Skip to main content
Log in

Altered left ventricular performance in aging physically active mice with an ankle sprain injury

  • Published:
AGE Aims and scope Submit manuscript

Abstract

We assessed the impact of differing physical activity levels throughout the lifespan, using a musculoskeletal injury model, on the age-related changes in left ventricular (LV) parameters in active mice. Forty male mice (CBA/J) were randomly placed into one of three running wheel groups (transected CFL group, transected ATFL/CFL group, SHAM group) or a SHAM Sedentary group (SHAMSED). Before surgery and every 6 weeks after surgery, LV parameters were measured under 2.5 % isoflurane inhalation. Group effects for daily distance run was significantly greater for the SHAM and lesser for the ATLF/CFL mice (p = 0.013) with distance run decreasing with age for all mice (p < 0.0001). Beginning at 6 months of age, interaction (group × age) was noted with LV posterior wall thickness-to-radius ratios (h/r) where h/r increased with age in the ATFL/CFL and SHAMSED mice while the SHAM and CFL mice exhibited decreased h/r with age (p = 0.0002). Passive filling velocity (E wave) was significantly greater in the SHAM mice and lowest for the ATFL/CFL and SHAMSED mice (p < 0.0001) beginning at 9 months of age. Active filling velocity (A wave) was not different between groups (p = 0.10). Passive-to-active filling velocity ratio (E/A ratio) was different between groups (p < 0.0001), with higher ratios for the SHAM mice and lower ratios for the ATFL/CFL and SHAMSED mice in response to physical activity beginning at 9 months of age. Passive-to-active filling velocity ratio decreased with age (p < 0.0001). Regular physical activity throughout the lifespan improved LV structure, passive filling velocity, and E/A ratio by 6 to 9 months of age and attenuated any negative alterations throughout the second half of life. The diastolic filling differences were found to be significantly related to the amount of activity performed by 9 months and at the end of the lifespan.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Bhella PS et al. (2014) Impact of lifelong exercise “dose” on left ventricular compliance and distensibility. J Am Coll Cardiol 64:1257–1266. doi:10.1016/j.jacc.2014.03.062

    Article  PubMed  PubMed Central  Google Scholar 

  • Bradshaw AD, Baicu CF, Rentz TJ, Van Laer AO, Bonnema DD, Zile MR (2010) Age-dependent alterations in fibrillar collagen content and myocardial diastolic function: role of SPARC in post-synthetic procollagen processing. Am J Physiol Heart Circ Physiol 298:H614–H622. doi:10.1152/ajpheart.00474.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brenner DA, Apstein CS, Saupe KW (2001) Exercise training attenuates age-associated diastolic dysfunction in rats. Circulation 104:221–226

    Article  CAS  PubMed  Google Scholar 

  • Carrick-Ranson G et al. (2012) Effect of healthy aging on left ventricular relaxation and diastolic suction. Am J Physiol Heart Circ Physiol 303:H315–H322. doi:10.1152/ajpheart.00142.2012

  • Carrick-Ranson G et al. (2014) The effect of lifelong exercise dose on cardiovascular function during exercise. J Appl Physiol 116:736–745. doi:10.1152/japplphysiol.00342.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Centers for Disease Control and Prevention (2009) National Center for Injury Prevention and Control. CDC Injury Research Agenda, 2009-2018. US Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta (GA)

    Google Scholar 

  • Cornelissen VA, Fagard RH, Lijnen PJ (2010) Serum collagen-derived peptides are unaffected by physical training in older sedentary subjects. J Sci Med Sport/Sports Med Aust 13:424–428. doi:10.1016/j.jsams.2009.08.001

    Article  Google Scholar 

  • Dai DF, Rabinovitch PS (2009) Cardiac aging in mice and humans: the role of mitochondrial oxidative stress. Trends Cardiovasc Med 19:213–220. doi:10.1016/j.tcm.2009.12.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dai DF et al. (2009) Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging. Circulation. 119:2789–2797. doi:10.1161/CIRCULATIONAHA.108.822403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N (1986) Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 57:450–458

    Article  CAS  PubMed  Google Scholar 

  • Downes TR, Nomeir AM, Stewart K, Mumma M, Kerensky R, Little WC (1990) Effect of alteration in loading conditions on both normal and abnormal patterns of left ventricular filling in healthy individuals. Am J Cardiol 65:377–382

    Article  CAS  PubMed  Google Scholar 

  • Dutta D, Calvani R, Bernabei R, Leeuwenburgh C, Marzetti E (2012) Contribution of impaired mitochondrial autophagy to cardiac aging: mechanisms and therapeutic opportunities. Circ Res 110:1125–1138. doi:10.1161/CIRCRESAHA.111.246108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ehsani AA et al. (2003) Attenuation of cardiovascular adaptations to exercise in frail octogenarians. Journal of Applied Physiology. 95:1781–1788. doi:10.1152/japplphysiol.00194.2003

    Article  PubMed  Google Scholar 

  • Emter CA, Baines CP (2010) Low-intensity aerobic interval training attenuates pathological left ventricular remodeling and mitochondrial dysfunction in aortic-banded miniature swine. Am J Physiol Heart Circ Physiol 299:H1348–H1356. doi:10.1152/ajpheart.00578.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fernandez WG, Yard EE, Comstock RD (2007) Epidemiology of lower extremity injuries among U.S. high school athletes. Acad Emerg Med: Off J Soc Acad Emerg Medicine 14:641–645. doi:10.1197/j.aem.2007.03.1354

    Article  Google Scholar 

  • Forman DE, Manning WJ, Hauser R, Gervino EV, Evans WJ, Wei JY (1992) Enhanced left ventricular diastolic filling associated with long-term endurance training. J Gerontol 47:M56–M58

    Article  CAS  PubMed  Google Scholar 

  • Fujimoto N et al. (2010) Cardiovascular effects of 1 year of progressive and vigorous exercise training in previously sedentary individuals older than 65 years of age. Circulation 122:1797–1805. doi:10.1161/CIRCULATIONAHA.110.973784

    Article  PubMed  PubMed Central  Google Scholar 

  • Garber CE et al. (2011) American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc 43:1334–1359. doi:10.1249/MSS.0b013e318213fefb

    Article  PubMed  Google Scholar 

  • Gates PE, Tanaka H, Graves J, Seals DR (2003) Left ventricular structure and diastolic function with human ageing. Relation to habitual exercise and arterial stiffness. Eur Heart J 24:2213–2220

    Article  PubMed  Google Scholar 

  • Gorza L, Mercadier JJ, Schwartz K, Thornell LE, Sartore S, Schiaffino S (1984) Myosin types in the human heart. An immunofluorescence study of normal and hypertrophied atrial and ventricular myocardium. Circ Res 54:694–702

    Article  CAS  PubMed  Google Scholar 

  • Groban L, Jobe H, Lin M, Houle T, Kitzman DA, Sonntag W (2008) Effects of short-term treadmill exercise training or growth hormone supplementation on diastolic function and exercise tolerance in old rats. J Gerontol Ser A Biol Sci Med Sci 63:911–920

    Article  Google Scholar 

  • Hirose K, Murakami G, Minowa T, Kura H, Yamashita T (2004) Lateral ligament injury of the ankle and associated articular cartilage degeneration in the talocrural joint: anatomic study using elderly cadavers. J Orthop Sci: Off J Jpn Ortho Assoc 9:37–43. doi:10.1007/s00776-003-0732-9

    Article  Google Scholar 

  • Hootman JM, Dick R, Agel J (2007) Epidemiology of collegiate injuries for 15 sports: summary and recommendations for injury prevention initiatives. J Athl Train 42:311–319

    PubMed  PubMed Central  Google Scholar 

  • Horn MA et al. (2012) Age-related divergent remodeling of the cardiac extracellular matrix in heart failure: collagen accumulation in the young and loss in the aged. J Mol Cell Cardiol 53:82–90. doi:10.1016/j.yjmcc.2012.03.011

    Article  CAS  PubMed  Google Scholar 

  • Hubbard-Turner T, Wikstrom EA, Guderian S, MJ T (2013) Acute ankle sprain in a mouse model. Med Sci Sports Exerc 45:1623–1628. doi:10.1249/MSS.0b013e3182897d25

    Article  PubMed  Google Scholar 

  • Janssen BJ, De Celle T, Debets JJ, Brouns AE, Callahan MF, Smith TL (2004) Effects of anesthetics on systemic hemodynamics in mice. Am J Physiol Heart Circ Physiol 287:H1618–H1624. doi:10.1152/ajpheart.01192.2003

    Article  CAS  PubMed  Google Scholar 

  • Kass DA (2002) Age-related changes in venticular-arterial coupling: pathophysiologic implications. Heart Fail Rev 7:51–62

    Article  PubMed  Google Scholar 

  • Kitzman DW (2000) Heart failure with normal systolic function. Clin Geriatr Med 16:489–512

    Article  CAS  PubMed  Google Scholar 

  • Knab AM, Bowen RS, Moore-Harrison T, Hamilton AT, Turner MJ, JT L (2009) Repeatability of exercise behaviors in mice. Physiol Behav 98:433–440. doi:10.1016/j.physbeh.2009.07.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lachance D et al. (2009) Moderate exercise training improves survival and ventricular remodeling in an animal model of left ventricular volume overload. Circ Heart Fail 2:437–445. doi:10.1161/CIRCHEARTFAILURE.108.845487

    Article  PubMed  Google Scholar 

  • Lakatta EG, Levy D (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part II: the aging heart in health: links to heart disease. Circulation 107:346–354

    Article  PubMed  Google Scholar 

  • Lee SD et al. (2012) Effects of exercise training on cardiac apoptosis in obese rats. Nutr Metab Cardiovasc Dis: NMCD. doi:10.1016/j.numecd.2011.11.002

    Google Scholar 

  • Lightfoot JT, Turner MJ, Daves M, Vordermark A, Kleeberger SR (2004) Genetic influence on daily wheel running activity level. Physiol Genomics 19:270–276. doi:10.1152/physiolgenomics.00125.2004

    Article  CAS  PubMed  Google Scholar 

  • Lightfoot JT, Turner MJ, Pomp D, Kleeberger SR, Leamy LJ (2008) Quantitative trait loci for physical activity traits in mice. Physiol Genomics 32:401–408. doi:10.1152/physiolgenomics.00241.2007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mandarakas M, Pourkazemi F, Sman A, Burns J, Hiller CE (2014) Systematic review of chronic ankle instability in children. J Foot Ankle Res 7:21. doi:10.1186/1757-1146-7-21

    Article  PubMed  PubMed Central  Google Scholar 

  • McMullen JR, Shioi T, Zhang L, Tarnavski O, Sherwood MC, Kang PM, Izumo S (2003) Phosphoinositide 3-kinase(p110alpha) plays a critical role for the induction of physiological, but not pathological, cardiac hypertrophy. Proc Natl Acad Sci U S A 100:12355–12360. doi:10.1073/pnas.1934654100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyata S, Minobe W, Bristow MR, LA L (2000) Myosin heavy chain isoform expression in the failing and nonfailing human. Heart Circ Res 86:386–390

    Article  CAS  PubMed  Google Scholar 

  • Molmen HE, Wisloff U, Aamot IL, Stoylen A, CB I (2012) Aerobic interval training compensates age related decline in cardiac function. Scand Cardiovasc J: SCJ 46:163–171. doi:10.3109/14017431.2012.660192

    Article  PubMed  Google Scholar 

  • Pandya K, Kim HS, Smithies O (2006) Fibrosis, not cell size, delineates beta-myosin heavy chain reexpression during cardiac hypertrophy and normal aging in vivo. Proc Natl Acad Sci U S A 103:16864–16869. doi:10.1073/pnas.0607700103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peters JW, Trevino SG, PA R (1991) Chronic lateral ankle instability. Foot Ankle 12:182–191

    Article  CAS  PubMed  Google Scholar 

  • Pierce GL, Magyari PM, Aranda JM Jr, Edwards DG, Hamlin SA, Hill JA, Braith RW (2007) Effect of heart transplantation on skeletal muscle metabolic enzyme reserve and fiber type in end-stage heart failure patients. Clin Transplant 21:94–100. doi:10.1111/j.1399-0012.2006.00589.x

    Article  PubMed  Google Scholar 

  • Reiser PJ, Portman MA, Ning XH, Schomisch Moravec C (2001) Human cardiac myosin heavy chain isoforms in fetal and failing adult atria and ventricles. Am J Physiol Heart Circ Physiol 280:H1814–H1820

    CAS  PubMed  Google Scholar 

  • Ren J, Li Q, Wu S, Li SY, SA B (2007) Cardiac overexpression of antioxidant catalase attenuates aging-induced cardiomyocyte relaxation dysfunction. Mech Ageing Dev 128:276–285. doi:10.1016/j.mad.2006.12.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodeheffer RJ, Gerstenblith G, Becker LC, Fleg JL, Weisfeldt ML, Lakatta EG (1984) Exercise cardiac output is maintained with advancing age in healthy human subjects: cardiac dilatation and increased stroke volume compensate for a diminished heart rate. Circulation 69:203–213

    Article  CAS  PubMed  Google Scholar 

  • Sahn DJ, DeMaria A, Kisslo J, Weyman A (1978) Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 58:1072–1083

    Article  CAS  PubMed  Google Scholar 

  • Samuel JL et al. (1983) Distribution of myosin isozymes within single cardiac cells. An immunohistochemical study. Circ Res 52:200–209

    Article  CAS  PubMed  Google Scholar 

  • Schulman SP, Lakatta EG, Fleg JL, Lakatta L, Becker LC, Gerstenblith G (1992) Age-related decline in left ventricular filling at rest and exercise. Am J Physiol 263:H1932–H1938

    CAS  PubMed  Google Scholar 

  • Seals DR, Hagberg JM, Spina RJ, Rogers MA, Schechtman KB, Ehsani AA (1994) Enhanced left ventricular performance in endurance trained older men. Circulation 89:198–205

    Article  CAS  PubMed  Google Scholar 

  • Shinmura K, Tamaki K, Sano M, Murata M, Yamakawa H, Ishida H, Fukuda K (2011) Impact of long-term caloric restriction on cardiac senescence: caloric restriction ameliorates cardiac diastolic dysfunction associated with aging. J Mol Cell Cardiol 50:117–127. doi:10.1016/j.yjmcc.2010.10.018

    Article  CAS  PubMed  Google Scholar 

  • Smith RW, Reischl SF (1986) Treatment of ankle sprains in young athletes. Am J Sports Med 14:465–471

    Article  CAS  PubMed  Google Scholar 

  • Soboroff SH, Pappius EM, Komaroff AL (1984) Benefits, risks, and costs of alternative approaches to the evaluation and treatment of severe ankle sprain. Clin Orthop Related Res. 160–168

  • Storer JB (1966) Longevity and gross pathology at death in 22 inbred mouse strains. Journal of Gerontology. 21:404–409

    Article  CAS  PubMed  Google Scholar 

  • Takemoto KA, Bernstein L, Lopez JF, Marshak D, Rahimtoola SH, Chandraratna PA (1992) Abnormalities of diastolic filling of the left ventricle associated with aging are less pronounced in exercise-trained individuals. Am Heart J 124:143–148

    Article  CAS  PubMed  Google Scholar 

  • Tillmann T, Kamino K, Mohr U (2000) Incidence and spectrum of spontaneous neoplasms in male and female CBA/J mice. Exp Toxicol Pathol: Off J Ges Toxikologische Pathol 52:221–225. doi:10.1016/S0940-2993(00)80032-9

    Article  CAS  Google Scholar 

  • Turner MJ, Chavis MN, Turner TH (2013) Enhanced diastolic filling performance with lifelong physical activity in aging mice. Med Sci Sports Exerc 45:1933–1940. doi:10.1249/MSS.0b013e318293b019

    Article  PubMed  Google Scholar 

  • Turner MJ, Kleeberger SR, Lightfoot JT (2005) Influence of genetic background on daily running-wheel activity differs with aging Physiol Genomics 22:76–85. doi:10.1152/physiolgenomics.00243.2004

    PubMed  Google Scholar 

  • Valderrabano V, Hintermann B, Horisberger M, TS F (2006) Ligamentous posttraumatic ankle osteoarthritis. The American Journal of Sports Medicine 34:612–620. doi:10.1177/0363546505281813

    Article  PubMed  Google Scholar 

  • Verhagen RA, de Keizer G, van Dijk CN (1995) Long-term follow-up of inversion trauma of the ankle. Arch Orthop Trauma Surg 114:92–96

    Article  CAS  PubMed  Google Scholar 

  • Waggoner AD, Bierig SM (2001) Tissue Doppler imaging: a useful echocardiographic method for the cardiac sonographer to assess systolic and diastolic ventricular function. J Am Soc Echocardiogr :Off Publ Am Soc Echocardiogr 14:1143–1152

    Article  CAS  Google Scholar 

  • Wang E, Naess MS, Hoff J, Albert TL, Pham Q, Richardson RS, Helgerud J (2014) Exercise-training-induced changes in metabolic capacity with age: the role of central cardiovascular plasticity. Age 36:665–676. doi:10.1007/s11357-013-9596-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The work was supported by grants from the University of North Carolina at Charlotte Faculty Research Grants Program. The authors would like to thank Nastassia Brown, Jason Cline, Karen Correa, Kristen Regan, and Robert Valderama for their assistance with animal care and data collection.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael J. Turner.

Ethics declarations

Funding

This study was funded by the UNC Charlotte Faculty Research Grants Program.

Conflict of interest

The authors declare that they have no competing interests.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Turner, M.J., Guderian, S., Wikstrom, E.A. et al. Altered left ventricular performance in aging physically active mice with an ankle sprain injury. AGE 38, 15 (2016). https://doi.org/10.1007/s11357-016-9877-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11357-016-9877-2

Keywords

Navigation