The impacts of age and frailty on heart rate and sinoatrial node function

Journal of Physiology

Volumn 594, Issue 23, 2016, Pages 7105-7126

  Moghtadaei, Motahareh ^a   Jansen, Hailey J ^a   Mackasey, Martin ^a   Rafferty, Sara A ^a   Bogachev, Oleg ^a   Sapp, John L ^a   Howlett, Susan E ^a   Rose, Robert A ^a  

^a DALHOUSIE UNIVERSITY   (Canada)

Author keywords

aging; frailty; heart rate; sinoatrial node

Indexed keywords

COLLAGEN TYPE 1; COLLAGEN TYPE 3; CONNECTIVE TISSUE GROWTH FACTOR; GELATINASE A; GELATINASE B; MESSENGER RNA; TISSUE INHIBITOR OF METALLOPROTEINASE 1; TISSUE INHIBITOR OF METALLOPROTEINASE 2; TISSUE INHIBITOR OF METALLOPROTEINASE 3; TISSUE INHIBITOR OF METALLOPROTEINASE 4; TRANSFORMING GROWTH FACTOR BETA;

ACTION POTENTIAL DURATION; AGED; AGING; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; FRAIL ELDERLY; GENE EXPRESSION; HEART ATRIUM REMODELING; HEART DEPOLARIZATION; HEART MUSCLE FIBROSIS; HEART MUSCLE POTENTIAL; HEART RATE; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; SINUS NODE; SINUS NODE CONDUCTION VELOCITY; SINUS NODE DISEASE; SINUS NODE RECOVERY TIME; ACTION POTENTIAL; ANIMAL; C57BL MOUSE; FIBROSIS; PATHOLOGY; PHYSIOLOGY;

ACTION POTENTIALS; AGING; ANIMALS; FIBROSIS; HEART RATE; MALE; MICE, INBRED C57BL; SINOATRIAL NODE;

EID: 84991687622     PISSN: 00223751     EISSN: 14697793     Source Type: Journal    
DOI: 10.1113/JP272979     Document Type: Article

References (67)

1. Adan V & Crown LA (2003). Diagnosis and treatment of sick sinus syndrome. Am Fam Physician 67, 1725–1732.
2. Alfaras I, Di Germanio C, Bernier M, Csiszar A, Ungvari Z, Lakatta EG & de Cabo R (2016). Pharmacological strategies to retard cardiovascular aging. Circ Res 118, 1626–1642.
3. Alings AM, Abbas RF & Bouman LN (1995). Age-related changes in structure and relative collagen content of the human and feline sinoatrial node. A comparative study. Eur Heart J 16, 1655–1667.
4. Azer J, Hua R, Krishnaswamy PS & Rose RA (2014). Effects of natriuretic peptides on electrical conduction in the sinoatrial node and atrial myocardium of the heart. J Physiol 592, 1025–1045.
5. Bonnema DD, Webb CS, Pennington WR, Stroud RE, Leonardi AE, Clark LL, McClure CD, Finklea L, Spinale FG & Zile MR (2007). Effects of age on plasma matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs). J Card Fail 13, 530–540.
6. Clegg A, Young J, Iliffe S, Rikkert MO & Rockwood K (2013). Frailty in elderly people. Lancet 381, 752–762.
7. Costa A & Richman DC (2016). Implantable devices: Assessment and perioperative management. Anesthesiol Clin 34, 185–199.
8. Csepe TA, Kalyanasundaram A, Hansen BJ, Zhao J & Fedorov VV (2015). Fibrosis: a structural modulator of sinoatrial node physiology and dysfunction. Front Physiol 6, 37.
9. de Vries NM, Staal JB, van Ravensberg CD, Hobbelen JS, Olde Rikkert MG & Nijhuis-van der Sanden MW (2011). Outcome instruments to measure frailty: a systematic review. Ageing Res Rev 10, 104–114.
10. Di Gennaro M, Bernabei R, Sgadari A, Carosella L & Carbonin PU (1987). Age-related differences in isolated rat sinus node function. Basic Res Cardiol 82, 530–536.
11. Dobrzynski H, Billeter R, Greener ID, Tellez JO, Chandler NJ, Flagg TP, Nichols CG, Lopatin AN & Boyett MR (2006). Expression of Kir2.1 and Kir6.2 transgenes under the control of the α-MHC promoter in the sinoatrial and atrioventricular nodes in transgenic mice. J Mol Cell Cardiol 41, 855–867.
12. Dobrzynski H, Boyett MR & Anderson RH (2007). New insights into pacemaker activity: promoting understanding of sick sinus syndrome. Circulation 115, 1921–1932.
13. Egom EE, Vella K, Hua R, Jansen HJ, Moghtadaei M, Polina I, Bogachev O, Hurnik R, Mackasey M, Rafferty S, Ray G & Rose RA (2015). Impaired sinoatrial node function and increased susceptibility to atrial fibrillation in mice lacking natriuretic peptide receptor C. J Physiol 593, 1127–1146.
14. Farman GP, Tachampa K, Mateja R, Cazorla O, Lacampagne A & de Tombe PP (2008). Blebbistatin: use as inhibitor of muscle contraction. Pflugers Arch 455, 995–1005.
15. Fedorov VV, Chang R, Glukhov AV, Kostecki G, Janks D, Schuessler RB & Efimov IR (2010). Complex interactions between the sinoatrial node and atrium during reentrant arrhythmias in the canine heart. Circulation 122, 782–789.
16. Fedorov VV, Glukhov AV & Chang R (2012). Conduction barriers and pathways of the sinoatrial pacemaker complex: their role in normal rhythm and atrial arrhythmias. Am J Physiol Heart Circ Physiol 302, H1773–H1783.
17. Fedorov VV, Hucker WJ, Dobrzynski H, Rosenshtraukh LV & Efimov IR (2006). Postganglionic nerve stimulation induces temporal inhibition of excitability in rabbit sinoatrial node. Am J Physiol Heart Circ Physiol 291, H612–H623.
18. Fedorov VV, Schuessler RB, Hemphill M, Ambrosi CM, Chang R, Voloshina AS, Brown K, Hucker WJ & Efimov IR (2009). Structural and functional evidence for discrete exit pathways that connect the canine sinoatrial node and atria. Circ Res 104, 915–923.
19. Feridooni HA, Sun MH, Rockwood K & Howlett SE (2015). Reliability of a frailty index based on the clinical assessment of health deficits in male C57BL/6J mice. J Gerontol A Biol Sci Med Sci 70, 686–693.
20. Glukhov AV, Fedorov VV, Anderson ME, Mohler PJ & Efimov IR (2010). Functional anatomy of the murine sinus node: high-resolution optical mapping of ankyrin-B heterozygous mice. Am J Physiol Heart Circ Physiol 299, H482–H491.
21. 1-mediated fibrosis and ion channel remodeling are key mechanisms in producing the sinus node dysfunction associated with SCN5A deficiency and aging. Circ Arrhythm Electrophysiol 4, 397–406.
22. Herrmann S, Fabritz L, Layh B, Kirchhof P & Ludwig A (2011). Insights into sick sinus syndrome from an inducible mouse model. Cardiovasc Res 90, 38–48.
23. Heuberger RA (2011). The frailty syndrome: a comprehensive review. J Nutr Gerontol Geriatr 30, 315–368.
24. Hua R, Adamczyk A, Robbins C, Ray G & Rose RA (2012). Distinct patterns of constitutive phosphodiesterase activity in mouse sinoatrial node and atrial myocardium. PLoS One 7, e47652.
25. Hua R, MacLeod SL, Polina I, Moghtadaei M, Jansen HJ, Bogachev O, O'Blenes SB, Sapp JL, Legare JF & Rose RA (2015). Effects of wild-type and mutant forms of atrial natriuretic peptide on atrial electrophysiology and arrhythmogenesis. Circ Arrhythm Electrophysiol 8, 1240–1254.
26. Irisawa H, Brown HF & Giles W (1993). Cardiac pacemaking in the sinoatrial node. Physiol Rev 73, 197–227.
27. Jones SA, Boyett MR & Lancaster MK (2007). Declining into failure: the age-dependent loss of the L-type calcium channel within the sinoatrial node. Circulation 115, 1183–1190.
28. Jones SA, Lancaster MK & Boyett MR (2004). Ageing-related changes of connexins and conduction within the sinoatrial node. J Physiol 560, 429–437.
29. Kassiri Z & Khokha R (2005). Myocardial extra-cellular matrix and its regulation by metalloproteinases and their inhibitors. Thromb Haemost 93, 212–219.
30. Katayama PL, Dias DP, Silva LE, Virtuoso-Junior JS & Marocolo M (2015). Cardiac autonomic modulation in non-frail, pre-frail and frail elderly women: a pilot study. Aging Clin Exp Res 27, 621–629.
31. Krishnaswamy PS, Egom EE, Moghtadaei M, Jansen HJ, Azer J, Bogachev O, Mackasey M, Robbins C & Rose RA (2015). Altered parasympathetic nervous system regulation of the sinoatrial node in Akita diabetic mice. J Mol Cell Cardiol 82, 125–135.
32. 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.
33. 2+ clocks and surface membrane voltage clocks controls the timekeeping mechanism of the heart's pacemaker. Circ Res 106, 659–673.
34. Larson ED, St Clair JR, Sumner WA, Bannister RA & Proenza C (2013). Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate. Proc Natl Acad Sci USA 110, 18011–18016.
35. Leask A (2015). Getting to the heart of the matter: new insights into cardiac fibrosis. Circ Res 116, 1269–1276.
36. Liu J, Dobrzynski H, Yanni J, Boyett MR & Lei M (2007). Organisation of the mouse sinoatrial node: structure and expression of HCN channels. Cardiovasc Res 73, 729–738.
37. 2+ signaling. Am J Physiol Heart Circ Physiol 306, H1385–H1397.
38. McNallan SM, Chamberlain AM, Gerber Y, Singh M, Kane RL, Weston SA, Dunlay SM, Jiang R & Roger VL (2013). Measuring frailty in heart failure: a community perspective. Am Heart J 166, 768–774.
39. Mangoni ME & Nargeot J (2008). Genesis and regulation of the heart automaticity. Physiol Rev 88, 919–982.
40. Mangrum JM & DiMarco JP (2000). The evaluation and management of bradycardia. N Engl J Med 342, 703–709.
41. Marionneau C, Couette B, Liu J, Li H, Mangoni ME, Nargeot J, Lei M, Escande D & Demolombe S (2005). Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart. J Physiol 562, 223–234.
42. Miragoli M & Glukhov AV (2015). Atrial fibrillation and fibrosis: beyond the cardiomyocyte centric view. Biomed Res Int 2015, 798768.
43. Mitnitski AB, Mogilner AJ & Rockwood K (2001). Accumulation of deficits as a proxy measure of aging. ScientificWorldJournal 1, 323–336.
44. Monfredi O & Boyett MR (2015). Sick sinus syndrome and atrial fibrillation in older persons – A view from the sinoatrial nodal myocyte. J Mol Cell Cardiol 83, 88–100.
45. Morley GE, Vaidya D, Samie FH, Lo C, Delmar M & Jalife J (1999). Characterization of conduction in the ventricles of normal and heterozygous Cx43 knockout mice using optical mapping. J Cardiovasc Electrophysiol 10, 1361–1375.
46. Morris GM, Monfredi O & Boyett MR (2011). Not so fast! Sick sinus syndrome is a complex and incompletely understood disease that might prove hard to model in animals. Cardiovasc Res 92, 178; author reply 179.
47. Nagase H, Visse R & Murphy G (2006). Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 69, 562–573.
48. Nygren A, Lomax AE & Giles WR (2004). Heterogeneity of action potential durations in isolated mouse left and right atria recorded using voltage-sensitive dye mapping. Am J Physiol Heart Circ Physiol 287, H2634–H2643.
49. Parks RJ, Fares E, Macdonald JK, Ernst MC, Sinal CJ, Rockwood K & Howlett SE (2012). A procedure for creating a frailty index based on deficit accumulation in aging mice. J Gerontol A Biol Sci Med Sci 67, 217–227.
50. Rockwood K & Mitnitski A (2007). Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci 62, 722–727.
51. Rockwood K & Mitnitski A (2011). Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriatr Med 27, 17–26.
52. Rockwood K, Mitnitski A, Song X, Steen B & Skoog I (2006). Long-term risks of death and institutionalization of elderly people in relation to deficit accumulation at age 70. J Am Geriatr Soc 54, 975–979.
53. Rose RA, Kabir MG & Backx PH (2007). Altered heart rate and sinoatrial node function in mice lacking the cAMP regulator phosphoinositide 3-kinase-γ. Circ Res 101, 1274–1282.
54. Sangaralingham SJ, Huntley BK, Martin FL, McKie PM, Bellavia D, Ichiki T, Harders GE, Chen HH & Burnett JC Jr (2011). The aging heart, myocardial fibrosis, and its relationship to circulating C-type natriuretic peptide. Hypertension 57, 201–207.
55. Sangaralingham SJ, Wang BH, Huang L, Kumfu S, Ichiki T, Krum H & Burnett JC Jr (2016). Cardiorenal fibrosis and dysfunction in aging: Imbalance in mediators and regulators of collagen. Peptides 76, 108–114.
56. Searle SD, Mitnitski A, Gahbauer EA, Gill TM & Rockwood K (2008). A standard procedure for creating a frailty index. BMC Geriatr 8, 24.
57. Singh M, Stewart R & White H (2014). Importance of frailty in patients with cardiovascular disease. Eur Heart J 35, 1726–1731.
58. Spinale FG (2002). Matrix metalloproteinases: regulation and dysregulation in the failing heart. Circ Res 90, 520–530.
59. Spinale FG (2007). Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 87, 1285–1342.
60. Springer J, Azer J, Hua R, Robbins C, Adamczyk A, McBoyle S, Bissell MB & Rose RA (2012). The natriuretic peptides BNP and CNP increase heart rate and electrical conduction by stimulating ionic currents in the sinoatrial node and atrial myocardium following activation of guanylyl cyclase-linked natriuretic peptide receptors. J Mol Cell Cardiol 52, 1122–1134.
61. 2+ clock genes underlying sino-atrial node pacemaking. Exp Physiol 96, 1163–1178.
62. Thannickal VJ, Zhou Y, Gaggar A & Duncan SR (2014). Fibrosis: ultimate and proximate causes. J Clin Invest 124, 4673–4677.
63. Travers JG, Kamal FA, Robbins J, Yutzey KE & Blaxall BC (2016). Cardiac fibrosis: The fibroblast awakens. Circ Res 118, 1021–1040.
64. Uretsky BF & Sheahan RG (1997). Primary prevention of sudden cardiac death in heart failure: will the solution be shocking? J Am Coll Cardiol 30, 1589–1597.
65. Verheijck EE, van Kempen MJ, Veereschild M, Lurvink J, Jongsma HJ & Bouman LN (2001). Electrophysiological features of the mouse sinoatrial node in relation to connexin distribution. Cardiovasc Res 52, 40–50.
66. Whitehead JC, Hildebrand BA, Sun M, Rockwood MR, Rose RA, Rockwood K & Howlett SE (2014). A clinical frailty index in aging mice: comparisons with frailty index data in humans. J Gerontol A Biol Sci Med Sci 69, 621–632.
67. Yanni J, Tellez JO, Sutyagin PV, Boyett MR & Dobrzynski H (2010). Structural remodelling of the sinoatrial node in obese old rats. J Mol Cell Cardiol 48, 653–662.