Arrhythmogenic Potential of Myocardial Edema: The Interstitial Osmolality Induces Spiral Waves and Multiple
Diana G Kiseleva1,2, Vitalii D Dzhabrailov3,4, Aleria A Aitova4,5
1Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky National Research Centre of Surgery, 119991 Moscow, Russia.
Insights
Myocardial edema, induced by low osmolality, significantly slows calcium wave propagation in heart cells. This cellular edema can lead to dangerous arrhythmias like spiral waves and multiple wavelets, potentially causing fatal heart rhythms.
Area of Science:
- Cardiology
- Cellular Physiology
- Biophysics
Background:
- Myocardial edema exacerbates cardiovascular diseases and is linked to arrhythmias.
- The impact of edema on cardiac calcium dynamics remains unstudied.
- Edema can cause irreversible myocardial remodeling.
Purpose of the Study:
- To investigate the effects of hypoosmolality-induced myocardial edema on calcium dynamics in cardiomyocytes.
- To determine if altered calcium dynamics under edema conditions can precipitate arrhythmias.
Main Methods:
- Optical mapping of intracellular calcium dynamics using Fluo-4 in neonatal rat cardiomyocyte monolayers.
- Experimental manipulation of solution osmolality using varying NaCl concentrations (140 mM, 105 mM, 70 mM).
- Analysis of calcium wave propagation speed and pattern under different osmotic conditions.
Main Results:
- A significant decrease in calcium wave propagation speed was observed with decreasing osmolality.
- Hypoosmotic conditions induced a transition from normal wavefronts to spiral waves and multiple wavelets.
- Specific findings include spiral wave emergence at 0.75T and multiple wavelets at 0.5T, previously unrecorded in this model.
Conclusions:
- Hypoosmolality, mimicking myocardial edema, disrupts normal calcium wave propagation in cardiomyocytes.
- These disruptions can lead to the formation of complex reentrant arrhythmias, such as spiral waves and wave break.
- The study suggests a novel cellular mechanism linking myocardial edema to potentially fatal ventricular arrhythmias.
Abstract:
Myocardial edema is a common symptom of pathological processes in the heart, causing aggravation of cardiovascular diseases and leading to irreversible myocardial remodeling. Patient-based studies show that myocardial edema is associated with arrhythmias. Currently, there are no studies that have examined how edema may influence changes in calcium dynamics in the functional syncytium. We performed optical mapping of calcium dynamics on a monolayer of neonatal rat cardiomyocytes with Fluo-4. The osmolality of the solutions was adjusted using the NaCl content. The initial Tyrode solution contained 140 mM NaCl (1T) and the hypoosmotic solutions contained 105 (0.75T) and 70 mM NaCl (0.5T). This study demonstrated a sharp decrease in the calcium wave propagation speed with a decrease in the solution osmolality. The successive decrease in osmolality also showed a transition from a normal wavefront to spiral wave and multiple wavelets of excitation with wave break. Our study demonstrated that, in a cellular model, hypoosmolality and, as a consequence, myocardial edema, could potentially lead to fatal ventricular arrhythmias, which to our knowledge has not been studied before. At 0.75T spiral waves appeared, whereas multiple wavelets of excitation occurred in 0.5T, which had not been recorded previously in a two-dimensional monolayer under conditions of cell edema without changes in the pacing protocol.
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