Akut ve Kronik Doksorubisin Uygulamalarının Elektrokardiyografik Ölçümler Aracılığıyla Kardiyak Fonksiyon Üzerine Etkilerinin Değerlendirilmesi
Öz
Amaç: Kanser tedavisinde kullanılan ilaçlar kalp sorunlarına neden olmakta ve bu da kullanımlarını kısıtlamaktadır. Ayrıca, bu ilaçların uygulanma yönteminin farklı sonuçlara neden olduğu görülmektedir. Bu nedenle bu çalışmada, doksorubisin (DOX) ajanının akut ve kronik olarak uygulanmasının kalbin elektriksel aktivitesi üzerinde farklı etkilerinin olup olmadığının incelenmesi amaçlandı.
Materyal ve Metod: Ağırlıkları 200-250 gram arasında değişen 26 adet erkek Wistar-Albino sıçan üç gruba ayrıldı: Kontrol grubu: hayvanlara herhangi bir tedavi uygulanmadı (n=8), DOX akut grubu; 3 haftanın sonunda 15,05 mg/kg DOX i.p. olarak verildi (n=10), DOX kronik grubu; 3 haftada yedi kez her defasında 2,15 mg/kg DOX intraperitoneal (i.p.) uygulandı (n=10). Deney süresi sonunda tüm hayvanlardan elektrokardiyogram (EKG) ölçümleri alınarak değerlendirildi.
Bulgular: EKG verilerine göre kalp atım hızı, P dalga genliği ve P süresinin akut ve kontrol grupları arasında farklılık göstermediğini ancak kronik grupta istatistiksel olarak anlamlı azaldığı görüldü. Her iki DOX grubunda da PR intervali kontrole göre değişmedi. Ayrıca kronik grupta RR intervali anlamlı derecede artarken akut DOX grubunda değişmedi. Her iki DOX grubunda da QRS süresinin oldukça arttığı görüldü. Ayrıca her iki DOX grubunda da QT aralığında ciddi bir artış olduğu ancak kronik grupta artışın daha belirgin olduğu görüldü.
Sonuç: Sonuç olarak bu ilaçların uygulanma şeklinin kalp fonksiyonlarında anlamlı değişikliklere yol açabileceği düşünülmektedir. Akut DOX tedavisi, özellikle P dalgası genliği (atriyal kasılmanın bir ölçüsü) ve P dalga süresi (kasılmanın uzunluğu) üzerinde olumsuz etkilerinin olmayışı ile, kronik maruziyetten daha az zararlı olabileceği düşünülmektedir. Ancak bu bulguları doğrulamak için daha ileri çalışmalara ihtiyaç vardır.
Anahtar Kelimeler
Teşekkür
Çalışma için etik kurul belgesi alınmıştır.
Kaynakça
- 1. Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin Cardiomyopathy. Cardiology 2010;115:155–62.
- 2. Renu K, V G A, P B TP, Arunachalam S. Molecular mecha-nism of doxorubicin-induced cardiomyopathy - An update. Eur J Pharmacol. 2018;818:241–53.
- 3. Page RL, O’Bryant CL, Cheng D, Dow TJ, Ky B, Stein CM, et al. Drugs That May Cause or Exacerbate Heart Failure. Cir-culation 2016;134:e32–69.
- 4. Rawat PS, Jaiswal A, Khurana A, Bhatti JS, Navik U. Doxo-rubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed Pharmacother 2021;139:111708.
- 5. Sonawane VK, Mahajan UB, Shinde SD, Chatterjee S, Chaudhari SS, Bhangale HA, et al. A Chemosensitizer Drug: Disulfiram Prevents Doxorubicin-Induced Cardiac Dysfunc-tion and Oxidative Stress in Rats. Cardiovasc Toxicol 2018;18:459–70.
- 6. Shinlapawittayatorn K, Chattipakorn SC, Chattipakorn N. The effects of doxorubicin on cardiac calcium homeostasis and contractile function. J Cardiol 2022;80:125–32.
- 7. Kinoshita T, Yuzawa H, Natori K, Wada R, Yao S, Yano K, et al. Early electrocardiographic indices for predicting chronic doxorubicin-induced cardiotoxicity. J Cardiol 2021;77:388–94.
- 8. Wellenius GA, Batalha JRF, Diaz EA, Lawrence J, Coull BA, Katz T, et al. Cardiac effects of carbon monoxide and am-bient particles in a rat model of myocardial infarction. Tox-icol Sci 2004;80:367–76. https://doi.org/10.1093/toxsci/kfh161.
- 9. Warhol A, George SA, Obaid SN, Efimova T, Efimov IR. Differential cardiotoxic electrocardiographic response to doxorubicin treatment in conscious versus anesthetized mice. Physiol Rep 2021;9:e14987.
- 10. Dulf PL, Mocan M, Coadă CA, Dulf DV, Moldovan R, Baldea I, et al. Doxorubicin-induced acute cardiotoxicity is associ-ated with increased oxidative stress, autophagy, and in-flammation in a murine model. Naunyn Schmiedebergs Arch Pharmacol 2023;396:1105–15.
- 11. Hengel CL, Russell PA, Gould PA, Kaye DM. Subacute An-thracycline Cardiotoxicity. Hear Lung Circ 2006;15:59–61.
- 12. Kinoshita T, Yuzawa H, Natori K, Wada R, Yao S, Yano K, et al. Early electrocardiographic indices for predicting chronic doxorubicin-induced cardiotoxicity. J Cardiol 2021;77:388–94.
- 13. Bhagat A, Kleinerman ES. Anthracycline-Induced Cardiotox-icity: Causes, Mechanisms, and Prevention. Adv. Exp. Med. Biol., vol. 2020;1257:81–92.
- 14. Cai F, Luis M, Lin X, Wang M, Cai L, Cen C, et al. Anthracy-cline‑induced cardiotoxicity in the chemotherapy treatment of breast cancer: Preventive strategies and treatment (Re-view). Mol Clin Oncol 2019;11:15–23.
- 15. Hazari MS, Haykal-Coates N, Winsett DW, Costa DL, Farraj AK. Continuous Electrocardiogram Reveals Differences in the Short-Term Cardiotoxic Response of Wistar-Kyoto and Spontaneously Hypertensive Rats to Doxorubicin. Toxicol Sci 2009;110:224–34.
- 16. Younis NS. Doxorubicin-Induced Cardiac Abnormalities in Rats: Attenuation via Sandalwood Oil. Pharmacology 2020;105:522–30.
- 17. Benjanuwattra J, Siri-Angkul N, Chattipakorn SC, Chattipa-korn N. Doxorubicin and its proarrhythmic effects: A com-prehensive review of the evidence from experimental and clinical studies. Pharmacol Res 2020;151:104542.
- 18. Funck-Brentano C, Jaillon P. Rate-corrected QT interval: Techniques and limitations. Am J Cardiol 1993;72:B17–22.
- 19. Alexander B, Haseeb S, van Rooy H, Tse G, Hopman W, Martinez-Selles M, et al. Reduced P-wave Voltage in Lead I is Associated with Development of Atrial Fibrillation in Pa-tients with Coronary Artery Disease. J Atr Fibrillation 2017;10:1657.
- 20. Emeka PM, Al-Ahmed A. Effect of metformin on ECG, HR and BP of rats administered with cardiotoxic agent doxoru-bicin. Int J Basic Clin Pharmacol 2017;6:1054.
- 21. Rudzinski T, Ciesielczyk M, Religa W, Bednarkiewicz Z, Krzeminska-Pakula M. Doxorubicin-induced ventricular ar-rhythmia treated by implantation of an automatic cardio-verter-defibrillator. EP Eur 2007;9:278– 80.
- 22. Villani F, Monti E, Piccinini F, Favalli L, Lanza E, Dionigi AR, et al. Relationship between Doxorubicin-Induced Ecg Changes and Myocardial Alterations in Rats. Tumori J 1986;72:323–9.
- 23. Yildirim N, Lale A, Yazıcı GN, Sunar M, Aktas M, Ozcicek A, et al. ). Ameliorative effects of Liv-52 on doxorubicin-induced oxidative damage in rat liver. Biotech Histochem. 2022;97:616–21.
Evaluating the Effects of Acute and Chronic Doxorubicin Administration on Cardiac Function Through Electrocardiographic Measurements
Öz
Background: The medications used to treat cancer can lead to cardiac problems, which restricts their use. Furthermore, the method these medications are taken seems to have an impact on varied out-comes. Therefore, this study aimed to examine whether administering doxorubicin (DOX) agent acutely and chronically has distinct impacts on the electrical activity of the heart.
Materials and Methods: Twenty-six male Wistar-Albino rats, weighing between 200-250 grams, were split into three groups: control group; no treatment was applied to animals (n=8), DOX acute group: a single dosage of 15.05 mg/kg of DOX was given at the end of the 3 weeks (n=8), DOX chronic group; which received an intraperitoneal (i.p.) 2.15 mg/kg DOX for 3 weeks, 7 doses in total (n=10). At the end of the experimental period, electrocardiogram (ECG) measurements were taken for all animals and evaluated.
Results: ECG data showed that heart rate (HR), P wave amplitude, and P duration did not differ between the acute and control groups but did statistically significantly declined in the chronic group. In both DOX groups, PR interval remained unchanged compared to the control. Also, RR interval increased significantly in the chronic group while it remained unchanged in the acute DOX dose group. The QRS duration was found to have considerably increased in both DOX groups. Furthermore, it was found that both DOX groups had a considerable increase in the QT interval, although the chronic group's increase was more noticeable.
Conclusions: In conclusion, it is thought that the ways in which these medications are administered may result in significant variations in heart function. Acute DOX treatment appears to be less harmful than chronic exposure, as evidenced by its lack of adverse effects, particularly on P wave amplitude (a measure of atrial contraction) and P wave duration (the length of the contraction). However, more research is required to validate these findings.
Key Words: Electrocardiogram (ECG), Doxorubicin (DOX), Cardiotoxicity
Anahtar Kelimeler
Kaynakça
- 1. Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin Cardiomyopathy. Cardiology 2010;115:155–62.
- 2. Renu K, V G A, P B TP, Arunachalam S. Molecular mecha-nism of doxorubicin-induced cardiomyopathy - An update. Eur J Pharmacol. 2018;818:241–53.
- 3. Page RL, O’Bryant CL, Cheng D, Dow TJ, Ky B, Stein CM, et al. Drugs That May Cause or Exacerbate Heart Failure. Cir-culation 2016;134:e32–69.
- 4. Rawat PS, Jaiswal A, Khurana A, Bhatti JS, Navik U. Doxo-rubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed Pharmacother 2021;139:111708.
- 5. Sonawane VK, Mahajan UB, Shinde SD, Chatterjee S, Chaudhari SS, Bhangale HA, et al. A Chemosensitizer Drug: Disulfiram Prevents Doxorubicin-Induced Cardiac Dysfunc-tion and Oxidative Stress in Rats. Cardiovasc Toxicol 2018;18:459–70.
- 6. Shinlapawittayatorn K, Chattipakorn SC, Chattipakorn N. The effects of doxorubicin on cardiac calcium homeostasis and contractile function. J Cardiol 2022;80:125–32.
- 7. Kinoshita T, Yuzawa H, Natori K, Wada R, Yao S, Yano K, et al. Early electrocardiographic indices for predicting chronic doxorubicin-induced cardiotoxicity. J Cardiol 2021;77:388–94.
- 8. Wellenius GA, Batalha JRF, Diaz EA, Lawrence J, Coull BA, Katz T, et al. Cardiac effects of carbon monoxide and am-bient particles in a rat model of myocardial infarction. Tox-icol Sci 2004;80:367–76. https://doi.org/10.1093/toxsci/kfh161.
- 9. Warhol A, George SA, Obaid SN, Efimova T, Efimov IR. Differential cardiotoxic electrocardiographic response to doxorubicin treatment in conscious versus anesthetized mice. Physiol Rep 2021;9:e14987.
- 10. Dulf PL, Mocan M, Coadă CA, Dulf DV, Moldovan R, Baldea I, et al. Doxorubicin-induced acute cardiotoxicity is associ-ated with increased oxidative stress, autophagy, and in-flammation in a murine model. Naunyn Schmiedebergs Arch Pharmacol 2023;396:1105–15.
- 11. Hengel CL, Russell PA, Gould PA, Kaye DM. Subacute An-thracycline Cardiotoxicity. Hear Lung Circ 2006;15:59–61.
- 12. Kinoshita T, Yuzawa H, Natori K, Wada R, Yao S, Yano K, et al. Early electrocardiographic indices for predicting chronic doxorubicin-induced cardiotoxicity. J Cardiol 2021;77:388–94.
- 13. Bhagat A, Kleinerman ES. Anthracycline-Induced Cardiotox-icity: Causes, Mechanisms, and Prevention. Adv. Exp. Med. Biol., vol. 2020;1257:81–92.
- 14. Cai F, Luis M, Lin X, Wang M, Cai L, Cen C, et al. Anthracy-cline‑induced cardiotoxicity in the chemotherapy treatment of breast cancer: Preventive strategies and treatment (Re-view). Mol Clin Oncol 2019;11:15–23.
- 15. Hazari MS, Haykal-Coates N, Winsett DW, Costa DL, Farraj AK. Continuous Electrocardiogram Reveals Differences in the Short-Term Cardiotoxic Response of Wistar-Kyoto and Spontaneously Hypertensive Rats to Doxorubicin. Toxicol Sci 2009;110:224–34.
- 16. Younis NS. Doxorubicin-Induced Cardiac Abnormalities in Rats: Attenuation via Sandalwood Oil. Pharmacology 2020;105:522–30.
- 17. Benjanuwattra J, Siri-Angkul N, Chattipakorn SC, Chattipa-korn N. Doxorubicin and its proarrhythmic effects: A com-prehensive review of the evidence from experimental and clinical studies. Pharmacol Res 2020;151:104542.
- 18. Funck-Brentano C, Jaillon P. Rate-corrected QT interval: Techniques and limitations. Am J Cardiol 1993;72:B17–22.
- 19. Alexander B, Haseeb S, van Rooy H, Tse G, Hopman W, Martinez-Selles M, et al. Reduced P-wave Voltage in Lead I is Associated with Development of Atrial Fibrillation in Pa-tients with Coronary Artery Disease. J Atr Fibrillation 2017;10:1657.
- 20. Emeka PM, Al-Ahmed A. Effect of metformin on ECG, HR and BP of rats administered with cardiotoxic agent doxoru-bicin. Int J Basic Clin Pharmacol 2017;6:1054.
- 21. Rudzinski T, Ciesielczyk M, Religa W, Bednarkiewicz Z, Krzeminska-Pakula M. Doxorubicin-induced ventricular ar-rhythmia treated by implantation of an automatic cardio-verter-defibrillator. EP Eur 2007;9:278– 80.
- 22. Villani F, Monti E, Piccinini F, Favalli L, Lanza E, Dionigi AR, et al. Relationship between Doxorubicin-Induced Ecg Changes and Myocardial Alterations in Rats. Tumori J 1986;72:323–9.
- 23. Yildirim N, Lale A, Yazıcı GN, Sunar M, Aktas M, Ozcicek A, et al. ). Ameliorative effects of Liv-52 on doxorubicin-induced oxidative damage in rat liver. Biotech Histochem. 2022;97:616–21.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | İnsan Biyofiziği |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Erken Görünüm Tarihi | 16 Nisan 2024 |
| Yayımlanma Tarihi | 29 Nisan 2024 |
| Gönderilme Tarihi | 12 Aralık 2023 |
| Kabul Tarihi | 20 Mart 2024 |
| Yayımlandığı Sayı | Yıl 2024 Cilt: 21 Sayı: 1 |
Harran Üniversitesi Tıp Fakültesi Dergisi / Journal of Harran University Medical Faculty