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Clinical and Experimental Biomedicine

Mieczyslaw Pokorski Editor

Advances in
Medicine and
Medical Research
Advances in Experimental Medicine
and Biology
Clinical and Experimental Biomedicine

Volume 1133

Subseries Editor
Mieczyslaw Pokorski
More information about this subseries at
Mieczyslaw Pokorski

Advances in Medicine
and Medical Research
Mieczyslaw Pokorski
Opole Medical School
Opole, Poland

ISSN 0065-2598 ISSN 2214-8019 (electronic)

Advances in Experimental Medicine and Biology
ISSN 2523-3769 ISSN 2523-3777 (electronic)
Clinical and Experimental Biomedicine
ISBN 978-3-030-12922-4 ISBN 978-3-030-12923-1 (eBook)

Library of Congress Control Number: 2019933306

# Springer Nature Switzerland AG 2019

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The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Left Ventricular Strain and Relaxation Are Independently

Associated with Renal Cortical Perfusion in Hypertensive
Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Arkadiusz Lubas, Robert Ryczek, Artur Maliborski,
Przemysław Dyrla, Longin Niemczyk, and Stanisław Niemczyk
Coupling of Blood Pressure and Subarachnoid Space
Oscillations at Cardiac Frequency Evoked by Handgrip
and Cold Tests: A Bispectral Analysis . . . . . . . . . . . . . . . . . . . . . . 9
Marcin Gruszecki, Yurii Tkachenko, Jacek Kot, Marek Radkowski,
Agnieszka Gruszecka, Krzysztof Basiński, Monika Waskow,
Wojciech Guminski, Jacek Sein Anand, Jerzy Wtorek,
Andrzej F. Frydrychowski, Urszula Demkow,
and Pawel J. Winklewski
Influence of Heart Rate, Age, and Gender on Heart
Rate Variability in Adolescents and Young Adults . . . . . . . . . . . . 19
Mario Estévez-Báez, Claudia Carricarte-Naranjo,
Javier Denis Jas-García, Evelyn Rodríguez-Ríos, Calixto Machado,
Julio Montes-Brown, Gerry Leisman, Adam Schiavi,
Andrés Machado-García, Claudia Sánchez Luaces,
and Eduardo Arrufat Pié
Hand-Foot Syndrome and Progression-Free Survival in
Patients Treated with Sunitinib for Metastatic Clear Cell Renal
Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Jakub Kucharz, Monika Budnik, Paulina Dumnicka,
Maciej Pastuszczak, Beata Kuśnierz-Cabala, Tomasz Demkow,
Katarzyna Popko, and Pawel Wiechno
Elastography in the Diagnosis of Pancreatic Malignancies . . . . . . . 41
Przemysław Dyrla, Jerzy Gil, Stanisław Niemczyk, Marek Saracyn,
Krzysztof Kosik, Sebastian Czarkowski, and Arkadiusz Lubas

vi Contents

Factors Affecting Health-Related Quality of Life in Liver

Transplant Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Anna Jagielska, Olga Tronina, Krzysztof Jankowski,
Aleksandra Kozłowska, Katarzyna Okręglicka, Paweł Jagielski,
Magdalena Durlik, Piotr Pruszczyk, and Aneta Nitsch–Osuch
Phagocytosis and Autophagy in THP-1 Cells Exposed
to Urban Dust: Possible Role of LC3-Associated Phagocytosis
and Canonical Autophagy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
A. Holownia, A. Niechoda, J. Lachowicz, E. Golabiewska,
and U. Baranowska
Gender-Dependent Growth and Insulin-Like Growth
Factor-1 Responses to Growth Hormone Therapy
in Prepubertal Growth Hormone-Deficient Children . . . . . . . . . . . 65
Ewelina Witkowska–Sędek, Małgorzata Rumińska, Anna Majcher,
and Beata Pyrżak
Vitamin D and Calcium Homeostasis in Infants
with Urolithiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Agnieszka Szmigielska, Małgorzata Pańczyk-Tomaszewska,
Małgorzata Borowiec, Urszula Demkow, and Grażyna Krzemień
Morphometric Analysis of the Lumbar Vertebrae
Concerning the Optimal Screw Selection for Transpedicular
Stabilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Jarosław Dzierżanowski, Monika Skotarczyk,
Zuzanna Baczkowska-Waliszewska, Mateusz Krakowiak,
Marek Radkowski, Piotr Łuczkiewicz, Piotr Czapiewski,
Tomasz Szmuda, Paweł Słoniewski, Edyta Szurowska,
Paweł J. Winklewski, Urszula Demkow, and Arkadiusz Szarmach
Stress and Dehumanizing Behaviors of Medical Staff
Toward Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Alicja Głębocka
Biological and Social Determinants of Maximum Oxygen
Uptake in Adult Men . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Stanisław B. Nowak, Andrzej Jopkiewicz, and Paweł Tomaszewski
Adv Exp Med Biol - Clinical and Experimental Biomedicine (2019) 4: 1–8
# Springer Nature Switzerland AG 2018
Published online: 4 December 2018

Left Ventricular Strain and Relaxation Are

Independently Associated with Renal
Cortical Perfusion in Hypertensive

Arkadiusz Lubas, Robert Ryczek, Artur Maliborski,

Przemysław Dyrla, Longin Niemczyk, and Stanisław Niemczyk

Abstract echocardiography with speckle tracking imaging

Renal perfusion, which depends on cardiac func- and the calculation of global longitudinal strain
tion, is a factor conditioning the work of kidneys. (GLS), diameter of vena cava inferior (VCI), and
The objective of the study was to assess the an ultrasound dynamic tissue perfusion measure-
influence of cardiac function, including left ven- ment of the renal cortex were performed. We
tricular contractility and relaxation, on renal corti- found that the renal cortical perfusion correlated
cal perfusion in patients with hypertension and significantly with age, renal function, cIMT, GLS,
chronic kidney disease treated pharmacologically. left ventricular ejection fraction (LVEF), left ven-
There were 63 patients (7 F and 56 M; aged tricular mass index (LVMI), diastolic peak values
56  14) with hypertension and stable chronic of early (E) and late (A) mitral inflow velocities
kidney disease enrolled into the study. Serum ratio (E/A) and E to early diastolic mitral annular
cystatin C, with estimated glomerular filtration tissue velocity (E/E0 ), but not with VCI, or the
rate (eGFR), ambulatory blood pressure monitor- right ventricle echocardiographic parameters. In
ing, carotid intima-media thickness (cIMT), multivariable regression analysis adjusted to age,
only eGFR, E/E0 , and GLS were independently
related to renal cortical perfusion (r2 ¼ 0.44;
A. Lubas and S. Niemczyk
Department of Internal Diseases, Nephrology and
p < 0.001). In conclusion, the intensity of left
Dialysis, Military Institute of Medicine, Warsaw, Poland ventricular strain and relaxation independently
R. Ryczek
influence renal cortical perfusion in hypertensive
Department of Cardiology and Internal Diseases, Military patients with chronic kidney disease. A reduction
Institute of Medicine, Warsaw, Poland in left ventricular global longitudinal strain is
A. Maliborski superior to left ventricular ejection fraction in the
Department of Radiology, Military Institute of Medicine, prediction of a decline in renal cortical perfusion.
Warsaw, Poland
P. Dyrla Keywords
Department of Gastroenterology, Military Institute of Blood pressure · Cardiac function · Doppler
Medicine, Warsaw, Poland
ultrasound · Hypertension · Kidney disease ·
L. Niemczyk (*) Left ventricular ejection · Left ventricular
Department of Nephrology, Dialysis and Internal
Medicine, Warsaw Medical University, Warsaw, Poland
strain · Renal function

2 A. Lubas et al.

1 Introduction The objective of the present study was to

assess the influence of hemodynamic cardiac
Renal perfusion depends on cardiac function. function, including contractility of the left ven-
Maintaining a proper renal blood circulation is a tricular longitudinal fibers, on renal perfusion in
prerequisite for normal kidney functioning. It is pharmacologically treated patients with hyperten-
believed that a reduction in the cardiac output to sion and chronic kidney.
less than 1.5 L/min/1.73m2 results in deficiency of
blood flow and oxygenation of kidneys leading to
their functional deterioration (Ljungman et al. 2 Methods
1990). In the physiological condition, intrarenal
mechanisms responsible for the renal blood flow The study included 63 consecutive patients (7 F
autoregulation ensure stabilization of renal func- and 56 M; aged 56  14) with hypertension and
tion in the mean arterial pressure range of stable chronic kidney disease, seeking medical
70–130 mmHg (Burke et al. 2014). However, attention in the nephrology clinic. Exclusion
many drugs used to treat hypertension interfere criteria were acute cardiac or renal disease, glo-
with the mechanisms of renal autoregulation, merulonephritis requiring immunosuppressive
which results in the kidney exposure to arterial therapy, renal focal lesions disallowing the ade-
pressure fluctuations (Meyrier 2015). On the other quate ultrasound assessment of renal perfusion,
hand, intrarenal changes occurring in the course of pelvicalyceal system dilatation, past renal artery
a chronic kidney disease also limit the efficiency stenosis, chronic kidney disease in stage
of renal autoregulation. Previous studies have 5 (National Kidney Foundation 2002), symptoms
shown a significant correlation of renal perfusion, of heart failure, significant valvular heart disease,
assessed by ultrasound dynamic tissue perfusion segmental contractility disturbances noticed in
measurement, with biochemical (troponin I, echocardiography, previous myocardial infarct,
NT-proBNP), functional (left ventricular ejection arrhythmias, tachycardia found in the perfusion
fraction (LVEF), cardiac index (CI), and stroke ultrasound or echocardiography, hyperkinetic
volume), and structural (left ventricular mass state, active inflammation, cardiorenal diseases
index (LVMI)) indices of cardiac function in the course of other pathologies (connective
(Lubas et al. 2013, 2015). In patients with acute tissue diseases, diabetes mellitus, or amyloidosis),
decompensated heart failure, there is a greater generalized neoplastic disease, and current or past
influence of venous congestion and elevated pres- anticancer treatment.
sure in the right ventricle than that of reduced
LVEF on the deterioration of renal function
(Gnanaraj et al. 2013). Further, studies on the 2.1 Cardiorenal Function
cardiotoxicity of anticancer drugs have shown
that severe disturbances in the contractility of left Ambulatory 24-h blood pressure monitoring was
ventricular longitudinal fibers, expressed as a conducted in all patients using an ABPM-04
global longitudinal strain (GLS), can be deter- monitor (Meditech, Budapest, Hungary), with
mined before the decrease in LVEF becomes sig- measurements taken every 15 min during daytime
nificant (Smiseth et al. 2016). Likewise, reduction and every 30 min during nighttime.
in GLS with normal LVEF has been reported in
patients with three-vessel coronary artery disease, Carotid Sonography To assess the severity of
heart failure with preserved LVEF, and tight aortic vascular changes occurring in the course of arte-
stenosis (Attias et al. 2013; Choi et al. 2009; Liu rial hypertension, which can affect renal perfu-
et al. 2009). All that suggests a greater sensitivity sion, each patient underwent a measurement of
of GLS, compared to LVEF, in the detection of left common carotid artery intima-media
subclinical damage to the left ventricular muscle. thickness (cIMT) using the 11 L transducer
Left Ventricular Strain and Relaxation Are Independently Associated with. . . 3

(10–13 MHz). To calculate cIMT, three manual mode, as previously described (Lubas et al. 2013,
measurements of intima-media complex on the 2015). Short sequences of video clips recorded in
far wall of the left carotid artery, at least 10 mm the DICOM format presenting the color-coded
from the carotid sinus, were averaged. flow velocity in the renal cortex were then
evaluated (PixelFlux medical device;
Cardiac Sonography Echocardiography was Chameleon-Software, Leipzig, Germany)
performed at the day when the blood pressure according to the ultrasound dynamic tissue perfu-
monitor was disconnected, using the Vivid S6 sion measurement method (Scholbach et al.
system with the M4S-RS sector transducer of 2004). The size of averaged total (arterial and
1.5–3.6 MHz (GE Healthcare, Chicago, IL). venous) renal cortical perfusion (RCP) in cm/s
Measurements of the tricuspid annular plane sys- was evaluated as a surrogate of right and left
tolic excursion (TAPSE), diameter of vena cava heart function on kidney perfusion.
inferior (VCI), and wall thickness and diameter of Estimated glomerular filtration rate (eGFR)
the left ventricular cavity were performed in the was assessed using the chronic kidney disease
M-mode imaging in accordance with the epidemiology formula based on the measurement
recommendations of the American Society of of cystatin C in the serum (Levey et al. 2009).
Echocardiography (Sahn et al. 1978). Left ven-
tricular mass was calculated from the Devereux
et al. (1986) formula and then normalized for 2.2 Statistical Analysis
body surface area, calculated according to
Mosteller (1987), to obtain the LVMI index. Data were presented as means SD. Correlations
The LVEF in the Simpson’s biplane method, CI, between variables were examined using the
and the indices of diastolic LV function such as Pearson or Spearman method depending on the
the peak values of early (E wave) and late fulfillment of the normal distribution condition.
(A wave) mitral inflow velocities and tissue The presence of intragroup differences was tested
Doppler early diastolic mitral annular velocity using the Kruskal-Wallis analysis of variance
(E0 ) at the septal corner of mitral annulus were (ANOVA). Stepwise multivariable regression
measured. Then, E/A and E/E0 ratios were calcu- analysis was used to identify the factors indepen-
lated as previously described (Lubas et al. 2017; dently associated with RCP. Receiver operating
Lang et al. 2006). The LV longitudinal strain characteristic (ROC) analysis was performed to
calculations were based upon the speckle tracking identify the nadir value of LVEF corresponding
technique, using the dedicated automated func- to the threshold value of RCP. For statistical
tional imaging protocol. The measurements were evaluation, a commercial Statistica 12 package
done at post-processing, using was used (StatSoft Inc., Tulsa, Oklahoma, USA).
electrocardiography-gained loop images acquired
in typical apical views. The tracked area was
detected automatically and then manually 3 Results
corrected. The GLS was the arithmetic mean of
longitudinal strain in four-, two-, and three- Baseline patient characteristics and the results of
chamber views. echocardiography and RCP measurements are
presented in Table 1.
Kidney Ultrasound After having the biochemis- In the study group, hypertension was treated
try tests done, patients underwent kidney ultra- with angiotensin-converting enzyme inhibitors or
sound examination using the 4 L 2–5 MHz angiotensin receptor blockers in 36 patients.
convex transducer (Logiq P6; GE Healthcare, Thirty-six patients received β-blockers,
Seoul, Korea). Renal perfusion was assessed 23 calcium channel blockers, and 38 diuretics,
using the same transducer in the color Doppler and 12 received α-blockers. RCP associated
4 A. Lubas et al.

Table 1 Baseline patient characteristics and results

All patients RCP
Indices (n ¼ 63) Correlation coefficient
Age (yr) 55.6  13.9 0.349*
BMI (kg/m2) 28.4  3.6 0.055
Cystatin C (mg/dL) 1.47  0.60 0.636*
eGFR (ml/min/1.73 m2) 59.2  30.8 0.663*
SBP (mmHg) 126.2  16.1 0.205
DBP (mmHg) 75.7  11.2 0.039
MAP (mmHg) 92.6  12.7 0.047
PP (mmHg) 50.5  10.3 0.270
cIMT (mm) 0.83  0.22 0.373*
VCI (cm) 1.77  0.39 0.149
TRPG (mmHg) 22.3  8.3 0.009
TAPSE (cm) 2.4  0.4 0.104
LVMI (g/m2) 102.7  33.3 0.300*
LVEF (%) 61.6  9.3 0.299*
CI (L/min/m2) 4.4  1.2 0.101
E/A 1.08  0.48 0.330*
E/E0 10.2  2.8 0.414*
GLS (%) 17.2  3.9 0.427*
RCP (cm/s) 0.25  0.18 –
Data are means SD and correlation coefficients; BMI body mass index, eGFR estimated glomerular filtration rate, CI
cardiac index, cIMT carotid intima-media thickness, E/A early and late mitral inflow velocities ratio, E/E0 early mitral
inflow velocity and mitral annular early diastolic velocity ratio, LVEF left ventricular ejection fraction, GLS left
ventricular global longitudinal strain, LVMI left ventricular mass index, SBP, DBP, MAP, PP, systolic, diastolic, mean
arterial pressure and pulse pressure, VCI diameter of vena cava inferior, TAPSE tricuspid annular plane systolic
excursion, TRPG Bernoulli equation-derived pressure gradient from the peak tricuspid regurgitation velocity, RCP
renal cortical perfusion
p < 0.05

Table 2 Comparison of left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (GLS) on
renal cortical perfusion (RCP) in groups stratified by quartiles of RCP
Quartile I Quartile II Quartile III Quartile IV p-value quartile
(n ¼ 16) (n ¼ 16) (n ¼ 16) (n ¼ 15) I:II:III:IV
RCP (cm/s) 0.06  0.04* 0.16  0.30* 0.29  0.05* 0.52  0.13* <0.001
eGFR (mL/min/1.73 m2) 34.6  14.1* 48.8  23.6** 74.8  26.7* 81.7  33.2** <0.001
GLS (%) 14.6  3.9*** 17.6  3.6 17.6  3.4 19.2  3.3*** 0.011
E/E0 11.6  3.0 11.2  3.3 9.1  2.0 9.0  1.9 0.015
LVEF (%) 57.1  11.5 62.2  8.2 61.6  8.4 65.9  7.2 0.094
eGFR estimated glomerular filtration rate, E/E0 early mitral inflow velocity and mitral annular early diastolic velocity
p < 0.001; **p ¼ 0.033; ***p ¼ 0.007

significantly with age, renal function, LVMI, and Although the initial LVEF significantly
with the functional indices of the left ventricle associated with RCP, after dividing patients into
(Table 1). However, the TAPSE and TRPG four groups by quartiles of RCP, the Kruskal-
indices of right ventricular function assessed in Wallis ANOVA showed significant differences
the standard echocardiographic examination and only in the E/E0 , GLS, and renal function, but
the diameter of VCI failed to associate with RCP. not in LVEF (Table 2; Fig. 1; Panel I and II). In
Left Ventricular Strain and Relaxation Are Independently Associated with. . . 5

Fig. 1 Imaging examples

of renal cortex perfusion in
a patient with normal left
ventricular global
longitudinal strain (GLS)
(Panel I) and with
abnormal GLS (Panel II)

the multivariable regression analysis performed threshold value of RCP ¼ 0.284 (95%CI 0.231;
in relation to age and taking into account the 0.337). In order to obtain an approximate LVEF
indices that associated with RCP, i.e., LVMI, result corresponding to the threshold value of
LVEF, GLS, E/E0 , IMT, PP, and eGFR, only the RCP, ROC analysis was performed in which the
eGFR (r ¼ 0.418; p < 0.001), E/E0 (r ¼ 0.259, highest sensitivity (70%) and specificity (52%)
p ¼ 0.022), and GLS (r ¼ 0.238, p ¼ 0.035) were found for LVEF of 64.8%. However, this
were found to independently affect the value of result was insignificant (AUC ¼ 0.611, p ¼ 0.121).
RCP (r2 ¼ 0.440, p < 0.001; power of the test
0.999 for probability of type I error α ¼ 0.05).
The examples of predicted RCP values with 4 Discussion
known LV GLS, E/E0 , and eGFR values are
shown in Table 3. The present study demonstrates that indices of
The use of the known threshold values for the renal function and left ventricular systolic and
results of normal and abnormal indices that sig- diastolic function are independent factors enable
nificantly related to RCP enabled to predict the to explain approximately 44% of the variability in
6 A. Lubas et al.

Table 3 Prediction of renal cortical perfusion (RCP) values based on multivariate regression analysis
(mL/min/1.73 m2) GLS (%) E/E0 Predicted RCP (95%CI) (cm/s)
90 16 8 0.36 (0.30; 0.42)
60 16 8 0.28 (0.23; 0.34)
60 20 8 0.33 (0.27; 0.39)
60 16 10 0.25 (0.21; 0.29)
eGFR estimated glomerular filtration rate, GLS left ventricular global longitudinal strain, E/E0 early mitral inflow velocity
and mitral annular early diastolic velocity ratio, 95%CI 95% confidence intervals

RCP. GLS assessed by speckle tracking echocar- the RCP value. This means that the higher the
diography is a measure of the averaged strain of E/E0 ratio (normal <8 cm/s, abnormal >13 cm/s),
the longitudinal myocardium fibers in all the lower the renal perfusion. Thus, both systolic
segments of the left ventricle, examined during (GLS) and diastolic (E/E0 ) left ventricular func-
contraction. The shortening of longitudinal fibers tion affect renal perfusion. The evaluation of the
is expressed in negative percentage values, where left ventricular function is therefore essential for
the higher is the absolute value the greater the the diagnosis of disorders of the cardiorenal axis.
shortening of the fibers in question (normal On the other hand, it may be expected that
GLS < 16%) (Yingchoncharoen et al. 2013). patients with heart failure with preserved ejection
GLS is considered an equivalent to the left ven- fraction (HFpEF), i.e., so-called isolated diastolic
tricular systolic function, and it appears an earlier insufficiency, would also be characterized by
and more sensitive marker of left ventricular mus- lower RCP indices compared to those without
cle damage than LVEF (Smiseth et al. 2016). heart failure with the same LVEF value. In this
Moreover, GLS has been found of predictive sense, the evaluation of RCP can be useful in the
value for LVEF decrease in patients with heart early diagnosis of cardiorenal syndrome.
failure (Adamo et al. 2017; Romano et al. 2017). The study by Gnanaraj et al. (2013) has shown
GLS is a quantitative, objective method, mostly a significant role of venous congestion in reduc-
dependent on the software, and is characterized ing renal perfusion in patients with acute
by a greater repeatability (intra-observer 3.3%; decompensated heart failure, while the observed
inter-observer 4.0%), while the variability of markers of decreased cardiac output are not of
LVEF results, largely conditioned by the experi- such significance. However, that study has used
ence of the experimenter, is nearly twice as high LVEF, without the GLS assessment. Further, in
(intra-observer 6.3%, inter-observer 10.3%) patients with decompensated heart failure, venous
(King et al. 2016). In the present study, GLS congestion is the main symptomatic problem
had a greater impact on the RCP value than the forcing the patients to seek hospital help. It is
calculated LVEF. Although the attempt to estimate thus difficult to expect that the impaired renal
the LVEF value corresponding to the borderline venous outflow will not cause a decrease in
RCP was estimated at approximately 65%, this renal blood flow, particularly in the presence of
result was not significant and due to the Ray et reduced arterial perfusion. In the present study,
al. (2010) criteria, had a poor diagnostic value. patients were in the optimal condition, with a
The E/E0 ratio is a quotient of the maximal well-controlled arterial pressure and without
velocity of early mitral valve inflow (E) and symptoms of heart failure. The functional indices
early diastolic velocity of the mitral annulus (E0 ) of the right heart (TAPSE, TRPG) and VCI diam-
and it correlates with the left ventricular filling eter measured directly before the right atrium
pressure that is higher in case of left ventricular were not significantly related to renal perfusion.
diastolic dysfunction. In this study, E/E0 was sig- The majority of antihypertensive drugs used in
nificantly inversely associated with renal perfu- the treatment of high blood pressure impair renal
sion, and it was an independent factor modifying autoregulation and significantly modify renal
Left Ventricular Strain and Relaxation Are Independently Associated with. . . 7

perfusion (Digne-Malcolm et al. 2016). Hence, The study protocol was approved by the Bioethics Com-
there is a greater dependence of renal perfusion mittee of the Military Institute of Medicine (No. 35/WIM/
2011 of June 15, 2016).
on functional indices of the heart in the patients.
On the other hand, in the studies performed so far,
Informed Consent Written informed consent was
a significant impact of antihypertensive drugs on obtained from all individual participants included in the
RCP has been found, which explains approxi- study.
mately 29% of RCP variability (Lubas et al.
2018). Such a relation of renal hemodynamics
may be reduced in patients who are not on hypo-
tensive treatment and have preserved renal
autoregulation. The active antihypertensive ther- Adamo L, Perry A, Novak E, Makan M, Lindman BR,
apy should not be considered an undesirable fac- Mann DL (2017) Abnormal global longitudinal strain
tor, because a vast majority of patients with predicts future deterioration of left ventricular function
in heart failure patients with a recovered left ventricular
cardiorenal disorders are undergoing
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cardioprotective or nephro-protective treatment, Attias D, Macron L, Dreyfus J, Monin JL, Brochet E,
which largely coincides with antihypertensive Lepage L, Hekimian G, Iung B, Vahanian A,
therapy. Messika-Zeitoun D (2013) Relationship between lon-
gitudinal strain and symptomatic status in aortic steno-
The present work has several limitations.
sis. J Am Soc Echocardiogr 26:868–874
Patients with a stable kidney disease during the Burke M, Pabbidi MR, Farley J, Roman RJ (2014) Molec-
preceding 3 months, without renal biopsy, were ular mechanisms of renal blood flow autoregulation.
qualified for the study; so the etiology of the Curr Vasc Pharmacol 12:845–858
Choi JO, Cho SW, Song YB, Cho SJ, Song BG, Lee SC,
kidney damage was unknown. Nonetheless,
Park SW (2009) Longitudinal 2D strain at rest predicts
patients were not on active immunosuppressive the presence of left main and three vessel coronary
therapy and showed no symptoms of artery disease in patients without regional wall motion
hypervolemia, which minimized the probability abnormality. Eur J Echocardiogr 10:695–701
Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ,
of active pathology of renal hemodynamics.
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# Springer Nature Switzerland AG 2018
Published online: 16 October 2018

Coupling of Blood Pressure

and Subarachnoid Space Oscillations at
Cardiac Frequency Evoked by Handgrip
and Cold Tests: A Bispectral Analysis

Marcin Gruszecki, Yurii Tkachenko, Jacek Kot,

Marek Radkowski, Agnieszka Gruszecka, Krzysztof Basiński,
Monika Waskow, Wojciech Guminski, Jacek Sein Anand,
Jerzy Wtorek, Andrzej F. Frydrychowski, Urszula Demkow,
and Pawel J. Winklewski

Abstract transforms during handgrip and cold tests.

The aim of the study was to assess blood The experiments were performed on a group
pressure–subarachnoid space (BP–SAS) of 16 healthy subjects (F/M; 7/9) of the mean
width coupling properties using time–fre- age 27.2  6.8 years and body mass index of
quency bispectral analysis based on wavelet 23.8  4.1 kg/m2. The sequence of challenges

M. Gruszecki and A. Gruszecka

Department of Radiology Informatics and Statistics,
Faculty of Health Sciences, Medical University of Gdansk, J. S. Anand
Gdansk, Poland Department of Clinical Toxicology, Faculty of Health
Sciences, Medical University of Gdansk, Gdansk, Poland
Y. Tkachenko and J. Kot
National Center for Hyperbaric Medicine, Faculty of J. Wtorek
Health Sciences, Medical University of Gdansk, Gdynia, Department of Biomedical Engineering, Faculty of
Poland Electronics, Telecommunications and Informatics, Gdansk
University of Technology, Gdansk, Poland
M. Radkowski
Department of Immunopathology of Infectious and A. F. Frydrychowski
Parasitic Diseases, Medical University of Warsaw, Department of Human Physiology, Faculty of Health
Warsaw, Poland Sciences, Medical University of Gdansk, Gdansk, Poland
K. Basiński U. Demkow (*)
Department of Quality of Life Research, Faculty of Health Department of Laboratory Diagnostics and Clinical
Sciences, Medical University of Gdansk, Gdansk, Poland Immunology of Developmental Age, Medical University
of Warsaw, Warsaw, Poland
M. Waskow
Department of Clinical Anatomy and Physiology, Faculty
of Health Sciences, Pomeranian University of Slupsk, P. J. Winklewski
Slupsk, Poland Department of Clinical Anatomy and Physiology, Faculty
of Health Sciences, Pomeranian University of Slupsk,
W. Guminski
Slupsk, Poland
Department of Computer Communications, Faculty of
Electronics, Telecommunications and Informatics, Gdansk Department of Human Physiology, Faculty of Health
University of Technology, Gdansk, Poland Sciences, Medical University of Gdansk, Gdansk, Poland

10 M. Gruszecki et al.

was first handgrip and then cold test. The ered an indirect marker of cerebrospinal fluid
handgrip challenge consisted of a 2-min strain, volume (CSF) (Gruszecki et al. 2018b).
indicated by oral communication from the Both stress and pain are associated with white
investigator, at 30% of maximum strength. matter dysfunction and changes in neural plastic-
The cold test consisted of 2 min of hand ity and overall neural architecture (Coppieters
immersion to approximately wrist level in et al. 2018; Bishop et al. 2017; Nugent et al.
cold water of 4  C, verified by a digital ther- 2015; Sheikh et al. 2014; Upadhyay et al. 2012).
mometer. Each test was preceded by 10 min at One of the possible mechanisms that might be
baseline and was followed by 10-min recovery involved in white matter alterations is abnormal
recordings. BP and SAS were recorded simul- CSF pulsatility (Beggs et al. 2016a, b; Bateman
taneously. Three 2-min stages of the proce- et al. 2008). CSF pulsatile flow is driven by heart-
dure, baseline, test, and recovery, were and lung-generated blood inflows and outflows to
analyzed. We found that BP–SAS coupling and from the brain (Gruszecki et al. 2018a, b; Shi
was present only at cardiac frequency, while et al. 2018).
at respiratory frequency both oscillators were Periodic oscillations in CSF volume can be
uncoupled. Handgrip and cold test failed to indirectly assessed using SAS width as a surrogate.
affect BP–SAS cardiac–respiratory coupling. In short, the main assumption for near-infrared
We showed similar handgrip and cold test transillumination/backscattering sounding
cardiac bispectral coupling for individual (NIR-T/BSS), the technique we use, is that trans-
subjects. Further studies are required to estab- lucent CSF in SAS acts as a propagation duct for
lish whether the observed intersubject infrared radiation, a technique resembling optical
variability concerning the BP–SAS coupling fiber engineering. This allows for measurement of
at cardiac frequency has any potential clinical SAS width to estimate changes in CSF volume
predictive value. (Frydrychowski and Pluciński 2007; Pluciński
and Frydrychowski 2007; Pluciński et al. 2000).
Keywords NIR-T/BSS has been validated against magnetic
Bispectral analysis · Blood pressure · Cardiac resonance imaging, showing comparable SAS
frequency · Cold test · Handgrip test · width alterations induced by shifts in the body
Subarachnoid space width position (Frydrychowski et al. 2012).
The handgrip test results in increased blood
pressure (BP) (Macey et al. 2012; Wszedybyl–
Winklewska et al. 2012). Therefore, it seemed
1 Introduction
logical that relatively quick BP elevation may
result in substantial alterations in the BP–SAS
The handgrip test and the cold test are widely
relationship. Quite surprisingly, analysis of
used to assess the stress response and activation
amplitude coherences between these two signals
of the sympathetic nervous system in humans.
has not revealed any substantial changes. On the
Nevertheless, the neural circuits involved in
contrary, sympathetic nervous system activation
information processing differ between these
seems to stabilize the BP–SAS relationship
tests. Particularly, neural processing of handgrip
(Winklewski et al. 2015a, b). Nevertheless, a
involves motor components, while cold test
lack of change in the amplitude coherence does
involves pain components (Vaegter et al. 2014;
not preclude alterations in the BP–SAS coupling
Macey et al. 2012). We and others also observed
detected with other mathematical methods.
significant differences in cerebral blood volume
The aim of the study was to assess the BP–
and subarachnoid space (SAS) width responses to
SAS coupling properties using time–frequency
handgrip and cold tests (Winklewski et al. 2015a,
bispectral analysis based on wavelet transforms
b; Wilson et al. 2005). SAS width can be consid-
(Clemson et al. 2016; Jamšek et al. 2004, 2007).
Coupling of Blood Pressure and Subarachnoid Space Oscillations at Cardiac. . . 11

Consequently, our goal was to track time 2.2 Measurements

variability in coupling between these two
oscillators at cardiac and respiratory frequencies. The mean BP was measured using continuous
We hypothesized that both handgrip and cold finger-pulse photoplethysmography (CNAP,
tests will show substantial intersubject heteroge- CNSystems Medizintechnik AG, Graz, Austria).
neity in the BP–SAS coupling. Nevertheless, as Finger blood pressure was calibrated against bra-
sympathetic nervous activation seems to domi- chial arterial pressure. Oxyhemoglobin saturation
nate in terms of inter-signal behavior, we (SaO2) was measured continuously (Massimo
expected a similar handgrip and cold test Oximeter, Massimo, Milan, Italy) with a finger-
bispectral coupling in individual volunteers. clip sensor. Expired air was analyzed with the
spirometry module of a medical monitoring sys-
tem (Datex-Ohmeda, GE Healthcare,
2 Methods Wauwatosa, WI) for respiratory rate (RR) and
minute ventilation (MV). Gas samples from the
2.1 Experimental Design mouthpiece were constantly analyzed using the
sidestream technique for end-tidal CO2 (EtCO2)
Experiments were performed on a group of and end-tidal O2 (EtO2) with the metabolic mod-
16 healthy volunteers, aged 27.2  6.8 years ule of the same medical monitoring system. The
and BMI of 23.8  4.1 kg/m2 (F/M; 7/9); none NIR-T/BSS SAS signal was recorded with a
of them were smokers. All the subjects received head-mounted SAS 100 Monitor (NIRTI SA,
detailed information about the study objectives Wierzbice, Poland). The theoretical and practical
and any potential adverse reactions. Although foundations of the NIR-T/BSS method have been
none of the participants suffered from known published previously (Frydrychowski and
disorders or were taking any medication, a gen- Pluciński 2007; Frydrychowski et al. 2002). All
eral and neurological examination was performed variables were recorded continuously or
before the experiment. Nicotine, coffee, tea, videotaped, and the signals were digitally saved
cocoa, and methylxanthine-containing food and on the computer for further analysis.
beverages were not permitted for 8 h before the
tests. Additionally, prior to each test, the subjects
were asked to rest comfortably for 30 min in the
2.3 Bispectral Analysis
supine position.
All tests were conducted breathing ambient air
Bispectrum analysis provides information about
at room temperature of 21 oC. The sequence of
the coupling properties between interacting
challenges was first handgrip and then cold test.
oscillators. The bispectrum is a frequency–fre-
For the handgrip challenge, subjects were
quency domain method that arises from higher-
instructed to squeeze an electronic dynamometer
order statistics (Jamšek et al. 2004). However, the
by the right hand at maximum force. They were
frequency–frequency domain is still unable to
initially directed to briefly squeeze at maximum
track time variability. Therefore, similarly to the
effort as a reference. The challenge consisted of a
time–frequency analysis, time–frequency–fre-
2-min strain, indicated by oral communication
quency analysis leads to a proposal of wavelet-
from the investigator, at 30% of the maximum.
based bispectral analysis (Jamšek et al. 2004,
After the practice, subjects were allowed to return
2007) given by:
to a baseline state. The cold test consisted of
10 min at baseline, 2 min of hand immersion to
the wrist level in the water of 4  C, verified by a
Bðf 1 ; f 2 Þ ¼ W T ðf 1 ; t ÞW T ðf 2 ; t ÞW ∗
T ðf 3 ; t Þdt
digital thermometer, and 10 min recovery. The
investigator helped insert the hand into the water
and take it out at the appropriate times.
12 M. Gruszecki et al.

where f 3 ¼ 1= 1
f1 þ f1 is the wavelet coefficient
b122 ðf 1 ; f 2 Þ

and “*” denotes complex conjugation.

j B122 ðf 1 ; f 2 Þ j
Additionally, to introduce the time-dependent ¼ qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
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Early ultrasonographic markers of atherosclerosis in patients with familial Mediterranean fever


Systemic inflammation plays an important role in the development of atherosclerosis (AS). The aim of this study was to evaluate the presence of early AS in patients with familial Mediterranean fever (FMF) that is characterized by recurrent inflammatory attacks of serositis. Sixty-one FMF patients (30 Male/31 Female; 31.5 [18–54] years) and 31 healthy controls (16 Male/15 Female; 31 [22–58] years) were studied. All FMF patients were on regular daily colchicine treatment and during attack-free periods. Both the FMF patients and controls with a history of diabetes mellitus (DM), hypertension, and hyperlipidemia were excluded. Body mass index (BMI) was calculated. Serum lipids, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were assessed. Two-hour oral glucose tolerance test was performed to rule out DM and glucose intolerance. To investigate early AS “endothelium-dependent flow-mediated dilatation (FMD%),” “nitroglycerin-induced endothelium-independent peripheral vasodilatation (NTG%),” and intima-media thickness (IMT) of common carotid arteries (CCA) were measured by ultrasonograpy. The median disease duration for FMF patients was 16 (1–45) years. Age, sex, BMI, smoking status, and serum lipids were comparable in patients and controls (p > 0.05). However, ESR and standard CRP were significantly higher in the patients group (p < 0.05). There were no differences in the measurements of right, left, and averaged IMT of CCA between patients and controls ([0.49 vs 0.5], [0.51 vs 0.52] and [0.5 vs 0.51]; p > 0.05, respectively). None of the subjects had carotid artery plaques. FMD% and NTG% were also similar in patients and controls group ([18.2 vs 20.6] and [24.2 vs 22.5]; p > 0.05, respectively). This study suggests that the markers of early AS are not impaired in FMF patients on regular daily colchicine treatment.

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brachial artery diameter

body mass index

common carotid artery

C-reactive protein


diabetes mellitus

erythrocyte sedimentation rate

flow-mediated dilatation

familial Mediterranean fever

high density lipoprotein


intima-media thickness

low density lipoprotein


rheumatoid arthritis

systemic lupus erythematosus

Statistical Package of Social Science

total cholesterol



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Download references

Author information


  1. Department of Internal Medicine, Division of Rheumatology, School of Medicine, Dokuz Eylul University, 35340, Inciralti, Izmir, Turkey

    Ismail Sari, Gercek Can, Servet Akar, Merih Birlik, Nurullah Akkoc & Fatos Onen

  2. Department of Radiology, School of Medicine, Dokuz Eylul University, 35340, Inciralti, Izmir, Turkey

    Oguzhan Karaoglu, Aytac Gulcu & Yigit Goktay

  3. Department of Internal Medicine, School of Medicine, Dokuz Eylul University, 35340, Inciralti, Izmir, Turkey

    Mehmet Tunca

  4. Tip Fakultesi, Ic hastaliklari ABD, Immunoloji-Romatoloji BD, Dokuz Eylul Universitesi, 35340, Inciralti, Izmir, Turkey

    Fatos Onen

Источник: []
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