Publication details
Arrhythmogenic Potential of Aminophylline and Its Modulation by Salbutamol: Insights from Human Pluripotent Stem Cell-Derived Cardiomyocytes
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| Year of publication | 2025 |
| Type | Conference abstract |
| MU Faculty or unit | |
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| Description | Cardiac side effects of pulmonary drugs are well-documented in clinical practice, with aminophylline, a methylxanthine bronchodilator, and salbutamol, a beta-2 adrenergic receptor agonist, both being associated with proarrhythmic effects. However, data on their direct impact on cardiac electrophysiology and contractility, particularly in combination, remain limited. Purpose: This study aimed to investigate the effects of aminophylline and salbutamol, both individually and in combination, on cardiac function using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and HL-1 cardiomyocytes. Methods: Beat rate (BR) and contraction force (CF) were assessed in hPSC-CMs using atomic force microscopy (AFM), while multielectrode array (MEA) recordings and calcium imaging were used to evaluate electrophysiological changes in HL-1 cardiomyocytes. Results: Aminophylline significantly increased BR, CF, and the frequency of rhythm irregularities in both hPSCCMs and HL-1 cardiomyocytes. Notably, calcium sparks were significantly elevated in HL-1 cardiomyocytes at 512 µM aminophylline, supporting its arrhythmogenic potential. In contrast, the combination of aminophylline and salbutamol exhibited a synergistic chronotropic and inotropic effect, while salbutamol mitigated aminophylline-induced arrhythmias. This protective effect is likely mediated via endothelial nitric oxide synthase activation through beta-2 adrenergic receptors. Conclusion: While aminophylline alone poses a significant risk of arrhythmias, its co-administration with salbutamol may enhance cardiovascular safety by reducing its proarrhythmic effects. These findings provide new insights into the cardiac safety of bronchodilator therapy and highlight the potential of hPSC-CM-based AFM platforms for evaluating direct drug effects on cardiac function |