Changes of shorten ing am plitude - frequency rela tion sh ip in hyperthyro id ra t card iom yocytes

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1 2306 Chinese Journal of Pathophysiology 2008, 24 (12) : [ ] (2008) , 1, 1, 2, 2 ( 1, 2, ) [ ] : ( ), :,, :, 2 ( T4), ;, 2 T4, 1 2 Hz, 4 Hz ;, 4 T4, T4 1 2 Hz, ; 4 Hz 2 T4, 4 T4 : 4 - [ ] ; ; [ ] R331 [ ] A Changes of shorten ing am plitude - frequency rela tion sh ip in hyperthyro id ra t card iom yocytes WANG Yun - ying 1, YU Zhi - bin 1, J IAO Bo 1, ZHANG Zi - tai 2, DENG J ing - lan 2 ( 1 D epartm ent of A erospace Physiology, 2 D epartm ent of N uclearm edicine, X ijing Hospital, Fourth M ilitary M edical U niversi2 ty, X iπan , China. E - m ail: yuzhib@ fmm u. edu. cn) [ ABSTRACT] A IM : The aim of this study was to observe the cardiac performance in 2 - week or 4 - week levo2 thyroxine ( T4) - induced cardiac hypertrophy and to elucidate the possible underlying mechanism of cardiac hypertrophy transition to heart failure in T4 treatment rats. M ETHOD S: The blood p ressure and pulse rate were measured by tail - cuff technique. The cardiac output and the p reload - cardiac output were measured in working heart mode. The shortening of unloading contraction in cardiomyocytes was observed by an edge - detector system. RESUL TS: Resting heart rate in T4 treatment rats increased significantly and the width of cardiomyocytes widened in T4 rats, but the length of cardiomyocytes had no difference compared with control values. The cardiac output in 2 - week T4 group was higher than that in control group. The cardiac output increased when the p reload increased from 5 mmhg to 15 mmhg. The unloading shortening am2 p litude at 1 Hz and 2 Hz increased in 2 - week T4 group. No difference between 2 - week T4 group and control group at 4 Hz was observed. W hen the stimulating frequency increased from 1 Hz to 4 Hz, the shortening amp litude also increased in control cardiomyocytes, but decreased in 2 - week or 4 - week T4 group. The shortening amp litude increased further in 4 - week T4 group as compared with that in control. The time to peak shortening and time from peak shortening to 75% relaxation reduced at each frequency in 2 - week and 4 - week T4 group. The shortening and relaxation rates in 2 - week or 4 - week T4 group were higher than those in control group at 1 Hz and 2 Hz. The shortening and relaxation rate kep t higher at 4 Hz in 2 - week T4 group, but showed no difference with control at 4 Hz in 4 - week T4 group. CO NCL US IO N: These above results suggest that shortening amp litude - frequency relationship of cardiomyocytes in 4 - week T4 rats is earli2 er to be altered than cardiac performance in working heart. [ KEY WO RD S] Hyperthyroidism; Cardiomyocytes; Myocardial contraction,, [ ] [ ] [ ] (No ) Tel: ; E - mail: yuzhib@ fmmu. edu. cn

2 2307, (mmol/l) : NaCl, 417 KCl, 112 MgCl 2,, 2010 NaHCO 3, 112 NaH 2 PO 4, 215 CaCl 2, 1010 [ 1 ],, ph % O 2 5 % CO 2 [ 2 ],,, T4,,,, [ 3 ],, [ 1 ],,, Radnoti (Radnoti),, ( ) 60 mmhg 10 mmhg, [ 4 ], 2 ml, 80 mmhg,, 37 [ 7 ], : ; ; 10 m in, ;,,,, 5 mmhg 15 mmhg, 5 m in [ 5 ], [ 6 ], 2. 2, [ 8 ] : T4, Langendorff ; T4, ;, 37, 0108 % - I Joklik, [ 9 ],, ml, O lympus IX70, 10 m in % HEPES 1. 1 Joklikπs MEM (m inimum essential, HEPES medium eagle) BSA ( bovine serum album in) (mmol/l) : NaCl, 418 KCl, 112 MgCl Sigma Levothyroxine sodium ( 2, 1010, T4) Merck HEPES, 510, 1010, 118 CaCl 2, ph 1. 2 SD ml /m in 6 m in, 24, g, 1,, T4 (1 mg kg - 1 BW ), 8,,, 5 m s, 15 V, Hz ( 23 2 ), 12 h 12 h 1 ml, Hz 5 % 1 ml T4, 1,, Edge - Detector 9 Am - 10 Am, 2 4 (Crescent), Felix ( PTI) [ 9 ], (50 mg kg - 1 BW ),, (, ), 3, 1,, 1 m in Krebs - Henseleit, t SPSS 1010 ( x s)

3 2308 1, T4 2 2 T4 / 40 % ( P < 0105), T4 4 ( P < 0105), 1, 59 % ( P < 0101) ; T4 4 2 Control Group 1, 13 % ( P < 0105) 3 T4, T4 2 4 Tab 1 General parameters in hyperthyroid and control rats( x s. n = 6) Heart rate ( beats/m in) SBP (mmhg) BW ( g) HW (mg) BW /HW week T week T # P < 0105, 3 3 P < 0101 vs control; HW: heart weight; 2 - week T4 or 4 - week T4: hyperthyroid for 2 or 4 weeks. T T4,, 3 ( P > 0105),, T4, 2, 2 T4 ( P < 0101), 1B, mmhg, T4 ( P < 0105), 1A # P < 0105 vs 2 - week T4 treatment group. SBP: systolic blood p ressure; BW: body weight; 2 Tab 2 The size of cardiomyocytes in hyperthyroid and control rats( x s. n = 20) Group W idth ( m) Length ( m) A rea ( m 2 ) Control LV week T4 LV week T4 LV # # # # 3 P < 0105 vs control; # P < 0105 vs 2 - week T4 treatment group. 2 - week T4 or 4 - week T4: hyperthyroid for 2 or 4 weeks; LV: left ventricle; : right ventricle. Fig 1 The cardiac output - p reload relationship and heart rate in working heart mode at 2 weeks in hyperthyroid and control group s. x s. n = 6. 3 P < 0105, 3 3 P < 0101 vs control Hz,, ( P > 0105) ;, 4 T4, Hz, ( 2) 2 T4 1 2 T4,, 2 Hz ( P < 0101), 4 Hz,, 4 Hz,

4 , Hz, 2 T4 75% ( P < 0101), 3 4 T4, ( P < 0101), 2 T4 ( P < 0101), 3, ( 4) 2 T4, 4 T4 1 2 Hz,, 4 Hz,,, 4 Fig 2 The shortening amp litude - frequency relationship in car2 diomyocytes of hyperthyroid and control rats. x s. n = P < 0101 vs control; ## P < 0101 vs 2 - week T4 treatment group. 2 - Fig 3 The unloading contraction duration of cardiomyocytes in hyperthyroid and control rats. x s. n = 12. ## P < 0101 vs 2 - week T4 treatment group. 3 3 P < 0101 vs control; 3 Fig 4 The shortening and relaxation rate in unloading contraction of cardiomyocytes in hyperthyroid and control rats. x s. n = P < 0105, 3 P < 0101 vs control. 4, ( ), T4 2, ; 4 T4, T4

5 2310 ( T4), [ 5 ], T4, 200 g kg - 1 BW,, 3,, T4,, 100 g kg - 1 BW Frank - Starling,, ( 1 ) ; 2 T4, Frank - Starling 2 T4 ( ), [ 10 ],,,,,, 2 T4,, [ 11 ],,,, [ 12 ], 2 T4, ( 1), T4, 2 478beats/m in, 8 Hz; 4 542beats/m in, 9 Hz 2 4 T4, ( 1 2 Hz), (4 Hz) ( 2 4) 8 Hz, [ 13 ],,,, 2 T4 -,, [ ] [ 1 ] Kinugawa K, Yonekura K, R ibeiro RC, et al. Regulation of thyroid hormone recep tor isoform s in physiological and pathological cardiac hypertrophy[ J ]. Circ Res, 2001, 89 (7) : [ 2 ] O renstein TL, Parker TG, Butany JW, et al. Favorable left ventricular remodeling following large myocardial in2 farction by exercise training. Effect on ventricular mor2 phology and gene exp ression[ J ]. J Clin Invest, 1995, 96 (2) : [ 3 ] Chang KC, Figueredo VM, Schreur JH, et al. Thyroid hormone imp roves function and Ca 2 + overload hypertrophy. p lasm ic reticulum Ca 2 + handling in p ressure A ssociation with increased sarco2 - ATPase and alpha - myosin heavy chain in rat hearts [ J ]. J Clin Invest, 1997, 100 (7) : [ 4 ] Gomberg - Maitland M, Frishman WH. Thyroid hormone and cardiovascular disease[ J ]. Am Heart J, 1998, 135 ( 2 Pt 1) : [ 5 ] Hu LW, BenvenutiLA, L iberti EA, et al. Thyroxine - in2 duced cardiac hypertrophy: influence of adrenergic nervous system versus renin - angiotensin system on myocyte re2 modeling[ J ]. Am J Physiol Regul Integr Comp Physiol, 2003, 285 (6) : R R1480. [ 6 ] Ogawa M, Zhou S, Tan AY, et al. Left stellate ganglion and vagal nerve activity and cardiac arrhythm ias in ambu2 latory dogs with pacing - induced congestive heart failure [ J ]. J Am Coll Cardiol, 2007, 50 (4) : [ 7 ] A raki Y, U sui A, Kawaguchi O, et al. Pressure - volume relationship in isolated working heart with crystalloid perfu2 sate in swine and imaging the valve motion[ J ]. diothorac Surg, 2005, 28 (3) : Eur J Car2 [ 8 ],,. [ J ]., 2005, 21 (4) : [ 9 ],,. [ J ]., 2004, 56 (5) : [ 10 ] Danzi S, Klein I. Thyroid hormone and the cardiovascular system [ J ]. M inerva Endocrinol, 2004, 29 ( 3 ) : [ 11 ] Schaub MC, Hefti MA, Harder BA, et al. Triiodothyro2 nine restricts myofibrillar growth and enhances beating fre2 quency in cultured adult rat cardiomyocytes [ J ]. Res Cardiol, 1998, 93 ( 5) : Basic [ 12 ] Langer M, L ttecke D, Schl ter KD. Mechanism of the positive contractile effect of nitric oxide on rat ventricular cardiomyocytes with positive force / frequency relationship [ J ]. Pflugers A rch, 2003, 447 (3) : [ 13 ] Holubarsch C, Ludemann J, W iessner S, et al. Shorten2 ing versus isometric contractions in isolated human failing and non - failing left ventricular myocardium: dependency of external work and force on muscle length, heart rate and inotrop ic stimulation [ J ]. Cardiovasc Res, 1998, 37 (1) :

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