Role of transdermal potential difference during intophoretic drug delivery.

Potential differences have been measured during transdermal iontophoresis in order to establish the effect of voltage, as opposed to current, on cutaneous blood flow. It is known that, even in the absence of drugs, the iontophoresis current can sometimes produce increased blood flow. The role of voltage in this process is studied through single-ended measurements (between electrode and body) of the potential difference during iontophoresis with 100-/spl mu/A, 20-s current pulses through deionized water, saturated 20.4% NaCl solution, 1 % acetylcholine, and 1 % sodium nitroprusside. It is found that the voltage needed to deliver the current varied by orders of magnitudes less than the differences in the conductance of these different electrolytes, and it is concluded that, at least for the present current protocol, the voltage as such is not an important factor in increasing the blood flow

Dynamics of cardiovascular ageing

We gain wrinkles and lose hair, as we age, but our bodies also change in less obvious but much more important ways. This project studied the age-related alterations that occur in the cardiovascular system – the heart, lungs and network of arteries and veins that carry oxygenated blood and nutrients to every cell of the body and remove the waste products of metabolism. It was already known that the phase of breathing affects the rate at which the heart beats, but that this effect decreases as we age. The research has associated this reduction in heart-lung interaction with changes in the endothelium, the inner lining of all the blood vessels. It involved making non-invasive measurements of blood flow in the skin of 200 healthy subjects of all ages. The analysis focused on very low frequency oscillations in blood flow that can give a measure of the state of the endothelium. The main conclusions are, first, that to age healthily, you should look after your endothelium and, secondly, that it should be feasible to design an instrument for assessing endothelial health – an endotheliometer

Monitoring the ageing of the cardiovascular system

This research developed a way of measuring blood flow through the capillaries and thereby monitoring the health of the endothelium, the inner lining of the blood vessels

Diurnal Differences in Risk of Cardiac Arrhythmias during Spontaneous Hypoglycemia in Young People with Type 1 Diabetes

OBJECTIVE Hypoglycemia may exert proarrhythmogenic effects on the heart via sympathoadrenal stimulation and hypokalemia. Hypoglycemia-induced cardiac dysrhythmias are linked to the “dead-in-bed syndrome,” a rare but devastating condition. We examined the effect of nocturnal and daytime clinical hypoglycemia on electrocardiogram (ECG) in young people with type 1 diabetes. RESEARCH DESIGN AND METHODS Thirty-seven individuals with type 1 diabetes underwent 96 h of simultaneous ambulatory ECG and blinded continuous interstitial glucose monitoring (CGM) while symptomatic hypoglycemia was recorded. Frequency of arrhythmias, heart rate variability, and cardiac repolarization were measured during hypoglycemia and compared with time-matched euglycemia during night and day. RESULTS A total of 2,395 h of simultaneous ECG and CGM recordings were obtained; 159 h were designated hypoglycemia and 1,355 h euglycemia. A median duration of nocturnal hypoglycemia of 60 min (interquartile range 40–135) was longer than daytime hypoglycemia of 44 min (30–70) (P = 0.020). Only 24.1% of nocturnal and 51.0% of daytime episodes were symptomatic. Bradycardia was more frequent during nocturnal hypoglycemia compared with matched euglycemia (incident rate ratio [IRR] 6.44 [95% CI 6.26, 6.63], P < 0.001). During daytime hypoglycemia, bradycardia was less frequent (IRR 0.023 [95% CI 0.002, 0.26], P = 0.002) and atrial ectopics more frequent (IRR 2.29 [95% CI 1.19, 4.39], P = 0.013). Prolonged QTc, T-peak to T-end interval duration, and decreased T-wave symmetry were detected during nocturnal and daytime hypoglycemia. CONCLUSIONS Asymptomatic hypoglycemia was common. We identified differences in arrhythmic risk and cardiac repolarization during nocturnal versus daytime hypoglycemia in young adults with type 1 diabetes. Our data provide further evidence that hypoglycemia is proarrhythmogenic

The discriminatory value of cardiorespiratory interactions in distinguishing awake from anaesthetised states: a randomised observational study

Depth of anaesthesia monitors usually analyse cerebral function with or without other physiological signals; noninvasive monitoring of the measured cardiorespiratory signals alone would offer a simple, practical alternative. We aimed to investigate whether such signals, analysed with novel, non-linear dynamic methods, would distinguish between the awake and anaesthetised states. We recorded ECG, respiration, skin temperature, pulse and skin conductivity before and during general anaesthesia in 27 subjects in good cardiovascular health, randomly allocated to receive propofol or sevoflurane. Mean values, variability and dynamic interactions were determined. Respiratory rate (p = 0.0002), skin conductivity (p = 0.03) and skin temperature (p = 0.00006) changed with sevoflurane, and skin temperature (p = 0.0005) with propofol. Pulse transit time increased by 17% with sevoflurane (p = 0.02) and 11% with propofol (p = 0.007). Sevoflurane reduced the wavelet energy of heart (p = 0.0004) and respiratory (p = 0.02) rate variability at all frequencies, whereas propofol decreased only the heart rate variability below 0.021 Hz (p < 0.05). The phase coherence was reduced by both agents at frequencies below 0.145 Hz (p < 0.05), whereas the cardiorespiratory synchronisation time was increased (p < 0.05). A classification analysis based on an optimal set of discriminatory parameters distinguished with 95% success between the awake and anaesthetised states. We suggest that these results can contribute to the design of new monitors of anaesthetic depth based on cardiovascular signals alone

Effect of Hypoglycemia on Inflammatory Responses and the Response to Low Dose Endotoxemia in Humans

Context: Hypoglycemia is emerging as a risk for cardiovascular events in diabetes. We hypothesized that hypoglycemia activates the innate immune system, which is known to increase cardiovascular risk. Objective: To determine whether hypoglycemia modifies subsequent innate immune system responses. Design and Setting: Single-blinded, prospective study of three independent parallel groups. Participants and Interventions: Twenty-four healthy participants underwent either a hyperinsulinemic-hypoglycemic (2.5 mmol/l), euglycemic (6.0 mmol/l) or sham-saline clamp (n=8 for each group). Forty-eight hours later, all participants received low-dose (0.3 ng/kg) intravenous endotoxin. Main outcome measures: We studied in-vivo monocyte mobilization and monocyte-platelet interactions. Results: Hypoglycemia increased total leucocytes (9.98±1.14 x109/l vs euglycemia: 4.38±0.53 x109/l; P<0.001 vs sham-saline: 4.76±0.36 x109/l; P<0.001) (mean±SEM), mobilized proinflammatory intermediate monocytes (42.20±7.52/μl vs euglycemia: 20.66±3.43/μl; P<0.01 vs sham-saline: 26.20±3.86/μl; P<0.05) and non-classical monocytes (36.16±4.66/μl vs euglycemia: 12.72±2.42/μl; P<0.001 vs sham-saline: 19.05±3.81/μl; P<0.001). Following hypoglycemia vs euglycemia, platelet aggregation to agonist (AUC) increased (73.87±7.30 vs 52.50±4.04; P<0.05) and formation of monocyte-platelet aggregates increased (96.05±14.51/μl vs 49.32±6.41/μl; P<0.05). Within monocyte subsets, hypoglycemia increased aggregation of intermediate monocytes (10.51±1.42/μl vs euglycemia: 4.19±1.08/μl; P<0.05 vs sham-saline: 3.81±1.42/μl; P<0.05) and non-classical monocytes (9.53±1.08/μl vs euglycemia: 2.86±0.72/μl; P<0.01 vs sham-saline: 3.08±1.01/μl; P<0.05) with platelets compared to controls. Hypoglycemia led to greater leucocyte mobilization in response to subsequent low-dose endotoxin challenge (10.96±0.97 vs euglycemia: 8.21±0.85 x109/l; P<0.05). Conclusions: Hypoglycemia mobilizes monocytes, increases platelet reactivity, promotes interaction between platelets and proinflammatory monocytes, and potentiates the subsequent immune response to endotoxin. These changes may contribute towards increased cardiovascular risk observed in people with diabetes

Importance of wavelet analysis in laser Doppler flowmetry time series.

Spectral analysis of microvascular laser Doppler flowmetry time series is performed to resolve their complex dynamics. The method of analysis should be carefully chosen such that as much information as possible of the signal is obtained. Conventional Fourier transform and short-time Fourier transform are compared with wavelet analysis to resolve several oscillatory components on a wide frequency interval. Wavelet transform with the Morlet mother wavelet is shown to have an advantage of adjustable window length as it detects each frequency with a window of a corresponding length. In this way good localization in time and frequency is provided. Low and high frequencies can be resolved and their variations traced in time. This is of crucial importance in analysis of oscillations in LDF signals and studies of their physiological origin as well as their changes in health and disease

Pulse transit times to the capillary bed evaluated by laser Doppler flowmetry

The pulse transit time (PTT) of a wave over a specified distance along a blood vessel provides a simple non-invasive index that can be used for the evaluation of arterial distensibility. Current methods of measuring the PTT determine the propagation times of pulses only in the larger arteries. We have evaluated the pulse arrival time (PAT) to the capillary bed, through the microcirculation, and have investigated its relationship to the arterial PAT to a fingertip. To do so, we detected cardiac-induced pulse waves in skin microcirculation using laser Doppler flowmetry (LDF). Using the ECG as a reference, PATs to the microcirculation were measured on the four extremities of 108 healthy subjects. Simultaneously, PATs to the radial artery of the left index finger were obtained from blood pressure recordings using a piezoelectric sensor. Both PATs correlate in similar ways with heart rate and age. That to the microcirculation is shown to be sensitive to local changes in skin perfusion induced by cooling. We introduce a measure for the PTT through the microcirculation. We conclude that a combination of LDF and pressure measurements enables simultaneous characterization of the states of the macro and microvasculature. Information about the microcirculation, including an assessment of endothelial function, may be obtained from the responses to perturbations in skin perfusion, such as temperature stress or vasoactive substances

Wavelet phase coherence analysis:application to skin temperature and blood flow

The technique of wavelet phase coherence analysis is introduced and used to explore relationships between oscillations on blood flow and temperature in the skin of 10 healthy subjects. Their skin temperature and blood flow were continuously recorded: under basal conditions for 30 min; during local cooling of the skin with an ice-pack for 20 min: and 30 min thereafter. The group mean basal skin temperature of 33.4°C was decreased to 29.2°C during the cooling period, and had recovered to 32.1°C by the end of the recording. The wavelet transform was used to obtain the time–frequency content of the two signals, and their coherence. It is shown that cooling increases coherence to a statistically significant extent in two frequency intervals, around 0.007 and 0.1 Hz, suggesting that these oscillatory components are involved in the regulation of skin temperature when cold is applied as a stress

Nonlinear dynamics of congestive heart failure

Preliminary results are reported from a research project analysing congestive heart failure in terms a stochastic coupled-oscillator model of the cardiovascular system. Measurements of blood flow by laser Doppler flowmetry (LDF) have been processed by use of the wavelet transform to separate its oscillatory components, which number at least five. Particular attention was concentrated on the frequency content near 0.01 Hz, which is known to be associated with endothelial function. The LDF was carried out in conjunction with iontophoretically administered acetylcholine (ACh) and sodium nitroprusside (SNP) in order to evaluate endothelial reactivity. Measurements were made on 17 congestive heart failure (CHF) patients (a) on first diagnosis, and (b) again several weeks later after their treatment with a β-blocker had been stabilised. The results of these two sets of measurements are being compared with each other, and with data from an age and sex-matched group of healthy controls. It is confirmed that endothelial reactivity is reduced in CHF patients, as compared to healthy controls, and it is found that one effect of the Beta-blocker is to ameliorate the loss of endothelial function in CHF. The implications of these results are discussed