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The effect of chloramphenicol and florfenicol on electrocardiogram in guinea pigs

Year 2011, Volume: 58 Issue: 3, 155 - 160, 01.09.2011
https://doi.org/10.1501/Vetfak_0000002467

Abstract

In this study, the effects of chloramphenicol and florfenicol on electrocardiogram of guinea pigs were investigated. Single dose of 20 mg/kg of chloramphenicol intramuscular and 20 mg/kg of florfenicol have been applied to the groups orally at the same time every day for one week duration. After the results of electrocardiograms obtained were examined, it was determined that there has been an increase (p<0.01) in P wave amplitude with chloramphenicol application and there has been a shortening (p<0.001) in the duration of P wave compared to the control group for both test groups. It was observed that there has been a shortening (p<0.01) in the duration of P-R interval in the chloramphenicol applied group compared to the control group. When we had an evaluation between groups in terms of R wave amplitude, shortening (p<0.05) was observed in the group of which florphenicol was applied. Shortening has been observed in the duration of QRS complex (p<0.001), the duration of QT interval (p<0.001), QTc value (p<0.05) in the test groups compared to the control group, on the other hand an increase has been observed in the duration of T wave (p<0.05) and the number of heartbeat as minute (p<0.01). As a result, because these changes have been observed after the application of chloramphenicol and florfenicol on electrocardiogram, it has been reached to an opinion that these medications may cause adverse effects on cardiovascular system

References

  • Abd Et-Aty AM, Goudah A, Abo El-Sooud K, El-Zorba HY, Shimoda M, Zhou HH (2004). Pharmacokinetics and bioavailability of florfenicol following intravenous, intramuscular and oral adminstrations in rabbits. Vet Res Communication, 28: 515-524.
  • Akkan HA, Karaca M (2003): Veteriner iç hastalıklarında antibiyotiklerin kullanımı. YYÜ Vet Fak Derg, 14(2)72-77.
  • Atterhög JH, Loogna E (1977): PR interval in relation to heart rate during exercise and the influence of posture and autonomic tone. J Electrocardiol, 10, 331-336.
  • Bjerregaard P, Gussak I (2005): Short QT syndrome: mechanisms, diagnosis and treatment. Nat Clin Pract Cardiovasc Med, 2, 84-87.
  • Braibant M, Chevalier J, Chaslus-Dancla E, Pages JM, Cloeckaert A (2005): Structural and functional study of the phenicol-specific efflux pump flor belonging to the major facilitator superfamily. AAC, 49, 2965-2971.
  • Carlson J, Johansson R, Olsson SB (2001): Classification of electrocardiographic P-wave morphology. IEEE Trans Biomed Eng, 48, 401-405.
  • Cheng HC, Incardona J, McCullough B (2006): Isolated perfused and paced guinea pig heart to test for drug- induced changes of. J Pharmacol Toxicol Methods, 54,
  • Cieslar G, Sieron A, Rzepka E, Zmudzinski J, Franek A (1986): Normal Electrocardiogram in guinea pig. Acta Physiol Pol, 37, 139-149.
  • Craene BA, Deprez P, D’Haese E, Nelis HJ, Van den Bossche W, De Leenheer P (1997): Pharmacokinetics of florfenicol in cerebrospinal fluid and plasma of calves. AAC, 41, 1991-1995.
  • Doggrell SA (2004): Inhibition of cardiac cytochrome P450: a new approach to cardiac ischaemia and reperfusion damage.Expert Opin Ther Targets, 8, 491- 493.
  • Etuk EU, Onyeyili PA (2005): The comparative study of the tissue kinetics of chloramphenicol in healthy and Salmonella infected goats. Pakistan J Biol Sci, 8, 369-373.
  • Garberoglio L, Giustetto C, Wolpert C, Gaita F (2007): Is acquired short QT due to digitalis intoxication responsible for malignant venticular arrhythmias. J Electrocardiol, 40, 43-46.
  • Goldberger AL (2006): Clinical electrocardiography: A simplified approach. Erişim: http://www.mdconsult.com/das/book/body/114879272- 2/0/1394/33.html (18.01.2010).
  • Granville DJ, Tashakkor B, Takeuchi C, Gustafsson AB, Huang C, Sayen MR, Wentworth P, Yeager M, Gottlieb RA (2004): Reduction of ischemia and reperfusion-induced myocardial damage by cytochrome P450 inhibitors. PNAS, 101, 1321-1326.
  • Granville DJ, Gottlieb RA (2005): Cytochromes P450 and ischemic heart injury: potential role for inhibitors in the treatment of myocardial infarction. Drug Discov Today Dis Mech, 2, 123-127.
  • Guengerich FP (2000): Cytochrome P450 enzymes in the heart. Lancet, 355, 945-946.
  • Gussak I, Chaitman BR, Kopecky SL, Nerbonne JM (2000): Rapid ventricular repolarization in rodents: Electrocardiographic manifestations, molecular mechanisms, and clinical insights. J Electrocardiol, 33, 1-12.
  • Guth BD (2007): Preclinical cardiovascular risk assessment in modern drug development. Toxicol Sci, 97, 4-20.
  • Hamlin RL, Kijtawornrat A, Keene BW, Hamlin DM (2003): QT and RR intervals in conscious and anesthetized guinea pigs with highly varying RR intervals and given QTc-lengthening test articles. Toxicol Sci, 76, 437-442.
  • Hanton G, Nahas K, Priou C, Rabemampianina Y, Baneux P (2001): The QT interval in the dog ECG: Importance in preclinical toxicology and relationship to heart rate. Toxicol Methods, 11, 21-40.
  • Hauser DS, Stade M, Schmidt A, Hanauer G (2005): Cardiovascular parameters in anaesthetized guinea pig: A safety pharmacology screening model. J Pharmacol Toxicol Methods, 52:106-114.
  • Hess P, Rey M, Wanner D, Steiner B, Clozel M (2007): Measurements of blood pressure and electrocardiogram in conscious freely moving guinea pig: a model for screening QT interval prolongation effects. Laboratory Anim, 41: 470-480.
  • Holbrook M, Malik M, Shah RR, Valentin JP (2008): Drug induced shortening of the QT/QTc interval. J Pharmacol and Toxicol Methods, 59: 21-28.
  • Iannini, PB (2002): Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval. Expert Opinion on Drug Safety, 1: 121-128.
  • Kawasaki T, Akakabe Y, Yamano M, Miki S, Kamitani T, Kuribayashi T, Sugihara H (2008): R-wave amplitude response to myocardial ischemia in hypertrophic cardiomyopathy. J Electrocardiol, 41, 68-71.
  • Kaya S (2007): Fenikoller. Alınmıştır (Ed) Kaya S, Veteriner Farmakoloji, Cilt 2, 4. Basım, Medisan Yayın Serisi: 65, Ankara.
  • Leiter LM, Thatte HS, Okafor C, Marks PW, Golan DE, Bridges KR (1999): Chloramphenicol-induced mitochondrial dysfunction is associated with decreased transferrin receptor expression and ferritin synthesis in K562 cells and is unrelated to IRE-IRP interactions. J Cell Physiol, 180, 334-344.
  • Lipicky, RJ (1993): A viewpoint on drugs that prolong the QTc interval. Am. J. Cardiol,72: 53-54.
  • Lu HR, Vlaminckx E, Hermans AN, Rohrbacher J, Van Ammel K, Towart R, Pugsley M, Gallacher DJ (2008): Predicting drug-induced changes in QT interval and arrhythmias: QT-shortening drugs point to gaps in the ICHS7B guidelines. Br J Pharmacol, 154, 1427-1438.
  • Marks AR (2003): Calcium and the heart: a question of life and death. J Clinical Invest, 111, 597-600.
  • Özaras R, Tabak F, Öztürk R (2002): Antibiyotikler III. Akılcı Antibiyotik Kullanım ve Erişkinde Toplumdan Edinilmiş Enfeksiyonlar Sempozyum Dizisi No:31, 55-82.
  • Picco EJ, Diaz DC, Valtorta SE, Boggio JC (2001): Chronotoxicology of florfenicol. Chronobiol Int, 18, 567- 572.
  • Pişkin İ, Şireli M, Sağmanlıgil V, Emre B (1999): Kobaylarda bazı anestezik maddelerin elektrokardiyogram üzerine etkileri.Turk J Vet Anim Sci, 23,161-166.
  • Sams RA (1995): Florfenicol: Chemistry and metabolism of novel broad-spectrum antibiotic. Tieraerztl Umsch, 50:
  • Tang SW, Helmeste DM, Vu R (1996): Cytochrome P450 inhibition: interactions with calcium and serotonin transporter. Europe Neuropsychopharmacol, 6, 195-195.
  • Thandroyen FT, Morris AC, Hagler HK, Ziman B, Pai L, Willerson JT, Buja LM (1991): Intracellular calcium transients and arrhythmia in isolated heart cells. Circ Res, 69, 810-819.
  • Tomaszewski T, Poznan MD (1951): Side-effects of chloramphenicol and aureomycin, with special reference to oral lesions. Br Med J, 1, 388-392.
  • Xiao YF, Huang L, Morgan JP (1998): Cytochrome P450: a novel system modulating Ca2+ channels and contraction in mammalian heart cells. J Physiol, 508, 777- 792.

Kobaylarda kloramfenikol ve florfenikol’ün elektrokardiyogram üzerine etkisi

Year 2011, Volume: 58 Issue: 3, 155 - 160, 01.09.2011
https://doi.org/10.1501/Vetfak_0000002467

Abstract

Çalışmada kobaylarda amfenikol grubundankloramfenikol ve florfenikolün elektrokardiyogram üzerine etkileri incelendi. Deney gruplarındaki hayvanlara bir hafta süre ile her gün aynı saatte tek doz 20 mg/kg kloramfenikol intramuskuler ve 20 mg/kg florfenikol oral yol ile uygulandı. Elde edilen elektrokardiyogramların incelenmesi sonrasında, P dalgası amplitüdünde kloramfenikol uygulamasıyla büyüme (p<0.01), P dalgasının süresinde her iki deney grubunda da kontrole göre kısalma (p<0.001) belirlendi. P-R aralığı süresinde kontrole oranla kloramfenikol uygulanan grupta kısalma (p<0.01) tespit edildi. R dalgasının amplitüdü açısından gruplar arasında değerlendirme yapıldığında kısalma (p<0.05) şeklindeki fark florfenikol uygulanan grupta belirlendi. QRS kompleksi süresi (p<0.001), QT aralığının süresi (p<0.001), QTc değerinde kontrole oranla deney gruplarına ait değerlerde kısalma (p<0.05), T dalgası süresi (p<0.05) ve dakika kalp atım sayısında ise artış (p<0.01) kaydedildi. Sonuç olarak, kloramfenikol ve florfenikol uygulanmasından sonra elektrokardiyogramda gözlenen değişiklikler bu iki ilacın kardiyovasküler sistemde istenmeyen etkilere neden olabileceği kanısını uyandırdı

References

  • Abd Et-Aty AM, Goudah A, Abo El-Sooud K, El-Zorba HY, Shimoda M, Zhou HH (2004). Pharmacokinetics and bioavailability of florfenicol following intravenous, intramuscular and oral adminstrations in rabbits. Vet Res Communication, 28: 515-524.
  • Akkan HA, Karaca M (2003): Veteriner iç hastalıklarında antibiyotiklerin kullanımı. YYÜ Vet Fak Derg, 14(2)72-77.
  • Atterhög JH, Loogna E (1977): PR interval in relation to heart rate during exercise and the influence of posture and autonomic tone. J Electrocardiol, 10, 331-336.
  • Bjerregaard P, Gussak I (2005): Short QT syndrome: mechanisms, diagnosis and treatment. Nat Clin Pract Cardiovasc Med, 2, 84-87.
  • Braibant M, Chevalier J, Chaslus-Dancla E, Pages JM, Cloeckaert A (2005): Structural and functional study of the phenicol-specific efflux pump flor belonging to the major facilitator superfamily. AAC, 49, 2965-2971.
  • Carlson J, Johansson R, Olsson SB (2001): Classification of electrocardiographic P-wave morphology. IEEE Trans Biomed Eng, 48, 401-405.
  • Cheng HC, Incardona J, McCullough B (2006): Isolated perfused and paced guinea pig heart to test for drug- induced changes of. J Pharmacol Toxicol Methods, 54,
  • Cieslar G, Sieron A, Rzepka E, Zmudzinski J, Franek A (1986): Normal Electrocardiogram in guinea pig. Acta Physiol Pol, 37, 139-149.
  • Craene BA, Deprez P, D’Haese E, Nelis HJ, Van den Bossche W, De Leenheer P (1997): Pharmacokinetics of florfenicol in cerebrospinal fluid and plasma of calves. AAC, 41, 1991-1995.
  • Doggrell SA (2004): Inhibition of cardiac cytochrome P450: a new approach to cardiac ischaemia and reperfusion damage.Expert Opin Ther Targets, 8, 491- 493.
  • Etuk EU, Onyeyili PA (2005): The comparative study of the tissue kinetics of chloramphenicol in healthy and Salmonella infected goats. Pakistan J Biol Sci, 8, 369-373.
  • Garberoglio L, Giustetto C, Wolpert C, Gaita F (2007): Is acquired short QT due to digitalis intoxication responsible for malignant venticular arrhythmias. J Electrocardiol, 40, 43-46.
  • Goldberger AL (2006): Clinical electrocardiography: A simplified approach. Erişim: http://www.mdconsult.com/das/book/body/114879272- 2/0/1394/33.html (18.01.2010).
  • Granville DJ, Tashakkor B, Takeuchi C, Gustafsson AB, Huang C, Sayen MR, Wentworth P, Yeager M, Gottlieb RA (2004): Reduction of ischemia and reperfusion-induced myocardial damage by cytochrome P450 inhibitors. PNAS, 101, 1321-1326.
  • Granville DJ, Gottlieb RA (2005): Cytochromes P450 and ischemic heart injury: potential role for inhibitors in the treatment of myocardial infarction. Drug Discov Today Dis Mech, 2, 123-127.
  • Guengerich FP (2000): Cytochrome P450 enzymes in the heart. Lancet, 355, 945-946.
  • Gussak I, Chaitman BR, Kopecky SL, Nerbonne JM (2000): Rapid ventricular repolarization in rodents: Electrocardiographic manifestations, molecular mechanisms, and clinical insights. J Electrocardiol, 33, 1-12.
  • Guth BD (2007): Preclinical cardiovascular risk assessment in modern drug development. Toxicol Sci, 97, 4-20.
  • Hamlin RL, Kijtawornrat A, Keene BW, Hamlin DM (2003): QT and RR intervals in conscious and anesthetized guinea pigs with highly varying RR intervals and given QTc-lengthening test articles. Toxicol Sci, 76, 437-442.
  • Hanton G, Nahas K, Priou C, Rabemampianina Y, Baneux P (2001): The QT interval in the dog ECG: Importance in preclinical toxicology and relationship to heart rate. Toxicol Methods, 11, 21-40.
  • Hauser DS, Stade M, Schmidt A, Hanauer G (2005): Cardiovascular parameters in anaesthetized guinea pig: A safety pharmacology screening model. J Pharmacol Toxicol Methods, 52:106-114.
  • Hess P, Rey M, Wanner D, Steiner B, Clozel M (2007): Measurements of blood pressure and electrocardiogram in conscious freely moving guinea pig: a model for screening QT interval prolongation effects. Laboratory Anim, 41: 470-480.
  • Holbrook M, Malik M, Shah RR, Valentin JP (2008): Drug induced shortening of the QT/QTc interval. J Pharmacol and Toxicol Methods, 59: 21-28.
  • Iannini, PB (2002): Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval. Expert Opinion on Drug Safety, 1: 121-128.
  • Kawasaki T, Akakabe Y, Yamano M, Miki S, Kamitani T, Kuribayashi T, Sugihara H (2008): R-wave amplitude response to myocardial ischemia in hypertrophic cardiomyopathy. J Electrocardiol, 41, 68-71.
  • Kaya S (2007): Fenikoller. Alınmıştır (Ed) Kaya S, Veteriner Farmakoloji, Cilt 2, 4. Basım, Medisan Yayın Serisi: 65, Ankara.
  • Leiter LM, Thatte HS, Okafor C, Marks PW, Golan DE, Bridges KR (1999): Chloramphenicol-induced mitochondrial dysfunction is associated with decreased transferrin receptor expression and ferritin synthesis in K562 cells and is unrelated to IRE-IRP interactions. J Cell Physiol, 180, 334-344.
  • Lipicky, RJ (1993): A viewpoint on drugs that prolong the QTc interval. Am. J. Cardiol,72: 53-54.
  • Lu HR, Vlaminckx E, Hermans AN, Rohrbacher J, Van Ammel K, Towart R, Pugsley M, Gallacher DJ (2008): Predicting drug-induced changes in QT interval and arrhythmias: QT-shortening drugs point to gaps in the ICHS7B guidelines. Br J Pharmacol, 154, 1427-1438.
  • Marks AR (2003): Calcium and the heart: a question of life and death. J Clinical Invest, 111, 597-600.
  • Özaras R, Tabak F, Öztürk R (2002): Antibiyotikler III. Akılcı Antibiyotik Kullanım ve Erişkinde Toplumdan Edinilmiş Enfeksiyonlar Sempozyum Dizisi No:31, 55-82.
  • Picco EJ, Diaz DC, Valtorta SE, Boggio JC (2001): Chronotoxicology of florfenicol. Chronobiol Int, 18, 567- 572.
  • Pişkin İ, Şireli M, Sağmanlıgil V, Emre B (1999): Kobaylarda bazı anestezik maddelerin elektrokardiyogram üzerine etkileri.Turk J Vet Anim Sci, 23,161-166.
  • Sams RA (1995): Florfenicol: Chemistry and metabolism of novel broad-spectrum antibiotic. Tieraerztl Umsch, 50:
  • Tang SW, Helmeste DM, Vu R (1996): Cytochrome P450 inhibition: interactions with calcium and serotonin transporter. Europe Neuropsychopharmacol, 6, 195-195.
  • Thandroyen FT, Morris AC, Hagler HK, Ziman B, Pai L, Willerson JT, Buja LM (1991): Intracellular calcium transients and arrhythmia in isolated heart cells. Circ Res, 69, 810-819.
  • Tomaszewski T, Poznan MD (1951): Side-effects of chloramphenicol and aureomycin, with special reference to oral lesions. Br Med J, 1, 388-392.
  • Xiao YF, Huang L, Morgan JP (1998): Cytochrome P450: a novel system modulating Ca2+ channels and contraction in mammalian heart cells. J Physiol, 508, 777- 792.
There are 38 citations in total.

Details

Primary Language English
Subjects Veterinary Surgery
Other ID JA85NM52UB
Journal Section Research Article
Authors

Burçan Bektemuroğlu

Meltem Şireli

Publication Date September 1, 2011
Published in Issue Year 2011Volume: 58 Issue: 3

Cite

APA Bektemuroğlu, B., & Şireli, M. (2011). The effect of chloramphenicol and florfenicol on electrocardiogram in guinea pigs. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 58(3), 155-160. https://doi.org/10.1501/Vetfak_0000002467
AMA Bektemuroğlu B, Şireli M. The effect of chloramphenicol and florfenicol on electrocardiogram in guinea pigs. Ankara Univ Vet Fak Derg. September 2011;58(3):155-160. doi:10.1501/Vetfak_0000002467
Chicago Bektemuroğlu, Burçan, and Meltem Şireli. “The Effect of Chloramphenicol and Florfenicol on Electrocardiogram in Guinea Pigs”. Ankara Üniversitesi Veteriner Fakültesi Dergisi 58, no. 3 (September 2011): 155-60. https://doi.org/10.1501/Vetfak_0000002467.
EndNote Bektemuroğlu B, Şireli M (September 1, 2011) The effect of chloramphenicol and florfenicol on electrocardiogram in guinea pigs. Ankara Üniversitesi Veteriner Fakültesi Dergisi 58 3 155–160.
IEEE B. Bektemuroğlu and M. Şireli, “The effect of chloramphenicol and florfenicol on electrocardiogram in guinea pigs”, Ankara Univ Vet Fak Derg, vol. 58, no. 3, pp. 155–160, 2011, doi: 10.1501/Vetfak_0000002467.
ISNAD Bektemuroğlu, Burçan - Şireli, Meltem. “The Effect of Chloramphenicol and Florfenicol on Electrocardiogram in Guinea Pigs”. Ankara Üniversitesi Veteriner Fakültesi Dergisi 58/3 (September 2011), 155-160. https://doi.org/10.1501/Vetfak_0000002467.
JAMA Bektemuroğlu B, Şireli M. The effect of chloramphenicol and florfenicol on electrocardiogram in guinea pigs. Ankara Univ Vet Fak Derg. 2011;58:155–160.
MLA Bektemuroğlu, Burçan and Meltem Şireli. “The Effect of Chloramphenicol and Florfenicol on Electrocardiogram in Guinea Pigs”. Ankara Üniversitesi Veteriner Fakültesi Dergisi, vol. 58, no. 3, 2011, pp. 155-60, doi:10.1501/Vetfak_0000002467.
Vancouver Bektemuroğlu B, Şireli M. The effect of chloramphenicol and florfenicol on electrocardiogram in guinea pigs. Ankara Univ Vet Fak Derg. 2011;58(3):155-60.