Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats
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...
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MDPI AG
2023-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/3/359 |
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| author | Brigitta Bernat Rita Erdelyi Laszlo Fazekas Greta Garami Reka Maria Szekeres Barbara Takacs Mariann Bombicz Balazs Varga Fruzsina Sarkany Arnold Peter Raduly Dana Diana Romanescu Zoltan Papp Attila Toth Zoltan Szilvassy Bela Juhasz Daniel Priksz |
| author_facet | Brigitta Bernat Rita Erdelyi Laszlo Fazekas Greta Garami Reka Maria Szekeres Barbara Takacs Mariann Bombicz Balazs Varga Fruzsina Sarkany Arnold Peter Raduly Dana Diana Romanescu Zoltan Papp Attila Toth Zoltan Szilvassy Bela Juhasz Daniel Priksz |
| author_sort | Brigitta Bernat |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T06:03:18Z |
| format | Article |
| id | doaj.art-7ca9d4e1689c4d959f45995e5fae7db7 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T06:03:18Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-7ca9d4e1689c4d959f45995e5fae7db72023-11-17T13:11:42ZengMDPI AGPharmaceuticals1424-82472023-02-0116335910.3390/ph16030359Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted RatsBrigitta Bernat0Rita Erdelyi1Laszlo Fazekas2Greta Garami3Reka Maria Szekeres4Barbara Takacs5Mariann Bombicz6Balazs Varga7Fruzsina Sarkany8Arnold Peter Raduly9Dana Diana Romanescu10Zoltan Papp11Attila Toth12Zoltan Szilvassy13Bela Juhasz14Daniel Priksz15Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Operative Techniques and Surgical Research, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDivision of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDivision of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Diabetology, Pelican Clinical Hospital, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, RomaniaDivision of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDivision of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryMulti-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.https://www.mdpi.com/1424-8247/16/3/359BGP-15telemetryarrhythmiaheart rate variabilityisoproterenolechocardiography |
| spellingShingle | Brigitta Bernat Rita Erdelyi Laszlo Fazekas Greta Garami Reka Maria Szekeres Barbara Takacs Mariann Bombicz Balazs Varga Fruzsina Sarkany Arnold Peter Raduly Dana Diana Romanescu Zoltan Papp Attila Toth Zoltan Szilvassy Bela Juhasz Daniel Priksz Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats Pharmaceuticals BGP-15 telemetry arrhythmia heart rate variability isoproterenol echocardiography |
| title | Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats |
| title_full | Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats |
| title_fullStr | Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats |
| title_full_unstemmed | Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats |
| title_short | Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats |
| title_sort | drug candidate bgp 15 prevents isoproterenol induced arrhythmias and alters heart rate variability hrv in telemetry implanted rats |
| topic | BGP-15 telemetry arrhythmia heart rate variability isoproterenol echocardiography |
| url | https://www.mdpi.com/1424-8247/16/3/359 |
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