Photoplethysmographic assessment of pulse wave reflection: blunted response to endothelium-dependent beta2-adrenergic vasodilation in type II diabetes mellitus.

OBJECTIVES: We sought to determine whether a simple index of pressure wave reflection may be derived from the digital volume pulse (DVP) and used to examine endothelium-dependent vasodilation in patients with type II diabetes mellitus. BACKGROUND: The DVP exhibits a characteristic notch or inflection point that can be expressed as percent maximal DVP amplitude (IP(DVP)). Nitrates lower IP(DVP), possibly by reducing pressure wave reflection. Response of IP(DVP) to endothelium-dependent vasodilators may provide a measure of endothelial function. METHODS: The DVP was recorded by photoplethysmography. Albuterol (salbutamol) and glyceryl trinitrate (GTN) were administered locally by brachial artery infusion or systemically. Aortic pulse wave transit time from the root of the subclavian artery to aortic bifurcation (T(Ao)) was measured by simultaneous Doppler velocimetry. RESULTS: Brachial artery infusion of drugs producing a greater than threefold increase in forearm blood flow within the infused limb was without effect on IP(DVP), whereas systemic administration of albuterol and GTN produced dose-dependent reductions in IP(DVP). The time between the first and second peak of the DVP correlated with T(Ao) (r = 0.75, n = 20, p < 0.0001). The effects of albuterol but not GTN on IP(DVP) were attenuated by N(G)-monomethyl-L-arginine. The IP(DVP) response to albuterol (400 microg by inhalation) was blunted in patients with type II diabetes mellitus as compared with control subjects (fall 5.9 +/- 1.8% vs. 11.8 +/- 1.8%, n = 20, p < 0.02), but that to GTN (500 microg sublingually) was preserved (fall 18.3 +/- 1.2% vs. 18.6 +/- 1.9%, p = 0.88). CONCLUSIONS: The IP(DVP) is influenced by pressure wave reflection. The effects of albuterol on IP(DVP) are mediated in part through the nitric oxide pathway and are impaired in patients with type II diabetes.

A family history of NIDDM is associated with decreased aortic distensibility in normal healthy young adult subjects.

OBJECTIVE: NIDDM is associated with stiffer arteries and an increased incidence of macrovascular disease. NIDDM has strong familial inheritance. We studied the associations of a family history of NIDDM with blood pressure-corrected aortic distensibility (Cp). RESEARCH DESIGN AND METHODS: Because age is a strong determinant of arterial distensibility, we studied an age-select cohort of 67 healthy normotensive normoglycemic young adults along with fasting measurements of glucose and insulin concentrations. Cp was calculated from noninvasive Doppler ultrasound measurements of pulse wave velocity along the descending thoracoabdominal aorta. RESULTS: The mean age of the subjects was 20.6 +/- 0.7 (mean +/- SD) years. A total of 22 subjects gave a positive family history of NIDDM in a parent or grandparent. Subjects with a positive family history of NIDDM had significantly less distensible (i.e., stiffer) aortas than their age- and sex-matched counterparts who gave no family history of NIDDM (Cp [dimensionless]: 0.22 +/- 0.04 vs. 0.25 +/- 0.04, P = 0.02). Subjects with a positive family history of NIDDM also had significantly higher fasting glucose (5.1 +/- 0.4 vs. 4.9 +/- 0.4 mmol/l, P = 0.009) and insulin (7.5 +/- 5.5 vs. 4.2 +/- 2.0 mU/l, P = 0.02) levels and BMIs (23.2 +/- 2.3 vs 21.1 +/- 2.5 kg/m2, P = 0.002). On multivariate regression analysis, family history of NIDDM (P = 0.03) was the only significant independent predictor of Cp. CONCLUSIONS: A positive family history of NIDDM is associated with decreased aortic distensibility in early adult life. The relevance of these observations to future cardiovascular events merits further investigation.

The dynamic and static elastic response of the abdominal aorta of the dog.

The dynamic and static elastic response of the abdominal aorta was studied in beagle dogs of similar age and weight. The dynamic response was measured in situ by means of an optical transmission wedge resting on the exposed vessel to record the pulsatile changes in wall displacement and the pressure pulse recorded at the same site via a hypodermic needle. The static response was recorded (1) in situ by observing the change in radius which occurred with a change in the mean blood pressure, (2) post mortem using both transmission wedge and radiographic techniques. The change in radius (deltaR) for a change in pressure (deltaP=20 mm Hg[2.67kPa]) was calculated for both the dynamic and static cases. It was found that the aorta was stiffer for the dynamic case, the extent of the stiffening being dependent on the mean pressure. At pressures less than 80 mm Hg (10.64 kPa) the dynamic/static deltaR ratio was 1.8 decreasing to 1.1 at 160 mm Hg (21.28 kPa). This behaviour is interpreted in terms of smooth muscle relaxation and the subsequent transference of circumferential tension to collagen.

Pulsed Doppler ultrasound compared with thermodilution for monitoring cardiac output responses to changing left ventricular function.

To determine the responsiveness of the pulsed Doppler technique to pacing and drug induced changes in left ventricular function 125 simultaneous cardiac output measurements by pulsed Doppler ultrasound and thermodilution were compared in 12 patients. The Doppler velocity frequencies were analysed using a signal averaging process and the validity of this method first tested in vitro. This showed almost perfect linearity of pulsed Doppler and electromagnetic flow determinations in a test rig. Although data points showed greater scatter in the clinical study, a highly significant linear relation between cardiac output measurements by pulsed Doppler and thermodilution was confirmed by regression analysis (r = 0.88, p less than 0.001). Certain mean values for cardiac output by the two techniques differed, however, by up to 0.9 litre.min-1. Despite this, changes in cardiac output in response to pacing, inotropic stimulation with dobutamine, and vasodilatation with nitrates were directionally similar, indicating a useful role for the pulsed Doppler technique in monitoring responses to treatment in the intensive care unit. Pulsed Doppler also provided a simple measure of left ventricular contractile function. Thus the inotropic response to dobutamine produced a significant rise in peak aortic flow velocity, and this variable was unaffected by either pacing or nitrate induced vasodilatation.

Screening for carotid junction disease by spectral analysis of Doppler signals.

The established test for disease in the internal carotid artery using continuous wave Doppler is to listen for flow velocity changes over the supraorbital artery with ipsilateral temporal (or facial) artery compression. This is only reliable when there is a reduction in mean pressure (and flow) distal to disease in the internal carotid artery, ie reduction of lumen diameter by more than 85%. In this study, 101 vessel segments (48 with disease at the carotid junction, 53 normal) were compared with the results of angiography. Seven gave a positive temporal artery occlusion test, all of which showed severe disease. However, spectral analysis of the Doppler signals from supraorbital and common carotid arteries showed sonagram changes both with ageing and with disease. In particular, the ratio of primary peak (A) to secondary peak (B) in systole falls, the A/B ratio being lower in disease than in health. At A/B ratios less than 1.05 there was an 88% probability of disease at the carotid junction. 36/48 (75%) diseased junctions were detected, including almost all major lesions. The method did not so reliably detect small lesions (less than 2 mm plaques, less than 60% lumen diameter stenosis, and 'minimal atheroma'). In 5/53 normal junctions the A/B ratio was in the disease range. Scanning the carotid junction for turbulence yielded additional information in some cases.

Relation between number of cardiovascular risk factors/events and noninvasive Doppler ultrasound assessments of aortic compliance.

The aim of this study was to establish the relation between noninvasive Doppler ultrasound assessments of aortic compliance, based on "foot-to-foot" aortic pulse wave velocity measurements, and presumed atherosclerotic load in patients with vascular disease and/or diabetes mellitus. One hundred ten patients with vascular disease and/or diabetes mellitus (arteriopaths) underwent measurement of in vivo aortic compliance using Doppler ultrasound. Demographic data on these subjects were recorded along with details of cardiovascular risk factors and events. Aortic compliance values were compared with data from 51 age-matched healthy, asymptomatic subjects putatively free of vascular disease (controls). Data are expressed as mean+/-SD. Arteriopaths were aged 64.1+/-8.4 years and had total cholesterol levels of 5.9+/-1.1 mmol/L and aortic compliance of 0.78+/-0.42%/10 mm Hg [1.33 kPa]. Most arteriopaths had 2 or more cardiovascular risk factors and events: diabetes (n=41), hypertension (n=45), smoking (n=86), cerebrovascular/transient ischemic event (n=13), myocardial infarction (n=44), angina (n=51), and/or peripheral vascular disease (n=33). Controls were aged 64.3+/-12.1 years with total cholesterol of 6.1+/-1.1 mmol/L and aortic compliance of 1.14+/-0.46%/10 mm Hg [1.33 kPa] (P<0.002 versus arteriopaths). Subset analysis revealed that patients with the greatest number of cardiovascular risk factors and events (n=5) had the stiffest aortas (aortic compliance, 0.58+/-0.15%/10 mm Hg [1.33 kPa]) compared with those patients with the median and mean (n=2) number of risk factors and events (aortic compliance, 0.80+/-0.50%/10 mm Hg [1.33 kPa]; P<0.02). The data suggest that a significant inverse relation exists between presumed atherosclerotic load (as assessed by the number of cardiovascular risk factors and events) and aortic compliance determined noninvasively based on aortic pulse wave velocity measurements. If these findings are confirmed by prospective, longitudinal follow-up studies, such measurements may prove useful as a noninvasive marker of vascular risk.

Insulin-like growth factor-binding protein-1 is correlated with low density lipoprotein cholesterol in normal subjects.

Insulin-like growth factor-I (IGF-I) has been inversely associated with low-density lipoprotein (LDL) cholesterol in normal women with slightly elevated cholesterol levels and hypothyroid women. More than 95% of IGF-I circulates bound to binding proteins (IGFBPs); of these IGFBP-1 is of particular interest as it is inversely regulated by insulin and is thought to inhibit the action of IGF-I and IGF-II. We examined the relationship between IGFBP-1 and LDL cholesterol in 41 healthy adult subjects. LDL cholesterol correlated with the body mass index (r = 0.40, P < 0.01), sex (r = 0.51, P < 0.001) and IGFBP-1 levels (r = 0.36, P < 0.02). LDL cholesterol did not correlate with age (r = 0.25, P = not significant) or IGF-I (r = 0.06, P = not significant). Upon multivariate regression analysis, sex, body mass index and IGFBP-1 were all independent predictors of LDL cholesterol (all P < 0.05). Elevated IGFBP-1 levels have been associated with an inhibition of serum IGF-I bioactivity in children with insulin-dependent diabetes. IGFBP-1 also appears to inhibit IGF-I hexose-stimulated uptake. IGFBP-1 may also be inhibiting the effect of IGFs on the cellular metabolism of LDL cholesterol.

The effect of arterial filtration on reduction of gaseous microemboli in the middle cerebral artery during cardiopulmonary bypass.

Noninvasive in vivo detection of gaseous microemboli in the middle cerebral artery, by transcranial Doppler ultrasound, was used to determine the effect of filtration in the arterial catheter using 25- and 40-microns filters and bubble oxygenators in patients undergoing cardiopulmonary bypass surgery. Eighteen patients undergoing coronary artery bypass surgery were studied using a closed cardiac (unvented heart) model. Group 1 patients (no filters) had the highest incidence of gaseous microemboli, as indicated by the ultrasound microemboli index, at both high and low oxygen flow rates. Group 2 patients (40-microns filters) had a significantly lower microemboli index, particularly at low oxygen flow rates (t = 4.9, p less than 0.001). The 25-microns group patients had the lowest values of all. No microemboli were detected at low oxygen flow rates, and microemboli were detected in only 0.1% of the samples at high oxygen flow rates. Additionally, observations on vented hearts in 3 patients undergoing cardiac valve surgery indicate that the origin of gaseous microemboli may be air trapped inside the heart.

The detection of microemboli in the middle cerebral artery during cardiopulmonary bypass: a transcranial Doppler ultrasound investigation using membrane and bubble oxygenators.

Twenty-seven patients were examined who were undergoing cardiopulmonary bypass (CPB) surgery with either a bubble oxygenator or a capillary membrane oxygenator. The latter incorporated an arterial filter and bubble trap. A noninvasive Doppler ultrasound technique is described for monitoring irregularities in the Doppler flow signals attributable to gaseous microemboli detected in the middle cerebral artery during CPB. The ultrasound index for detecting gaseous microemboli (MEI) indicated the presence of such microemboli in 22 of the 27 patients during insertion of the aortic cannula. Measurements during CPB showed the MEI ranged from 4 to 39 in the 17 patients with a bubble oxygenator. However, all 10 patients with a membrane oxygenator had an MEI of 0. Varying the gas flow rates in 3 patients with bubble oxygenators showed a change in MEI from 4 +/- 4 (SD) at a flow rate of 2 L/min to 17 +/- 9 at a flow rate of 5 L/min. This observation supports the assumption that the MEI is providing quantitative information regarding the presence of gaseous emboli in the middle cerebral artery.

Chromaticity-coded Doppler blood velocity sonagrams: preliminary observations.

This paper describes the application of chromaticity to spectrally analysed Doppler blood velocity signals. Chromaticity enables a particular colour to be assigned to the power/frequency distribution within each instantaneous spectral sweep of a sonagram. Successive spectral sweeps of a sonagram can then be colour-coded in this fashion to produce a chromaticity-coded sonagram. Two chromaticity-coded sonagrams are presented to illustrate various blood flow features. Standard sonagram display formats are also presented for comparison purposes. It appears that the chromaticity-coded sonagram offers the ability to digitally encode the instantaneous power spectral distribution with a single chromaticity vector.

Aortic compliance measurements using Doppler ultrasound: in vivo biochemical correlates.

A noninvasive Doppler ultrasound technique for the assessment of aortic compliance based on the in vivo measurement of pulse wave velocity along the thoraco-abdominal aortic pathway is described. An approach for correcting for the effect of blood pressure on aortic distensibility is considered. The derivation of an index of intrinsic distensibility, Cp, which is independent of blood pressure, is provided and applied to data collected from normal, healthy volunteers. Overviews are provided of studies utilising the technique to determine aortic compliance in medical disorders, which are known to predispose to premature cardiovascular disease, such as diabetes mellitus, familial hypercholesterolaemia and growth hormone deficiency. The significance of correlations between in vivo aortic compliance measurements and plasma concentrations of total cholesterol, low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol and insulin-like growth factor-I are discussed. It is proposed that the measurement of aortic compliance in normal, healthy individuals may potentially be a useful in vivo research tool for investigating the effects of biochemical factors on the biophysical properties of the aortic wall. Furthermore, we believe that the routine measurement of blood pressure-corrected aortic distensibility may prove a useful, noninvasive clinical tool for assessing patients' susceptibility to atherosclerosis, as well as for monitoring their response to therapeutic interventions.

Ultrasound screening for internal carotid disease-II. Sensitivity and specificity of a single site periorbital artery test.

Supraorbital artery blood flow was examined non-invasively with continuous wave Doppler-shifted ultrasound and spectral analysis. The results were used to assess the ipsilateral internal carotid artery in 155 patients undergoing carotid angiography. The ultrasound parameters used were the temporal artery occlusion test and A/B ratios of both resting and augmented supraorbital sonagrams. A retrospective study showed this combination to have a sensitivity of 65% for internal carotid disease which did not encroach on the lumen and for all other angiographically demonstrated lesions an average sensitivity of 94% and specificity of 92%. Augmented supraorbital pulses were more sensitive for detection of carotid artery disease than resting supraorbital pulses. Of the 61 lesions in which both resting and augmented supraorbital A/B ratios were obtained, the augmented supraorbital pulse detected 48 (79%) whilst the resting supraorbital pulse detected 29 (48%). Localised carotid bruits were poor indicators of carotid artery disease, having a sensitivity of only 27%.

Ultrasound screening for internal carotid disease-I. The temporal artery occlusion test--which periorbital artery?

Using continuous wave Doppler-shifted ultrasound and spectral analysis the response to the temporal artery occlusion test was compared when insonating the supraorbital and supratrochlear arteries of 203 internal carotid pathways. The test involved monitoring the periorbital artery whilst simultaneously compressing a single branch of the external carotid artery, the ipsilateral superficial temporal artery. In 41 instances carotid angiography demonstrated severe disease of the internal carotid artery, that is lesions of 75% or more reduction in lumen diameter. A positive response to the temporal artery occlusion test, when performed on the supraorbital artery, indicated severe disease with a sensitivity of 90% and a specificity of 89%. When this test was performed on the supratrochlear artery a low sensitivity of 36% was obtained, although specificity was high at 96%.

Transcranial measurement of blood velocities in the basal cerebral arteries using pulsed Doppler ultrasound: velocity as an index of flow.

Blood velocities have been measured transcranially, at small Doppler angles, in the middle cerebral artery of normal volunteers. Cerebral blood flow was changed by varying carbon dioxide tension. In four volunteers, the relationships between arterial pCO2 and percentage change in intensity weighted mean, median, and maximum Doppler-shifted frequencies in the internal carotid and middle cerebral arteries were linear with slopes of 2.5 and 2.8% per mm Hg change in pCO2. In 38 volunteers, the relationship between end-expiratory pCO2 and time-averaged maximum Doppler frequency was linear over the range of pCO2 20-60 mm Hg with slopes of 2.5 and 2.9 percentage change per mm Hg, for internal carotid and middle cerebral, respectively. These results are very similar to those reported using direct methods of measuring cerebral blood flow. As the transcranial Doppler method is reproducible, this indicates that changes in middle cerebral blood velocity may be used to monitor changes in flow.

Transcranial measurement of blood velocities in the basal cerebral arteries using pulsed Doppler ultrasound: a method of assessing the Circle of Willis.

Transcranial pulsed Doppler ultrasound and spectral analysis were used for detection of blood velocities in the basal cerebral arteries. The Doppler transducer was placed superior to the zygomatic arch and during insonation of the middle cerebral artery care was taken to obtain maximum Doppler-shift frequency signals since this allowed a small angle between the ultrasound beam and this artery. Doppler signals were obtained from the middle, anterior, and posterior cerebral arteries in 20 volunteers with the average depth of the Doppler gate at 4.9 (4.6-5.2 cm), 5.2 (4.9-5.4 cm), and 6.3 cm (6.0-6.9 cm), respectively. These measurements were in agreement with those obtained for 15 cadaver studies, in whom the distance from the proposed site of the Doppler transducer to each basal cerebral artery was measured as 4.7 +/- 0.6, 5.3 +/- 0.5, and 5.9 +/- 0.9 cm, respectively. The reproducibility of middle cerebral artery blood velocity values was tested in seven subjects and showed a variation of not more than 8% in any individual. The method was used in combination with common carotid compression to assess four patients who had occlusive extracranial carotid disease; in three the disease was more severe on one side and reversal of blood flow in the proximal ipsilateral anterior cerebral artery was demonstrated, consistent with cross flow from the contralateral side via the anterior communicating artery of the Circle of Willis. In the fourth patient augmentation of posterior cerebral artery blood velocities during common carotid compression indicated the major collateral source was from the vertebrobasilar system.

An alternative approach to the semi-quantitative assessment of the transplanted renal artery velocity sonogram.

There are theoretical problems with the use of resistance based indices, i.e. pulsatility index (PI) or resistive index (RI) as stand alone measures in the renal allograft. PI and RI are heart rate dependent and input pressure dependent for autoregulating organs. A new non-invasive index, termed Pz, has been proposed. Pz may be thought of as the arterial back pressure generated by the kidney representing the pressure which needs to be overcome in perfusing the glomeruli. On a theoretical basis Pz can be shown to be independent of heart rate and resistance and to allow for variations in mean systemic blood pressure. In an initial study, a group of 53 well functioning renal allografts demonstrated a significant reduction in the coefficient of variance for Pz (12.8%) when compared to PI (25.4%). A second study on recently transplanted allografts indicated that acute tubular necrosis could not be separated from rejection on the basis of Pz. Pz did however consistently perform better than PI in terms of reduced variability within pathological groups. We conclude that Pz is more useful than PI in this application.

Quickscan: Doppler ultrasound emulation of angiography--its value prior to arteriography in peripheral vascular disease.

The prevalence of peripheral vascular disease demands a quick, reliable, non-invasive technique for initial assessment. We have devised a new method which combines the two physical principles that (1) Doppler shift is proportional to blood velocity and (2) blood velocity is inversely proportional to arterial cross-section with the ability to track probe position using a non-contacting method. An image of the probe track and any arterial narrowing is shown superimposed on an outline of the patient. Pressure measurement, scan and graphics with final report take about 20 minutes. The accuracy of this system in peripheral vascular disease was evaluated. Thirty-one patients underwent quickscan (QS) and arteriography within an average time of 7 days. Abdominal aorta, common iliac-common femoral, superficial femoral and popliteal artery segments were graded independently as normal, significant stenosis (greater than 50% of diameter) or occluded by both techniques. Of 197 segments, QS correctly assessed 106 normal, 22 stenosed and 28 occluded segments. Four equivocal angiographic stenoses were normal on QS and three severe stenoses were graded occlusion. Fifteen segments on angiography and five on QS were not assessed. For the iliac and superficial femoral artery segments, sensitivity and specificity averaged 77% and 86%, respectively, for all grades. Aortic statistics were invalid (only one significant lesion). Six out of eight popliteal occlusions were correctly diagnosed by QS, but no popliteal stenoses were detected out of six shown on arteriography. Low numbers may contribute to this discrepancy but an improved popliteal scanning method may be necessary. We find initial QS an invaluable aid to direct percutaneous angiography and to indicate potential sites for angioplasty.

A blood pressure independent index of aortic distensibility.

A non-invasive Doppler ultrasound technique for the assessment of aortic compliance based on the in vivo measurement of pulse wave velocity along the thoraco-abdominal aortic pathway is described. An approach for correcting for the effect of blood pressure on aortic compliance is considered. The derivation of an index of distensibility, Cp, which is independent of blood pressure is provided and applied to data collected from 58 normal, healthy volunteers. Medical disorders such as atherosclerosis, diabetes mellitus and familial hypercholesterolaemia have all been shown to affect arterial distensibility. We suggest that the clinical measurement of Cp may be a useful, non-invasive tool for assessing such patients' susceptibility to atheromatous arterial disease as well as for monitoring their response to therapy.

Aortic distensibility in post-menopausal women receiving Tibolone.

Both oestrogen and androgens have been shown to affect the structural composition and biophysical properties of the arterial wall in vitro. A non-invasive Doppler ultrasound technique, based on the measurement of pulse wave velocity along the thoraco-abdominal aortic pathway, was used to assess aortic compliance C in vivo in 49 normotensive, normal, healthy post-menopausal female subjects. 23 of the women had been receiving Tibolone, a synthetic steroid structurally related to norethisterone, for at least 3 years. Since C varies with non-chronic changes in blood pressure, an index of intrinsic aortic distensibility, Cp, normally independent of blood pressure, was also calculated. No significant difference was found between the control group and those subjects receiving Tibolone for age, body mass index, systolic blood pressure, diastolic blood pressure, C or Cp. As one would expect the control group Cp values did not show a significant relationship with blood pressure (r = -0.1, not significant). However, in the Tibolone group some dependence of Cp values on pressure still remained (r = -0.58, p < 0.004), suggesting that oral administration of Tibolone had altered the dynamic relationship between structural and functional biophysical properties of the aortic wall in vivo.

Monitoring cerebral perfusion during carotid endarterectomy.

Transcranial pulsed Doppler ultrasound was used to monitor blood velocity in the middle cerebral artery (MCA) of two patients during ipsilateral carotid endarterectomy. In the first patient the ultrasound data demonstrated a non-functioning shunt which was corrected by repositioning the distal end of the shunt. In the second patient MCA blood velocity data demonstrated that clamping of the external carotid artery would have resulted in complete cessation of MCA flow throughout endarterectomy. These cases illustrate the benefit that this technique offers to the individual patient undergoing carotid surgery.