Abstract
Purpose
Whether blood volume (BV) primarily determines the synchronous nature of the myocardium remains unknown. This study determined the impact of standard blood withdrawal on left ventricular mechanical dyssynchrony (LVMD) in women.
Methods
Transthoracic speckle-tracking echocardiography and central hemodynamic measurements were performed at rest and during moderate- to high-intensity exercise in healthy women (n = 24, age = 53.6 ± 16.3 year). LVMD was determined via the time to peak standard deviation (TPSD) of longitudinal and transverse strain and strain rates (LSR, TSR). Measurements were repeated within a week period immediately after a 10% reduction of BV.
Results
With intact BV, all individuals presented cardiac structure and function variables within normative values of the study population. Blood withdrawal decreased BV (5.3 ± 0.7 L) by 0.5 ± 0.1 L. Resting left ventricular (LV) end-diastolic volume (− 8%, P = 0.040) and passive filling (− 16%, P = 0.001) were reduced after blood withdrawal. No effect of blood withdrawal was observed for any measure of LVMD at rest (P ≥ 0.225). During exercise at a fixed submaximal workload (100 W), LVMD of myocardial longitudinal strain (LS TPSD) was increased after blood withdrawal (36%, P = 0.047). At peak effort, blood withdrawal led to increased LVMD of myocardial transverse strain rate (TSR TPSD) (31%, P = 0.002). The effect of blood withdrawal on TSR TPSD at peak effort was associated with LV concentric remodeling (r = 0.59, P = 0.003).
Conclusion
Marked impairments in the mechanical synchrony of the myocardium are elicited by moderate blood withdrawal in healthy women during moderate and high intensity exercise.
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Data availability
All data relevant to this study are presented in the manuscript.
References
American Thoracic S, American College of Chest P (2003) ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 167 (2):211–277. https://doi.org/10.1164/rccm.167.2.211
Asch FM, Miyoshi T, Addetia K, Citro R, Daimon M, Desale S, Fajardo PG, Kasliwal RR, Kirkpatrick JN, Monaghan MJ, Muraru D, Ogunyankin KO, Park SW, Ronderos RE, Sadeghpour A, Scalia GM, Takeuchi M, Tsang W, Tucay ES, Tude Rodrigues AC, Vivekanandan A, Zhang Y, Blitz A, Lang RM, Investigators W (2019) Similarities and differences in left ventricular size and function among races and nationalities: results of the world alliance societies of echocardiography normal values study. J Am Soc Echocardiogr 32(11):1396–1406. https://doi.org/10.1016/j.echo.2019.08.012
Astorino TA, Rietschel JC, Tam PA, Taylor K, Johnson SM, Freedman TP, Sakarya CE (2004) Reinvestigation of optimal duration of VO2max testing. J Exerc Physiol 7(6):1–8
Biering-Sorensen T, Shah SJ, Anand I, Sweitzer N, Claggett B, Liu L, Pitt B, Pfeffer MA, Solomon SD, Shah AM (2017) Prognostic importance of left ventricular mechanical dyssynchrony in heart failure with preserved ejection fraction. Eur J Heart Fail 19(8):1043–1052. https://doi.org/10.1002/ejhf.789
Biton Y, Goldenberg I, Kutyifa V, Baman JR, Solomon S, Moss AJ, Szepietowska B, McNitt S, Polonsky B, Zareba W, Barsheshet A (2016) Relative wall thickness and the risk for ventricular tachyarrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol 67(3):303–312. https://doi.org/10.1016/j.jacc.2015.10.076
Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1(8476):307–310
Bransford DR, Howley ET (1977) Oxygen cost of running in trained and untrained men and women. Med Sci Sports 9(1):41–44
Brink-Elfegoun T, Kaijser L, Gustafsson T, Ekblom B (2007) Maximal oxygen uptake is not limited by a central nervous system governor. J Appl Physiol (1985) 102(2):781–786. https://doi.org/10.1152/japplphysiol.00566.2006
Cheng YJ, Zhang J, Li WJ, Lin XX, Zeng WT, Tang K, Tang AL, He JG, Xu Q, Mei MY, Zheng DD, Dong YG, Ma H, Wu SH (2014) More favorable response to cardiac resynchronization therapy in women than in men. Circ Arrhythm Electrophysiol 7(5):807–815. https://doi.org/10.1161/CIRCEP.113.001786
Covell JW, Ross J Jr, Sonnenblick EH, Braunwald E (1966) Comparison of the force-velocity relation and the ventricular function curve as measures of the contractile state of the intact heart. Circ Res 19(2):364–372. https://doi.org/10.1161/01.res.19.2.364
Crystal GJ, Salem MR (2012) The Bainbridge and the “reverse” Bainbridge reflexes: history, physiology, and clinical relevance. Anesth Analg 114(3):520–532. https://doi.org/10.1213/ANE.0b013e3182312e21
Delgado V, Ypenburg C, van Bommel RJ, Tops LF, Mollema SA, Marsan NA, Bleeker GB, Schalij MJ, Bax JJ (2008) Assessment of left ventricular dyssynchrony by speckle tracking strain imaging comparison between longitudinal, circumferential, and radial strain in cardiac resynchronization therapy. J Am Coll Cardiol 51(20):1944–1952. https://doi.org/10.1016/j.jacc.2008.02.040
Diaz-Canestro C, Montero D (2020) Female sex-specific curtailment of left ventricular volume and mass in HFpEF patients with high end-diastolic filling pressure. J Hum Hypertens. https://doi.org/10.1038/s41371-020-00394-3
Diaz-Canestro C, Montero D (2022a) Blood volume primarily determines orthostatic tolerance in women. J Intern Med 291(3):371–373. https://doi.org/10.1111/joim.13397
Diaz-Canestro C, Montero D (2022b) Sex and age interaction in fundamental circulatory volumetric variables at peak working capacity. Biol Sex Differ 13(1):1. https://doi.org/10.1186/s13293-021-00409-9
Diaz-Canestro C, Pentz B, Sehgal A, Montero D (2021a) Blood withdrawal acutely impairs cardiac filling, output and aerobic capacity in proportion to induced hypovolemia in middle-aged and older women. Appl Physiol Nutr Metab 47:1–8. https://doi.org/10.1139/apnm-2021-0196
Diaz-Canestro C, Pentz B, Sehgal A, Montero D (2021b) Sex differences in cardiorespiratory fitness are explained by blood volume and oxygen carrying capacity. Cardiovasc Res. https://doi.org/10.1093/cvr/cvab028
Diaz-Canestro C, Pentz B, Sehgal A, Montero D (2021c) Sex dimorphism in cardiac and aerobic capacities: the influence of body composition. Obesity (silver Spring) 29(11):1749–1759. https://doi.org/10.1002/oby.23280
Haugaa KH, Smedsrud MK, Steen T, Kongsgaard E, Loennechen JP, Skjaerpe T, Voigt JU, Willems R, Smith G, Smiseth OA, Amlie JP, Edvardsen T (2010) Mechanical dispersion assessed by myocardial strain in patients after myocardial infarction for risk prediction of ventricular arrhythmia. JACC Cardiovasc Imaging 3(3):247–256. https://doi.org/10.1016/j.jcmg.2009.11.012
Haugaa KH, Goebel B, Dahlslett T, Meyer K, Jung C, Lauten A, Figulla HR, Poerner TC, Edvardsen T (2012) Risk assessment of ventricular arrhythmias in patients with nonischemic dilated cardiomyopathy by strain echocardiography. J Am Soc Echocardiogr 25(6):667–673. https://doi.org/10.1016/j.echo.2012.02.004
Hiteshi AK, Li D, Gao Y, Chen A, Flores F, Mao SS, Budoff MJ (2014) Gender differences in coronary artery diameter are not related to body habitus or left ventricular mass. Clin Cardiol 37(10):605–609. https://doi.org/10.1002/clc.22310
Kim MS, Kim HK, Chang SA, Kim SY, Cho GY, Kim YJ, Sohn DW, Oh BH, Park YB (2011) Impact of preload alteration on left ventricular mechanical dyssynchrony using tissue velocity imaging echocardiography. Echocardiography 28(2):196–202. https://doi.org/10.1111/j.1540-8175.2010.01288.x
Kirwan LD, MacLusky NJ, Shapiro HM, Abramson BL, Thomas SG, Goodman JM (2004) Acute and chronic effects of hormone replacement therapy on the cardiovascular system in healthy postmenopausal women. J Clin Endocrinol Metab 89(4):1618–1629. https://doi.org/10.1210/jc.2003-030324
Kou S, Caballero L, Dulgheru R, Voilliot D, De Sousa C, Kacharava G, Athanassopoulos GD, Barone D, Baroni M, Cardim N, Gomez De Diego JJ, Hagendorff A, Henri C, Hristova K, Lopez T, Magne J, De La Morena G, Popescu BA, Penicka M, Ozyigit T, Rodrigo Carbonero JD, Salustri A, Van De Veire N, Von Bardeleben RS, Vinereanu D, Voigt JU, Zamorano JL, Donal E, Lang RM, Badano LP, Lancellotti P (2014) Echocardiographic reference ranges for normal cardiac chamber size: results from the NORRE study. Eur Heart J Cardiovasc Imaging 15(6):680–690. https://doi.org/10.1093/ehjci/jet284
Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American society of echocardiography and the European association of cardiovascular imaging. Eur Heart J Cardiovasc Imaging 16(3):233–270. https://doi.org/10.1093/ehjci/jev014
Lim P, Buakhamsri A, Popovic ZB, Greenberg NL, Patel D, Thomas JD, Grimm RA (2008) Longitudinal strain delay index by speckle tracking imaging: a new marker of response to cardiac resynchronization therapy. Circulation 118(11):1130–1137. https://doi.org/10.1161/CIRCULATIONAHA.107.750190
Maillet M, van Berlo JH, Molkentin JD (2013) Molecular basis of physiological heart growth: fundamental concepts and new players. Nat Rev Mol Cell Biol 14(1):38–48. https://doi.org/10.1038/nrm3495
Mao SS, Ahmadi N, Shah B, Beckmann D, Chen A, Ngo L, Flores FR, Gao YL, Budoff MJ (2008) Normal thoracic aorta diameter on cardiac computed tomography in healthy asymptomatic adults: impact of age and gender. Acad Radiol 15(7):827–834. https://doi.org/10.1016/j.acra.2008.02.001
Miyazaki C, Powell BD, Bruce CJ, Espinosa RE, Redfield MM, Miller FA, Hayes DL, Cha YM, Oh JK (2008) Comparison of echocardiographic dyssynchrony assessment by tissue velocity and strain imaging in subjects with or without systolic dysfunction and with or without left bundle-branch block. Circulation 117(20):2617–2625. https://doi.org/10.1161/CIRCULATIONAHA.107.733675
Miyoshi T, Addetia K, Citro R, Daimon M, Desale S, Fajardo PG, Kasliwal RR, Kirkpatrick JN, Monaghan MJ, Muraru D, Ogunyankin KO, Park SW, Ronderos RE, Sadeghpour A, Scalia GM, Takeuchi M, Tsang W, Tucay ES, Tude Rodrigues AC, Vivekanandan A, Zhang Y, Blitz A, Lang RM, Asch FM, Investigators W (2020) Left ventricular diastolic function in healthy adult individuals: results of the world alliance societies of echocardiography normal values study. J Am Soc Echocardiogr 33(10):1223–1233. https://doi.org/10.1016/j.echo.2020.06.008
Modin D, Biering-Sorensen SR, Mogelvang R, Jensen JS, Biering-Sorensen T (2018) Prognostic importance of left ventricular mechanical dyssynchrony in predicting cardiovascular death in the general population. Circ Cardiovasc Imaging 11(10):e007528. https://doi.org/10.1161/CIRCIMAGING.117.007528
Montero D, Cathomen A, Jacobs RA, Fluck D, de Leur J, Keiser S, Bonne T, Kirk N, Lundby AK, Lundby C (2015) Haematological rather than skeletal muscle adaptations contribute to the increase in peak oxygen uptake induced by moderate endurance training. J Physiol 593(20):4677–4688. https://doi.org/10.1113/JP270250
Montero D, Houben AJ, Koster A, Muris DM, Schram MT, Gronenschild EH, Sep SJ, Henry RM, van der Kallen CJ, Schaper NC, Dagnelie PC, van Geel TA, Kremers SP, Savelberg HH, Stehouwer CD (2016) Physical activity is associated with glucose tolerance independent of microvascular function: the Maastricht study. J Clin Endocrinol Metab 101(9):3324–3332. https://doi.org/10.1210/jc.2016-1526
Montero D, Breenfeldt-Andersen A, Oberholzer L, Haider T, Goetze JP, Meinild-Lundby AK, Lundby C (2017) Erythropoiesis with endurance training: dynamics and mechanisms. Am J Physiol Regul Integr Comp Physiol 312(6):R894–R902. https://doi.org/10.1152/ajpregu.00012.2017
Morris DA, Vaz Perez A, Blaschke F, Eichstadt H, Ozcelik C, Haverkamp W (2012) Myocardial systolic and diastolic consequences of left ventricular mechanical dyssynchrony in heart failure with normal left ventricular ejection fraction. Eur Heart J Cardiovasc Imaging 13(7):556–567. https://doi.org/10.1093/ehjci/jes042
Patel HN, Miyoshi T, Addetia K, Henry MP, Citro R, Daimon M, Gutierrez Fajardo P, Kasliwal RR, Kirkpatrick JN, Monaghan MJ, Muraru D, Ogunyankin KO, Park SW, Ronderos RE, Sadeghpour A, Scalia GM, Takeuchi M, Tsang W, Tucay ES, Tude Rodrigues AC, Vivekanandan A, Zhang Y, Schreckenberg M, Blankenhagen M, Degel M, Rossmanith A, Mor-Avi V, Asch FM, Lang RM, Investigators W (2021) Normal values of cardiac output and stroke volume according to measurement technique, age, sex, and ethnicity: results of the world alliance of societies of echocardiography study. J Am Soc Echocardiogr 34(10):1077–1085. https://doi.org/10.1016/j.echo.2021.05.012
Patterson SW, Starling EH (1914) On the mechanical factors which determine the output of the ventricles. J Physiol 48(5):357–379. https://doi.org/10.1113/jphysiol.1914.sp001669
Pellikka PA, Nagueh SF, Elhendy AA, Kuehl CA, Sawada SG, American Society of E (2007) American society of echocardiography recommendations for performance, interpretation, and application of stress echocardiography. J Am Soc Echocardiogr 20(9):1021–1041. https://doi.org/10.1016/j.echo.2007.07.003
Pentz B, Diaz-Canestro C, Sehgal A, Montero D (2021) Effects of blood withdrawal on cardiac, hemodynamic, and pulmonary responses to a moderate acute workload in healthy middle-aged and older females. J Sci Med Sport. https://doi.org/10.1016/j.jsams.2021.10.012
Phan TT, Abozguia K, Shivu GN, Ahmed I, Patel K, Leyva F, Frenneaux M (2010) Myocardial contractile inefficiency and dyssynchrony in heart failure with preserved ejection fraction and narrow QRS complex. J Am Soc Echocardiogr 23(2):201–206. https://doi.org/10.1016/j.echo.2009.11.004
Raj SR, Robertson D (2007) Blood volume perturbations in the postural tachycardia syndrome. Am J Med Sci 334(1):57–60. https://doi.org/10.1097/MAJ.0b013e318063c6c0
Regitz-Zagrosek V, Kararigas G (2017) Mechanistic pathways of sex differences in cardiovascular disease. Physiol Rev 97(1):1–37. https://doi.org/10.1152/physrev.00021.2015
Rosner A, Barbosa D, Aarsaether E, Kjonas D, Schirmer H, D’Hooge J (2015) The influence of frame rate on two-dimensional speckle-tracking strain measurements: a study on silico-simulated models and images recorded in patients. Eur Heart J Cardiovasc Imaging 16(10):1137–1147. https://doi.org/10.1093/ehjci/jev058
Sandgren T, Sonesson B, Ahlgren R, Lanne T (1999) The diameter of the common femoral artery in healthy human: influence of sex, age, and body size. J Vasc Surg 29(3):503–510. https://doi.org/10.1016/s0741-5214(99)70279-x
Santos AB, Kraigher-Krainer E, Bello N, Claggett B, Zile MR, Pieske B, Voors AA, McMurray JJ, Packer M, Bransford T, Lefkowitz M, Shah AM, Solomon SD (2014) Left ventricular dyssynchrony in patients with heart failure and preserved ejection fraction. Eur Heart J 35(1):42–47. https://doi.org/10.1093/eurheartj/eht427
Shah AM, Solomon SD (2016) Mechanical dyssynchrony: a risk factor but not a target. Eur Heart J 37(1):60–62. https://doi.org/10.1093/eurheartj/ehv458
Siebenmann C, Keiser S, Robach P, Lundby C (2017) CORP: the assessment of total hemoglobin mass by carbon monoxide rebreathing. J Appl Physiol 123(3):645–654. https://doi.org/10.1152/japplphysiol.00185.2017
Sims DT, Onambele-Pearson GL, Burden A, Payton C, Morse CI (2018) The oxygen consumption and metabolic cost of walking and running in adults with achondroplasia. Front Physiol 9:410. https://doi.org/10.3389/fphys.2018.00410
Suffoletto MS, Dohi K, Cannesson M, Saba S, Gorcsan J 3rd (2006) Novel speckle-tracking radial strain from routine black-and-white echocardiographic images to quantify dyssynchrony and predict response to cardiac resynchronization therapy. Circulation 113(7):960–968. https://doi.org/10.1161/CIRCULATIONAHA.105.571455
Tan YT, Wenzelburger FW, Sanderson JE, Leyva F (2013) Exercise-induced torsional dyssynchrony relates to impaired functional capacity in patients with heart failure and normal ejection fraction. Heart 99(4):259–266. https://doi.org/10.1136/heartjnl-2012-302489
Tanaka H, Nesser HJ, Buck T, Oyenuga O, Janosi RA, Winter S, Saba S, Gorcsan J 3rd (2010) Dyssynchrony by speckle-tracking echocardiography and response to cardiac resynchronization therapy: results of the speckle tracking and resynchronization (STAR) study. Eur Heart J 31(14):1690–1700. https://doi.org/10.1093/eurheartj/ehq213
van der Heijden-Spek JJ, Staessen JA, Fagard RH, Hoeks AP, Boudier HA, van Bortel LM (2000) Effect of age on brachial artery wall properties differs from the aorta and is gender dependent: a population study. Hypertension 35(2):637–642. https://doi.org/10.1161/01.hyp.35.2.637
Williams AM, Shave RE, Stembridge M, Eves ND (2016) Females have greater left ventricular twist mechanics than males during acute reductions to preload. Am J Physiol Heart Circ Physiol 311(1):H76-84. https://doi.org/10.1152/ajpheart.00057.2016
Xu YZ, Friedman PA, Webster T, Brooke K, Hodge DO, Wiste HJ, Hua W, Zhang S, Hayes DL, Cha YM (2012) Cardiac resynchronization therapy: do women benefit more than men? J Cardiovasc Electrophysiol 23(2):172–178. https://doi.org/10.1111/j.1540-8167.2011.02168.x
Zusterzeel R, Spatz ES, Curtis JP, Sanders WE, Selzman KA, Pina IL, Bao H, Ponirakis A, Varosy PD, Masoudi FA, Canos DA, Strauss DG (2015) Cardiac resynchronization therapy in women versus men: observational comparative effectiveness study from the national cardiovascular data registry. Circ Cardiovasc Qual Outcomes 8(2 Suppl 1):S4-11. https://doi.org/10.1161/CIRCOUTCOMES.114.001548
Acknowledgements
The authors thank the study participants for their willingness, time and effort devoted to this study.
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This work was funded by the Swiss National Science Foundation (P2ZHP3-184211, to C.D.) and the Natural Sciences and Engineering Research Council of Canada (Discovery Grant, RGPIN-2019-04833, to D.M.).
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Conception and Design of experiments: CD, DM. Collection, analysis and interpretation: JK, CD, KYC, MG, DM. Drafting the article or revising it critically for important intellectual content: JK, CD, KYC, MG, DM.
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The study was approved by the Conjoint Health Research Ethics Board (REB18-1654) of the University of Calgary and conducted in accordance with the declaration of Helsinki. All participants provided informed oral and written consents before starting the measurements.
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Khor, J., Diaz-Canestro, C., Chan, K.Y. et al. Blood volume contributes to the mechanical synchrony of the myocardium during moderate and high intensity exercise in women. Eur J Appl Physiol 124, 1227–1237 (2024). https://doi.org/10.1007/s00421-023-05355-5
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DOI: https://doi.org/10.1007/s00421-023-05355-5