Intra-arterial Measurements Research Articles

Reversal of Heparin by Novel Synthetic Antagonist PMX-60056 Exhibits a Linear Dose-Response Relationship

AbstractAbstract 3329PMX-60056 is a small-molecule first-in-class new chemical entity designed to bind to the pentasaccharide group in unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH), and reverse their anticoagulation effects. It has been shown to reverse UFH and the LMWH tinzaparin to date, and without rebound anticoagulation.When no UFH or LMWH is present, PMX-60056 dosing has been limited by transient hypotension at doses over 0.4 mg/kg in volunteers, but its use for heparin reversal should eliminate this effect as PMX-60056 preferentially binds to heparin. A study with UFH at 70 U/kg and reversal with 0.3 mg/kg PMX-60056 showed full efficacy, and mild blood-pressure reductions in half the subjects that suggested excess PMX-60056.Therefore, we examined the dose-response, efficacy, and safety at higher doses of UFH as used in cardiac surgery. Hemodynamic effects were recorded with lithium-dilution cardiac output, and blood pressures were continuous intra-arterial measurements. PMX-60056 dose was titrated using activated clotting times (ACTs), and protamine requirements were also estimated by heparin-protamine titrations to determine heparin levels.350 U/kg of heparin was reversed in 6 normal volunteers, after an initial 10-minute infusion of 0.7 mg/kg PMX-60056 and subsequent smaller doses as needed to normalize ACT. Hemodynamics were unaffected until total PMX-60056 dose exceeded 1 mg/kg – the initial dose of 0.7 mg/kg never produced a change. When a hemodynamic effect did occur (in 3 of the 6), it was initiated by a fall in systemic vascular resistance. Only 1 of these 6 subjects had a clinically significant hypotension, which lasted 15 minutes with pressor agents and limb elevation; this subject was subsequently found to have a past history suggestive of vaso-vagal instability. The other 5 subjects had no appreciable change in blood pressure.Per protocol the antagonist doses were in discrete amounts, so some overshoot was inevitable. Therefore, the total dose of PMX-60056 to the point immediately preceding full reversal of ACT was correlated with ACT, with initial protamine requirement according to heparin levels, and with estimated residual heparin (calculated from dose given and time elapsed). These data were highly correlated with a straight line from zero: R-squared was 0.90 with initial ACT, 0.96 with initial protamine requirement according to heparin levels, and 0.97 with estimated residual heparin (calculated).These data suggest that measurements routinely available during cardiac surgery are sufficient for predicting a single reversing dose of PMX-60056 that will safely and effectively neutralize UFH-induced anticoagulation.After reversal, the ability to re-anticoagulate is sometimes important. The same study also established that reversal of anticoagulation with PMX-60056 did not inhibit subsequent repeat anticoagulation with heparin a few minutes later, which was then also reversed with PMX-60056.This study was conducted according to cGCP at Duke University's Anesthesiology Research Unit. More results will be forthcoming as the analysis proceeds. Disclosures:McAllister:PolyMedix, Inc.: Employment.

Early glomerular alterations in genetically determined low nephron number

An association between low nephron number and subsequent development of hypertension in later life has been demonstrated. The underlying pathomechanisms are unknown, but glomerular and postglomerular changes have been discussed. We investigated whether such changes are already present in prehypertensive "glial cell line-derived neurotrophic growth factor" heterozygous mice (GDNF+/-) with lower nephron number. Twenty-six-week-old mice [22 GDNF+/-, 29 C57B6 wild-type control (wt)] were used for in vivo experiments with intra-arterial and tail cuff blood pressure measurements. After perfusion fixation, kidneys were investigated with morphological, morphometric, stereological, and immunohistochemical techniques and TaqMan PCR analysis. As expected at this age, blood pressure was comparable between GDNF+/- and wt. Nephron number per kidney was significantly lower in GDNF+/- than in wt (-32.8%, P < 0.005), and mean glomerular volume was significantly higher (+49.5%, P < 0.001). Renal damage scores, glomerular and tubular proliferation, analysis of intrarenal arteries and peritubular capillaries, expression of relevant tubular transporter proteins, as well as gene expression of profibrotic, proinflammatory, or prohypertensive markers were not significantly different between GDNF+/- and wt. Compensatory glomerular hypertrophy in GDNF+/- was accompanied by higher numbers of endothelial and mesangial cells as well as PCNA-positive glomerular cells, whereas podocyte density was significantly reduced. Further electron microscopic analysis showed marked thickening of glomerular basement membrane. In conclusion, lower nephron number is associated with marked early glomerular structural changes, in particular lower capillary supply, reduced podocyte density, and thickened glomerular basement membrane, that may predispose to glomerular sclerosis.

In Response

In Response We agree with Vos et al.1 that the absence of liver enzyme measurements in some of our patients may be a drawback in our study. However, biochemical hepatic function testing may not offer the key information on hepatocellular dysfunction2 as Vos et al. suggest. Hultcrantz et al.3 described that chronically elevated liver enzymes without symptoms or physical signs of liver disease correspond with various forms of liver disease preferably in the presence of a positive history on alcohol consumption, drug abuse, hepatitis, or obesity. All patients displaying these factors were excluded from our study population, thus removing those patients that may exhibit elevated hepatic enzymes in the absence of physical signs or symptoms of liver disease. Regarding the importance of hemodynamics and indocyanine green plasma disappearance rate (ICG-PDR), we originally intended to use the noninvasive method of ICG measurement, pulse dye densitometry, to measure cardiac output in our study population. To validate the transcutaneous method versus intraarterial measurement of ICG, we performed simultaneous measurements in a subpopulation. In this subpopulation, we had to conclude that, for individual measurement of cardiac output, the transcutaneous measurement of ICG by pulse dye densitometry is not accurate enough.4 For the purpose of this discussion, the measurements of cardiac output versus the ICG-PDR value in the patients in whom we performed arterial blood sampling is shown in Figure 1. The open diamonds represent the patients receiving a propofol induction. Inspection of Figure 1 leads to the conclusion that the absence or presence of propofol did not induce significant hemodynamic changes in this otherwise healthy population nor did it affect ICG-PDR.Figure 1: Representation of cardiac output measurements based on arterial blood indocyanine green (ICG) concentrations versus ICG– plasma disappearance rate (PDR) values determined in patients who underwent simultaneous arterial ICG sampling. The circles represent the measurements in awake subjects; the diamonds represent the measurements during propofol induction.We thus maintain our conclusion4 that ICG-PDR values in a population without clinical signs of liver failure range well below 18% min−1, cited as the cutoff value for hepatic failure and propagated as criterion for clinical intervention. This cutoff value needs to be reconsidered as has been suggested elsewhere.5 We agree with the reviewers that further studies are needed and that the final word on this subject has not yet been written.

Increased Intervisit Blood Pressure Variability and β-Blockade: Measurement Imprecision Related to Bradycardia?

To the Editor: In their editorial commentary, Dolan and O'Brien1 reviewed and provided clinical perspective to the series of articles last March in which Rothwell and colleagues2,3 established a clear link between long-term blood pressure variability and hypertension-related outcome. The conceptual introduction of intervisit variability in blood pressure consolidated previous findings based on intra-arterial and noninvasive 24-hour ambulatory measurements.4 Additional observations will help shape the ripening assimilation to management guidelines. In this regard, Webb …

Targeted Genomic Disruption of H-Ras Induces Hypotension Through a NO-cGMP-PKG Pathway–Dependent Mechanism

The aim of the present experiments was to evaluate the differences in arterial pressure between H-Ras lacking mice and control mice and to analyze the mechanisms involved in the genesis of the differences. H-Ras lacking mice and mouse embryonic fibroblasts from these animals were used. Blood pressure was measured using 3 different methods: direct intraarterial measurement in anesthetized animals, tail-cuff sphygmomanometer, and radiotelemetry. H-Ras lacking mice showed lower blood pressure than control animals. Moreover, the aorta protein content of endothelial nitric oxide synthase, soluble guanylyl cyclase, and cyclic guanosine monophosphate-dependent protein kinase was higher in H-Ras knockout mice than in control animals. The activity of these enzymes was increased, because urinary nitrite excretion, sodium nitroprusside-stimulated vascular cyclic guanosine monophosphate synthesis, and phosphorylated vasoactive-stimulated phosphoprotein in aortic tissue increased in these animals. Furthermore, mouse embryonic fibroblasts from H-Ras lacking mice showed higher cyclic guanosine monophosphate-dependent protein kinase promoter activity than control cells. These results strongly support the upregulation of the nitric oxide-cyclic guanosine monophosphate pathway in H-Ras-deficient mice. Moreover, they suggest that H-Ras pathway could be considered as a therapeutic target for hypertension treatment.

Effects of Weightlifting and Breathing Technique on Blood Pressure and Heart Rate

Weight training is a method commonly used to increase strength. The purpose of this investigation was to examine the effect of breathing technique during weight training on heart rate (HR) and blood pressure (BP). After completing a health history questionnaire, 30 subjects (16 men: 21.25 +/- 1.21 years, 180.26 +/- 2.36 cm, 84.31 +/- 19.32 kg; and 14 women: 21.29 +/- 2.37 years, 170.08 +/- 2.15 cm, 137.36 +/- 62.31 kg) were familiarized and tested for an estimated 1 repetition maximum, on the chest press and leg press lifts using each of the 2 breathing techniques, hold breath (HB), and controlled breathing. Lifts were examined using each breathing technique with 1 set of 10 repetitions on separate days. Data were collected during the push phase on average of 3.72 times per set and again at 1 and 5 minutes post lift. Resting, during lift (peak, average); 1-minute and 5-minute post lift BP; and HR values were measured using the NIBP100A noninvasive BP system (Biopac Systems, Inc), for both breathing technique within each lift. The HB technique posted higher but statistically insignificant (p < 0.05) values for systolic BP (p = 0.420), diastolic BP (p = 0.531), and HR (p = 0.713) than the controlled breath technique. The HB technique used in this investigation produced minimal elevations in HR and BP and appears to be safe when performing the chest press and leg press lifts at a moderate resistance. Education on proper weight training techniques can help limit unwanted risks during these exercises.

A comparison of blood pressure and pulse pressure values obtained by oscillometric and central measurements in hypertensive patients

Objective. Wide pulse pressure (PP) affects the accuracy of oscillometric blood pressure measurements (OBPM): however, the degree of this impact on different patient groups with wide PPs is unclear. This study will investigate the accuracy of OBPM in achieving target BP and PP in isolated systolic hypertension (ISH) group compared with mixed hypertension (MHT) group. Method. A total of 115 patients (70 with ISH and 45 with MHT) were enrolled in the study. Upper arm and wrist OBPM, obtained by OmronM3 and OmronR6 devices respectively, were compared with the simultaneously measured values from the ascending aorta. The ISH was defined as a systolic blood pressure (SBP) ≥140 mmHg and a diastolic blood pressure (DBP) <90 mmHg. MHT was defined as a SBP≥140 mmHg and a DBP≥90 mmHg. Results. The mean central arterial blood pressure (BP) and central PP were higher in the ISH group than those in the MHT group. The upper arm OBPM underestimated the central SBP in two groups (−5 mmHg, −3 mmHg, p=0.5, respectively), but overestimated DBP in the ISH group compared with MHT patients (6.8 mmHg, 1 mmHg, p=0.04, respectively). Wrist OBPM similarly underestimated to the central SBP in each group (−16 mmHg, −19 mmHg, p=0.15), whereas the sum of overestimation of DBP was significantly higher in the ISH than in the MHT group (+6 mmHg, − 1 mmHg, p=0.001, respectively). Also, each of the devices underestimated the central PP in the ISH group (about 10 mmHg) as being higher than that of the MHT group. Conclusion. Oscillometric devices may be used for self-BP measurement in patients with ISH without clinically important disadvantages compared with the patients with MHT. For PP measurement in patients with ISH, there were substantial differences between intra-arterial and indirect arm BP measurements.

Long-Term Stability of Cardiovascular and Catecholamine Responses to Stress Tests

Cardiovascular (CV) hyperreactivity to stress must be reasonably stable if it is considered to be important in the development of hypertension and CV disease. The aim of the present study was to assess long-term stability of blood pressure, heart rate, epinephrine, and norepinephrine responses to a cold pressor test and a mental arithmetic stress test. Eighty-one subjects selected from the first (n=30), 50th (n=30), and 95th to 99th (n=39) percentiles of the mean blood pressure distribution at a military draft procedure were tested on 2 occasions 18 years apart. Stress responses were measured during a cold pressor test (hand immersed in ice water for 1 minute) and during a mental stress test (subtraction for 5 minutes). Intra-arterial blood pressure measurements and arterial catecholamine samples were taken at the initial examination. At follow-up, noninvasive Finapres beat-to-beat blood pressure measurements and venous plasma catecholamine samples were used. The 18-year correlations of the CV and epinephrine absolute responses during mental stress ranged from 0.6 to 0.8. The entry/follow-up correlation of systolic blood pressure during the mental stress test (95% CI: 0.69 to 0.86) was significantly higher than during the cold pressor test (95% CI: 0.30 to 0.65), and responses to mental stress overall appeared to be more stable than responses to the cold pressor test. Our study suggests that CV and sympathoadrenal reactivity, specifically to mental stress, are relatively stable individual characteristics. These results support one of the necessary preconditions to consider hyperreactivity involved in the development of hypertension and CV disease.

Pulse Wave Velocity Assessment by External Noninvasive Devices and Phase-Contrast Magnetic Resonance Imaging in the Obese

Carotid-femoral pulse wave velocity (PWV) is considered the gold-standard measurement of arterial stiffness. Obesity, however, can render inaccurate the measurement of PWV by external noninvasive devices. Phase-contrast MRI allows the determination of aortic PWV in multiple aortic locations with intra-arterial distance measurements, as well as the assessment of aortic mechanical properties. The purpose of this study was to assess the reliability of external carotid-femoral PWV values measured by well-validated external devices in comparison with MRI acquisitions of PWV and aortic mechanical properties in a population of obese subjects. PWV was measured with PulsePen and Complior II devices in 32 volunteers (18 men and 14 women), aged 46 to 65 years (mean: 55.7+/-5.1 years), presenting with isolated abdominal obesity, with a waist circumference >102 cm for men and >88 cm for women, and a body mass index between 27 and 35. These results were then compared with MRI PWV values and cross-sectional MRI thoracic aorta distensibility values. MRI PWV values were positively correlated with PWV measured by both PulsePen (r=0.47; P=0.005) and Complior (r=0.43; P=0.01). Aortic cross-sectional stiffness was positively correlated with PulsePen PWV (r=0.42; P=0.02). The same trend was also observed with Complior PWV (r=0.33; P=0.06). This is the first study comparing transcutaneous PWV measurements with MRI aortic elastic properties in obese subjects. Our results indicate that, for body mass index values < or =35 kg m(-2), PWV measured externally with Complior or PulsePen validly reflect values obtained directly in the thoracic aorta through MRI.

Central Blood Pressure and Hypertension

During the 20th century, the brachial artery auscultatory method of blood pressure (BP) measurement has been the major basis for our understanding of clinical hypertension. First, the height of systolic (S) and diastolic (D) BP was used to define cardiovascular (CV) risk. Second, BP reduction by drug treatment was shown to be associated with a substantial decrease of CV risk in several varieties of high BP, including systolic hypertension in the elderly.1,2 However, drug treatment often reduced DBP more than SBP, resulting in increased pulse pressures (PP) and the related arterial stiffness. An associated increase in coronary risk was also observed.1,3 Because PP and arterial stiffness did not respond readily to drug treatment and was made even less responsive by aging, it has been suggested and shown that mechanical factors such as PP, arterial stiffness, and wave reflections, preferably measured by central (aortic or carotid) BP, should be fully investigated. Because the majority of the studies used noninvasive peripheral BPs the need arose for invasive methods to verify and validate central BP measurement in the evaluation of CV risk.4 In the present issue of this journal, Jankowski et al5 established, in a 4.5-year follow-up of 1109 patients undergoing coronary angiography, that central BP was a significant and independent predictor of CV risk, as potent as cardiac ejection fraction and more powerful than brachial sphygmomanometric measurements. For these coronary patients, the pulsatile …

Impact of Aortic Stiffness on Cardiovascular Disease in Patients With Chest Pain: Assessment With Direct Intra-Arterial Measurement

Aortic stiffness is an independent risk factor for cardiovascular (CV) events and mortality. However, there are few studies about the predictive role of aortic stiffness. We investigated the association between aortic pulse-wave velocity (aPWV), using direct intra-arterial measurement and future CV events, in patients with chest pain. Aortic pulse-wave velocity was measured through an aorto-femoral, fluid-filled system at baseline in 1004 patients with chest pain. Among these patients, 497 (237 male) were enrolled in the study. Aortic pulse-wave velocity was examined using tertiles. Tertiles were defined as follows: tertile 1, <9.20 m/sec; tertile 2, 9.21 to 12.49 m/sec; and tertile 3, >12.50 m/sec. The impact of aPWV on newly developed CV events, coronary artery disease (CAD), stroke, and congestive heart failure was evaluated. A higher aPWV was associated with new CV events (odds ratio, 2.18 for tertile 3 v tertile 1; 95% confidence interval [CI], 1.32 to 3.60) and new CAD (odds ratio, 1.87 for tertile 3 v tertile 1; 95% CI, 1.10 to 3.18) in univariate analysis. In multivariate analysis, aPWV was associated with new CV events (odds ratio, 2.05 for tertile 3 v tertile 1; 95% CI, 1.18 to 3.55) and new CAD (odds ratio, 1.86 for tertile 3 v tertile 1; 95% CI, 1.03 to 3.35). Aortic pulse-wave velocity was not associated with either new stroke (P = .096) or congestive heart failure (P = .63). These results suggest that aPWV is an independent risk factor for future CV events and CAD in patients with chest pain.

THE “ULTRASONOGRAPHIC OSLER'S MANEUVER” AND ITS USE IN IDENTIFYING PATIENTS WITH PSEUDOHYPERTENSION

THE “ULTRASONOGRAPHIC OSLER'S MANEUVER” AND ITS USE IN IDENTIFYING PATIENTS WITH PSEUDOHYPERTENSION

Comparison of noninvasive oscillometric and intra-arterial blood pressure measurements in hyperacute stroke

This study aims to compare automatic oscillometric blood pressure recordings with simultaneous direct intra-arterial blood pressure measurements in hyperacute stroke patients to test the accuracy of oscillometric readings. A total of 51 first-ever stroke patients underwent simultaneous noninvasive automatic oscillometric and intra-arterial blood pressure monitoring within 3 h of ictus. Casual blood pressure was measured in both arms using a standard mercury sphygmomanometer on hospital admission. Patients who received antihypertensive medication during the blood pressure monitoring were excluded. The estimation of systolic blood pressure (SBP) using oscillometric recordings underestimated direct radial artery SBP by 9.7 mmHg (95% confidence interval: 6.5-13.0, P<0.001). In contrast, an upward bias of 5.6 mmHg (95% confidence interval: 3.5-7.7, P<0.001) was documented when noninvasive diastolic blood pressure (DBP) recordings were compared with intra-arterial DBP recordings. For SBP and DBP, the Pearson correlation coefficients between noninvasive and intra-arterial recordings were 0.854 and 0.832, respectively. When the study population was stratified according to SBP bands (group A: SBP<or=160 mmHg; group B: SBP>160 mmHg and SBP<or=180 mmHg, group C: SBP>180 mmHg), higher mean DeltaSBP (intra-arterial SBP-oscillometric SBP) levels were documented in group C (+19.8 mmHg, 95% confidence intervals: 12.2-27.4) when compared with groups B (+8.5 mmHg, 95% confidence intervals: 2.7-14.5; P=0.025) and A (+5.9 mmHg, 95% confidence intervals: 1.8-9.9; P=0.002). Noninvasive automatic oscillometric BP measurements underestimate direct SBP recordings and overestimate direct DBP readings in acute stroke. The magnitude of the discrepancy between intra-arterial and oscillometric SBP recordings is even more prominent in patients with critically elevated SBP levels.

Blood Pressure Measurement in Morbid Obesity: Comparison between Forearm and Intra-Arterial Assessment of Blood pressure

Background: Obesity is associated with high blood pressure. Measurement of blood pressure (BP) in morbid obesity with a larger cuff bladder may be erroneous due to the anatomy of their upper limb and/or a nonsuitable cuff bladder. The objective of the study was to compare a non-invasive technique of BP measurement on the forearm with an appropriate standard blood cuff bladder to an invasive method (intra-arterial measurement in the radial artery) in two groups of subjects; non obese (NO) and morbidly obese (MO). &#x0D; &#x0D; Methods: Twenty-seven NO subjects with a mean body mass index (BMI) of 25,6 ± 2,7 kg/m2 were evaluated using two different techniques for blood pressure measurement. Measures were performed, in a supine position, at the forearm level with a standard cuff bladder (Welch Allyn, NY, USA) and on the opposite forearm using an intra-arterial access. The NO group was compared to 20 MO subjects with a mean BMI of 5,1 ± 8,7 kg/m2. The MO group was evaluated during a bariatric surgery procedure, with regular intervals (10 to 15 min) using the same two methods described above.&#x0D; &#x0D; Results: A difference was observed between the two techniques of blood pressure measurements (P &lt; 0.05 and P &lt; 0.01 intra-arterial vs. cuff bladder for the NO and the MO groups respectively) (see Table). Correlations between the two techniques were observed in the NO group (P &lt; 0.001) for the systolic BP (r=0,823) and the diastolic BP (r=0,769). Similar correlations were also observed in the MO group for the systolic BP (r=0,792, P &lt; 0,001) and the diastolic BP (r=0,830, P &lt; 0,001; Table).&#x0D; &#x0D; *** Table in Full Text PDF. ***&#x0D; &#x0D; Conclusion: Although different, BP measurements at the forearm level in MO subjects seems to be clinically valid. This technique may be used in this specific population as an alternative for the measurement of BP.

Best Duplex-Sonographic Criteria for the Assessment of Renal Artery Stenosis - Correlation with Intra- Arterial Pressure Gradient

Colour coded duplex sonography (DS) is widely used for the assessment of renal artery stenosis (RAS). Different criteria have been specified for the detection of significant RAS. The aim of our study was to compare routinely used DS criteria, both with intra-arterial pressure gradients and arteriographic degree of stenosis, and to validate different cut-off points of these DS criteria for the assessment of haemodynamically significant RAS. We retrospectively analysed forty-nine patients (median age 67 years, 29 male) with RAS documented by duplex sonography, referred for renal arterial subtraction arteriography and intra-arterial pressure measurement (93 renal arteries). DS measurement of peak systolic velocity (PSV) in the main renal artery, the renal/aortal velocity ratio (RAR) and the side-to-side differences of the intrarenal resistive indices (DeltaRI) were correlated to intra-arterial pressure measurements and arteriographic degree of stenosis. Receiver operating characteristics (ROC) were used to determine the best cut-off value of DS criteria. 39 (41 %) renal arteries had normal findings or non significant stenosis < 50 %, 23 (25 %) had a diameter reduction between 50 % and 69 %, and 31 (33 %) > or = 70 %. The systolic pressure gradient showed good correlation with the arteriographic degree of RAS (r = 0.77, p < 0.001) and the PSV measured by duplex sonography (r = 0.67, p < 0.001). Mean systolic pressure gradient was 24 mmHg at 50 % stenosis and 23 mmHg at PSV of 200 cm/sec. A PSV of > or = 200 cm/sec provided a sensitivity of 92 % and specificity of 81 % for detecting RAS of > or = 50 %. Similar results were found for RAR > or = 2.5 with a sensitivity of 92 % and specificity of 79 %. These cut-off values have a negative predictive value of 100 % for excluding high-grade RAS of > or = 70 %. A DeltaRI of > or =0.05 has low sensitivity of 31 %, but a high specificity of 97 % for detecting RAS of > or = 50 %. DS measurements and the severity of arteriographic diameter reduction correlate well with systolic pressure gradients. Clinically expedient DS criteria for detecting RAS of > or = 50 % are a PSV of > or = 200 cm/sec or a RAR of > or =2.5. These criteria allow reliable exclusion of severe RAS of > or = 70 %.

Cerebral critical closing pressure estimation from Finapres and arterial blood pressure measurements in the aorta

Estimates of cerebral critical closing pressure (CrCP) and resistance–area product (RAP) are often derived using noninvasive measurements of arterial blood pressure (ABP) in the finger, but the errors introduced by this approach, in relation to intra-vascular measurements of ABP, are not known. Continuous recordings of ABP (Finapres and solid-state catheter-tip transducer in the ascending aorta), cerebral blood flow velocity (CBFV, bilateral Doppler), ECG and transcutaneous CO2 were performed following coronary catheterization. CrCP and RAP were calculated for each of 12 784 cardiac cycles from 27 subjects using the classical linear regression (LR) of the instantaneous CBFV–ABP relationship and also the first harmonic (H1) of the Fourier transform. There was a better agreement between LR and H1 for the aortic measurements than for the Finapres (p < 0.000 01). For LR there were no significant differences for either CrCP or RAP due to the source of ABP measurement, but for H1 the differences were highly significant (p < 0.000 03). The coherence functions between either CrCP or RAP values calculated with aortic pressure (input) or the Finapres (output) were significantly higher for H1 than for LR for most harmonics below 0.2 Hz. When using the Finapres to estimate CrCP and RAP values, the LR method produces similar results to intra-arterial measurements of ABP for time-averaged values, but H1 should be preferred in applications analysing beat-to-beat changes in these parameters.

Survival Benefits of Different Antiadrenergic Interventions in Pressure Overload Left Ventricular Hypertrophy/Failure

We observed previously that in rats with aortic banding (Bd), development of left ventricular (LV) hypertrophy is opposed by beta-blockade, whereas interventions interfering with alpha-adrenoceptor function also inhibit interstitial fibrosis. To assess whether these differential structural effects do translate into different effects on LV function and on heart failure mortality, Bd or sham Bd 8-week-old rats were randomized to vehicle treatment (Vh), chemical sympathectomy ([Sx] 6-hydroxydopamine, 150 mg/kg IP twice a week), beta-adrenoceptor blockade (propranolol [Pro], 40 mg/kg per day PO), or alpha-adrenoceptor blockade (doxazosin [Dox], 5 mg/kg per day PO). After monitoring survival for 10 weeks, the survivors were anesthetized to undergo echocardiography and intraarterial blood pressure measurement. Bd-Vh rats showed increased LV and lung weights, as well as LV dilation, depressed endocardial and midwall fractional shortening and a restrictive transmitral diastolic flow velocity pattern. Compared with Bd-Vh rats, all of the actively treated Bd rats showed less LV hypertrophy, LV dilation, and lung congestion but no less depression of midwall fractional shortening. In contrast, Sx and Dox but not Pro treatment were also associated with lesser degrees of diastolic dysfunction and, even more importantly, with a striking increase in survival (sham banded rats, 100%; Bd-Vh, 40%; Bd-Pro, 51%; Bd-Sx, 83%; and Bd-Dox, 82%). Although Pro, Sx, and Dox provide similar midterm protection from development of LV hypertrophy and dysfunction and from circulatory congestion, only Sx and Dox favorably affected mortality. These findings indicate that in the aortic banding rat model, alpha-adrenoceptors are importantly involved in the pathogenesis of cardiovascular deterioration and disease progression.

Comparison of Simultaneous Measurements of Blood Pressure by Tail-Cuff and Carotid Arterial Methods in Conscious Spontaneously Hypertensive and Wistar-Kyoto Rats

We determined the validity of systolic blood pressure (SBP) measured by tail-cuff blood pressure (TCBP) with direct intra-arterial measurements. In conscious, restrained Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), carotid artery (CA) BP and TCBP were simultaneously measured. In both WKY and SHR strains, highly significant correlations between CABP and TCBP were found and Bland-Altman analyses showed no bias when the two methods were compared. The limits of agreement between CABP and TCBP in WKY and SHR were wide and reproducibility of pressure measurements by either technique was poor, with some evidence for strain-dependent differences. Pressure measurements made over short time frames, however, showed close agreement between CABP and TCBP. Acetylcholine-induced reductions in pressure were equivalently detected by tail-cuff and direct arterial measurement in both strains but angiotensin II-induced pressure elevations were over-estimated by tail-cuff in SHR. Telemetered SBP measurements in conscious rats were highly variable in a strain-dependent manner.

Value of duplex scanning compared with angiography and pressure measurement in the assessment of aortoiliac arterial lesions

To detect haemodynamically significant lesions in the aortoiliac arteries, invasive tests such as angiography and intra-arterial pressure measurement (IAPM) are considered valuable diagnostic tools. The value of duplex scanning as a direct non-invasive examination technique was prospectively compared with intra-arterial digital subtraction angiography (IADSA) and IAPM at rest, and after the administration of papaverine in 60 patients. Excellent agreement, as assessed by the kappa statistic, was shown between duplex scanning and IADSA (kappa = 0.81). A fair agreement was shown between duplex scanning and IAPM (kappa = 0.63), and between IADSA and IAPM (kappa = 0.63). Duplex scanning and IADSA both missed some less haemodynamically critical lesions if IAPM was considered the 'gold standard'. It is concluded that duplex scanning detects haemodynamically significant lesions as effectively as angiography and so may be considered a new and valuable diagnostic tool. IAPM remains necessary to detect some lesions of borderline haemodynamic significance. However, with future developments, duplex scanning has the potential to replace the need even for IAPM.

Criteria from intra-arterial femoral artery pressure measurements combined with reactive hyperaemia to assess the aorto-iliac segment; A prospective study

Direct femoral artery blood pressure measurements combined with reactive hyperaemia (FAP study) were performed on 50 extremities (45 patients) with multilevel arterial occlusive disease of the lower extremities. In a previous retrospective study we established criteria for detection of significant aorto-iliac occlusive disease. These criteria were used in a prospective way in this study. Twenty-seven extremities were subjected to a proximal and 23 extremities to a distal reconstruction. The half-year postoperative results were evaluated. The criteria used were 86 per cent sensitive, 100 per cent specific and 93 per cent accurate in relation to predicting the postoperative haemodynamic result. The positive predictive value was 100 per cent and the negative predictive value 89 per cent. The criteria are presented and compared with data from the literature. It is concluded that FAP studies are a simple and excellent way to assess the aorto-iliac segment and to predict the outcome of a reconstruction in multilevel arterial occlusive disease.