EMPAGLİFLOZİNİN SIÇANLARDA DOKSORUBİSİN İLE OLUŞTURULAN KARDİYOMİYOPATİ ÜZERİNE ETKİSİ

Barış V.Ö. Empagliflozin’s Effect on Doxorubicin induced Cardiyomyopathy in Rats Hacettepe University Graduate School of Health Sciences, Doctor of Philosophy Thesis for Physiology, Ankara, 2021 Empagliflozin is an SGLT-2 inhibitor that reduces cardiovascular deaths and hospitalizations for heart failure. In this study, we aimed to evaluate the possible protective effects of empagliflozin against doxorubicin-induced cardiotoxicity. Non-diabetic Sprague-Dawley rats were randomly divided into four groups in this study. Physiological saline (SF) (1 ml) was given to the control group by intraperitoneal (I.P.) and orogastric (O.G.) routes, and to the EMPA group empagliflozin 10 mg/kg/day by O.G. route, SF was given by I.P. route. DOX group as a cumulative 18 mg / kg body weight / 6 days doxorubicin by IP route, SF was given via O.G. route. Doxorubicin and empagliflozin were administered at the same doses for 14 days to the DOX + EMPA group. On the 15th day, echocardiographic and electrocardiographic examinations were performed under anesthesia. Blood samples were taken to evaluate biochemical parameters and heart tissues were excised to evaluate histopathological findings. Left ventricular systolic (P <0.05) and diastolic diameters (P <0.01), QTc interval (P <0.001), karyololysis and karyorexis ratio (P <0.001) and infiltrative cell proliferation (P < 0.01) in the DOX group compared to the control group 0.001), while left ventricular ejection fraction, fractional shortening and normal cell morphology were found to be lower (P <0.001). In the DOX + EMPA group; Compared to the Dox group, left ventricular diastolic diameters (P <0.05) and systolic (P <0.01) diameters, QTc interval (P <0.001), karyolysis and karyorexis rates (P <0.001) and infiltrative cell proliferation were significantly lower. (P < 0.01); normal cell morphology and left ventricular ejection fraction were significantly higher than in the DOX group (P <0.001). Biochemical results were similar between groups. As a result; This study showed that empagliflozin significantly improved doxorubicin-induced QTc prolongation, left ventricular dilatation, left ventricular systolic dysfunction, infiltrative cell proliferation and necrosis. The data obtained in the current study indicate that the protective effect of empagliflozin is due to the increase in mitochondrial biogenesis and prevention of sarcoplasmic reticulum degeneration rather than natriuretic or antioxidant effects.Barış V.Ö. Empagliflozinin Sıçanlarda Doksorubisin ile Oluşturulan Kardiyomiyopati Üzerine Etkisi Hacettepe Üniversitesi Sağlık Bilimleri Enstitüsü Fizyoloji Programı Doktora Tezi, Ankara, 2021 Empagliflozin, kardiyovasküler ölümleri ve kalp yetersizliğine bağlı hastaneye yatışları azaltan bir SGLT-2 inhibitörüdür. Bu çalışmada, empagliflozinin doksorubisine bağlı kardiyotoksisiteye karşı olası koruyucu etkilerini değerlendirmeyi amaçladık. Diyabetik olmayan Sprague-Dawley sıçanlar bu çalışmada rastgele dört gruba ayrıldı. Kontrol grubuna intraperitoneal (I.P.) ve orogastrik (O.G.) yol ile serum fizyolojik (SF) (1 ml) verildi, EMPA grubuna O.G. yol ile 10 mg/kg/gün empagliflozin, I.P. olarak SF verildi, DOX grubuna IP yol ile kümülatif 18 mg / kg vücut ağırlığı / 6 gün doksorubisin, O.G. yol ile SF verildi. DOX + EMPA grubuna 14 gün boyunca aynı dozlarda doksorubisin ve empagliflozin uygulandı. 15. günde anestezi altında ekokardiyografik ve elektrokardiyografik incelemeler yapıldı. Biyokimyasal parametreleri değerlendirmek için kan örnekleri alındı ve histopatolojik bulguları değerlendirmek için kalp dokuları eksize edildi. DOX grubunda kontrol grubuna göre sol ventrikül sistolik (P <0,05) ve diyastolik çapları (P <0,01), QTc intervali (P <0,001), karyololiz ve karyoreksis oranı (P <0,001) ve infiltratif hücre proliferasyonu (P <0,001) önemli ölçüde daha yüksek bulunurken sol ventrikül ejeksiyon fraksiyonu, fraksiyonel kısalması ve normal hücre morfolojisi ise daha düşük (P <0,001) saptandı. DOX + EMPA grubunda; Dox grubuna göre sol ventrikül diyastolik çapları (P <0,05) ve sistolik (P <0,01) çapları, QTc intervali (P <0,001), karyolizis ve karyoreksis oranları (P <0,001) ve infiltratif hücre proliferasyonu anlamlı olarak daha düşüktü (P <0,01); normal hücre morfolojisi ve sol ventrikül ejeksiyon fraksiyonu DOX grubuna göre anlamlı olarak daha yüksekti (P <0,001). Biyokimyasal sonuçlar gruplar arasında benzerdi. Sonuç olarak; bu çalışma empagliflozinin doksorubisine bağlı olarak gelişen QTc uzamasını, sol ventrikül dilatasyonunu, sol ventrikül sistolik fonksiyonun bozukluğunu, infiltratif hücre proliferasyonunu ve nekrozu önemli ölçüde iyileştirdiğini göstermiştir. Mevcut çalışmada elde edilen veriler, empagliflozinin koruyucu etkisinin, natriüretik veya antioksidan etkilerden çok mitokondriyal biyogenezdeki artış ve sarkoplazmik retikulum dejenerasyonunun önlenmesinden kaynaklandığını göstermektedir

Empagliflozin significantly attenuates sotalol-induced QTc prolongation in rats

Background: Sotalol is a class III antiarrhythmic drug commonly used in various arrhythmia treatments. However, due to its potent potassium channel inhibition, it can prolong the QT interval and lead to malignant arrhythmias. Empagliflozin is an inhibitor of sodium‑glucose cotransporter 2 (SGLT2) and has a positive effect on cardiovascular outcomes. Since the effect of empagliflozin on the activation of potassium channels is unknown, there is no recommendation regarding the coadministration of these drugs. Aims: The study aimed to evaluate the possible protective effects of empagliflozin on sotalol‑induced QT prolongation. Methods: We randomized 24 rats into 4 groups. The control group received only physiological saline, the EMPA group, empagliflozin; the SOT group, sotalol; and the EMPA+SOT group, empagliflozin and sotalol. PR and QT intervals and heart rates were measured under anesthesia at baseline and at 1, 2, and 3 hours in lead II. Results: In the SOT group, the QT and QTc intervals as well as T‑wave duration were statistically longer, whereas heart rates were lower than in the control group (P &lt; 0.001 for all parameters). Empagliflozin ameliorated sotalol‑induced QT and QTc prolongation in the EMPA+SOT group. The QT interval, T‑wave duration, and QTc interval were shorter, and the heart rate was greater than in the SOT group (P &lt; 0.001, P = 0.002, P &lt; 0.001, and P &lt; 0.001, respectively). Conclusion: Empagliflozin significantly ameliorates sotalol‑induced QT prolongation and could be used safely with sotalol in clinical practice. Future clinical trials might recommend the routine use of empagliflozin to prevent QTc prolongation in diabetic patients receiving sotalol

Relationship between Cardiovascular Disease Risk and Neck Circumference Shown in the Systematic Coronary Risk Estimation (SCORE) Risk Model

Introduction: The most important way to reduce CVD-related mortality is to apply appropriate treatment according to the risk status of the patients. For this purpose, the SCORE risk model is used in Europe. In addition to these risk models, some anthropometric measurements are known to be associated with CVD risk and risk factors. Objectives: This study aimed to investigate the association of these anthropometric measurements, especially neck circumference (NC), with the SCORE risk chart. Methods: This was planned as a cross-sectional study. The study population were classified according to their SCORE risk values. The relationship of NC and other anthropometric measurements with the total cardiovascular risk indicated by the SCORE risk was investigated. Results: A total of 232 patients were included in the study. The patients participating in the study were analysed in four groups according to the SCORE ten-year total cardiovascular mortality risk. As a result, the NC was statistically significantly lower among the SCORE low and moderate risk group than all other SCORE risk groups (low-high and very high 36(3)–38(4) (IQR) p: 0.026, 36(3)–39(4) (IQR) p &lt; 0.001, 36(3)–40(4) (IQR) p &lt; 0.001), (moderate-high and very high 38(4) vs. 39(4) (IQR) p: 0.02, 38(4) vs. 40(4) (IQR) p &lt; 0.001, 39(4) vs. 40(4) (IQR) p &gt; 0.05). NC was found to have the strongest correlation with SCORE than the other anthropometric measurements. Conclusions: Neck circumference correlates strongly with the SCORE risk model which shows the ten-year cardiovascular mortality risk and can be used in clinical practice to predict CVD risk