Download FIRST EXPERIENCE WITH SALBUTAMOL

FIRST EXPERIENCE WITH SALBUTAMOL - INDUCED CHANGES IN THE
PHOTOPLETHYSMOGRAPHIC DIGITAL VOLUME PULSE
Aleksandras Laucevičius, Ligita Ryliškytė, Žaneta Petruionienė, Milda Kovaitė, Nerijus Misonis
Department of Cardiology, Vilnius University and Vilnius University Santarishkes Hospital, Medical Center
"Kardivita"
Vilniaus universiteto ir Vilniaus universitetinės ligoninės Santariškių klinikų Kardiologijos klinika, Medicinos
centras Kardivita
Keywords: photoplethysmographic digital volume pulse, endothelial function, coronary heart disease, arterial
hypertension.
Summary. Photoplethysmographic digital volume pulse analysis provides an additional possibility to evaluate
arterial stiffness and to analyze the reflected pulse waves from the lower part of the body. Systemic effect of
beta2-adrenergic agonist salbutamol is partially mediated through the L-arginine-NO pathway. Attenuation of
photoplethysmographic digital volume pulse parameters under salbutamol inhalation could be a means of
evaluating vasomotor endothelial dysfunction in cardiovascular patients. The aim of the present study was to
estimate the digital volume pulse parameters after the inhalation of salbutamol in patients with arterial
hypertension, coronary heart disease and to compare them with the results obtained in healthy adults. Normal
response of digital volume pulse to salbutamol in healthy subjects was a decreased height of the inflection point
(IP) and the prolongation of peak - to -peak time (PPT). In groups of patients with arterial hypertension and
coronary heart disease the typical response was attenuation in the drop of the height of the inflection point and
the corresponding minimal or absent prolongation of the PPT interval. The blunted response of
photoplethysmographic digital volume pulse parameters to inhaled salbutamol in hypertensive and coronary
patients could suggest a disturbed endothelial vasomotor function in these patients. Seminars in Cardiology.
2002; 8(1):87-93
Salbutamolio sukelti fotopletizmografinio digitalinio turinio pulso pakitimai: pirmoji patirtis
Raktažodžiai: fotopletizmografinis digitalinis tūrinis pulsas, endotelio funkcija, koronarine sirdies liga, arterine
hipertenzija.
Reziume. Fotopletizmografinio digitalinio turinio pulso analizė suteikia papildomą. galimybę jvertinti arterijų
standumą bei isanalizuoti pulsines bangas, atspindėtas is apatinės kūno dalies. Sisteminis beta2adrenerginio
agonisto salbutamolio poveikis yra dalinai medijuojamas per L-arginino NO kelia.. Fotopletizmografinio
digitalinio pulso parametrq kitimas po salbutamolio inhaliacijos gali būti kardiovaskulinių pacientų
vazomotorinės endotelio disfunkcijos jvertinimo būdas. Šios studijos tikslas buvo jvertinti digitalinio turinio
pulso parametrus po salbutamolio inhaliacijos pacientams, sergantiems arterine hipertenzija, koronarine sirdies
liga, ir palyginti juos su sveikq suaugusiųjų. rezultatais. Normalus sveikq asmenij digitalinio turinio pulso
atsakas j salbutamolj buvo linkio tasko aukscio sumažėjimas ir intervalo tarp viršūnių prailgejimas. Pacientų,
sergančių arterine hipertenzija ir koronarine sirdies liga grupėse tipingas atsakas buvo mažesnis linkio tasko
auksčio kritimas ir tai atitinkantis minimalus intervalo tarp virsuniq prailgejimas. Fotopletizmografinio
digitalinio turinio pulso susilpnėjęs atsakas i jkvėptą sulbutamolj sergantiems hipertenzija ar koronarine sirdies
liga pacientams leidžia jtarti sutrikusią vazomotorinę šių pacientų endotelio funkcija. Kardiologijos seminarai.
2002; 8(1):87-93
Photoplethysmography (PPG) - non invasive technique where non-visible infrared light is emitted into the skin.
PPG device should measure the volume by optical methods. Light may be transmitted through a capillary bed
such as is found in the ear lobe or finger tip. As arterial pulsations fill the capillary bed, the changes in the
volume of the blood vessels modify the absorption, reflection and scattering of the light. Depending on the
blood volume in the skin, more or less light is absorbed. By measuring the non-absorbed light, the changes in
the blood volume can be measured [1]. Transmission of the infrared light through the finger and its
photoplethysmographic measurement gives a digital volume pulse (DVP) [2]. The DVP exhibits a systolic and
diastolic components "a" and "b", characteristic "notch" or point of inflection (IP) in its downslope and the time
interval between the first (systolic) and second (diastolic) peaks of the DVP (AT) [3] (Fig. 1A).
The second [2] or the first [3] derivatives are used for estimating the inflection point IP and its changes. The
inflection point contributes to the smoothening of the pulsation of the arteries - the so called "windkessel effect"
[4,5]. Two features of the arteries - elasticity and peripheral resistance - allow them to smooth out the pulsations.
The mechanism is similar to the type of the pump the Germans in the 19th century called
windkessel, so the smoothing of the pulsations by the arteries is often called the windkessel effect. It results
from the increased compliance of the large arteries and to a decreased venous return to the heart [5]. Pressure
pulse waveforms are being studied more extensively than the volume pulse [6]. The decreasing of the pressure
wave reflection from the peripheral arteries accompanied by changes in pressure pulse is a typical response to
glyceryl trinitrate (GTN) [7]. Changes in the DVP produced by GTN parallel those in the pressure pulse [8].
Recently Chowienczyk et al. [3] proposed studying vascular reactivity and endothelial dysfunction by
measuring the systemic effect of beta2-adrenergic agonist salbutamol on the inflection point (IP) of
photoplethysmographic digital volume pulse. Vasodilator responses to beta2-adrenoceptor agonists, are
mediated in part through the nitric oxide pathway [9,10]. The vasodilating effect of salbutamol on the forearm
resistance arteries in humans is partially mediated through the L-arginine-NO pathway [3, 9,10]. This response
could be attenuated during the concurrent blockade of NO synthesis . by A/G-monomethyl-L-arginine
(LNNMA).
The aim of this article was to present our initial experience with the analysis of salbutamol induced changes of
photoplethysmographic digital volume wave parameters in
patients with arterial hypertension and coronary heart disease and to compare them with the measurements in
healthy adults.
Methods
Study population
Fifteen healthy subjects (7 men and 8 women; aged 30.72±6.93 years) with no evidence of arterial hypertension
(blood pressure < 140/90 mm Hg), hypercholesterolemia, diabetes mellitus, cardiac or peripheral vascular
disease, or any other systemic condition were included in the study.
Out of 322 patients participating in the long - time follow-up program in which PPG digital volume pulse
assessment was performed 56 patients (21 women and 35 men) with mean age of 53 ±11 years were selected for
the present analysis. The patients were divided into two groups - the first group consisted of 26 patients with
angiographically proven coronary heart disease and second of 30 patients with primary arterial hypertension.
The most relevant characteristics of the coronary and hypertensive patients and control subjects are shown in the
Table 1.
There was no significant difference between the patient groups with regard to age, but subjects in the control
group were younger than the patients of both groups. Blood pressure
was significantly higher in the arterial hypertension (AH) group than in the coronary heart disease (CHD) group
and subjects in the control group. There was no significant difference of blood pressure in the CHD group and
control subjects. Most of the patients in both AH and CHD groups had at least 2 cardio-vascular risk factors.
Subjects in the control group were without any cardiovascular risk factors.
The coronary heart disease group consisted of 26 patients (9 women and 17 men) with the mean age of
55.35±10.12 years. The mean arterial pressure in this group was 127.35± 17.64 mm Hg; there was no evidence
of present or past hypertension in these patients. Coronary heart disease was proven angiographically in these
patients. Arterial hypertension group consisted of 30 patients with primary hypertension (12 women and 8 men)
with the mean age 51.07±11.56 years. The mean systolic arterial pressure in this group was 144.97±27.20 and
diastolic87.27± 14.50 mm Hg and they were significantly higher than in group with the CHD. The blood
pressure was defined as an average of 3 sitting blood pressure readings taken after 5 minutes of rest on 3
different occasions during a 3- to 4-week period. Acute coronary events were present in 20 (77%) patients from
the CHD group.
The lipidogram parameters (total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides) did not differ
significantly between the CHD and AH groups but were significantly higher in both patient groups than in the
control group (Table 2).
Pts with AH,
Pts with CHD
Control
P*
p**
All pts n=71
group
p***
n=30
n=26
n=15
17
7
42
9
8
29
Age
51,07±11,56
55,35±10,12
30,72±6,93 0,15
<0,001
<0,001
BMI
30,26±7,14
28,56±3,67
22,76±2,83 0,27
0,02
Systolic BP
144,97±27,20
127,35± 17,64
121,33±11,66
0,006
0,01
0,32
133,52±23,39
76,35±9,40
73,47±8,06 0,002
0,007
0,36
80,35± 12,97
22
0
Sex
male
female
18
12
DiastolicBP
87,27±14,50
>2 risk factors 24
Table 1 . Clinical characteristics of patient groups (AH and
patients
CHD patients) and control
subjects.
48,34± 13,75
0,03 28,05±5,99
46
p* - comparing AH and CHD groups
p** - comparing AH and control groups
p***.
comparing CHD and control groups
Pts with AH, n=30 Total
Cholest.
6,98 ±1 ,96
LDL-Ch
4,41
±1,58 HDL-Ch
1,37±0,38 TG
2,72±2,22
Pts with CHD
Control
group n=26
n=15 6,48±1,46
5,47±0,97 4,18±1,71
3,12±0,87 1,19±0,34
1,45±1,05 2,13±1,16
1,8±0,74
Table 2. Level of lipids in patients groups (AH and CHD
groups) and in control subjects group.
p*
p***
0,15
<0,05 0,66
<0,05 0,11
<0,05 0,28
<0,05
p**
<0,01
<0,05
<0,05
<0,01
All pts n=71
6,75±1,74 4,28
±1,63 1,29±0,37
2,42 ±1,76
p* - comparing AH and CHD groups p**
- comparing AH and control groups p***
- comparing CHD and control groups
All AH and CHD patients were taking antihypertensive or vasodilating medication at the time of their
investigation but never tissue ACE inhibitors, third generation calcium antagonists or statins that could
significantly influence the endothelial function.
The study was approved by the local institution ethics committee.
Protocol. All studies were performed in a quiet room with a temperature controlled (25 ± 1°C). All participants
were asked to refrain from drinking alcohol or beverages containing coffeine and from smoking for at least 24
hours before studies. They were studied in the morning after overnight fasting.
A portable photoplethysmograph Micro Medical MP2000 (Gillingham, Kent, United Kingdom) was used for
digital volume pulse analysis. The assessment was performed using the protocol of Chowienczyk et al [3],
which was modified by us. Data were collected with the patient sitting in a specially designed arm-chair with the
hands comfortably placed slightly below the level of the heart with out stretched legs. The measurements were
started after the calmdown period of 20 minutes. The probe was placed on the index finger of the right hand. In
the cases when the finger was cold, steady additional warming was applied and only in the absence of peripheral
vasoconstriction the measurements were started. Three baseline 30 seconds recordings were carried out at 5
minute interval and then the results were averaged and presented as the mean basal parameter of the digital
volume pulse. Three parallel blood pressure measurements were performed using the advanced oscillometric
automatic digital blood pressure monitor UA-767 (A&D Company, Limited) during the baseline recordings, the
results were averaged and presented as the mean value.
Salbutamol (Ventolin Inhaler, GlaxoWelcome) was given by inhalation using the spacer device (four doses of
100mg each). Every dose was inhaled by two deep breaths in from the spacer. Repeated 30 seconds recordings
of the PPG digital volume pulse were performed at 5,10,15, 20, 25, 40 and 60 minutes after the inhalation of
Salbutamol (SLBTM).
The data were averaged by the unit and several mean parameters were calculated (Fig. 1A):
IP - inflection point - defined as the relative height of the inflection point expressed as a percentage of the ratio
between the amplitudes of two waves: systolic forward (a) and reflected (b):
IP=b/ax100%
The second point, or inflection point, is thought to be due to a reflection of the aortic pressure wave from the
lower part of the body. The height of the reflected pulse is proportional to the amount of reflection from the
lower body, which is inversely proportional to the dilatation of the peripheral arteries.
PPT - peak -to- peak time - measured between the waveform peak "a" and the point of inflection "b". PPT is
inversely proportional to the arterial stiffness.
SI - stiffness index - defined as the patient's height divided by the PPT with units of meters per second.
Several additional derivative parameters were calculated:
A IPmax normalized for corresponding APPT (Alpmax X
10/APPT)
APPTmax normalized for corresponding AlP (AIPX 10/
A PPTmax)
A IPmax normalized for PPTmax (Alpmax X10/APPTmax)
IR PPT and SI parameters after salbutamol inhalation are presented as a mean of the measurements after 10, 15
and 20 minutes (modified protocol) and as a mean after 15 and 20 minutes (original protocol). Maximal IP and
maximal PPT were selected from the all recordings: at 10, 15, 20, 25, 40 and 60 minutes after salbutamol
inhalation. The basal measurements were compared with those achieved after salbutamol inhalation. Typical
response of DVP to inhaled SLBTM in healthy adult is presented in Rg.1B
Statistical Analysis. Statistical analysis was performed using the GB-Stat V7.0 for Windows (Dynamic
Microsystems, Inc). All measurements are presented as the mean ± standard deviation. Differences between the
2 groups were estimated by the unpaired Student's t test; correlation matrix was used searching for correlations
between changes of parameters. All calculated probability values are 2-tailed, and P<0.05was considered to
indicate statistical significance.
Results. Photoplethysmographic digital volume parameters in all three studied groups before and after
salbutamol inhalation are presented in table 3.
The typical normal response to salbutamol inhalation showed a drop in the height of inflection point and
prolongation of corresponding PPT (Fig. 1B, Fig. 2).
The typical blunted response of DVP to inhaled salbutamol consists of attenuated decrease in the height of the
inflection point with the absence or only a minimal prolongation of the corresponding PPT (Fig. 3).
A decrease in the height of the A IP after inhaled SLBTML was attenuated in most of the patients of the AH and
CHD groups compared with normal sinking response observed in the control group although this tendency did
not reach statistical significance in the present study. The changes in PPT parameters after inhaled SLBTML
significantly differed in both groups (AH and CHD) of patients of the control group. The mean A PPT at 10, 15,
20 min after SLBTM was significantly shorter in the AH group than in the control group; the same tendency
was seen in the CHD group but it did not reach statistical significance. The mean APPT at 15, 20 min after
SLBTM was found to be significantly shorter in both CHD and AH groups than in the control group. The
maximal PPT was also significantly shorter both in AH and CHD groups compared with the control group. The
mean Asi at 10,15, 20
PPG DVP parameters
Pts with
Pts with CHD Control group
P*
p**
p*** All pts (AH and
AH,
CHD)
n=30
n=26
n=15
4,82±6,28
4,82± 10,09
10,24± 13,97
0,99
0,17
0,22
5,97+9,84
4,76±7,23
4,44±10,91
11,31±14,36
0,90
0,11
0,14
6,03± 10,63
9,07±44,91 16,89±40,60
45,91+48,98
0,50
0,03
0,07
19,27±45,86
5,41 ±37,49 15,49±47,77
48,97+51,10
0,39
0,01
0,04
18,30±46,85
0,45±1,88
0,57±3,71
2,29±2,84
0,88
0,04
0,12
0,86+2,92
0,56±1,97
0,87±2,27
2,05±2,94
0,59
0,11
0,22
0,97±2,33
Maximal A IPt
9,66±6,79
10,73± 10,29 18,24± 16,42
0,66
0,09
0,13
11,86±11,05
Maximal A PPTt
37,19±47,71 55,81 ±56,41 110,14+83,01
0,19
0,006 0,04
59,42 + 65,00
Maximal Asit
2,00±2,22
3,92±3,58
0,24
0,07
0,22
2,65+2,52
AlPmax normalized for
1,15±10,21 2,84±3,64
2,98±5,37
0,41
0,44
0,93
2,16+7,38
Mean AlPatIO, 15,
n=71
20 min after SLBTM
Mean AlPat 15,
20 min after SLBTM
Mean APPT at 10, 15,
20 min after SLBTM
Mean APPTat 15,
20 min after SLBTM
Mean Asiatic, 15,
20 min after SLBTM
Mean Asian 5,
20 min after SLBTM
corresponding APPT
( AlPmax X 10/APPT)
2, 67 ±1,87
A PPTmax normalized for 0,71 ±3,29
2,10±3,50
1,64+1,73
0,14
0,24
0,57
1,42+3,14
2,69±3,42
0,23±0,16
0,14
0,07
0,001 1,61+3,06
correspondingAlP
(AlPXIO/ A PPTmax)
A IPmax normalized for
1,34±3,23
A PPTmax
( AlPmax X10/ A
PPTmax)
Table 3. Photoplethysmographic DVP parameters in patients (AH and CHD) and in the control subject groups.
p* - comparing AH and CHD groups
p** - comparing AH and control groups
p*** - comparing CHD and control groups
t - maximal valves measured at 10, 15,
20, 25,
40, 60 min.
min after SLBTM was found to be significantly smaller in the AH group and had the same tendency in the CHD
group although it did not reach statistical significance. The derivative parameter AlPmax normalized for A
PPTmax was bigger in both groups of the patients compared with the control group but reached statistical
significance only in the CHD group.
The inhalation of salbutamol in doses used had no accompanying alteration of the heart rate or the mean blood
pressure. We explored the possible influence of the heart rate upon PPG DVP parameters after the inhalation of
SLBTM (Table 4).
Parameters
R
P value
(correlation coefficient
Mean A IP at 10, 15, 20 min after SLBTM
0,303
<0,05
Mean AIP at 1 5, 20 min after SLBTM
0,241
n.s.
Mean APPT at 10, 15, 20 min after SLBTM
-0,155
n.s.
Mean APPT at 15, 20 min after SLBTM
-0,213
n.s.
Mean ASI at 10, 15, 20 min after SLBTM
0,203
n.s.
Mean ASI at 1 5, 20 min after SLBTM
0,168
n.s.
Maximal A IP
0,305
<0,05
Maximal A PPT
-0,204
n.s.
Maximal ASI
0,197
n.s.
AlPmax normalized for corresponding A PPT (A IPmax X TO/
-0,059
n.s.
APPT))
A PPTmax normalized for corresponding A IP (A IPX 10/
APPTmax)
0,142
n.s.
AlPmax normalized for A PPTmax ( AlPmaxXIO'/ APPTmax)
0,116
n.s.
Table 4. Correlation coefficients between changes of IP, PPT, SI
parameters and heart rate occurring after salbutamol inhalation.
Only the mean A IP at 10, 15 and 20 minutes after SLBTM (r=0,303) and maximal the A IP (r=0,305) after the
SLBTML statistically significantly correlated with the changes in the heart rate. There was no significant
connection between the changing heart rate and PPT parameters after the inhalation of salbutamol.
We investigated the cumulative rate of time when a maximal decrease in the inflection point - A Ipmax was
present in order to find out how long after the inhaled SLBTM measurements must be performed. When this
time interval was only 15 minutes, the cumulative rate of the decrease in A IPmax was only 41%; it increased to
86 % when the period was prolonged to 25 min (Table 5).
The same tendencies were found after the cumulative rate of maximal PPT prolongation analysis was performed
(Table 6).
Time
Cumulative
Cumulative
Frequency
%
interval (min.)
of pts)
(number
(number of pts)
5
8
8
14.2857
10
7
15
26.7857
15
8
23
41.0714
20
14 37
66.0714
25
11 48
85.7143
40
6
54
96.4286
60
2
56
100
Table 5. Cumulative Frequency of distribution of the A
IPmax decrease time.
Interval
Cumulative
(min.)
%
5
3
10
10
15
18
20
32
Frequency
(number of pts)
Cumulative
(number of pts)
3
5,3571
7
17,8571
8
32,1429
14
57,1429
25
43
11
76,7857
40
52
9
92,8571
60
56
4
100
Table 6. Cumulative rate of maximal prolongation of PPT
interval.
On the basis of these results, we recommend to measure DVP response to salbutamol inhalation after 15, 20 and
25 minutes and to monitor DVP parameters after 40 and 60 minutes in order to observe returning to the baseline
of DVP parameters.
Discussion. The currently accepted method forthe noninvasive clinical assessing of the vasomotor endothelial
function based on the analysis of the flow - mediated vasodilatation in the brachial artery [12]. The reason it can
not be used very widely is the necessity of a sophisticated, expensive ultrasound unit and special skills of the
investigator [13]. Therefore, wide application noninvasive methods used for the assessment of the endothelial
vasomotor function are required. One of the attempts could be the method proposed by Chowienczyk et al in
1999 [3]. They demonstrated that beta2 - adrenergic agonist albuterol (salbutamol) in partly reduces the wave
reflection by the activation of the L-arginine - NO pathway and suggested that photoplethysmographic digital
volume pulse analysis combined with provocative administration of albuterol might be used for noninvasive
assessment of endothelial function. Adrenergic-mediated vasodilation involves a combination of endothelial and
smooth muscle mechanisms because salbutamol induces direct smooth muscle relaxation and NO release from
endothelial cells [9,10]. The method was applied only to patients with type II diabetes mellitus and revealed a
disturbed endothelial function in these patients [3,14].
It is clear from the numerous studies that the endothelial function is disturbed in most patients with coronary
heart disease and primary arterial hypertension [15,16].
The main purpose of the present study was to estimate the characteristic influences of inhaled beta2-adrenergic
agonist salbutamol on photoplethysmographic digital volume pulse parameters in healthy control subjects,
patients with arterial hypertension and coronary heart disease. The normal response of PPG DVP parameters to
SLBTM in healthy adult subjects was a distinct decrease in the height of the inflection point with the
corresponding prolongation of PPT the interval. In both groups of patients (AH and CHD) the most typical
response to inhaled SBTM was a decrease in the height of the inflection point (AlP) with a
minimal or absent prolongation of PPT interval. This blunted response of photoplethysmographic digital volume
pulse parameters to inhaled salbutamol was found in most the patients with arterial hypertension and coronary
heart disease. Statistically different from the values in the control group, the changes in the mean and maximal
peak - to - peak time (Mean A PPT and A PPTmax.) parameters- their values were smaller in both AH and CHD
groups. The additional parameter - AlPmax normalized forA PPTmax, was found to be significantly elevated in
the CHD group patients and its growing almost reached statistical significance in the AH patients in the present
study. Attenuated lowering of the height of IP after salbutamol was also present in most of the patients of both
groups although did not reach statistical significance in the present study.
Changes in PPG DVP parameters after the inhalation of SLBTM, observed in the present study of patients with
arterial hypertension and coronary heart disease are in keeping with the results of Chowienczyk et al [3] and
Gopaul et al [14] who were able to show similar changes in patients with type II diabetes. Chowienczyk et al [3]
showed that the administration of L-NMMA attenuated the salbutamol-induced vasodilation thus proving it to
be NO dependent.
It was postulated by Chowienczyk et al [3] that A PPT correlates with the delay between the foot of the velocity
sonogram at the subclavian vein and that at the aortic bifurcation, i.e. with the time taken for pressure waves to
pass from the heart to the site of the reflection and back to the heart. It is comparable with Pulse Transit Time
(PTT) obtained during pulse wave analysis - the time the pulse pressure waveform takes to propagate through
the length of the arterial tree [3]. It was said that PTT decreases in the stiff arteries in patients with elevated
pulse pressure. In our study we could not confirm this proposition. A PPT after inhaled SLBTM did not differ in
the group with arterial hypertension, where arterial stiffness was elevated, from the group with coronary heart
disease, where arterial elasticity was more preserved. In our opinion, PPT changes after SLBTM go together
with a change in the height of the inflection point on the DVP
We estimated that the response to SLBTM could not have been contributed to merely heart rate and blood
pressure changes. We were not able to discover correlations between the heart rate and A PPT changes under
SLBTM. A correlation was revealed (r=0,303, p <0.05) between the heart rate and mean A IP at 10, 15, 20 min
after SLBTM.
It was shown in the previous studies [3,11] that the blunted response of digital pulse volume and pulse wave
parameters to inhaled salbutamol is NO related. Hence we could speculate that the mechanism responsible for
the changes in the PPT and IP parameters of photoplethysmographic digital volume pulse under SLBTM found
in the present study in patients with arterial hypertension and coronary heart disease could be contributed to a
possible endothelial vasomotor dysfunction in these patients.
The new technique for noninvasive evaluation of endothelial vasomotor dysfunction must be verified using
already available methods. Comparison of SLBTM - induced changes in digital volume pulse with venous
occlusion plethysmography coupled with an intra-arterial infusion of acetylcholine revealed a good correlation
between both methods in patients with type II diabetes [3,11 ]. The study is under in our institution evaluating
the changes in PPG DVP parameters in the groups of patients with and without endothelial vasomotor
dysfunction as assessed by the direct infusion of acethylcholine into the coronary artery as well as assessed
using the flow - mediated dilatation of the brachial artery on vascular ultrasound images.
Several technical details of the study must be discussed. The protocol used in the present study slightly differs
from the originally described one by Chowienczyk et al [3]. Data in our study were collected with the patient
sitting in a specially designed arm-chair with the hands comfortably placed only slightly below the level of the
heart with out stretched legs but not in supine position as was described in the original protocol. The sitting
measurements are better because the DVP waveform depends upon the venous return.
For the minimization of erratic absorption of inhaled salbutamol the spacer device is used. It was shown by
Wilkinson et al [11] that the measured plasma salbutamol concentration is stable between 5 and 20 minutes after
inhalation. SLBTM was given in the present study by inhalation using the spacer device (four doses of 10Omg
each). We recommended the patient to inhale the dose of SLBTM (1 OOmg) from the spacer two times for more
complete appropriation of salbutamol.
Repeated 30 seconds recordings of the potoplethysmographic digital volume pulse were performed at 5,10,15,
20, 25, 40 and 60 minutes after the inhalation of SLBTM. Averaging of the measurements was performed at 15,
20 and 25 minutes - the extension of measurements to 25 minutes allowed to increase the cumulative frequency
of parameters changes could be seen. Measurements after 40 and 60 minutes were performed in order
to demonstrate a return to the baseline of DVP parameters. This was necessary in order to confirm that changes
in the parameters are salbutamol - related but not determined by the physiological relaxation of the patient.
Among the limitations of the present study must be mentioned a relatively small number of subjects in the
control group. Therefore, we could not completely confirm the height of the inflection point as the parameter
statistically significantly discriminating patients from control subjects. We also understand that within the
groups with arterial hypertension and coronary heart disease there could have been patients with and without
endothelial dysfunction and this might weaked the statistical significance of the results.
Conclusions. In conclusion, the present study has demonstrates that patients with essential hypertension and
coronary heart disease have blunt response to inhaled salbutamol with attenuation of the drop in the inflection
point and the minimal or absent prolongation of the corresponding peak - to - peak time on the
photoplethysmographic digital volume pulse. Hence, taken in conjunction with the results of the previous
investigations, the present study findings suggest that the impaired vasomotor endothelial function could be
responsible for a blunted responsiveness of digital volume pulse parameters to salbutamol in hypertensive and
coronary patients.
References
1. Lund L. Digital pulse plethysmography in studies of of the haemodynamic response to nitrates: a survey of
recording methods and principles of analysis. Acta Pharmacol Toxicol 1986; 59: 79-96.
2. Takazawa K, Tanaka N, Fujita M, et al. Assessment of vasoactive agents and vascular aging by the second
derivative of photoplethysmographic waveform. Hypertension 1998; 32:365-370.
3. Chowienczyk PJ, Kelly RP, MacCallum H, et al. Photoplethysmographic assessment of pulse wave reflection.
Blunted response to endothelium-dependent vasodilation in type II diabetes mellitus. J Am Coll Cardiol 1999;
34: 2007-2014.
4. Goldwyn R, Watt T. Arterial pressure pulse contour analysis via a mathematical model for the clinical
quantification of human vascular properties. IEEE Trans Biomed Eng 1967; 14: 11-17.
5. Stengele E, Winkler F, Trenk D, et al. Digital pulse plethysmography as a non-invasive method for predicting
drug-induced changes in left ventricular preload. Eur J Clin Pharmacol 1996; 50: 279-282.
6. Nichols WW, O'Rourke MF. McDonald's blood flow in arteries: theoretical, experimental and clinical
principles. London: Arnold, 1998.
7. Yaginuma T, Avolio A, O'Rourke M, et al. Effect of glyceryl trinitrate on peripheral arteries alters left
ventricular hydraulic load in man. Cardiovasc Res 1986; 20: 153-160.
8. Millasseau SC, Bland JE, Kelly RP, et al. Comparison of effects of GTN on the digital volume and radial
pressure pulse waveforms (abstr.). Br J Clin Pharmacol 1999; 16: 2218.
9. Dawes M, Chowienczyk PJ, Ritter JM. Effects of of inhibition of the L-arginine/nitric oxide pathway on
vasodilation caused by beta-adrenergic agonists in human forearm Circulation 1997; 95:2293-2297.
10. Whalen EJ, Johnson AK, Lewis SJ. Beta-adrenoreceptor dysfunction after inhibition of NO synthesis.
Hypertension 2000; 36: 376-382.
11. Wilkinson IB, Hall IR, MacCallum H, et al. Pulse-wave analysis. Clinical evaluation of a non-invasive,
widely applicable method for assessing endothelial function. Arterioscler Thromb Vase Biol 2002; 22: 147-152.
12. Corretti MC, Anderson TJ, Benjamin EJ, et al. Guidelines for the ultrasound assessment of
endothelial-dependent flow-mediated vasodilation of the brachial artery. J Amm Coll Cardiol 2001; 39:
257-265.
13. Laucevicius A, Petrulioniene Z, Ryliskyte L, Zakarkaite D, Stravinskiene D. Ultrasound assessment of the
brachial artery reactivity - methodological aspects and first clinical experience. Seminars in Cardiology 2001; 7:
5-11.
14. Gopaul NK, Manraj MD, Hebe A, et al. Oxidative stress could precede endothelial dysfunction and insulin
resistence in indian mauritians with impaired glucose metabolism. Diabetologia 2001; 44: 706-712.
15. Cannon RO. Role of nitric oxide in cardiovascular disease: focus on endothelium. Clinical Chemistry 1998;
44:18091819.
16. Celermajer DS. Endothelial dysfunction: does it matter? Is it reversible? J Am Coll Cardiol 1997; 30:
325-333.