000055110862_XXXLargeBotulinum toxin (botox, BTX) and bacteria which produce it were identified for the first time in 1897 by Belgian bacteriologist Emile Pierre van Ermenghen [1]. Although many decades have passed since this historical moment, its “hidden” properties are still an unsolved mystery. However, already today it can be said that botulinum toxin is an amazing substance. The best evidence of that are results of research published on 20th October 2015 in American magazine Circulation: Arrhythmia and Electrophysiology. On the basis of conducted randomized study it was shown that in the nearest future botulinum toxin may be used on a large scale in long-term prevention of paroxysmal atrial fibrillation recurrence (PAF), especially in patients after cardiac surgeries [2].


Atrial fibrillation (AF) is the most frequent heart arrhythmia characterized by rapid and irregular activation of atria, leading to loss of their hemodynamic effectiveness. As the latest epidemiological data report, about 85% of patients with AF are over 65 and most of them are males. This disease is a huge problem for contemporary cardiology because of the fact that diagnosis is very often made after occurrence of complications such as thromboembolic disorders, ischemic stroke, or heart failure. What is more, AF is the most frequent heart rhythm disorder in patients after cardiac surgeries thus causing 30-40% of complications occurring within 1 week after surgeries of Coronary Artery Bypass Graft (CABG) [3].

Regarding above mentioned data, research conducted by scientists from State Research Institute of Circulation Pathology and Institute of Cardiology (Academy of Medical Sciences) from Russia in collaboration with scientists from the United States seem to be extremely innovative and prospective. They showed that botulinum toxin significantly decreases the risk and frequency of paroxysmal atrial fibrillation episodes in patients after CABG. Prospective and randomized double-blind study involved a group of 60 patients at the age of about 62 with episodes of PAF in interview and indication for CABG. Botulinum toxin in a form of Xeomin was injected (n=30) to the patients into layer of epicardial fat deposits in a dose of 50 U/1 ml of coronary fat tissue in 3-5 spheres of infiltration. People from control group (n=30) were administered 1ml of 0,9% physiological saline. In order to monitor condition of the patients and ability to maintain sinus rhythm, heartbeat was monitored with the use of ILR (implantable loop recorder), which is a small device sized as a package of chewing gums implanted under the skin of the chest, 24-hour Holter monitor, and control EKG. Results obtained during observations which lasted for a month and a year each, turned out to be extremely promising because after a year since CABG and administration of the toxin none of the patients from study group had recurrence of AF in comparison with control group where episodes of PAF were observed in 27% of the participants. What is more, as the year-long observation showed, administration of botulinum toxin did not cause any complications what favors safety of this innovative method [2,4].

Therefore, the question is whether BTX is a poison or a medicine for human organism. The answer is really difficult because botulinum toxin is an amazing substance of two faces. It is commonly known as one of the most toxic and lethal biological substances. It is produced by bacteria of Clostridium botulinum type – anaerobic, Gram-positive, spore-forming bacteria living in the ground, water, and digestive system of animals [5]. BTX activity as neurotoxin is based on blocking acetylocholine secretion which is the main neurotransmitter in neuromuscular connections from presynaptic endings of motor neurons. It takes place through fragmentation of SNAP-25 protein which is necessary to release the neurotransmitter into synaptic cleft. As the results of research show, intramuscular injection of botulinum toxin causes descending flaccid paralysis of muscles, progressing from the outside, usually symmetrical. Mechanisms based on blocking sinus node stimulation with BTX are the basis of effectiveness in AF prevention. What is more, the substance leads to transitional inhibition of gangionated plexi (GP) activity and does not damage GP in contrast with other invasive and currently used treatment methods [6, 7].

Therefore, it turns out that botulinum toxin is a substance which raises many controversies but at the same time it gives huge hopes in the world of medicine. Maybe in the nearest future botox – “the queen of all beauty salons” will become extremely important agent not only to fight stomach cancer [8], chronic migraine headaches [9], and dysfunctions of urinary bladder [10], but also it may be a breakthrough in therapy and prevention of atrial fibrillation recurrence, especially in patients after cardiac surgeries.

Written by: Magdalena Szydełko, Joanna Szydełko

Source:
1. Erbguth F.J., Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin. Movement Disorders 2004; 19(8): 2-6.
2. Pokushalov E., Kozlov B., Romanov A., Strelnikov A., Bayramova S., Sergeevichev D., Bogachev-Prokophiev A., Zheleznev S., Shipulin V., Lomivorotov V.V., Karaskov A., Po S.S., Steinberg J.S., Long-Term Suppression of Atrial Fibrillation by Botulinum Toxin Injection into Epicardial Fat Pads in Patients Undergoing Cardiac Surgery: One Year Follow Up of a Randomized Pilot Study. Circulation. Arrhythmia and Electrophysiology 2015 Oct 20. pii: CIRCEP.115.003199.
3. Rho R.W., The management of atrial fibrillation after cardiac surgery. Heart 2009; 95(5): 422-429.
4. Pokushalov E., Kozlov B., Romanov A., Strelnikov A., Bayramova S., Sergeevichev D., Bogachev-Prokophiev A., Zheleznev S., Shipulin V., Salakhutdinov N., Lomivorotov V.V., Karaskov A., Po S.S., Steinberg J.S., Botulinum toxin injection in epicardial fat pads can prevent recurrences of atrial fibrillation after cardiac surgery: results of a randomized pilot study. Journal of the American College of Cardiology 2014; 64(6):628-629.
5. Nigam P.K., Nigam A., Botulinum toxin., Indian Journal of Dermatology 2010; 55(1): 8-14.
6. Oh S., Choi E.K., Zhang Y., Mazgalev T.N., Botulinum toxin injection in epicardial autonomic ganglia temporarily suppresses vagally mediated atrial fibrillation. Circulation. Arrhythmia and Electrophysiology 2011; 4(4):560-565.
7. Filardo G., Hamilton C., Hebeler R.F. Jr., Hamman B., Grayburn P., New-onset postoperative atrial fibrillation after isolated coronary artery bypass graft surgery and long-term survival. Circulation. Cardiovascular Quality and Outcomes 2009; 2(3):164-169.
8. Zhao C.-M., Hayakawa Y., Kodama Y., Muthupalani S., Westphalen C. B., Andersen G. T., Flatberg A., Johannessen H., Friedman R. A., Renz B. W., Sandvik A. K., Beisvag V., Tomita H., Hara A., Quante M., Li Z., Gershon M. D., Kaneko K., Fox J. G., Wang T. C., Chen D., Denervation suppresses gastrin tumorigenesis. Science Translational Medicine 2014; 6(250):250ra115.
9. Lacković Z., Filipović B., Matak I., Helyes Z., Botulinum toxin type A activity in cranial dura: implications for treatment of migraine and other headaches. British Journal of Pharmacology 2015 Oct 22.
10. Andersson K.E., Drug therapy of overactive bladder – What is coming next? Korean Journal of Urology 2015; 56(10):673-679.

Would You like to know more? Watch on MEDtube.net: Myobloc – Mechanism of Action 3D Medical Animation

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