SALBUTAMOL ATTENUATES THE ARRHYTHMOGENIC EFFECT OF AMINOPHYLLINE IN CARDIAC ORGANOIDS EXPERIMENTAL MODEL
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| Year of publication | 2025 |
| Type | Conference abstract |
| MU Faculty or unit | |
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| Description | The aminophylline-salbutamol combination is widely implemented in clinical settings for the management of obstructive pulmonary disease. While the adverse effects, including arrhythmogenicity, of each bronchodilator are well-documented, the arrhythmogenic potential of their combined use remains largely uncharacterized. This study [1] aimed to delineate the proarrhythmic risk associated with aminophylline and salbutamol co-administration in vitro. Atomic force microscopy (AFM) coupled with cardiac organoids derived from human pluripotent stem cells (hPSC-CMs) was employed as previously described [2,3]. We assessed the chronotropic, inotropic, and arrhythmogenic responses of hPSC-CMs as reviewed [4]. Screened were responses to salbutamol monotherapy and aminophylline-salbutamol co-treatment. Heart rate variability (HRV) and beat rate variability (BRV) analyses enabled the detection of arrhythmic events in AFM-based hPSC-CM recordings. Results demonstrated a synergistic chronotropic and inotropic effect with combination therapy versus monotherapy. Crucially, salbutamol attenuated aminophylline’s arrhythmogenic impact, likely through endothelial nitric oxide synthase activation mediated by beta-2 adrenergic receptor engagement. Findings were corroborated across two hPSC-CM lines (CCTL4 and CCTL12), indicating that salbutamol may confer cardiovascular protection when co-administered with aminophylline by mitigating its arrhythmogenic potential, in addition to providing bronchodilation. |
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