BACKGROUND AND OBJECTIVE: Respiration is known to affect cerebrospinal fluid (CSF) movement. We hypothesised that increased inspiratory resistance would affect the dynamic relationship between blood pressure (BP) changes and subarachnoid space width (SAS) oscillations. METHODS: Experiments were performed in a group of 20 healthy volunteers undergoing controlled intermittent Mueller Manoeuvres (the key characteristic of the procedure is that a studied person is subjected to a controlled, increased inspiratory resistance which results in marked potentiation of the intrathoracic negative pressure). BP and heart rate (HR) were measured using continuous finger-pulse photoplethysmography; oxyhaemoglobin saturation with an ear-clip sensor; end-tidal CO2 with a gas analyser; cerebral blood flow velocity (CBFV), pulsatility and resistive indices with Doppler ultrasound. Changes in SAS were recorded with a new method i.e. near-infrared transillumination/backscattering sounding. Wavelet transform analysis was used to assess the BP and SAS oscillations coupling. RESULTS: Initiating Mueller manoeuvres evoked cardiac SAS component decline (-17.8%, P<0.001), systolic BP, diastolic BP and HR increase (+6.3%, P<0.001; 6.7%, P<0.001 and +2.3%, P<0.05, respectively). By the end of Mueller manoeuvres, cardiac SAS component and HR did not change (+2.3% and 0.0%, respectively; both not statistically significant), but systolic and diastolic BP was elevated (+12.6% and +8.9%, respectively; both P<0.001). With reference to baseline values there was an evident decrease in wavelet coherence between BP and SAS oscillations at cardiac frequency in the first half of the Mueller manoeuvres (-32.3%, P<0.05 for left hemisphere and -46.0%, P<0.01 for right hemisphere) which was followed by subsequent normalization at end of the procedure (+3.1% for left hemisphere and +23.1% for right hemisphere; both not statistically significant). CONCLUSIONS: Increased inspiratory resistance is associated with swings in the cardiac contribution to the dynamic relationship between BP and SAS oscillations. Impaired cardiac performance reported in Mueller manoeuvres may influence the pattern of cerebrospinal fluid pulsatility.

Centre for Medical Simulation Medical University of Gdansk Gdansk Poland

Department of Biomedical Engineering Faculty of Electronics Telecommunications and Informatics Gdansk University of Technology Gdansk Poland

Department of Cardiovascular Diseases International Clinical Research Center St Anne's University Hospital in Brno Brno Czech Republic

Department of Hypertension and Diabetology Medical University of Gdansk Gdansk Poland

Department of Radiology Informatics and Statistics Medical University of Gdansk Gdansk Poland

Institute of Health Sciences Pomeranian University of Slupsk Slupsk Poland

Institute of Human Physiology Medical University of Gdansk Gdansk Poland

See more in PubMed

Guntheroth WG, Morgan BC. Effect of respiration on venous return and stroke volume in cardiac tamponade. Circ Res. 1967;20: 381–390. PubMed

Schrijen F, Ehrlich W, Permutt S. Cardiovascular changes in conscious dogs during spontaneous deep breaths. Pflugers Archiv 1975;355: 205–215. PubMed

Robotham JL, Rabson J, Permutt S, Bromberger-Barnea B. Left ventricular hemodynamics during respiration. J Appl Physiol. 1979;47: 1295–1303. PubMed

Konecny T, Khanna AD, Novak J, Jama AA, Zawadowski GM, Orban M, et al. Interatrial pressure gradients during simulated obstructive sleep apnea: a catheter-based study. Catheter Cardiovasc Interv. 2014;84: 1138–45. doi: 10.1002/ccd.25433 PubMed DOI PMC

Koshino Y, Villarraga HR, Orban M, Bruce CJ, Pressman GS, Leinveber P, et al. Changes in left and right ventricular mechanics during the Mueller maneuver in healthy adults: a possible mechanism for abnormal cardiac function in patients with obstructive sleep apnea. Circ Cardiovasc Imaging 2010;3: 282–9. doi: 10.1161/CIRCIMAGING.109.901561 PubMed DOI

Orban M, Bruce CJ, Pressman GS, Leinveber P, Romero-Corral A, Korinek J, et al. Dynamic changes of left ventricular performance and left atrial volume induced by the mueller maneuver in healthy young adults and implications for obstructive sleep apnea, atrial fibrillation, and heart failure. Am J Cardiol. 2008;102: 1557–61. doi: 10.1016/j.amjcard.2008.07.050 PubMed DOI PMC

Schroth G, Klose U. Cerebrospinal fluid flow. II. Physiology of respiration-related pulsations. Neuroradiology 1992;35: 10–5. PubMed

Chen L, Beckett A, Verma A, Feinberg DA. Dynamics of respiratory and cardiac CSF motion revealed with real-time simultaneous multi-slice EPI velocity phase contrast imaging. Neuroimage 2015;122: 281–7. doi: 10.1016/j.neuroimage.2015.07.073 PubMed DOI PMC

Dreha-Kulaczewski S, Joseph AA, Merboldt KD, Ludwig HC, Gärtner J, Frahm J. Inspiration is the major regulator of human CSF flow. J Neurosci. 2015; 35: 2485–91. doi: 10.1523/JNEUROSCI.3246-14.2015 PubMed DOI PMC

Frydrychowski AF, Gumiński W, Rojewski M, Kaczmarek J, Juzwa W. Technical foundations for noninvasive assessment of changes in the width of the subarachnoid space with near-infrared transillumination-backscattering sounding (NIR-TBSS). IEEE Trans Biomed Eng. 2002;49: 887–904. doi: 10.1109/TBME.2002.800786 PubMed DOI

Frydrychowski AF, Pluciński J. New aspects in assessment of changes in width of subarachnoid space with near-infrared transillumination-backscattering sounding, part 2: clinical verification in the patient. J Biomed Opt. 2007;12: 044016 doi: 10.1117/1.2753756 PubMed DOI

Winklewski PJ, Gruszecki M, Wolf J, Swierblewska E, Kunicka K, Wszedybyl-Winklewska M, et al. Wavelet transform analysis to assess oscillations in pial artery pulsation at the human cardiac frequency. Microvasc Res. 2015;99: 86–91. doi: 10.1016/j.mvr.2015.03.003 PubMed DOI

Winklewski PJ, Barak O, Madden D, Gruszecka A, Gruszecki M, Guminski W, et al. Effect of Maximal Apnoea Easy-Going and Struggle Phases on Subarachnoid Width and Pial Artery Pulsation in Elite Breath-Hold Divers. PLoS One. 2015;10:e0135429 doi: 10.1371/journal.pone.0135429 PubMed DOI PMC

Winklewski PJ, Tkachenko Y, Mazur K, Kot J, Gruszecki M, Guminski W, et al. Sympathetic Activation Does Not Affect the Cardiac and Respiratory Contribution to the Relationship between Blood Pressure and Pial Artery Pulsation Oscillations in Healthy Subjects. PLoS One 2015;10: e0135751 doi: 10.1371/journal.pone.0135751 PubMed DOI PMC

Wszedybyl-Winklewska M, Wolf J, Swierblewska E, Kunicka K, Gruszecka A, Gruszecki M, et al. Acute hypoxia diminishes the relationship between blood pressure and subarachnoid space width oscillations at the human cardiac frequency. PLoS One 2017; accepted for publication. PubMed PMC

Carlson JT, Hedner J, Elam M, Ejnell H, Sellgren J,Wallin BG. Augmented resting sympathetic activity in awake patients with obstructive sleep apnea. Chest 1993;103: 1763–1768. PubMed

Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96: 1897–1904. doi: 10.1172/JCI118235 PubMed DOI PMC

Stefanovska A, Bracic M, Kvernmo HD. Wavelet analysis of oscillations in the peripheral blood circulation measured by laser Doppler technique. IEEE Trans Biomed Eng. 1999;46: 1230–9. PubMed

Bernjak A, Stefanovska A, McClintock PVE, Owen-Lynch PJ, Clarkson PBM. Coherence between fluctuations in blood flow and oxygen saturation. Fluct Noise Lett. 2012;11: 1240013–12.

Torrence C, Webster P. Interdecadal Changes in the ESNO-Monsoon System. J Clim. 1999;12: 2679–90.

Schreiber T, Schmitz A. Surrogate time series. Physica D 2000;142: 346–382.

Clemson PT, Stefanovska A. Discerning non-autonomous dynamics. Physics Rep. 2014;542: 297–368.

Linninger AA, Tsakiris C, Zhu DC, Xenos M, Roycewicz P, Danziger Z, et al. Pulsatile cerebrospinal fluid dynamics in the human brain. IEEE Trans Biomed Eng. 2005;52: 557–565. doi: 10.1109/TBME.2005.844021 PubMed DOI

Bateman GA. Pulse-wave encephalopathy: a comparative study of the hydrodynamics of leukoaraiosis and normal pressure hydrocephalus. Neuroradiology 2002;44: 740–748. doi: 10.1007/s00234-002-0812-0 PubMed DOI

Jolly TA, Bateman GA, Levi CR, Parsons MW, Michie PT, Karayanidis F. Early detection of microstructural white matter changes associated with arterial pulsatility. Front Hum Neurosci. 2013;7: 782 doi: 10.3389/fnhum.2013.00782 PubMed DOI PMC

Shiogai Y, Stefanovska A, McClintock PV. Nonlinear dynamics of cardiovascular ageing. Phys Rep. 2010;488: 51–110. doi: 10.1016/j.physrep.2009.12.003 PubMed DOI PMC

Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA 2003;290: 1906–14. doi: 10.1001/jama.290.14.1906 PubMed DOI

Hanly PJ, George CF, Millar TW, Kryger MH. Heart rate response to breath-hold, valsalva and Mueller maneuvers in obstructive sleep apnea. Chest 1989;95: 735–9. PubMed

Somers VK, Dyken ME, Skinner JL. Autonomic and hemodynamic responses and interactions during the Mueller maneuver in humans. J Auton Nerv Syst. 1993;44: 253–9. PubMed

Condos WR Jr, Latham RD, Hoadley SD, Pasipoularides A. Hemodynamics of the Mueller maneuver in man: right and left heart micromanometry and Doppler echocardiography. Circulation. 1987;76:1020–8. PubMed

Reinhard M, Hetzel A, Hinkov V, Lücking CH. Cerebral haemodynamics during the Mueller manoeuvre in humans. Clin Physiol. 2000;20:292–303. PubMed

Greitz D, Franck A, Nordell B. On the pulsatile nature of intracranial and spinal CSF-circulation demonstrated by MR imaging. Acta Radiol. 1993;34: 321–8. PubMed

Wszedybyl-Winklewska M, Wolf J, Swierblewska E, Kunicka K, Gruszecki M, Guminski W, et al. Pial artery and subarachnoid width response to apnoea in normal humans. J Hypertens 2015;33: 1811–7; discussion 1817–8. doi: 10.1097/HJH.0000000000000613 PubMed DOI

Wszedybyl-Winklewska M, Frydrychowski AF, Michalska BM, Winklewski PJ. Effects of the Valsalva maneuver on pial artery pulsation and subarachnoid width in healthy adults. Microvasc Res. 2011;82: 369–73. doi: 10.1016/j.mvr.2011.08.003 PubMed DOI

Beggs CB, Magnano C, Shepherd SJ, Belov P, Ramasamy DP, Hagemeier J, et al. Dirty-Appearing White Matter in the Brain is Associated with Altered Cerebrospinal Fluid Pulsatility and Hypertension in Individuals without Neurologic Disease. J Neuroimaging. 2016;26:136–43. doi: 10.1111/jon.12249 PubMed DOI

Beggs CB, Magnano C, Shepherd SJ, Marr K, Valnarov V, Hojnacki D, et al. Aqueductal cerebrospinal fluid pulsatility in healthy individuals is affected by impaired cerebral venous outflow. J Magn Reson Imaging. 2014;40:1215–22. doi: 10.1002/jmri.24468 PubMed DOI

Frydrychowski AF, Winklewski PJ, Guminski W. Influence of acute jugular vein compression on the cerebral blood flow velocity, pial artery pulsation and width of subarachnoid space in humans. PLoS One. 2012;7:e48245 doi: 10.1371/journal.pone.0048245 PubMed DOI PMC

Magnano C, Schirda C, Weinstock-Guttman B, Wack DS, Lindzen E, Hojnacki D, et al. Cine cerebrospinal fluid imaging in multiple sclerosis. J Magn Reson Imaging. 2012;36:825–34. doi: 10.1002/jmri.23730 PubMed DOI

Beggs CB, Magnano C, Belov P, Krawiecki J, Ramasamy DP, Hagemeier J, et al. Internal Jugular Vein Cross-Sectional Area and Cerebrospinal Fluid Pulsatility in the Aqueduct of Sylvius: A Comparative Study between Healthy Subjects and Multiple Sclerosis Patients. PLoS One. 2016;11:e0153960 doi: 10.1371/journal.pone.0153960 PubMed DOI PMC

Frydrychowski AF, Szarmach A, Czaplewski B, Winklewski PJ. Subarachnoid space: new tricks by an old dog. PLoS One. 2012;7:e37529 doi: 10.1371/journal.pone.0037529 PubMed DOI PMC

Wagner BP, Gertsch S, Ammann RA, Pfenninger J. Reproducibility of the blood flow index as noninvasive, bedside estimation of cerebral blood flow. Intensive Care Med. 2003;29: 196–200. doi: 10.1007/s00134-002-1592-z PubMed DOI