FUNCTIONAL DYNAMICS OF MYOCARDIAL INJURY BIOMARKERS PRODUCTION DURING ACUTE ISOPRENALINE TREATMENT IN RATS
Keywords:
Acute myocardial injury, Isoprenaline, Cardiac injury biomarkers, ECG, Rat
Abstract
Introduction: Isoprenaline s. isoproterenol (1-(3,4-dihydroxyphenyl)-2-isopropylaminoethanolhydrochloride; ISO), a synthetic β-adrenergic agonist, can be used to establish myocardial ischemia, cardiotoxicity, necrosis and/or an experimental model of infarction in rats.
Aim: Determination of the dynamics of myocardial injury biomarkers production: aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), and high-sensitive troponin T (hsTnT) with changes on electrocardiogram (ECG) parameters during the subcutaneous aplication of ISO in male Wistar rats.
Material and methods: All animals (n = 23) were divided into two groups: control group (n = 11) treated with a saline solution, during two consecutive days (0,2 ml/kg b.m. daily, s.c); and the ISO group (n = 12) treated with isoprenaline, during two consecutive days (85 mg/kg b.m. daily, s.c). Blood was drawn from the rat tail vein in both groups in order to determine serum activity levels of myocardial injury biomarkers, and an ECG (n= 6) was registered prior to the application as well as 48 h following the first dose of of saline solution or isoprenaline.
Results: In comparison to the control, in which no significant enzyme activities elevation (p > 0.05) nor ECG changes were registered, ISO group presented a significant rise of two clinically significant biomarkers of acute myocardial injury/myocardial infarction (AMI), CK (p = 0.05) and hsTnT (p < 0.01) as well as an ST segment elevation, a patognomonic ECG change.
Conclusion: Obtained results support previous studies, that isoprenaline represents an adequate experimental model for myocardial injury/AMI induction, and a „golden standard“ for evaluating potential cardioprotective effects of pharmacological and non-pharmacological therapeutic modalities, with the ultimate goal of lowering the degree of lesions and improving post-infarction myocardium function.
References
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9. Rona G. Catecholamine cardiotoxicity. J Mol Cell Cardiol. 1985;17(4):291-306.
10. Tang Y, He X, Ye M, Huang H, Chen H, Peng W et al. Cardioprotective effect of total saponins from three medicinal species of Dioscorea against isoprenaline-induced myocardial ischemia. J Ethnopharmacol. 2015;175:451-455.
11. Suchal K, Malik S, Gamad N, Malhotra RK, Goyal SN, Bhatia J, et al. Kampeferol protects against oxidative stress and apoptotic damage in experimental model of isoproterenolinduced cardiac toxicity in rats. Phytomedicine. 2016;23:1401-1408.
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14. Tang Y, He X, Ye M, Huang H, Chen H, Peng W et al. Cardioprotective effect of total saponins from three medicinal species of Dioscorea against isoprenaline-induced myocardial ischemia. J Ethnopharmacol. 2015;175:451-455.
15. Anandan R, Ganesan B, Obulesu T, Mathew S, Kumar RS, Lakshmanan PT, et al. Dietary chitosan supplementation attenuates isoprenaline-induced oxidative stress in rat myocardium. Int J Biol Macromol. 2012;51:783-787.
16. Aman U, Vaibhav P, Balaraman R. Tomato lycopene attenuates myocardial infarction induced by isoproterenol: Electrocardiographic, biochemical and anti-apoptotic study. Asian Pac J Trop Biomed. 2012;2:345–351.
17. Fathiazad F, Matlobi A, Khorrami A, et al. Phytochemical screening and evaluation of cardioprotective activity of ethanolic extract of Ocimum basilicum L. (basil) against isoproterenol induced myocardial infarction in rats. Daru. 2012;20:87.
18. Huang H, Geng Q, Yao H, Shen Z, Wu Z, Miao X, Shi P. Protective effect of scutellarin on myocardial infarction induced by isoprenaline in rats. Iran J Basic Med Sci. 2018;21(3): 267–276.
19. Hollaar L, Van Der Laarse A. Interference of the measurement of lactate dehydrogenase (LDH) activity in human serum and plasma by LDH from blood cells. Clin Chim Acta. 1979;99(2):135-142.
20. Ojha S, Golechha M, Kumari S, Bhatia J, Arya D. Glycyrrhiza glabra protects from myocardial ischemia–reperfusion injury by improving hemodynamic, biochemical, histopathological and ventricular function. Exp Toxicol Pathol. 2013;65(1-2):219-227.
21. Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS, Katus HA. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem. 2010;56(2):254-61.
22. Armbruster AA, Pry T. Limit of Blank, Limit of Detection and Limit of Quantitation. Clin Biochem Rev. 2008;29(Suppl 1):S49–S52.
23. Ghazouani L, Khdhiri E, Elmufti A, Feriani A, Tir M, Baaziz I et al. Cardioprotective effects of (E)-4-hydroxy-N′-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide: a newly synthesized coumarin hydrazone against isoproterenol-induced myocardial infarction in a rat model. Can J Physiol Pharmacol. 2019;97(10):989-998.
24. Hammerschmidt S, Bell M, Büchler N, Wahn H, Remkes H, Lohse M et al. Acute changes of myocardial creatine kinase gene expression under β-adrenergic stimulation. Biochim Biophys Acta. 2000;1502(3):471-480.
25. Saravanan G, Ponmurugan P, Sathiyavathi M, Vadivukkarasi S, Sengottuvelu S. Cardioprotective activity of Amaranthus viridis Linn: Effect on serum marker enzymes, cardiac troponin and antioxidant system in experimental myocardial infarcted rats. Int J Cardiol. 2013;165(3):494-498.
26. Preus M, Bhargava AS, Khater Abd El R, Gunzel P. Diagnostic value of serum creatine kinase and lactate dehydrogenase isoenzyme determinations for monitoring early cardiac damage in rats. Toxicol Lett. 1998;42:225-33.
27. Ljubunčić P, Mujić, F, Winterhalter M, Huković N, Vidović Z, Đuričić S. Toksičnost izoproterenola za miokard u eksperimentalnim uvjetima. Arh hig rada toksikol. 1992;43:11-20.
28. Wang TY, Godfrey JH, Graham LG. Clinical evaluation of immunochemical assay of lactate dehydrogenase isoenzyme-1 in early detection of acute myocardial infarction. Clin Chem. 1982;28:2152-4.
29. Lott JA. Serum enzyme determinations in the diagnostics of acute myocardial infarction. Hum Pathol. 1984;15:706-16.
30. SchultheissHP, Bispink G, Neuhoff V, Bolte HD. Myocardial lactate dehydrogenase isoenzyme distribution in the normal heart. Basic Res Cardiol. 1981;76:681-9.
31. Khalil M, Ahmmed I, Ahmed R, Tanvir E, Afroz R, Paul S et al. Amelioration of Isoproterenol-Induced Oxidative Damage in Rat Myocardium by Withania somnifera Leaf Extract. Biomed Res Int. 2015;2015:1-10.
32. Kumar M, Kasala E, Bodduluru L, Dahiya V, Lahkar M. Baicalein protects isoproterenol induced myocardial ischemic injury in male Wistar rats by mitigating oxidative stress and inflammation. Inflamm Res. 2016;65(8):613-622.
33. Rotenberg Z, Weinberger I, Davidson E, Fuchs J, Sperling O, Agmon J. Atypical patterns of lactate dehydrogenase isoenzymes in acute myocardial infarction. Clin Chem. 1988;34:1096-8.
34. Wexler BS. Prolonged protective effects following propranololwithdrawal against isoproterenol-induced myocardial infarction in normotensive and hypertensive rats. Br J Exp Pathol. 1985;66:143-54.
35. Ramos K, Combs AB, Acosta D. Role of calcium in isoproterenol cytotoxicity to cultured myocardial cells. Biochem Pharmacol. 1984;33:1989-92.
36. Todd GL, Baroldi G, Pieper GM, Clayton FC, Eliot RS. Experimental catecholamine-induced myocardial necrosis. I. Morphology, quantification and regional distribution of acute contraction band lessions. J Moll Cell Cardiol. 1985;17:317-38.
37. Panda S, Kar A, Ramamurthy V. Cardioprotective effect of vincristine on isoproterenol-induced myocardial necrosis in rats. Eur J Pharmacol. 2014;723:451-458.
38. Kannan M, Quine S. Ellagic acid ameliorates isoproterenol induced oxidative stress: Evidence from electrocardiological, biochemical and histological study. Eur J Pharmacol. 2011;659(1):45-52.
39. Shaikh S, Bhatt L, Barve K. Attenuation of isoproterenol-induced cardiotoxicity in rats by Narirutin rich fraction from grape fruit. Phytomedicine. 2019;55:222-228.
40. Patel V, Upaganlawar A, Zalawadia R, Balaraman R. Cardioprotective effect of melatonin against isoproterenol induced myocardial infarction in rats: A biochemical, electrocardiographic and histoarchitectural evaluation. Eur J Pharmacol. 2010;644(1-3):160-168.
41. Mnafgui K, Hajji R, Derbali F, Gammoudi A, Khabbabi G, Ellefi H et al. Anti-inflammatory, Antithrombotic and Cardiac Remodeling Preventive Effects of Eugenol in Isoproterenol-Induced Myocardial Infarction in Wistar Rat. Cardiovasc Toxicol. 2015;16(4):336-344.
42. Mnafgui K, Hajji R, Derbali F, Khlif I, Kraiem F, Ellefi H et al. Protective Effect of Hydroxytyrosol Against Cardiac Remodeling After Isoproterenol-Induced Myocardial Infarction in Rat. Cardiovasc Toxicol. 2015;16(2):147-155.
43. Brembilla-Perrot B, Muhanna I, Nippert M, Popovic B, Beurrier D, Houriez P et al. Paradoxal effect of isoprenaline infusion. Europace. 2005;7(6):621-627.
44. Stratton J, Cerqueira M, Schwartz R, Levy W, Veith R, Kahn S et al. Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men. Circ J. 1992;86(2):504-512.
45. Elmes M, Haase A, Gardner D, Langley-EvansS. Sex differences in sensitivity to β-adrenergic agonist isoproterenol in the isolated adult rat heart following prenatal protein restriction. Br J Nutr. 2008;10(5):725-734.
46. Dhein S, Röhnert P, Markau S, Kotchi-Kotchi E, Becker K, Poller U et al. Cardiac beta-adrenoceptors in chronic uremia: studies in humas and rats. J Am Coll Cardiol. 2000;36(2):608-617.
47. Yin Q, Yang C, Wu J, Lu H, Zheng X, Zhang Y et al. Downregulation of β-Adrenoreceptors in Isoproterenol-Induced Cardiac Remodeling through HuR. PLoS ONE. 2016;11(4):e0152005.
48. Mullabaeva G. QT interval dispersion in patients with Q-wave myocardial infarction. Eur Sci J. 2017;79-81.
49. Upaganlawa A, Gandhi H, Balaraman R. Isoproterenol Induced Myocardial Infarction: Protective Role of Natural Products. Am J Pharmacol Toxicol. 2011;6(1):1-17.
2. Kirby R, Novak C, Thurnhorst R, Johnson A. The role of beta 1 and beta 2 adrenoceptors in isoproterenol-induced drinking. Brain Research. 1994;656(1):79-84.
3. Amano S, Arai M, Goto S, Togari A. Inhibitory effect of NPY on isoprenaline-induced osteoclastogenesis in mouse bone marrow cells. Biochim Biophys Acta. 2007;1770:966-973.
4. Beregovich J, Reicher-Reiss H, Grishman A. Haemodynamic effects of isoprenaline in acute myocardial infarction. Heart. 1972;34(7):705-710.
5. Long J, Gao M, Kong Y, Shen X, Du X, Son YO, et al. Cardioprotective effect of total paeony glycosides against isoprenaline-induced myocardial ischemia in rats. Phytomedicine. 2012;19:672-676.
6. Rona G, Chappel CI, Balazs T, Gaudry R. An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. AMA Arch Pathol. 1595;67(4):443-55.
7. Rona G, Zsoter R, Chappel CI, Gaudry R. Myocardial lesions, circulatory and electrocardiographic changes produced by isoproterenol in the dog. Rev Canad Biol. 1959;18(1):83-94.
8. Chappel CI, Rona G, Balazs T, Gaudry R. Severe myocardial necrosis produced by isoproterenol in the rat. Arch Int Pharmacodyn Ther. 1959;122:123-8.
9. Rona G. Catecholamine cardiotoxicity. J Mol Cell Cardiol. 1985;17(4):291-306.
10. Tang Y, He X, Ye M, Huang H, Chen H, Peng W et al. Cardioprotective effect of total saponins from three medicinal species of Dioscorea against isoprenaline-induced myocardial ischemia. J Ethnopharmacol. 2015;175:451-455.
11. Suchal K, Malik S, Gamad N, Malhotra RK, Goyal SN, Bhatia J, et al. Kampeferol protects against oxidative stress and apoptotic damage in experimental model of isoproterenolinduced cardiac toxicity in rats. Phytomedicine. 2016;23:1401-1408.
12. Allijn IE, Czarny BM, Wang X, Chong SY, Weiler M, da Silva AE, et al. Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction. J Control Release. 2017;247:127-133.
13. Geng ZH, Huang L, Song MB, Song YM. Protective effect of a polysaccharide from Salvia miltiorrhiza on isoproterenol (ISO)- induced myocardial injury in rats. Carbohydr Polym. 2015;132:638-642.
14. Tang Y, He X, Ye M, Huang H, Chen H, Peng W et al. Cardioprotective effect of total saponins from three medicinal species of Dioscorea against isoprenaline-induced myocardial ischemia. J Ethnopharmacol. 2015;175:451-455.
15. Anandan R, Ganesan B, Obulesu T, Mathew S, Kumar RS, Lakshmanan PT, et al. Dietary chitosan supplementation attenuates isoprenaline-induced oxidative stress in rat myocardium. Int J Biol Macromol. 2012;51:783-787.
16. Aman U, Vaibhav P, Balaraman R. Tomato lycopene attenuates myocardial infarction induced by isoproterenol: Electrocardiographic, biochemical and anti-apoptotic study. Asian Pac J Trop Biomed. 2012;2:345–351.
17. Fathiazad F, Matlobi A, Khorrami A, et al. Phytochemical screening and evaluation of cardioprotective activity of ethanolic extract of Ocimum basilicum L. (basil) against isoproterenol induced myocardial infarction in rats. Daru. 2012;20:87.
18. Huang H, Geng Q, Yao H, Shen Z, Wu Z, Miao X, Shi P. Protective effect of scutellarin on myocardial infarction induced by isoprenaline in rats. Iran J Basic Med Sci. 2018;21(3): 267–276.
19. Hollaar L, Van Der Laarse A. Interference of the measurement of lactate dehydrogenase (LDH) activity in human serum and plasma by LDH from blood cells. Clin Chim Acta. 1979;99(2):135-142.
20. Ojha S, Golechha M, Kumari S, Bhatia J, Arya D. Glycyrrhiza glabra protects from myocardial ischemia–reperfusion injury by improving hemodynamic, biochemical, histopathological and ventricular function. Exp Toxicol Pathol. 2013;65(1-2):219-227.
21. Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS, Katus HA. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem. 2010;56(2):254-61.
22. Armbruster AA, Pry T. Limit of Blank, Limit of Detection and Limit of Quantitation. Clin Biochem Rev. 2008;29(Suppl 1):S49–S52.
23. Ghazouani L, Khdhiri E, Elmufti A, Feriani A, Tir M, Baaziz I et al. Cardioprotective effects of (E)-4-hydroxy-N′-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide: a newly synthesized coumarin hydrazone against isoproterenol-induced myocardial infarction in a rat model. Can J Physiol Pharmacol. 2019;97(10):989-998.
24. Hammerschmidt S, Bell M, Büchler N, Wahn H, Remkes H, Lohse M et al. Acute changes of myocardial creatine kinase gene expression under β-adrenergic stimulation. Biochim Biophys Acta. 2000;1502(3):471-480.
25. Saravanan G, Ponmurugan P, Sathiyavathi M, Vadivukkarasi S, Sengottuvelu S. Cardioprotective activity of Amaranthus viridis Linn: Effect on serum marker enzymes, cardiac troponin and antioxidant system in experimental myocardial infarcted rats. Int J Cardiol. 2013;165(3):494-498.
26. Preus M, Bhargava AS, Khater Abd El R, Gunzel P. Diagnostic value of serum creatine kinase and lactate dehydrogenase isoenzyme determinations for monitoring early cardiac damage in rats. Toxicol Lett. 1998;42:225-33.
27. Ljubunčić P, Mujić, F, Winterhalter M, Huković N, Vidović Z, Đuričić S. Toksičnost izoproterenola za miokard u eksperimentalnim uvjetima. Arh hig rada toksikol. 1992;43:11-20.
28. Wang TY, Godfrey JH, Graham LG. Clinical evaluation of immunochemical assay of lactate dehydrogenase isoenzyme-1 in early detection of acute myocardial infarction. Clin Chem. 1982;28:2152-4.
29. Lott JA. Serum enzyme determinations in the diagnostics of acute myocardial infarction. Hum Pathol. 1984;15:706-16.
30. SchultheissHP, Bispink G, Neuhoff V, Bolte HD. Myocardial lactate dehydrogenase isoenzyme distribution in the normal heart. Basic Res Cardiol. 1981;76:681-9.
31. Khalil M, Ahmmed I, Ahmed R, Tanvir E, Afroz R, Paul S et al. Amelioration of Isoproterenol-Induced Oxidative Damage in Rat Myocardium by Withania somnifera Leaf Extract. Biomed Res Int. 2015;2015:1-10.
32. Kumar M, Kasala E, Bodduluru L, Dahiya V, Lahkar M. Baicalein protects isoproterenol induced myocardial ischemic injury in male Wistar rats by mitigating oxidative stress and inflammation. Inflamm Res. 2016;65(8):613-622.
33. Rotenberg Z, Weinberger I, Davidson E, Fuchs J, Sperling O, Agmon J. Atypical patterns of lactate dehydrogenase isoenzymes in acute myocardial infarction. Clin Chem. 1988;34:1096-8.
34. Wexler BS. Prolonged protective effects following propranololwithdrawal against isoproterenol-induced myocardial infarction in normotensive and hypertensive rats. Br J Exp Pathol. 1985;66:143-54.
35. Ramos K, Combs AB, Acosta D. Role of calcium in isoproterenol cytotoxicity to cultured myocardial cells. Biochem Pharmacol. 1984;33:1989-92.
36. Todd GL, Baroldi G, Pieper GM, Clayton FC, Eliot RS. Experimental catecholamine-induced myocardial necrosis. I. Morphology, quantification and regional distribution of acute contraction band lessions. J Moll Cell Cardiol. 1985;17:317-38.
37. Panda S, Kar A, Ramamurthy V. Cardioprotective effect of vincristine on isoproterenol-induced myocardial necrosis in rats. Eur J Pharmacol. 2014;723:451-458.
38. Kannan M, Quine S. Ellagic acid ameliorates isoproterenol induced oxidative stress: Evidence from electrocardiological, biochemical and histological study. Eur J Pharmacol. 2011;659(1):45-52.
39. Shaikh S, Bhatt L, Barve K. Attenuation of isoproterenol-induced cardiotoxicity in rats by Narirutin rich fraction from grape fruit. Phytomedicine. 2019;55:222-228.
40. Patel V, Upaganlawar A, Zalawadia R, Balaraman R. Cardioprotective effect of melatonin against isoproterenol induced myocardial infarction in rats: A biochemical, electrocardiographic and histoarchitectural evaluation. Eur J Pharmacol. 2010;644(1-3):160-168.
41. Mnafgui K, Hajji R, Derbali F, Gammoudi A, Khabbabi G, Ellefi H et al. Anti-inflammatory, Antithrombotic and Cardiac Remodeling Preventive Effects of Eugenol in Isoproterenol-Induced Myocardial Infarction in Wistar Rat. Cardiovasc Toxicol. 2015;16(4):336-344.
42. Mnafgui K, Hajji R, Derbali F, Khlif I, Kraiem F, Ellefi H et al. Protective Effect of Hydroxytyrosol Against Cardiac Remodeling After Isoproterenol-Induced Myocardial Infarction in Rat. Cardiovasc Toxicol. 2015;16(2):147-155.
43. Brembilla-Perrot B, Muhanna I, Nippert M, Popovic B, Beurrier D, Houriez P et al. Paradoxal effect of isoprenaline infusion. Europace. 2005;7(6):621-627.
44. Stratton J, Cerqueira M, Schwartz R, Levy W, Veith R, Kahn S et al. Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men. Circ J. 1992;86(2):504-512.
45. Elmes M, Haase A, Gardner D, Langley-EvansS. Sex differences in sensitivity to β-adrenergic agonist isoproterenol in the isolated adult rat heart following prenatal protein restriction. Br J Nutr. 2008;10(5):725-734.
46. Dhein S, Röhnert P, Markau S, Kotchi-Kotchi E, Becker K, Poller U et al. Cardiac beta-adrenoceptors in chronic uremia: studies in humas and rats. J Am Coll Cardiol. 2000;36(2):608-617.
47. Yin Q, Yang C, Wu J, Lu H, Zheng X, Zhang Y et al. Downregulation of β-Adrenoreceptors in Isoproterenol-Induced Cardiac Remodeling through HuR. PLoS ONE. 2016;11(4):e0152005.
48. Mullabaeva G. QT interval dispersion in patients with Q-wave myocardial infarction. Eur Sci J. 2017;79-81.
49. Upaganlawa A, Gandhi H, Balaraman R. Isoproterenol Induced Myocardial Infarction: Protective Role of Natural Products. Am J Pharmacol Toxicol. 2011;6(1):1-17.
Published
2021/07/21
Section
Original Scientific Paper