Aminophylline Infusion Rate Can Affect the Cardiac Rate and Electrocardiographic Findings in Neonate Rats

Document Type : Original Article

Authors

1 Department of Pediatrics, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran.

2 Department of Physiology, Persian Gulf Physiology Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran.

3 Department of Pediatrics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Background: Cardiac arrhythmias are identified as the major cause of mortality and morbidity in neonates. Most term and preterm infants admitted to the neonatal intensive care unit (NICU) suffer from respiratory diseases, and generally aminophylline as a nonselective phosphodiesterase inhibitor is used. Although aminophylline has several physiological effects on the heart tissue, it has been recognized to have some side effects. Neonates are more prone to its cardiac side effects, notably arrhythmias.
Objectives: This study aimed to evaluate and compare the effects of fast and slow aminophylline injections on electrocardiographic parameters and arrhythmias in neonate rats.
 
Methods: Thirty-two male Sprague-Dawley rats (10 days old, 50 g) were divided into 4 groups (8 in each): Group I and Group II were treated with 5 mg/kg of normal saline intravenously for 3 and 20 minutes, correspondingly, and Group III and Group IV were treated with a 5-mg/kg bolus of aminophylline intravenously for 3 and 20 minutes, respectively. On the experiment day, the rats were anesthetized with a mixture of ketamine (50 mg/kg) and xylazine (10 mg/kg) with intraperitoneal injection, and lead II electrocardiograms were recorded. The femoral vein was cannulated using polyethylene catheters (PE50) for the intravenous injection of aminophylline (5 mg/kg) or normal saline.
 
Results: The rats receiving aminophylline showed a dramatic reduction in the heart rate. Additionally, the PR interval and QTc significantly increased in the rats receiving aminophylline for 3 minutes. Moreover, complete heart blocks, premature ventricular beats, atrioventricular blocks (Mobitz I and Mobitz П), sustained and nonsustained ventricular tachycardias, and AV dissociations were observed.
 
Conclusions: The results of the current study indicated that a slow infusion rate could prevent the cardiac complications of aminophylline, particularly arrhythmias, in neonate rats.(Iranian Heart Journal 2020; 21(4): 33-42)
 

Highlights

 

 

Keywords

Full Text

 

 

References

  1. Turner CJ, Wren C. The epidemiology of arrhythmia in infants: a population-based study. J Paediatr Child Health. 2013;49(4):278-81. doi: 10.1111/jpc.12155.
  2. Jaeggi E, Ohman A. Fetal and Neonatal Arrhythmias. Clin Perinatol. 2016;43(1):99-112. doi: 10.1016/j.clp.2015.11.007.
  3. Baruteau AE, Perry JC, Sanatani S, Horie M, Dubin AM, at al. Evaluation and management of bradycardia in neonates and children. Eur J Pediatr. 2016; 175(2):151-61. doi: 10.1007/s00431-015-2689-z.
  4. Goodacre S, McLeod K. ABC of clinical electrocardiography: Paediatric electrocardiography. Bmj. 2002; 324(7350):1382-5. PMID: 12052812.
  5. Badrawi N, Hegazy RA, Tokovic E, Lotfy W, Mahmoud F, Aly H, at al. Arrhythmia in the neonatal intensive care unit. Pediatr Cardiol. 2009;30(3):325-30. doi: 10.1007/s00246-008-9355-4.
  6. Kundak AA, Dilli D, Karagol B, Karadag N, Zenciroglu A, Okumus N, Dogan V, Uzunalic N, at al. Non benign neonatal arrhythmias observed in a tertiary neonatal intensive care unit.  Indian J Pediatr. 2013;80 (7):555-9. doi: 10.1007/s12098-012-0852-3.
  7. Hoffman TM, Wernovsky G, Wieand TS, Cohen MI, Jennings AC, Vetter VL, Godinez RI, Gaynor JW, Spray TL, Rhodes LA, at al. The incidence of arrhythmias in a pediatric cardiac intensive care unit.  Pediatr Cardiol. 2002; 23 (6):598-604. doi: 10.1007/s00246-001-0079-y.
  8. Bar-Cohen Y, Silka MJ. Sudden cardiac death in pediatrics.  Curr Opin Pediatr. 2008; 20(5):517-21. doi: 10.1097/MOP.0b013e32830c9037.
  9. 9.       Jhang WK, Lee SC, Seo DM, Park JJ. Mechanical circulatory support to control medically intractable arrhythmias in pediatric patients after cardiac surgery. Korean Circ J. 2010;40(9):471-4. doi: 10.4070/kcj.2010.40.9.471.
  10. 10.    Barnes BJ, Hollands JM. Drug-induced arrhythmias. Crit Care Med. 2010; 38(6):S188-S97.  doi: 10.1097/CCM.0b013e3181de112a.
  11. 11.    Pramanik AK, Rangaswamy N, Gates T. Neonatal respiratory distress: a practical approach to its diagnosis and management. Pediatr Clinics North America. 2015;62(2):453-69.  doi: 10.1016/j.pcl.2014.11.008.
  12. 12.    Reuter S, Moser C, Baack M. Respiratory distress in the newborn. Pediatr Rev.2014;35(10):417-28. doi: 10.1542/pir.35-10-417.
  13. Henderson-Smart DJ, De Paoli AG. Prophylactic methylxanthine for prevention of apnoea in preterm infants. Cochrane Database Syst Rev.2010; 8(12): CD000432. doi: 10.1002/14651858.CD000432.pub2.
  14. Rodriguez RJ. Management of respiratory distress syndrome: an update.  Respir Care. 2003; 48(3): 279-87. PMID: 12667277.
  15. Armanian AM, Badiee Z, Afghari R, Salehimehr N, Hassanzade A, Sheikhzadeh S, Tehrani MS, Rezvan G. Prophylactic aminophylline for prevention of apnea at higher-risk preterm neonates. Iran Red Crescent Med J. 2014; 16(8),e12559. doi: 10.5812/ircmj.12559.
  16. Tilley SL. Methylxanthines in asthma. Handb Exp Pharmacol. 2011;200:439-56. doi: 10.1007/978-3-642-13443-2_17.
  17. Grover S, Jindal A, Bansal A, Singhi SC, at al. Acute bronchial asthma. Indian J Pediatr. 2011;78(11):1388-95. doi: 10.1007/s12098-011-0524-8.
  18. Henderson-Smart DJ, Steer PA. Caffeine versus theophylline for apnea in preterm infants. Cochrane Database Syst Rev. 2010;1: 1-19:CD000273. doi: 10.1002/14651858.CD000273.pub2.
  19. Riksen NP, Smits P, Rongen GA. The cardiovascular effects of methylxanthines.  Methylxanthines: Springer; 2011. 200, p. 413-37. doi: 10.1007/978-3-642-13443-2_16.
  20. D'Avila RS, Piva JP, Marostica PJ, Amantea SL. Early administration of two intravenous bolus of aminophylline added to the standard treatment of children with acute asthma. Respir Med. 2008;102(1):156-61. doi: 10.1016/j.rmed.2007.07.030
  21. Monks TJ, Smith RL, Caldwell J. A metabolic and pharmacokinetic comparison of theophylline and aminophylline (theophylline ethylenediamine). J Pharm Pharmacol. 1981; 33:93-7. PMID: 6111606.
  22. Neame M, Aragon O, Fernandes RM, Sinha I. Salbutamol or aminophylline for acute severe asthma: how to choose which one, when and why? Archives of Disease in Childhood-Education and Practice. 2015;100(4):215-22. doi: 10.1136/archdischild-2014-306186.
  23. Bender AT, Beavo JA. Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev. 2006; 58(3):488-520. doi: 10.1124/pr.58.3.5.
  24. Muller CE, Jacobson KA. Recent developments in adenosine receptor ligands and their potential as novel drugs.Biochim Biophys Acta.2011;1808(5):1290-308.doi: 10.1016/j.bbamem.2010.12.017.
  25. Chiba S, Hashimoto K. Effect of aminophylline on the SA node of the dog heart in situ. Tohoku J Exp Med.1973; 109(2):203-4. PMID: 4722724.
  26. 26. Xiang Y, Kobilka BK. Myocyte adrenoceptor signaling pathways. Science. 2003; 300 (5625):1530-2. doi: 10.1126/science.1079206.
  27. Chen L, Marquardt ML, Tester DJ, Sampson KJ, Ackerman MJ, Kass RS, at al. Mutation of an A-kinase-anchoring protein causes long-QT syndrome. Proc Natl Acad Sci U S a 2007; 104(52):20990-5. doi: 10.1073/pnas.0710527105.
  28. Greenberg, Harry B. Antin, Sidney H. Conduction in Atrial Flutter after Intravenous Injection of Aminophylline. J Electrocardiol.1972; 5(4):391-393. PMID: 4651658.
  29. Patel AK, Skatrud JB, Thomsen JH. Cardiac Arrhythmias Due to Oral Aminophylline in Patients with Chronic Obstructive Pulmonary Disease. Chest. 1981; 80(6): 661-5. PMID: 7307587.
  30. Hirota K, Yoshioka H, Kabara S, Kudo T, Ishihara H, Matsuki A, at al. A comparison of the relaxant effects of olprinone and aminophylline on methacholine-induced bronchoconstriction in dogs. Anesth Analg. 2001; 93(1):230-3. PMID: 11429372.
  31. Miller CL, Yan C. Targeting cyclic nucleotide phosphodiesterase in the heart: therapeutic implications. J Cardiovasc Transl Res. 2010;3(5):507-15. doi: 10.1007/s12265-010-9203-9.
  32. D. Mokra IT, H. Pistekova, Z. Visnovcova, J. Mokry, A. Drgova, M. Repcakova, A. Calkovska, at al. Short-term cardiovascular effects of selective phosphodiesterase 3 inhibitor olprinone versus non-selective phosphodiesterase inhibitor aminophylline in a meconium-induced acute lung injury. J Physiol  Pharmacol. 2013;64(6):751-9. PMID: 24388890.
  33. Aggelopoulou E, Tzortzis S, Tsiourantani F, Agrios I, Lazaridis K. Atrial Fibrillation and Shock: Unmasking Theophylline Toxicity. Med Princ Pract. 2018;27(4):387-91. doi: 10.1159/000490145.

 

Iranian Heart Journal
Volume 21, Issue 4
October 2020
Pages 22-31

Files

Share

How to cite

Statistics