Wistar sıçanlarda tadalafilin miyokard üzerindeki etkilerinin elektriksel ve izometrik kasılmalar ve kardiyak belirteçler yoluyla araştırılması

Yıl 2024, Cilt: 49 Sayı: 3, 639 - 645, 30.09.2024

Duygun Altıntaş Aykan , Selma Yaman , Muhammed Seyithanoğlu , Ahmet Çağrı Aykan

https://doi.org/10.17826/cumj.1457346

Öz

Amaç: Uzun etkili bir fosfodiesteraz-5 (PDE-5) inhibitörü olan tadalafil, erektil disfonksiyon tedavisinde yaygın olarak kullanılmaktadır. Bu çalışma, sıçanlarda miyokardın izometrik ve elektriksel kasılmalarını ölçerek tadalafilin kalp fonksiyonuna katkısını araştırmaktadır.
Gereç ve Yöntem: Otuz sıçan beş gruba ayrıldı. Bazal elektriksel kasılmalar elektrokardiyogram (EKG) aracılığıyla PR (ms), QRS (ms), QT (ms), Tp (ms), Te (ms), patolojik Q ve kalp atım/dakika aralıklarında kaydedildi. Daha sonra grup 1'e 7 gün boyunca salin verildi (kontrol); grup 2'ye 1 mg/kg tadalafil verildi; grup 3'e 10 mg/kg tadalafil verildi; grup 4'e 7 gün süreyle 1 mg/kg tadalafil verildi; grup 5'e 7 gün süreyle 10 mg/kg tadalafil verildi. Tedavilerden sonra EKG'deki farklılıkları analiz etmek için elektriksel kasılmalar yeniden gerçekleştirildi. İzometrik kasılmalar için kalpler, miyokardiyal kasılma kuvvetlerini (g), sürelerini (ms) ve frekanslarını (Hz) belirlemek için izometrik güç dönüştürücüye bağlandı. ELISA yoluyla kardiyak kreatin kinaz (CK-MB) ve kardiyak troponin I için serum örnekleri toplandı.
Bulgular: CK-MB değerlerinde Grup 2'de (395,56±124,38 pg/ml) ve Grup 3'te (377,81±79,61 pg/ml), Grup 1'e (575,32±83,54 pg/ml) göre anlamlı bir azalma bulduk. Kardiyak kasılma kuvvetleri, kasılma süreleri veya frekanslarındaki farklılıklar istatistiksel olarak anlamlı değildi.
Sonuç: Tadalafil, miyokardın elektriksel veya izometrik kasılmaları üzerinde belirgin bir bozulma yaratmadı. Tadalafil 1 ve 10 mg/kg'ın serum CK-MB'yi azalttığı dikkat çekicidir. QT'deki kısalma ve kalp hızındaki azalmanın miyokardiyal fonksiyonlar üzerinde önemli etkileri olabilir.

Anahtar Kelimeler

Tadalafil, Kas kontraksiyonu, Miyokard, Elektrokardiyografi

Etik Beyan

All experiments were conducted in accordance with the National Institute of Health Guidelines for the Care and Use of Laboratory Animals. Experimental protocols were approved by Kahramanmaraş Sütçü İmam University Local Animal Experimentation Ethics Committee (File No: 2019/01/04, Approval date: 19.02.2019).

Investigation of the effects of tadalafil on the myocardium via electrical and isometric contractions and cardiac markers in Wistar rats

Öz

Purpose: Tadalafil, a long-acting phosphodiesterase-5 (PDE-5) inhibitor, is commonly used in the treatment of erectile dysfunction. This study investigates the contribution of tadalafil in cardiac function by measuring isometric and electrical contractions of myocardium in rats.
Materials and Methods: Thirty rats were divided into five groups. Basal electrical contractions were recorded via electrocardiogram (ECG) for intervals PR (ms), QRS (ms), QT (ms), Tp (ms), Te (ms), pathological Q and heart beats/min. Then group 1 received saline for 7 days (control); group 2 received tadalafil 1 mg/kg; group 3 received tadalafil 10 mg/kg; group 4 received tadalafil 1 mg/kg for 7 days; group 5 received tadalafil 10 mg/kg for 7 days. After treatments, electrical contractions were re-performed to analyze the differences in ECG. For isometric contractions, hearts were connected to isometric power transducer to determine myocardial contractile forces (g), durations (ms) and frequencies (Hz). Serum samples were collected for cardiac creatine kinase (CK-MB) and cardiac troponin I via ELISA.
Results: We found a significant decrease in CK-MB in Group 2 (395.56±124.38 pg/ml) and 3 (377.81±79.61 pg/ml), compared to Group 1 (575.32±83.54 pg/ml). The differences in cardiac contractile forces, contraction durations or frequencies were not statistically significant.
Conclusion: Tadalafil did not exert obvious distruption on myocardial electrical or isometrical contractions. It is noteworthy that tadalafil 1 and 10 mg/kg reduced serum CK-MB. Shortening in QT and decrease in heart rate may have important implications on myocardial functions.

Anahtar Kelimeler

Tadalafil, Muscle contraction, Myocardium, Electrocardiography

Kaynakça

• Shen X, Chen F, Wang F, Huang P, Luo W. The effect of grapefruit juice on the pharmacokinetics of tadalafil in rats. Biomed Res Int. 2020;2020:1631735.
• Amano T, Earle C, Imao T, Matsumoto Y, Kishikage T. Administration of daily 5 mg tadalafil improves endothelial function in patients with benign prostatic hyperplasia. Aging Male. 2018;21:77-82.
• Mora AG, Andrade DR, Janussi SC, Goncalves TT, Krikorian K, Priviero FBM et al. Tadalafil treatment improves cardiac, renal and lower urinary tract dysfunctions in rats with heart failure. Life Sci. 2022;289:120237.
• Saad NS, Floyd K, Ahmed AA, Mohler PJ, Janssen PM, Elnakish MT. The effect of sorafenib, tadalafil and macitentan treatments on thyroxin-induced hemodynamic changes and cardiac abnormalities. PLoS One. 2016;11:e0153694.
• Ural A, Bilgen F, Altıntaş Aykan D, Koçarslan S, Altıntaş Ural D, Seyithanoğlu M et al. The effect of udenafil on stasis zone in an experimental burn model. Ann Plast Surg. 2022;88:38-43.
• Altıntaş Ural D, Altıntaş Aykan D, Koçarslan S, Doganer A. Effect of tadalafil treatment on ovarian ischemia injury in rats. Cukurova Medical Journal. 2021;46:55-62.
• Altintas Aykan D, Yaman S. Evaluation of the effects of tadalafil on pain response in thermal plantar and dynamic plantar tests in rats. Ann Med Res. 2020;27:749-54.
• Tzoumas N, Farrah TE, Dhaun N, Webb DJ. Established and emerging therapeutic uses of PDE type 5 inhibitors in cardiovascular disease. Br J Pharmacol. 2020;177:5467-88.
• Tham YK, Bernardo BC, Ooi JY, Weeks KL, McMullen JR. Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets. Arch Toxicol. 2015;89:1401-38.
• Abdel Aziz MT, Rezq AM, Atta HM, Fouad H, Zaahkouk AM, Ahmed HH et al. Molecular signalling of a novel curcumin derivative versus Tadalafil in erectile dysfunction. Andrologia. 2015;47:616-25.
• Mostafa T, Rashed L, Kotb K, Taymour M. Effect of testosterone and frequent low-dose sildenafil/tadalafil on cavernous tissue oxidative stress of aged diabetic rats. Andrologia. 2012;44:411-5.
• Abdelrady AM, Zaitone SA, Farag NE, Fawzy MS, Moustafa YM. Cardiotoxic effect of levofloxacin and ciprofloxacin in rats with/without acute myocardial infarction: Impact on cardiac rhythm and cardiac expression of Kv4.3, Kv1.2 and Nav1.5 channels. Biomed Pharmacother. 2017;92:196-206.
• Aykan DA, Yaman S, Eser N, Özcan Metin T, Seyithanoğlu M, Aykan AÇ et al. Bisoprolol and linagliptin ameliorated electrical and mechanical isometric myocardial contractions in doxorubicin-induced cardiomyopathy in rats. Pharmacol Rep. 2020;72:867-876.
• Coşkun B, Cömelekoğlu U, Polat A, Kaymaz FF. Evaluation of the toxic effects of cypermethrin inhalation on the frog heart. Ecotoxicol Environ Saf. 2004;57:220-5.
• Danese E, Montagnana M. An historical approach to the diagnostic biomarkers of acute coronary syndrome. Ann Transl Med. 2016;4:194.
• El sayed AO, Nasr NZ, Samia MME, Hanan TE, Fatma FH. Cardioprotective effect of ivabradine versus carvedilol in rats. Int J Pharm Sci Res. 2015;6:1862.
• Waz S, Matouk AI. Cardioprotective effect of allyl isothiocyanate in a rat model of doxorubicin acute toxicity. Toxicol Mech Methods. 2022;32:194-203.
• Al-Hesayen A, Floras JS, Parker JD. The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure. Eur J Heart Fail. 2006;8:864-8.
• Zhang M, Koitabashi N, Nagayama T, Rambaran R, Feng N, Takimoto E et al. Expression, activity, and pro-hypertrophic effects of PDE5A in cardiac myocytes. Cell Signal. 2008;20:2231-6.
• Salloum FN, Chau VQ, Hoke NN, Kukreja RC. Tadalafil prevents acute heart failure with reduced ejection fraction in mice. Cardiovasc Drugs Ther. 2014;28:493-500.
• Andersen A, Nielsen JM, Peters CD, Schou UK, Sloth E, Nielsen-Kudsk JE. Effects of phosphodiesterase-5 inhibition by sildenafil in the pressure overloaded right heart. Eur J Heart Fail. 2008;10:1158-65.
• Patrucco E, Domes K, Sbroggió M et al. Roles of cGMP-dependent protein kinase I (cGKI) and PDE5 in the regulation of Ang II-induced cardiac hypertrophy and fibrosis. Proc Natl Acad Sci U S A. 2014;111:12925-9.
• Dai W, Kloner RA. Is inhibition of phosphodiesterase type 5 by sildenafil a promising therapy for volume-overload heart failure? Circulation. 2012;125:1341-3.
• Schwartz BG, Levine LA, Comstock G, Stecher VJ, Kloner RA. Cardiac uses of phosphodiesterase-5 inhibitors. J Am Coll Cardiol. 2012;59:9-15.
• Salloum FN, Chau VQ, Hoke NN, Abbate A, Varma A, Ockaili RA et al. Phosphodiesterase-5 inhibitor, tadalafil, protects against myocardial ischemia/reperfusion through protein-kinase g-dependent generation of hydrogen sulfide. Circulation. 2009;120:S31-6.
• Aykan AÇ, Karabay CY, Yıldız M. Evaluation of cardiac functions after catheter ablation of atrioventricular nodal reentrant tachycardia. Turk J Med Sci. 2021;51:589-94.
• Nagy O, Hajnal Á, Parratt JR, et al. Sildenafil (Viagra) reduces arrhythmia severity during ischaemia 24 h after oral administration in dogs. Brit J Pharmacol. 2004;141:549–51.
• Salama A, Mostafa RE, Omara EA. Effects of phosphodiestrase type 5 inhibitors in epinephrine-induced arrhythmia in rats: Involvement of lactate dehydrogenase and creatine kinase downregulation and adiponectin expression. Hum Exp Toxicol. 2018;37:256-64