13 research outputs found
Innovative multi-site photoplethysmography measurement and analysis demonstrating increased arterial stiffness in paediatric heart transplant recipients
Objective: It has been documented that heart transplantation in children is often complicated by arterial hypertension and increased arterial stiffness. We use innovative multi-site photoplethysmography (MPPG) pulse measurement and analysis technology to assess changes in arterial stiffness in paediatric heart transplant recipients (HTRs) in comparison with healthy control (HC) children. Approach: A group of 20 HTRs (median age 13.5 years, eight male) were compared to an overall age- and gender-matched group of 161 HCs (median age 11.6 years, 74 male). Peripheral pulse was recorded bilaterally using MPPG at the ear lobe, index finger and great toe sites, along with an electrocardiogram cardiac timing reference. Segmental pulse arrival times between peripheral sites (finger–ear, PATf–e; toe–finger, PATt–f; and toe–ear PATt–e) were calculated as arterial stiffness measures, and differences between subject groups were tested using multivariate analysis. Normalised ear, finger and toe pulse shapes were also studied and compared between groups. Main results: After correction for heart rate and diastolic and mean arterial blood pressures, the HTR group was found to have significantly lower segmental PATt–e and PATt–f measurements, with median values of 150 ms versus 172 ms in the HC group (p  =  0.02), and 104 ms versus 118 ms in the HC group (p  =  0.01), respectively, consistent with increased arterial stiffness in the patient group. The normalised ear, finger and toe sites showed only a mild elongation in each pulse rise time for the transplant group. Significance: This study shows that innovative and easy-to-do MPPG gives further evidence for increased arterial stiffness in children who have undergone successful cardiac transplantation
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Photoplethysmography for the Assessment of Arterial Stiffness
This review outlines the latest methods and innovations for assessing arterial stiffness, along with their respective advantages and disadvantages. Furthermore, we present compelling evidence indicating a recent growth in research focused on assessing arterial stiffness using photoplethysmography (PPG) and propose PPG as a potential tool for assessing vascular ageing in the future. Blood vessels deteriorate with age, losing elasticity and forming deposits. This raises the likelihood of developing cardiovascular disease (CVD), widely reported as the global leading cause of death. The ageing process induces structural modifications in the vascular system, such as increased arterial stiffness, which can cause various volumetric, mechanical, and haemodynamic alterations. Numerous techniques have been investigated to assess arterial stiffness, some of which are currently used in commercial medical devices and some, such as PPG, of which still remain in the research space
Inhibition of phosphodiesterase type 5 in cardiovascular disease
Nitric oxide is released from the endothelium and causes relaxation of vascular
smooth muscle by stimulating guanylate cyclase to produce guanosine 3’,5’-cyclic
monophosphate (cGMP) which, in turn, is degraded by phosphodiesterase type 5
(PDE5). Inhibition of PDE5, with drugs like sildenafil citrate, promotes NOstimulated
relaxation of vascular smooth muscle. The overall aim of the work
contained within this thesis was to further characterise the systemic vascular effects
of PDE5 inhibition. Four clinical studies were performed.
The aims of the first study were to investigate in healthy men the effect of smoking
on endothelium-dependent vasomotor function measured as the change in peripheral
arterial wave reflection with inhaled salbutamol, and the effect of acute sildenafil
100 mg on this response. Smokers (n=12) exhibited a reduced response to inhaled
salbutamol compared to non-smokers (n=11) [mean(standard deviation) area under
the curve of the change in central augmentation index following salbutamol 400 μg:
-29(143) AU in smokers vs -159(124) AU in non-smokers, P=0.03]. In the smokers,
there was a trend to an improvement in the response to salbutamol following
sildenafil [-96(266) AU vs -29(143) AU with matched placebo; P=0.2].
The co-administration of glyceryl trinitrate (GTN) and sildenafil is absolutely
contraindicated because of the potential for profound hypotension. The aim of the
second study was to characterise the time course of this interaction. Twenty men
with stable angina, maintained on their usual medicines, were administered
sublingual GTN 400 μg 1, 4, 6 and 8 hours after sildenafil 100 mg or matched
placebo. Compared to the combination of GTN and placebo, the combination of
GTN and sildenafil resulted in greater mean maximum reductions from baseline in
sitting systolic blood pressure (BP) at 1, 4 and 8 hours, and in sitting diastolic BP at
all time points (all P<0.05). Compared to placebo, sildenafil alone reduced systolic
BP at 1, 4, 6 and 8 hours (P<0.01 at 1 hour and P<0.05 at 4, 6, and 8 hours) and
diastolic BP at 4, 6, and 8 hours (all P<0.01). Analysis of the change in BP from the
measures taken before each GTN challenge suggested that the interaction on BP might be synergistic at 1 hour after sildenafil, but no more than additive at 6 and 8
hours after sildenafil. Symptoms consistent with hypotension occurred following
GTN in 6 subjects at 1 hour and 3 subjects at 4 hours after sildenafil, but in no
subjects at 6 and 8 hours after sildenafil or at any time after placebo.
In the third study, 25 otherwise untreated hypertensives were given sildenafil 50 mg
or matched placebo three times daily for 16 days and the effects on ambulatory BP,
clinic BP, arterial wave reflection, carotid-femoral pulse wave velocity and brachial
artery flow-mediated dilatation were measured. Three subjects were withdrawn
because of side effects and the data from the remaining 22 subjects were analysed.
Sildenafil reduced ambulatory BP [change from baseline in average daytime BP:
systolic -8(9) mmHg vs 2(9) mmHg with placebo, P<0.01; diastolic -6(5) mmHg vs
0(6) mmHg, P<0.01] and clinic BP [change from baseline to 1 hour after drug
administration on day 16: systolic -5(11) mmHg vs 4(10) mmHg, P<0.01; diastolic
-5(5) mmHg vs 2(7) mmHg, P<0.01]. Sildenafil, but not placebo, reduced arterial
wave reflection [central augmentation index from 32(9)% at baseline to 30(10)% at 1
hour after administration on day 16, P<0.05; radial augmentation index from
88(13)% to 84(13)%, P<0.01], but the change in arterial wave reflection was not
statistically significant compared to the change with placebo. Sildenafil did not affect
pulse wave velocity or flow-mediated dilatation.
The fourth study investigated the potential of combined PDE5 inhibition and organic
nitrate for the management of treatment-resistant hypertension (TRH). In 6 patients
with TRH, maintained on their usual antihypertensives sildenafil 50 mg alone,
isosorbide mononitrate (ISMN) 10 mg alone and co-administered sildenafil and
ISMN all acutely reduced systolic BP and diastolic BP compared to placebo
(quantified as the area under the curve of the change from baseline to 4 hours after
drug administration; all P≤0.01). The combination produced a greater reduction in
systolic BP than did either sildenafil alone (P=0.03) or ISMN alone (P=0.01) and a
greater reduction in diastolic BP than did sildenafil alone (P=0.02). Compared to
placebo, from 1 to 3 hours after drug administration BP was on average 13/10 mmHg lower with sildenafil alone, 18/14 mmHg lower with ISMN alone and 26/18 mmHg
lower with the combination.
The following conclusions were made. (1) Smokers exhibit impaired vascular
responsiveness to inhaled salbutamol, indicating systemic endothelial dysfunction,
which may be improved by sildenafil. (2) In men with stable angina there is an
interaction on BP reduction between sildenafil 100 mg and sublingual GTN 400 μg
for at least 8 hours after sildenafil administration, but this interaction is no more than
additive from 6 hours after sildenafil administration. (3) Regular sildenafil
monotherapy reduces BP in hypertension. (4) In patients with TRH maintained on
their usual antihypertensives sildenafil alone and ISMN alone both acutely reduce
BP and there is additional BP reduction when these drugs are given in combination
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Analysis of risk factors for catheter-related bloodstream infection in a parenteral nutrition population
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Device for measuring bronchodilator delivery and response in resource-limited settings
Arterial stiffness and endothelial function in obstructive sleep apnoea: the effect of Continuous Positive Airway Pressure (CPAP) therapy
Introduction: Obstructive sleep apnoea (OSA) is common and is caused by
repetitive obstruction of the upper airway during sleep. OSA is associated with
increased cardiovascular morbidity and mortality and is an independent risk factor
for hypertension. The immediate physiological effects of OSA include intermittent
hypoxia, repeated arousal from sleep and intra-thoracic pressure swings. The
resulting activation of the sympathetic nervous system, systemic inflammation and
oxidative stress may result in increased arterial stiffness and endothelial dysfunction,
potentially explaining any causal link between OSA and cardiovascular disease
(CVD). Continuous positive airway pressure (CPAP) therapy improves excessive
daytime sleepiness (EDS) and in non-randomised studies, reduces cardiovascular
mortality. Prior to starting this study, there was a limited amount of evidence
suggesting that CPAP therapy improved arterial stiffness and endothelial function,
but the effects in subjects without pre-existing CVD were unclear.
Aims: i) to determine whether CPAP therapy has an effect upon measures of arterial
stiffness and endothelial function in patients with OSA, in the absence of known
CVD. ii) To compare arterial stiffness and endothelial function in a subset of patients
with OSAHS (defined as OSA and EDS), with a group of well-matched control
subjects.
Methods: Fifty three patients with OSA, defined as an apnoea/hypopnoea index of
≥15, and without known CVD, entered a double-blind placebo-controlled crossover
trial of 12 weeks CPAP therapy, of whom forty three completed the study protocol.
Sham CPAP was used in the placebo arm of the study and vascular assessments were
made at baseline and after each arm of the study. Arterial stiffness was determined
by measuring aortic distensibility using cardiovascular magnetic resonance imaging
and by measuring the augmentation index (AIx) and aortic pulse wave velocity
(PWV) by applanation tonometry. Endothelial function was assessed non-invasively
by measuring vascular reactivity after administration of salbutamol and glyceryl
trinitrate. In a subset of twenty patients with OSAHS, arterial stiffness and
endothelial function at baseline were compared to readings obtained from healthy
control subjects, matched on a one-to-one basis for age, sex and BMI.
Results: Patients with OSAHS (n=20) had increased arterial stiffness [AIx
19.3(10.9) vs. 12.6(10.2) %; p=0.017] and impaired endothelial function, measured
as the change in AIx following salbutamol [-4.3(3.2) vs. -8.0(4.9) %; p=0.02]
compared to controls. Twelve weeks of CPAP therapy had no significant effect upon
any measure of arterial stiffness or endothelial function in patients with OSA (n=43).
A trend towards a reduction in AIx following CPAP therapy was seen, but this was
non-significant. There was a reduction in systolic blood pressure following CPAP
therapy [126(12) vs. 129(14) mmHg]. Sub group analysis showed CPAP to have no
effect on arterial stiffness or endothelial function in patients with EDS or in patients
using CPAP for ≥4 hours per night.
Conclusions: This study demonstrates that even in the absence of known CVD,
patients with OSAHS have evidence of increased arterial stiffness and impaired
endothelial function. However, in patients with OSA, free from CVD, CPAP therapy
did not lead to an improvement in any measure of arterial stiffness or endothelial
function after 12 weeks