Cardioprotective Effect of Spontaneous Activity

Abstract

In the perspective of giving a better understanding of the cardioprotective effects attributable to the tandem low caloric intake and training, Lou/C rats would be an interesting model since these animals exhibit spontaneously these two characteristics for months, without any dietary manipulations or stressor stimuli. No information was so far available on their cardiac function. Therefore, the aim of this pilot study was (i) to document cardiac function before and after ischemia in this strain, and (ii) to investigate whether spontaneous wheel-running activity can improve the ability of cardiac muscle to recover its function after an ischemic period. Cardiac mechanical and metabolic functions were measured in isolated Langendorff hearts from Wistar sedentary, Lou/C sedentary, and Lou/C wheel-running male rats submitted to a 20-min low-flow ischemia and 20-min reperfusion. In Lou/C sedentary rats, rate-pressure product, an index of cardiac work, was decreased before ischemia as compared to Wistar sedentary animals (- 24 %, p < 0.05). After ischemia, cardiac mechanical function recovery did not significantly differ between these two groups. Nevertheless, flux of non-oxidative glycolysis was lower before and after ischemia in Lou/C sedentary animals than in Wistar sedentary rats. In Lou/C rats, during normoxic perfusion, wheel-running activity significantly decreased heart rate (- 15 %), oxygen consumption (- 2.2 %) and cardiac efficiency (- 37 %), whereas coronary flow and flux of non-oxidative glycolysis were significantly increased (+ 15 % and + 263 %, respectively). After ischemia, recovery of cardiac mechanical function and cardiac efficiency were improved in Lou/C wheel-running rats versus Lou/C sedentary animals (p < 0.05). In conclusion, the impact of ischemia-reperfusion is similar between Lou/C- and Wistar sedentary rats. Spontaneous wheel-running activity decreases cardiac efficiency before ischemia and confers a protection against ischemia- and reperfusion-induced injury in isolated Lou/C rat hearts.

training - low caloric intake - ischemia‐reperfusion - Lou/C rats

References

• 1 Abete P, Testa G, Galizia G, Mazzella F, Della Morte D, de Santis D, Calabrese C, Cacciatore F, Gargiulo G, Ferrara N, Rengo G, Sica V, Napoli C, Rengo F. Tandem action of exercise training and food restriction completely preserves ischemic preconditioning in the aging heart.  Exp Gerontol. 2005;  40 43-50
• 2 Ahmet I, Wan R, Mattson M P, Lakatta E G, Talan M. Cardioprotection by intermittent fasting in rats.  Circulation. 2005;  112 3115-3121
• 3 Bazin H. The Louvain (Lou) Rats. Rat Hybridomas and Rat Monoclonal Antibodies. Cleveland, OH; CRC Press 1990: 43-51
• 4 Benjamin I J, McMillan D R. Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease.  Circ Res. 1998;  83 117-132
• 5 Bergmeyer H U. Methods of Enzymatic Analysis. 3rd edn. London; John Wiley and Sons 1974: 1464-1468
• 6 Bodkin N L, Alexander T M, Ortmeyer H K, Johnson E, Hansen B C. Mortality and morbidity in laboratory-maintained rhesus monkeys and effects of long-term dietary restriction.  J Gerontol A Biol Sci Med Sci. 2003;  58 212-219
• 7 Bowles D K, Farrar R P, Starnes J W. Exercise training improves cardiac function after ischemia in the isolated working rat heart.  Am J Physiol. 1992;  263 H804-H809
• 8 Bowles D K, Starnes J W. Exercise training improves metabolic response after ischemia in isolated working rat heart.  J Appl Physiol. 1994;  76 1608-1614
• 9 Broderick T L, Driedzic W R, Gillis M, Jacob J, Belke T. Effects of chronic food restriction and exercise training on the recovery of cardiac function following ischemia.  J Gerontol A Biol Sci Med Sci. 2001;  56 B33-B37
• 10 Burelle Y, Wambolt R B, Grist M, Parsons H L, Chow J C, Antler C, Bonen A, Keller A, Dunaway G A, Popov K M, Hochachka P W, Allard M F. Regular exercise is associated with a protective metabolic phenotype in the rat heart.  Am J Physiol. 2004;  287 H1055-H1063
• 11 Couturier K, Servais S, Koubi H, Sempore B, Sornay-Mayet M H, Cottet-Emard J M, Lavoie J M, Favier R. Metabolic characteristics and body composition in a model of anti-obese rats (Lou/C).  Obes Res. 2002;  10 188-195
• 12 Crandall D L, Feirer R P, Griffith D R, Beitz D C. Relative role of caloric restriction and exercise training upon susceptibility to isoproterenol-induced myocardial infarction in male rats.  Am J Clin Nutr. 1981;  34 841-847
• 13 Demetrius L. Caloric restriction, metabolic rate, and entropy.  J Gerontol A Biol Sci Med Sci. 2004;  59 B902-B915
• 14 Diniz Y S, Cicogna A C, Padovani C R, Silva M D, Faine L A, Galhardi C M, Rodrigues H G, Novelli E L. Dietary restriction and fibre supplementation: oxidative stress and metabolic shifting for cardiac health.  Can J Physiol Pharmacol. 2003;  81 1042-1048
• 15 Feuers R J, Duffy P H, Leakey J A, Turturro A, Mittelstaedt R A, Hart R W. Effect of chronic caloric restriction on hepatic enzymes of intermediary metabolism in the male Fisher 344 rat.  Mech Ageing Dev. 1989;  48 179-189
• 16 Goodrick C L, Ingram D K, Reynolds M A, Freeman F R, Cider N. Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction of genotype and age.  Mech Ageing Dev. 1990;  55 69-87
• 17 Hak J B, Van Beek J H, Van Wijhe M H, Westerhof N. Influence of temperature on the response time of mitochondrial oxygen consumption in isolated rabbit heart.  J Physiol. 1992;  447 17-31
• 18 Korvald C, Elvenes O P, Myrmel T. Myocardial substrate metabolism influences left ventricular energetics in vivo.  Am J Physiol. 2000;  278 H1345-H1351
• 19 Langendorff O. Untersuchungen am überlebenden Säugetierherzen.  Pflügers Arch. 1895;  61 291-352
• 20 Leong H S, Grist M, Parsons H, Wambolt R B, Lopaschuk G D, Brownsey R, Allard M F. Accelerated rates of glycolysis in the hypertrophied heart: are they a methodological artefact?.  Am J Physiol. 2002;  282 E1039-E1045
• 21 Levy E, Hasin Y, Navon G, Horowitz M. Chronic heat improves mechanical and metabolic response of trained rat heart on ischemia and reperfusion.  Am J Physiol. 1997;  272 H2085-H2094
• 22 Liedtke A J. Lipid burden in ischemic myocardium.  J Mol Cell Cardiol. 1988;  20 65-74
• 23 Liu B, Clanachan A S, Schulz R, Lopaschuk G D. Cardiac efficiency is improved after ischemia by altering both the source and fate of protons.  Circ Res. 1996;  79 940-948
• 24 Locke M. The cellular stress response to exercise: role of stress proteins.  Exerc Sport Sci Rev. 1997;  25 105-136
• 25 Long P, Nguyen Q, Thurow C, Broderick T L. Caloric restriction restores the cardioprotective effects of preconditioning in the rat heart.  Mech Ageing Dev. 2002;  123 1411-1413
• 26 Lopaschuk G D, Belke D D, Gamble J, Itoi T, Schonekess B O. Regulation of fatty acid oxidation in the mammalian heart in health and disease.  Biochim Biophys Acta. 1994;  1213 263-276
• 27 Mattison J A, Lane M A, Roth G S, Ingram D K. Caloric restriction in rhesus monkeys.  Exp Gerontol. 2003;  38 35-46
• 28 Mattson M P, Wan R. Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems.  J Nutr Biochem. 2005;  16 129-137
• 29 McCay C M, Crowell M F, Maynard L A. The effect of retarded growth upon the length of lifespan and upon ultimate body size.  J Nutr. 1935;  10 63-79
• 30 Moore R L, Palmer B M. Exercise training and cellular adaptations of normal and diseased hearts.  Exerc Sport Sci Rev. 1999;  27 285-315
• 31 Moreau D, Guilland J C, Athias P, Dumas J P, Klepping J, Didier J P. Utilization of free fatty acids and triglycerides by the perfused isolated rat heart after a prolonged swimming training program.  CR Seances Soc Biol Fil. 1978;  172 465-469
• 32 Morris J N, Everitt M G, Pollard R, Chave S P, Semmence A M. Vigorous exercise in leisure-time: protection against coronary heart disease.  Lancet. 1980;  2 1207-1210
• 33 Murray J L, Lopez A D. Alternative projections of mortality and disability by cause 1990 - 2020: Global Burden of Disease Study.  Lancet. 2000;  349 1498-1504
• 34 Naito H, Powers S K, Demirel H A, Aoki J. Exercise training increases heat shock protein in skeletal muscles of old rats.  Med Sci Sports Exerc. 2001;  33 729-734
• 35 Paffenbarger Jr R S, Hyde R T, Wing A L, Hsieh C C. Physical activity, all-cause mortality, and longevity of college alumni.  N Eng J Med. 1986;  314 605-613
• 36 Peltier S, Burelle Y, Novel-Chate V, Demaison L, Verdys M, Saks V, Keriel C, Leverve X M. Effect of exogenous adenosine and monensin on glycolytic flux in isolated perfused normoxic rat hearts: role of pyruvate kinase.  Mol Cell Biochem. 2005;  277 55-61
• 37 Servais S, Couturier K, Koubi H, Rouanet J L, Desplanches D, Sornay-Mayet M H, Sempore B, Lavoie J M, Favier R. Effect of voluntary exercise on H2O2 release by subsarcolemmal and intermyofibrillar mitochondria.  Free Radic Biol Med. 2003;  35 24-32
• 38 Shinmura K, Tamaki K, Bolli R. Short-term caloric restriction improves ischemic tolerance independent of opening of ATP-sensitive K⁺ channels in both young and aged hearts.  J Mol Cell Cardiol. 2005;  39 285-296
• 39 Weindruch R, Sohal R S. Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging.  N Engl J Med. 1997;  337 986-994