Pabel’s new findings on disease mechanisms could be important for the future treatment of not only about 1.8 million patients with AF, the most common cardiac arrhythmia, but also for an estimated four million people with congestive heart failure (heart failure). Might as well be important. Because AF and cardiac insufficiency often occur together – with adverse effects during the course of the disease for those affected. Atrial fibrillation can also lead to heart failure in the long term. Clinical studies (including the Castle-AF study and the camera-MRI study) have already demonstrated that rhythm therapy can improve left ventricle function and reduce mortality in patients with heart failure and atrial fibrillation. can do www.herzstiftung.de/forschung-und-foerderung . research fund information on
Impaired calcium balance affecting the left ventricle
Dr. Pabel and his team analyzed heart muscle tissue from the left ventricle of patients with a normal heart rhythm (sinus rhythm) or patients with atrial fibrillation. Left ventricle function was preserved in all patients (ejection fraction [EF] over 50). Patients with atrial fibrillation showed a condition known as rate-controlled atrial fibrillation. That is, his heart rate was normal, but the irregular heartbeat, like atrial fibrillation, persisted. Examinations showed no structural differences such as scar tissue in the heart muscle (fibrosis) of the left ventricle between patients with sinus rhythm and patients with atrial fibrillation. “However, we were able to determine in patients with atrial fibrillation that calcium balance, which is important for heart muscle contraction, was disturbed in the heart muscle cells, the cardiomyocytes of the left heart chamber,” says Pabel. In in-vitro experiments with cardiomyocytes, Pabel was able to confirm that artificially generated atrial fibrillation also impaired calcium balance.
A systematic inflow and outflow of calcium (Ca² .),) as well as sodium (Na,) and potassium (K.),) The heart muscle cell in each individual is important for the heart muscle to contract and then relax. To do this, a so-called action potential must first be created, which then propagates through the muscle tissue. An action potential is a brief change in the state of electrical stimulation within a muscle cell, caused by the transfer of various ions (Ca²).,n/a, and to,) is generated. Finally, the excitation wave in the heart triggers an electromechanical coupling, at which Ca² is very important.,If involved, the contraction, ie the heartbeat, stops. “Low systolic concentrations of calcium ions in heart cells may therefore be associated with limited contractility of the heart and may indicate heart failure in the systole, contraction phase,” said Dr. pabel
Laboratory test confirms adverse effect on ventricle
Pabel and his team at Regensburg University Hospital were able to confirm this process in further investigations on laboratory models with human heart muscle cells coming from donors with healthy hearts. To this end, Pabel set up a simulation of atrial fibrillation in the laboratory (in vitro). “Low Ca² was also shown in this simulation,-Transition of the left ventricle into the cells of the human heart muscle, ”explains Pabel. Furthermore, further experiments with standardized heart chamber cells made from stem cells showed that artificially generated atrial fibrillation causes processes that are also known to occur in adverse remodeling processes associated with cardiac insufficiency (remodeling). goes, eg. b Increased oxidative stress in the heart muscle of the left ventricle. In addition, the activity of a specific enzyme, Ca²,There is an increase in calmodulin-dependent protein kinase IIδc (CaMKII), which is critically involved in the progression of heart failure. If CaMKII activity was blocked and oxidative stress was reduced, Ca². dissolution of,/n / a,The balance that previously triggered atrial fibrillation can be stopped. “We were thus able to reasonably confirm these mechanisms,” explains Pabel.
The researchers and Winterstein draw the following conclusions from the award-winning data: “Our findings on the adverse effects of atrial fibrillation on the ventricle should encourage clinicians and scientists to understand atrial fibrillation not only as a disease of the atrium, but as a disease.” As in full heart.”
(1) Pabel S et al, Effects of atrial fibrillation on the human ventricle, February 2022, https://doi.org/10.1161/CIRCRESAHA.121.319718
Cardiovascular research close to the patient
Thanks to the financial support of the founders, donors and bequests, the German Heart Foundation, together with the German Heart Research Foundation (DSHF), which it established in 1988, can fund research projects on a scale that is sufficient for cardiovascular research. mandatory. www.herzstiftung.de/forschung-und-foerderung . research information on
tip: Patient information on the topic of atrial fibrillation (causes, risk factors, diagnosis and therapy) is available at www.herzstiftung.de/vorhofflimmern.
Research for the Medicine of Tomorrow: New Research Brochure
The brochure “Research for the Medicine of Tomorrow” provides information about the research funding of the German Heart Foundation and the German Foundation for Heart Research. This section presents a selection of funded patient-related research projects and also reports on the awarding of science and the donors and examiners behind the awards and funded projects. Brochures can be requested free of charge on telephone 069 955128400.
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