Co-administration of Apelin and T4 Protects Inotropic and Chronotropic Changes Occurring in Hypothyroid Rats / Coadministração de Apelina e T4 tem Efeito Protetor nas Alterações Inotrópicas e Cronotrópicas que Ocorrem em Ratos Hipotireoideos

AbstractBackground:One of the most important thyroid hormone targets is the cardiovascular system. Hemodynamic changes, such as decreased resting heart rate (HR), myocardial contractility, and cardiac output, and increased diastolic pressure and systemic vascular resistance, have been observed in hypothyroid patients. Moreover, in these patients, ECG changes include sinus bradycardia and low voltage complexes (P waves or QRS complexes).Objective:This study aimed at evaluating the prophylactic effect of apelin on HR changes and QRS voltage that occur in propylthiouracil (PTU)-induced hypothyroid rats.Method:In this study, 48 adult male Wistar rats weighing 170-235g were randomly divided into 6 groups: Control group (normal saline ip injection + tap water gavage); P group (PTU 0.05%, in drinking water); A group (apelin 200 µg.kg-1.day-1, ip); PA group [co-administration of PTU and apelin]; PT group [co-administration of PTU + T4 (0.2 mg/g per day, gavage)]; and PAT group (co-administration of PTU, apelin and T4). All experiments were performed for 28 consecutive days, and then the animals were anesthetized with an ip injection of ketamine (80 mg/kg) and xylazine (12 mg/kg). Lead II electrocardiogram was recorded to calculate HR and QRS voltage.Results:Heart rate and QRS voltage increased more significantly in the hypothyroid group that consumed both apelin and T4 (201 ± 4 beat/min, 0.71 ± 0.02 mv vs. hypothyroid 145 ± 9 beat/min, 0.563 ± 0.015 mv; respectively).Conclusion:The co-administration of apelin and T4 showed a protective effect on QRS voltage and HR in PTU‑induced hypothyroid rats.

ResumoFundamento:O sistema cardiovascular é um dos alvos mais importantes dos hormônios tireoidianos. As seguintes alterações hemodinâmicas foram observadas em pacientes com hipotireoidismo: redução da frequência cardíaca (FC) de repouso, da contratilidade miocárdica e do débito cardíaco; e aumento da pressão diastólica e da resistência vascular sistêmica. Além disso, tais pacientes apresentam alterações eletrocardiográficas, como bradicardia sinusal e baixa voltagem dos complexos (ondas P e complexos QRS).Objetivo:Avaliar o efeito profilático da apelina nas alterações de FC e voltagem de QRS que ocorrem em ratos com hipotireoidismo induzido por propiltiouracil (PTU).Método:Este estudo dividiu de maneira aleatória 48 ratos Wistar machos adultos, pesando 170-235g, em seis grupos: grupo controle (CO), injeção intraperitoneal (ip) de solução salina + água potável gavagem; grupo hipotireoideo (P), PTU 0,05% em água potável; grupo A, apelina ip (200 µg.kg-1.dia-1); grupo PA, coadministração de PTU e apelina; grupo PT, coadministração de PTU e T4, 0.2 mg/g por dia por gavagem; e grupo PAT, coadministração de PTU, apelina e T4. Todos os experimentos foram realizados durante 28 dias consecutivos, sendo então os animais anestesiados com injeção ip de cetamina (80 mg/kg) e xilazina (12 mg/kg). Utilizou-se o registro do ECG na derivação DII para calcular a FC e a voltagem do QRS.Resultados:Houve aumento mais significativo da FC e da voltagem do QRS no grupo hipotireoideo que recebeu apelina e T4 (201±4 bpm, 0,71±0,02mV) do que no hipotireoideo (145±9 bpm, 0,563±0,015 mV), respectivamente.Conclusão:A coadministração de apelina e T4 mostrou efeito protetor na voltagem do QRS e FC em ratos com hipotireoidismo induzido por PTU.

Co-administration of Apelin and T4 protects inotropic and chronotropic changes occurring in hypothyroid rats.

BACKGROUND: One of the most important thyroid hormone targets is the cardiovascular system. Hemodynamic changes, such as decreased resting heart rate (HR), myocardial contractility, and cardiac output, and increased diastolic pressure and systemic vascular resistance, have been observed in hypothyroid patients. Moreover, in these patients, ECG changes include sinus bradycardia and low voltage complexes (P waves or QRS complexes). OBJECTIVE: This study aimed at evaluating the prophylactic effect of apelin on HR changes and QRS voltage that occur in propylthiouracil (PTU)-induced hypothyroid rats. METHOD: In this study, 48 adult male Wistar rats weighing 170-235g were randomly divided into 6 groups: Control group (normal saline ip injection + tap water gavage); P group (PTU 0.05%, in drinking water); A group (apelin 200 µg.kg-1.day-1, ip); PA group [co-administration of PTU and apelin]; PT group [co-administration of PTU + T4 (0.2 mg/g per day, gavage)]; and PAT group (co-administration of PTU, apelin and T4). All experiments were performed for 28 consecutive days, and then the animals were anesthetized with an ip injection of ketamine (80 mg/kg) and xylazine (12 mg/kg). Lead II electrocardiogram was recorded to calculate HR and QRS voltage. RESULTS: Heart rate and QRS voltage increased more significantly in the hypothyroid group that consumed both apelin and T4 (201 ± 4 beat/min, 0.71 ± 0.02 mv vs. hypothyroid 145 ± 9 beat/min, 0.563 ± 0.015 mv; respectively). CONCLUSION: The co-administration of apelin and T4 showed a protective effect on QRS voltage and HR in PTU­induced hypothyroid rats.

Negative Chronotropic and Antidysrhythmic Effects of Hydroalcoholic Extract of Lemon Balm (Melissa Officinalis L.) on CaCl2-Induced Arrhythmias in Rats.

BACKGROUND: In many cases, myocardial infarction leads to arrhythmia. Since antioxidant agents have an important protective role in heart disease, these compounds in medicinal plants are used in traditional medicine. Lemon balm extract, compared to other plants of the lamiaceae family, has been proven to have significant amounts of antioxidant compounds. The aim of this study was to assess the effect of the hydroalcoholic extract of lemon balm (Melissa officinalis L.) on CaCl2-induced arrhythmias in rats. METHODS: This research is an experimental study; male adult Sprague Dawley rats that weighed 200-250 g were divided randomly into three groups, i.e., 1) control (normal saline, 1 ml/kg/day), 2) extract (100 mg/kg), and 3) extract (200 mg/kg). The normal saline and the extracts were gavaged for 14 consecutive days. After anesthesia, lead II electrocardiograms were recorded for calculating the rats' heart rates (HRs). Arrhythmia was induced by intravenous injection of CaCl2 solution (140 mg/kg), and the percentages of incidence of ventricular tachycardia (VT), ventricular fibrillation (VF), and ventricular premature beats (VPB) were recorded. The results were analyzed by using Fisher's exact test and one-way ANOVA. P-values less than 0.05 were considered as significant level. RESULTS: Heart rates and percentages of incidence of VPB, VT, and VF were reduced significantly in extract groups (with the highest activity at 200 mg/kg) in comparison with the control group. CONCLUSION: Melissa officinalis was considered to be an antiarrhythmic agent because it reduced the percentage of incidence of VPB, VT, and VF in the groups that received it. The results indicated that Melissa officinalis had a protective effect on the heart.