The Combined Effect of Endurance Training and Various Doses of Atorvastatin on Cardiac Remodeling after Myocardial Infarction in Male Rats

Authors

  • Hadi Abdi1 1- Dept. of Physical Education & Sports Sciences, Payam-e Noor University, Tehran, Iran.
  • Akbar Azamian Jazi2 2- Dept. of Physical Education & Sports Sciences, School of Literature and Human Sciences, Shahrekord University, Chaharmahal and Bakhtiari, Iran.
  • Mohammad Reza Hafezi3 3- Dept. of Pathobiology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
  • Mehdi Khaksari4 4- School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
  • Nabi Shamsaei5 5- Dept. of Physical Education & Sports Sciences, School of Literature and Humanities, Ilam University, Ilam, Iran

DOI:

https://doi.org/10.22100/jkh.v11i1.1176

Keywords:

Endurance training, Atorvastatin, Myocardial infarction, Cardiac remodeling

Abstract

Introduction: Statins and exercise have beneficial effects in preventing cardiovascular diseases. However, prolonged use of statins particularly at high doses has unpleasant side effects. This study aimed to investigate the combined effect of endurance training and three doses of Atorvastatin on cardiac remodeling after myocardial infarction in male rats.

Methods: 75 male wistar rats (weighing 210-250g) were randomly divided to 9 groups. Sham, control, endurance training, Atorvastatin (5, 10 and 15 mg/kg), and exercise plus Atorvastatin (5, 10 and 15 mg/kg): Myocardial infarction was induced by subcutaneous injection of isoprenaline (150 mg/kg) in two consecutive days. Drug and training intervention was initiated 2 days after infarction and continued for 4 weeks. In order to assess the necrosis lesion and fibrosis tissue, hematoxylin & eosin and masson trichrome staining were used respectively.

Results: The combination of endurance training and various doses of Atorvastatin significantly reduced the amount of necrosis and fibrosis tissue compared with the control group (P<0.01). Endurance exercise training alone did not cause significant changes in the extent of necrosis damage, but significantly increased fibrosis tissue compared with the control group (P<0.001). Various doses of Atorvastatin alone significantly reduced necrosis damage (P<0.001), but the difference between these groups and the control group in terms of fibrous tissue was statistically significant only at dose of 15 mg/kg (P<0.001).

Conclusion: The results of this study showed that the combination of training and various doses of Atorvastatin are more effective in improving of tissue damage caused by myocardial infarction than exercise and Atorvastatin alone. However, the use of endurance training with medical therapy can not reduce the dose of Atorvastatin.

References

Zaafan MA, Zaki HF, El-Brairy AI, Kenawy SA. Protective effects of atorvastatin and quercetin on isoprenaline-induced myocardial infarction in rats. Bulletin of Faculty of Pharmacy, Cairo University. 2013;51:35-41.

Jorge L, Rodrigues B, Rosa KT, Malfitano C, Loureiro TCA, Medeiros A, et al. Cardiac and peripheral adjustments induced by early exercise training intervention were associated with autonomic improvement in infarcted rats: role in functional capacity and mortality. Eur Heart J 2011:32:904-12.

Chen CY, Hsu HC, Lee BC, Lin HJ, Chen YH, Huang HC, et al. Exercise training improves cardiac function in infarcted rabbits: involvement of autophagic function and fatty acid utilization. Eur J Heart Fail 2010;12:323-30.

Sun Y. Myocardial repair/remodelling following infarction: roles of local factors. Cardiovasc Res 2009;81:482-90.

Llevadot J, Asahara T. Efecto de las estatinas en la inducción de angiogénesis y vasculogénesis. Revista Española de Cardiología 2002;55:838-44.

Landmesser U, Engberding N, Bahlmann FH, Schaefer A, Wiencke A, Heineke A, et al. Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation 2004;110:1933-9.

Toyama K, Sugiyama S, Oka H, Iwasaki Y, Sumida H, Tanaka T, et al. Combination treatment of rosuvastatin or atorvastatin, with regular exercise improves arterial wall stiffness in patients with coronary artery disease. PloS One 2012;7:e41369.

Qiu R, Cai A, Dong Y, Zhou Y, Yu D, Huang Y, et al. SDF-1alpha upregulation by atorvastatin in rats with acute myocardial infarction via nitric oxide production confers anti-inflammatory and anti-apoptotic effects. J Biomed Sci 2012;19:99.

Golomb BA, Evans MA. Statin adverse effects. Am J Cardiovasc Drugs 2008;8:373-418.

Doustar Y, Mohajeri D. The anti-apoptotic effects of atorvastatin in isoproterenol induced experimental heart failure. Zahedan Journal of Research in Medical Sciences 2011;13:13-9.

Jain M, Liao R, Ngoy S, Whittaker P, Apstein CS, Eberli FR. Angiotensin II receptor blockade attenuates the deleterious effects of exercise training on post-MI ventricular remodelling in rats. Cardiovascular Research 2000;46:66-72.

Haykowsky M, Scott J, Esch B, Schopflocher D, Myers J, Paterson I, et al. A meta-analysis of the effects of exercise training on left ventricular remodeling following myocardial infarction: start early and go longer for greatest exercise benefits on remodeling. Trials 2011;12:92.

Xu X, Wan W, Ji L, Lao S, Powers AS, Zhao W, et al. Exercise training combined with angiotensin II receptor blockade limits post-infarct ventricular remodelling in rats. Cardiovasc Res 2008;78:523-32.

Calvert JW. Cardioprotective effects of nitrite during exercise. Cardiovascular Research 2011;89:499-506.

Lenk K, Uhlemann M, Schuler G, Adams V. Role of endothelial progenitor cells in the beneficial effects of physical exercise on atherosclerosis and coronary artery disease. J Appl Physiol 2011;111:321-8.

Galvão TF, Matos KC, Brum PC, Negrão CE, Luz PLd, Chagas ACP. Cardioprotection conferred by exercise training is blunted by blockade of the opioid system. Clinics 2011;66:151-7.

Shukla SK, Sharma SB, Singh UR. β-Adrenoreceptor agonist isoproterenol alters oxidative status, inflammatory signaling, injury markers and apoptotic cell death in myocardium of rats. Indian J Clin Biochem 2015:30:27-34.

Xu X, Zhao W, Lao S, Wilson BS, Erikson JM, Zhang JQ. Effects of exercise and L-arginine on ventricular remodeling and oxidative stress. Med Sci Sports Exerc 2010;42:346-54.

Orenstein TL, Parker TG, Butany JW, Goodman JM, Dawood F, Wen WH, et al. Favorable left ventricular remodeling following large myocardial infarction by exercise training. Effect on ventricular morphology and gene expression. J Clin Inves 1995;96:858-66.

Chiong M, Wang Z, Pedrozo Z, Cao D, Troncoso R, Ibacache M, et al. Cardiomyocyte death: mechanisms and translational implications. Cell Death Dis 2011;2:e244.

Zouhal H, Jacob C, Delamarche P, Gratas-Delamarche A. Catecholamines and the effects of exercise, training and gender. Sports Med 2008;38:401-23.

Husain K, Hazelrigg SR. Oxidative injury due to chronic nitric oxide synthase inhibition in rat: effect of regular exercise on the heart. Biochim Biophys Acta 2002;1587:75-82.

Guazzi M, Tumminello G, Reina G, Vicenzi M, Guazzi MD. Atorvastatin therapy improves exercise oxygen uptake kinetics in post‐myocardial infarction patients. Eur J Clin Invest 2007;37:454-62.

Parker BA, Capizzi JA, Augeri AL, Grimaldi AS, White CM, Thompson PD. Atorvastatin increases exercise leg blood flow in healthy adults. Atherosclerosis 2011;219:768-73.

Tanaka K, Honda M, Takabatake T. Anti apoptotic effect of atorvastatin, a 3 hydroxy 3 methylglutaryl coenzyme a reductase inhibitor, on cardiac myocytes through protein kinase c activation. Clin Exp Pharmacol Physiol 2004;31:360-4.

Zhou R, Xu Q, Zheng P, Yan L, Zheng J, Dai G. Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat. Eur J Pharmacol 2008;586:244-50.

Miura S-i, Saku K. Effects of statin and lipoprotein metabolism in heart failure. J Cardiol 2010;55:287-90.

Serra AJ, Santos MH, Bocalini DS, Antônio EL, Levy RF, Santos AA, et al. Exercise training inhibits inflammatory cytokines and more than prevents myocardial dysfunction in rats with sustained β‐adrenergic hyperactivity. J Physiol 2010;588:2431-42.

Batista DF, Gonçalves AF, Rafacho BP, Santos PP, Minicucci MF, Azevedo PS, et al. Delayed rather than early exercise training attenuates ventricular remodeling after myocardial infarction. Int J Cardiol 2013;170:e3-4.

Wan W, Powers AS, Li J, Ji L, Erikson JM, Zhang JQ. Effect of post-myocardial infarction exercise training on the renin-angiotensin-aldosterone system and cardiac function. Am J Med Sci 2007;334:265-73.

de Waard MC, van der Velden J, Bito V, Ozdemir S, Biesmans L, Boontje NM, et al. Early exercise training normalizes myofilament function and attenuates left ventricular pump dysfunction in mice with a large myocardial infarction. Circulation Research 2007;100:1079-88.

Gaudron P, Hu K, Schamberger R, Budin M, Walter B, Ertl G. Effect of endurance training early or late after coronary artery occlusion on left ventricular remodeling, hemodynamics, and survival in rats with chronic transmural myocardial infarction. Circulation 1994;89:402-12.

Jugdutt BI, Michorowski BL, Kappagoda CT. Exercise training after anterior Q wave myocardial infarction: importance of regional left ventricular function and topography. J Am Coll Cardiol 1988;12:362-72.

Published

2015-12-28

Issue

Section

Original Article(s)

How to Cite

The Combined Effect of Endurance Training and Various Doses of Atorvastatin on Cardiac Remodeling after Myocardial Infarction in Male Rats. (2015). Knowledge and Health in Basic Medical Sciences, 11(1), Page:32-40. https://doi.org/10.22100/jkh.v11i1.1176

Most read articles by the same author(s)

<< < 58 59 60 61 62 63 64 65 > >>