Treatment with empagliflozin improves cardiac function in infarcted animals associated with increased baroreflex sensitivity

B. Da Silva,B. Nascimento-Carvalho, L. I. De Souza, M. B. Da Silva, J. R. Marques,P. M. M. Dourado,F. Consolim-Colombo,M. C. C. Irigoyen

European Heart Journal(2023)

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摘要
Abstract Background Several clinical and experimental studies have shown an improvement in cardiac function in infarcted patients and animals (diabetic or not) when treated with empagliflozin, as well as an improvement in outcomes in patients with heart failure with reduced ejection fraction or with preserved ejection fraction. Hypothesis: Treatment with empagliflozin for 14 days (10 mg/kg) improves cardiac function in infarcted rats, secondary to increased baroreflex sensitivity. Methods Wistar rats were divided into 2 groups: AMI - acute myocardial infarction (n=8) and AMI+EMPA - acute myocardial infarction + Empagliflozin (n=8). The animals in both groups were anesthetized and submitted to thoracotomy and ligature of the left coronary artery. The animals in the AMI+EMPA group received daily, through oral gavage, 10 mg/kg of empagliflozin, for 14 days. After this period, an echocardiographic examination was performed, followed by cannulation of the femoral vein and artery, to assess hemodynamic parameters and baroreflex activity. The results were evaluated for normality. Data were compared by Student's t tests. And the relationship between the parameters was tested by Pearson's correlation. Results are presented as mean and standard deviation. Results In the echocardiographic evaluation, an improvement in diastolic function indexes was observed in the AMI+EMPA group in relation to the AMI group: E'/A' ratio (1.584 ± 0.437 vs 0.589 ± 0.129), E/E' ratio (14.11 ± 3.946 vs 29.92 ± 6.878) and systolic function: SF (29.30% ± 7.974 vs 19.20% ± 2.445), EF (53.86% ± 11.78 vs 37.91% ± 4.212), FAC (39.31% ± 7.135 vs 23.51 ± 3.940). There was a reduction in mean blood pressure in the AMI+EMPA group (102.4 mmHg ± 6,408) compared to the AMI group (110.7 mmHg ± 8,514) and in diastolic blood pressure (84.4 mmHg ± 3.889 vs 92.8 mmHg ± 7.664). In the assessment of baroreflex sensitivity, an improvement in tachy and bradycardic indexes was observed in the treated animals: tachycardic index (5.021 bpm/mmHg ± 0.346 vs 3.214 bpm/mmHg ± 0.418) and bradycardic index (1.569 bpm/mmHg ± 0.148 vs 0.73 bpm/ mmHg ± 0.046). In addition, the systolic function expressed by the FAC was positively associated with the reflex tachycardic index (p: 0.008; r: 0.616) and to the E'/A' ratio (p: 0.025; r: 0.576) and negatively with PAD (p: 0.040; r: -0.503). Conclusion Treatment with Empagliflozin in infarcted rats was able to improve left ventricular systolic and diastolic function associated with improved performance of arterial baroreceptors.
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empagliflozin,cardiac function,infarcted animals
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