Annals of Clinical & Laboratory Science 35:73-78 (2005)
© 2005 Association of Clinical Scientists
Swimming Exercise Training Prior to Acute Myocardial Infarction Attenuates Left Ventricular Remodeling and Improves Left Ventricular Function in Rats
Anat Dayan1,
Micha S. Feinberg3,
Radka Holbova1,
Naamit Deshet1 and
Mickey Scheinowitz1,2
1 Neufeld Cardiac Research Institute, 2 Department of Biomedical Engineering, and 3 The Heart Institute, Sheba Medical Center, Tel-Hashomer; Tel-Aviv University, Israel
Address correspondence to Dr. M. Scheinowitz, Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer, 52621, Israel; tel 972 3 635 1672; fax 972 3 535 1139; e-mail mickeys{at}post.tau.ac.il.
 |
Abstract
|
|---|
The effect of exercise training prior to acute myocardial infarction (AMI) on left ventricular (LV) remodeling is poorly understood. This study investigated the protective effect of 3 weeks of swimming exercise training prior to AMI on cardiac morphology and function. Male Sprague-Dawley rats (n = 35) were randomly assigned to 3 groups: swimming training (n = 14, 90 min, 5 days/wk, 3 wk), sedentary (n =14), and controls (n = 7, no exercise, no MI). At the end of the training/sedentary period, rats were subjected to AMI (ExMI and SedMI) induced by surgical ligation of the left coronary artery. Thereafter, the rats remained sedentary for a 4-wk recovery period. Trans-thoracic echocardiography was performed in each group at the end of the exercise/sedentary period (pre-AMI), 24 hr after AMI, and following recovery (4 wk after AMI). No differences were observed in LV dimensions and function pre-AMI among the 3 groups; however, LV-end systolic diameter (LVESD) and LV-end systolic area (LVES-area) were significantly lower in the prior trained rats, 24 hr post-AMI with no additional change 4 wk post-AMI, during remodeling. Both LV-shortening fraction (SF%) and fractional area change (FAC%) were higher in the trained animals 4 wk post-AMI (39±12% vs 23±8%; p 0.002, and 48±14% vs. 38±9%; p 0.07, r espectively). In conclusion, 3 wk of swimming exercise training prior to AMI significantly attenuated LV remodeling and improved LV function, despite no changes in LV dimensions or systolic function at the end of the exercise session. The data suggest that even a short-term training period is sufficient to induce cardiac protection.
(received 23 September 2004; accepted 21 October 2004)
Keywords: swimming exercise training, left ventricular remodeling, acute myocardial infarction
|
Introduction
|
|---|
Physical inactivity has been declared a primary cause of multiple chronic health disorders in sedentary societies [1,2]. Supported by evidence-based medicine, it was also concluded that physical inactivity is a major risk factor for cardiovascular diseases [1,2]. Exercise can improve myocardial function by increasing myocardial mass and ventricular chamber dimensions, increased stroke volume and cardiac output [3,4].
Little is known about the effect of exercise training prior to AMI on subsequent cardiac remodeling and function. McElroy et al [5] were the first to demonstrate that exercise training in rats prior to AMI reduced the infarct area 2 days after MI. This finding was attributed to elevated neovascularization in trained hearts [5]. However, limited data are available concerning the effect of prior exercise training on LV function at the acute and chronic healing phases following AMI.
The aim of the present study was to investigate the functional effect of short-term exercise training (3 wk) prior to AMI on the healing heart 24 hr and 4 wk after AMI, in order to assess its protective effect during the remodeling period.
|
Methods
|
|---|
Animals.
The experimental protocol was approved by the Institutional Committee for Animal Care and Use at Tel-Aviv University. All animals were handled in accordance with the guide for the Care and Use of Laboratory Animals published by the US National Institute of Health (NIH Publication No. 85-23, revised 1996). Sprague-Dawley male rats (n = 35) were randomly assigned to 3 groups: exercise (Ex) (n = 14), sedentary (Sed) (n = 14), and control (no MI) (n = 7). The exercising rats were subjected to a 90-min daily swimming exercise session, 5 days per wk for 3 wk. The first swimming session lasted 20–30 min and was gradually increased by 30 min each session up to 90 min on the 4th day, and it was maintained so until the end of training period [6]. At the end of the 3 wk sedentary vs exercise program, both Sed and Ex groups were subjected to AMI and were kept sedentary thereafter for a 4-wk period, until sacrifice, while the control (no MI) group remained sedentary during the 7 wk before sacrifice.
Functional measurements.
Trans-thoracic echo-cardiography was performed at 3 time-points: (a) immediately after the end of the 3 wk sedentary vs training program (pre-AMI); (b) 24 hr post-AMI; and (c) 4 wk post-AMI. The echocardiograms were performed using a 12 MHz transducer (S12, Sonos-5500, Hewlett-Packard, Andover, MA). M-mode tracings of the LV were obtained from the parasternal long- and short-axis view. LV end systolic (LVESD) and end diastolic diameter (LVEDD) and areas (LVESD area; LVEDD area) were measured; LV shortening fraction (SF%) and fractional area change (FAC%) were calculated. Each measurement was repeated on at least 3 consecutively beats.
Acute myocardial infarction and sacrifice.
To induce acute MI, a 5/0 silk thread was permanently tied around the left anterior descending coronary artery of anesthetized (im, Xylazine, 10 mg/kg and Ketamin, 90 mg/kg) and ventilated (Harvard respirator, 2.5 ml, 75–78 strokes/min) rats. Following closure of the chest, all rats remained sedentary with no additional exercise for 4 wk. At 7 wk after the initiation of the training program all rats were anesthetized and sacrificed with overdose of anesthetics and KCl.
Statistical analysis.
All data are reported by mean ± SD. Single factor ANOVA followed by Student’s t-test was used to compare in-group and between-group differences. Values of p 0.05 w ere considered statistically significant.
|
Results
|
|---|
Post-operative mortality.
Post-operative mortality in the sedentary group was 36%, almost 5-fold higher than the mortality in the exercised group (8%). One additional rat (Ex-MI) died during the 4 wk follow-up; the mortality rate did not change further until sacrifice.
Heart characteristics.
A comparison of heart weight and heart/body weight ratio measured 4 wk post-AMI is presented in Table 1
. Both MI groups (Sedentary vs Exercise) had significantly higher heart weights and HW/BW ratios compared to the control group. The ExMI group had a significantly higher heart weight and HW/BW ratio compared to the SedMI group at 4 wk post-AMI.
View this table:
[in this window]
[in a new window]
|
Table 1. Comparison of heart weight and heart/body weight ratio (mean ± SD) among groups, measured at 4-wk post-AMI
|
|
LV function.
The results of the echocardiography LV morphometric and functional assessment are presented in Figs. 1 and 2. Although no differences in LV end-diastolic diameter (LVEDD) were observed before and/or after AMI between the exercised (Ex) and the sedentary (Sed) groups, LVEDD did increase in both groups significantly at 4 wk post-MI (Fig. 1A). Fig. 1B presents a significant increase of the LV-end systolic diameter (LVESD) in both groups at 24 hr and 4 wk post-MI. However, the increase in LEVSD was significantly lower in the exercised group compared to the sedentary (Sed) group at 24 hr post-AMI, and remained unchanged after 4 wk. This result indicates better-preserved LV systolic diameter in the exercised group, leading to better LV systolic function. As shown in Fig. 1C, the shortening fraction was similar in both groups before MI (normal LV function). At 24 hr post-MI there was 50% reduction in shortening fraction in the sedentary group compared to only 20% reduction in the exercise group (p 0.05). These results remained unchanged at 4 wk post-AMI.
View larger version (41K):
[in this window]
[in a new window]
|
Fig. 1. Panel A: LV-End Diastolic Diameter (LVEDD) at 24 hr post-MI and 4 wk post-MI, of pre-MI 3 wk exercised (Ex) and sedentary (Sed) groups: *p <0.05 4 wk post-MI vs pre-MI; #p <0.05 4 wk post-AMI vs 24 hr post-MI; p <0.001 pre-MI compared to post-MI (24 hr post-MI vs 4 wk post-MI) in both Ex and Sed groups. Panel B: LV-End Systolic Diameter (LVESD) at 24 hr post-MI and 4 wk post-MI, of pre-MI 3 wk exercised (Ex) and sedentary (Sed) groups: •p <0.05 Ex vs Sed; p <0.05 24 hr post-MI vs pre-MI; #p <0.05 4 wk post-MI vs 24 hr post-MI; *p <0.05 4 wk post-MI vs pre-MI; p <0.05, p<0.001 pre-MI compared to post-MI (24 hr post-MI vs 4 wk post-MI) in both Ex and Sed groups, respectively. Panel C: Shortening fraction (SF%) at 24 hr post-MI and 4 wk post-MI, of pre-MI 3 wk exercised (Ex) and sedentary (Sed) groups: p <0.05; • Ex vs Sed; 24 hr post-MI vs pre-MI; *4 wk post-MI vs pre-MI; p <0.001 pre-MI compared to post-MI (24 hr post-MI vs 4 wk-post-MI) in Sed group only.
|
|
View larger version (44K):
[in this window]
[in a new window]
|
Fig. 2. Panel A: LV-End Diastolic Area at 24 hr post-MI and 4 wk post-MI, of pre-MI 3 wk exercised (Ex) and sedentary (Sed) groups: p <0.05; *4 wk post-MI vs pre-MI; #4 wk post-MI vs 24 hr post-MI; p <0.05, p <0.001 pre-MI compared to post-MI (24 hr post-MI vs 4 wk post-MI) in both Ex and Sed groups, respectively. Panel B: LV-End Systolic Area at 24 hr post-MI and 4 wk post-MI of pre-MI 3 wk exercised (Ex) and sedentary (Sed) groups: p<0.05; 24 hr post-MI vs pre-MI; #4 wk post-MI vs 24 hr post-MI; *4 wk post-MI vs pre-MI; p <0.001 pre-MI compared to post-MI (24 hr post-MI vs 4 wk post-MI) in both Ex and Sed groups. Panel C: Fraction Area Change (FAC%) at 24 hr post-MI and 4 wk post-MI of pre-MI 3 wk exercised (Ex) and sedentary (Sed) groups: p<0.05; 24 hr post-MI vs pre-MI; *4 wk post-MI vs pre-MI; p<0.05, p<0.001 pre-MI compared to post-MI (24 hr post-MI vs 4 wk post-MI) in both Ex and Sed groups, respectively.
|
|
No significant differences were observed between the Ex and the Sed groups in the LV end-diastolic area (LVED area) and the LV end-systolic area (LVESD area) (Figs. 2A and 2B
, respectively). Although in both groups there was a significant increase in LVEDD area at 4 wk after MI and in LVESD area at 24 hr and 4 wk after MI, the LVESD area was better preserved in the Ex group. These results can also explain the higher FAC% (p 0.07) observed in the Ex group compared to the Sed group at 24 hr, which remained unchanged at 4 wk after MI (Fig. 2C).
|
Discussion
|
|---|
This study shows for the first time that although the short exercise training period did not induce significant echocardiographic morphologic or functional changes in the rat heart before MI, it did have a substantial anti-remodeling effect following MI. LV dilatation observed in both the Ex and Sed groups occurred early after AMI (24 hr post-AMI) and remained significant during the remodeling phase (4 wk post-AMI), leading to decreased global LV systolic contraction. This deterioration was significantly greater in the Sed group compared to the Ex group.
We did not detect any echocardiographic, morphological, and functional differences between the 3 wk Ex and Sed groups prior to MI. This result is in accordance with previous studies [4,7] which did not detect structural differences even after long-term exercise training periods (13 wk of treadmill exercise training [4] or 10 wk of swimming exercise training [7]). Nevertheless, previous animal studies showed that molecular adaptive changes can be provoked prior to exercise-induced LV hypertrophy, and have a significant impact on subsequent remodeling [4,6,8]. These adaptive changes include higher 
myosin heavy chain (MHC) and lower ß myosin heavy chain (ßMHC) gene expression [6,8], and elevated expression of pro-angiogenic cytokines and/or hypertrophic growth factors such as insulin-like growth factor-I (IGF-I) [6]. Therefore, although we did not detect any structural changes following the exercise-training period, we assume that post-training adaptive molecular level changes did occur and may have played a role in attenuating myocardial injury.
LV remodeling after AMI leads to progressive ventricular dilatation and heart failure [7–12]. Although cardiac rehabilitation programs include exercise training post-MI [9,13,14], it is controversial whether exercise training conducted after AMI is beneficial or deleterious in patients post MI [15–20] or in animal studies [21,22]. The present study points to the importance of the primary preventive effect of exercise training on the clinical outcome post-AMI, and suggests that even a short-term exercise training period can have a significant protective effect on LV remodeling.
In conclusion, this is the first study to demonstrate the effect of short-term exercise training, conducted prior to AMI, on LV function during the sub-acute and remodeling phases post-MI. Additional studies are warrented to elucidate the molecular and morphological changes that are associated with such adaptation in the remodeling heart.
|
Acknowledgment
|
|---|
The authors acknowledge the assistance of Stanislava Gilman, RDMS, Pat Benjamin, RDMS, and Lena Shoval, RDMS. This study was performed as partial fulfillment of requirements for the Ph.D. degree of Anat Dayan, Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
|
References
|
|---|
- Booth FW, Gordon SE, Carlson CJ, Hamilton MT. Waging war on modern chronic diseases: primary prevention through exercise biology. J Appl Physiol 2000;88:774–787.[Abstract/Free Full Text]
- Booth FW, Chakravarthy MV, Gordon SE, Spangenburg EE. Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy. J Appl Physiol 2002;93:3–30.[Abstract/Free Full Text]
- Perrault H, Turcotte RA. Exercise-induced cardiac hypertrophy fact or fallacy? Sports Med 1994;17:286–308.
- Hongkui J, Renhui Y, Wei L, Hsienwie L, Ryan AM, Ogasawara AK, Peborgh JV, Paoni NF. Effects of exercise training on cardiac function, gene expression, and apoptosis in rats. Am J Physiol 2000;279:H2994–3002.
- McElroy CL, Gissen SA, Fishbein MC. Exercise induced reduction in myocardial infarct size after coronary artery occlusion in the rat. Circulation 1978;57:958–962.[Abstract/Free Full Text]
- Scheinowitz M, Kessler-Icekson G, Freimann S, Zimmermann R, Schaper W, Golomb E, Savion N, Eldar M. Short- and long-term swimming exercise training increases myocardial insulin-like growth factor-I gene expression. GH & IGF Res 2003;13:19–25.
- Derumeaux G, Mulder P, Richard V, Chagraoui A, Nafeh C, Bauer F, Henry JP, Thuillez C. Tissue Doppler imaging differentiates physiological from pathological pressure-overload left ventricular hypertrophy in rats. Circulation 2002;105:1602–1608.[Abstract/Free Full Text]
- Orenstein TL, Parker TG, Butany JW, Goodman JM, Dawood F, Wen WH, Wee L, Martino T, McLaughlin PR, Liu PP. Favorable left ventricular remodeling following large myocardial infarction by exercise training. J Clin Invest 1995;96:858–866.
- Yousef ZR, Redwood SR, Bucknall CA, Sulke AN, Marber MS. Late intervention after myocardial infarction: effects on left ventricular size, function, quality of life and exercise tolerance. J Am Coll Cardiol 2002;40:869–876.[Abstract/Free Full Text]
- Udelson JE, Konstam MA. Relation between left ventricular remodeling and clinical outcomes in heart failure patients with left ventricular systolic dysfunction. J Cardiac Fail 2002;8:S465–471.[Medline]
- Gao XM, Dart AM, Dewar E, Jennings G, Du XJ. Serial echocardiographic assessment of left ventricular dimensions and function after myocardial infarction in mice. Cardiovasc Res 2000;45:330–338.[Abstract/Free Full Text]
- Moises VA, Ferreira RL, Nozawa E, Kanashiro RM, Campos OF, Lazaro de Andrade J, Carvalho ACC, Tucci PJF. Structural and functional characteristics of rat hearts with and without myocardial infarct. Initial experience with Doppler echocardiography. Arq Bras Cardiol 2000;75:131–136.
- Gordon NF, Gulanick M, Costa F, Fletcher G, Franklin BA, Roth EJ, Shephard T. Physical activity and exercise recommendations for stroke survivors. Circulation 2004;109:2031–2041.[Free Full Text]
- Goto Y, Itoh H, Adachi H, Ueshima K, Nohara R. Use of exercise cardiac rehabilitation after acute myocardial infarction. Circ J 2003;67:411–415.[Medline]
- Dubach P, Myers J, Dziekan G, Goebbels U, Reinhart W, Vogt P, Ratti R, Muller P, Miettunen R, Buser P. Effect of exercise training on myocardial remodeling in patients with reduced left ventricular function after myocardial infarction. Circulation 1997;95:2060–2067.[Abstract/Free Full Text]
- Otsuka Y, Takaki H, Okano Y, Satoh T, Aihara N, Matsumoto T, Yasumura Y, Morii I, Goto Y. Exercise training without ventricular remodeling in patients with moderate to severe left ventricular dysfunction early after myocardial infarction. Int J Cardiol 2003;87:237–244.[Medline]
- Giannuzzi P, Temporelli PL, Corra U, Tavazzi L. Anti-remodeling effect of long-term exercise training in patients with stable chronic heart failure. Results of exercise in left ventricular dysfunction and chronic heart failure (ELVD-CHF) trial. Circulation 2003;108:554–559.[Abstract/Free Full Text]
- Myers J, Goebbels U, Dzeikan G, Froelicher V, Bremerich J, Mueller P, Buser P, Dubach P. Exercise training and myocardial remodeling in patients with reduced ventricular function: one-year follow-up with magnetic resonance imaging. Am Heart J 2000;139(2pt1):252–261.[Medline]
- Lancellotti P, Lebrun FL, Pierard LA. Determinants of exercise-induced changes in mitral-regurgitation in patients with coronary artery disease and left ventricular dysfunction. J Am Coll Cardiol 2003;42:1921–1928.[Abstract/Free Full Text]
- Kubo N, Ohmura N, Nakada I, Yasu T, Katsuki T, Fujii M, Saito M. Exercise at ventilatory threshold aggravates left ventricular remodeling in patients with extensive anterior acute myocardial infarction. Am Heart J 2004;147:113–120.[Medline]
- Libonati JR. Execrise and diastolic function after myocardial infarction. Med Sci Sports Exerc 2003;35:1471–1476.[Medline]
- 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;89:402–412.[Abstract/Free Full Text]
Top
Abstract
Introduction
