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001-es BibID:	BIBFORM109368
035-os BibID:	(cikkazonosító)359 (Scopus)85152371525 (WoS)000959873600001
Első szerző:	Bernát Brigitta (farmakológus)
Cím:	Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats / Bernat Brigitta, Erdelyi Rita, Fazekas Laszlo, Garami Greta, Szekeres Reka Maria, Takacs Barbara, Bombicz Mariann, Varga Balazs, Sarkany Fruzsina, Raduly Arnold Peter, Romanescu Dana Diana, Papp Zoltan, Toth Attila, Szilvassy Zoltan, Juhasz Bela, Priksz Daniel
Dátum:	2023
ISSN:	1424-8247
Megjegyzések:	Multi-target drug candidate BGP-15 has shown cardioprotective and antiarrhythmic actions in diseased models. Here, we investigated the effects of BGP-15 on ECG and echocardiographic parameters, heart rate variability (HRV), and arrhythmia incidence in telemetry-implanted rats, under beta-adrenergic stimulation by isoproterenol (ISO). In total, 40 rats were implanted with radiotelemetry transmitters. First, dose escalation studies (40?160 mg/kg BGP-15), ECG parameters, and 24 h HRV parameters were assessed. After, rats were divided into Control, Control+BGP-15, ISO, and ISO+BGP-15 subgroups for 2 weeks. ECG recordings were obtained from conscious rats, arrhythmias and HRV parameters were assessed, and echocardiography was carried out. ISO-BGP-15 interaction was also evaluated on an isolated canine cardiomyocyte model. BGP-15 had no observable effects on the ECG waveforms; however, it decreased heart rate. HRV monitoring showed that BGP-15 increased RMSSD, SD1, and HF% parameters. BGP-15 failed to counteract 1 mg/kg ISO-induced tachycardia, but diminished the ECG of ischemia and suppressed ventricular arrhythmia incidence. Under echocardiography, after low-dose ISO injection, BGP-15 administration lowered HR and atrial velocities, and increased end-diastolic volume and ventricle relaxation, but did not counteract the positive inotropic effects of ISO. Two weeks of BGP-15 treatment also improved diastolic function in ISO-treated rats. In isolated cardiomyocytes, BGP-15 prevented 100 nM ISO-induced aftercontractions. Here, we show that BGP-15 increases vagally mediated HRV, reduces arrhythmogenesis, enhances left ventricle relaxation, and suppresses the aftercontractions of cardiomyocytes. As the drug is well tolerated, it may have a clinical value in preventing fatal arrhythmias.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk BGP-15 telemetry arrhythmia heart rate variability isoproterenol echocardiography
Megjelenés:	Pharmaceuticals. - 16 : 3 (2023), p. 1-22. -
További szerzők:	Erdélyi Rita Fazekas László (1994-) (általános orvos) Garami Gréta Szekeres Réka (1995-) (orvos) Takács Barbara (1992-) (orvos) Bombicz Mariann (1987-) (gyógyszerész) Varga Balázs (1984-) (kísérletes farmakológus) Sárkány Fruzsina (1996-) (orvos) Ráduly Arnold Péter (1993-) Romanescu, Dana Diana Papp Zoltán (1965-) (kardiológus, élettanász) Tóth Attila (1971-) (biológus) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Juhász Béla (1978-) (kísérletes farmakológus) Priksz Dániel (1989-) (farmakológus)
Pályázati támogatás:	GINOP-2.3.4-15-2020-00008 GINOP TKP2020-NKA-04 Egyéb ÚNKP-21-2-I-DE-392 Egyéb
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