| Full text | |
| Author(s): |
Souza, Diego Santos
;
Marques, Leisiane Pereira
;
Costa, Alexandre Dantas
;
Cruz, Jader Santos
;
Rhana, Paula
;
Santos-Miranda, Artur
;
Joviano-Santos, Julliane Vasconcelos
;
Durco, Aimee Obolari
;
Lins Vasconcelos, Carla Maria
;
Roman-Campos, Danilo
Total Authors: 10
|
| Document type: | Journal article |
| Source: | Life Sciences; v. 308, p. 13-pg., 2022-09-13. |
| Abstract | |
Aims: Hypothyroidism is associated with an increased risk of cardiovascular disease and enhanced susceptibility to arrhythmias. In our investigation, we evaluated the potential involvement of late sodium current (INa,late) in cardiac arrhythmias in an experimental murine model of hypothyroidism.Main methods: Male Swiss mice were treated with methimazole (0.1 % w/vol, during 21 days) to induce experimental hypothyroidism before ECG, action potential (AP) and intracellular Ca2+ dynamics were evaluated. Susceptibility to arrhythmia was measured in vitro and in vivo.Key findings: The results revealed that hypothyroid animals presented ECG alterations (e.g. increased QTc) with the presence of spontaneous sustained ventricular tachycardia. These changes were associated with depolarized resting membrane potential in isolated cardiomyocytes and increased AP duration and dispersion at 90 % of the repolarization. Aberrant AP waveforms were related to increased Ca2+ sparks and out-of-pace Ca2+ waves. These changes were observed in a scenario of enhanced INa,late. Interestingly, ranolazine, a clinically used blocker of INa, late, restored the ECG alterations, reduced Ca2+ sparks and aberrant waves, decreased the in vitro events and the severity of arrhythmias observed in isolated cardiomyocytes from hypothyroid animals. Using the in vivo dobutamine + caffeine protocol, animals with hypothyroidism developed catecholaminergic bidirectional ven-tricular tachycardia, but pre-treatment with ranolazine prevented this.Significance: We concluded that animals with hypothyroidism have increased susceptibility to developing ar-rhythmias and ranolazine, a clinically used blocker of INa,late, is able to correct the arrhythmic phenotype. (AU) | |
| FAPESP's process: | 20/14635-1 - Modeling of monogenic diseases for physiopathological studies and pharmacological tests using specialized cells derived from iPSCs |
| Grantee: | João Bosco Pesquero |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 21/05584-7 - Assessment of acute and chronic toxicity of the heart and brain exposed to pesticides found in potable water in Brazil |
| Grantee: | Danilo Roman Campos |
| Support Opportunities: | Research Grants - Young Investigators Grants - Phase 2 |
| FAPESP's process: | 19/21304-4 - Arrhythmogenic mechanisms in right heart diseases |
| Grantee: | Danilo Roman Campos |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 19/18918-0 - Role of nitric oxide in cardiac arrhythmias during Hypothyroidism |
| Grantee: | Diego Santos de Souza |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |