Residual stress distribution in a lamellar model of the arterial wall.

Excessive wall circumferential stress in arteries caused by luminal pressure leads to endothelial damage and clinical consequences. In addition to circumferential stress, arterial wall contains residual stress with compressive and tensile components on intima and adventitia sides. The intimal compressive component compensates part of tensile stress induced by blood pressure, hence reduces severity of endothelial tension. The opening angle caused by radial cut of arterial ring defines residual stress. In this study, finite element modelling is used to evaluate residual stress in a lamellar model of human aorta with differing opening angle and elastic modulus. Results show non-linear residual stress profiles across wall thickness, influenced by structural and mechanical parameters. Elevation of opening angle from 50° to 90° leads to increase of intimal compressive component compensating up to 32.6% of the pressure-induced tensile stress. Results may be applied in study of endothelial injury caused by excessive stress in situations such as aging, hypertension and atherosclerosis.

Central arterial pulse wave augmentation is greater in girls than boys, independent of height.

OBJECTIVES: Central arterial pulse wave augmentation, quantified by the augmentation index (AIx), is a key marker of arterial health, an important contributor to cardiac afterload and is significantly greater in older women than men. We measured carotid AIx in 8-year-old children to examine the influences of sex, height and arterial stiffness on central arterial pulse wave augmentation METHODS: Four hundred and five children (age 8.0 +/- 0.1 years, 49% girls) had anthropometry, brachial systolic and diastolic blood pressure, heart rate and carotid artery pressure waveforms (by applanation tonometry), diastolic diameter and distensibility assessed. RESULTS: Carotid AIx was significantly higher in girls than boys (-11.7 +/- 8.1 versus -16.5 +/- 9.3%, respectively, P < 0.001). Boys and girls had similar height (129 +/- 6 versus 128 +/- 6 cm), systolic blood pressure (100 +/- 7 versus 101 +/- 7 mmHg), diastolic blood pressure (59 +/- 6 versus 60 +/- 5 mmHg) and heart rate (80 +/- 10 versus 82 +/- 10 bpm). Carotid diastolic diameter was smaller in girls than boys (0.45 +/- 0.03 versus 0.47 +/- 0.04 cm, P < 0.001). The sex difference in AIx remained significant after adjustment for height, heart rate, blood pressure, diastolic diameter and birth weight. The time to the onset of the reflected wave was shorter in girls (155 +/- 19 versus 163 +/- 18 ms, P < 0.001). Girls had greater carotid artery distensibility (6.2 +/- 1.8 versus 5.8 +/- 1.5% per 10 mmHg, P = 0.016), suggesting lower regional carotid artery stiffness. CONCLUSION: Greater pulse wave augmentation in prepubertal girls results from earlier wave reflection and is independent of height, carotid artery diameter and stiffness. When combined with age-related changes in arterial compliance, this may contribute to adverse cardiovascular outcomes in older women.

Blood pressure waveform analysis by means of wavelet transform.

The assessment of cardiovascular function by means of arterial pulse wave analysis (PWA) is well established in clinical practice. PWA is applied to study risk stratification in hypertension, with emphasis on the measurement of the augmentation index as a measure of aortic pressure wave reflections. Despite the fact that the prognostic power of PWA, in its current form, still remains to be demonstrated in the general population, there is general agreement that analysis and interpretation of the waveform might provide a deeper insight in cardiovascular pathophysiology. We propose here the use of wavelet analysis (WA) as a tool to quantify arterial pressure waveform features, with a twofold aim. First, we discuss a specific use of wavelet transform in the study of pressure waveform morphology, and its potential role in ascertaining the dynamics of temporal properties of arterial pressure waveforms. Second, we apply WA to evaluate a database of carotid artery pressure waveforms of healthy middle-aged women and men. Wavelet analysis has the potential to extract specific features (wavelet details), related to wave reflection and aortic valve closure, from a measured waveform. Analysis showed that the fifth detail, one of the waveform features extracted applying the wavelet decomposition, appeared to be the most appropriate for the analysis of carotid artery pressure waveforms. What remains to be assessed is how the information embedded in this detail can be further processed and transformed into quantitative data, and how it can be rendered useful for automated waveform classification and arterial function parameters with potential clinical applications.

Sutureless nerve repair with laser-activated chitosan adhesive: a pilot in vivo study.

OBJECTIVE: The anastomosis of peripheral nerves is a demanding procedure that has potential complications due to foreign body reactions elicited by sutures. In this study, the sutureless in vivo anastomosis of rat tibial nerves was successfully performed, using for the first time a chitosan-based laser-activated adhesive. The nerve thermal damage caused by the laser irradiation was quantitatively assessed. MATERIALS AND METHODS: A novel adhesive composed of chitosan, indocyanine green, acetic acid, and water, was fabricated in thin sheets. Its adhesive strength was tested in vitro by bonding strips (surface area approximately 20 mm2, thickness approximately 20 microm) onto rat sciatic nerves and sheep intestine by laser activation with low fluence ( approximately 50 J/cm2), using a fiber-coupled diode laser (n = 13). The tensile strength of the adhesive/tissue bonds was measured after tissue repair. The chitosan adhesive was then used to perform sutureless anastomosis of tibial nerves in vivo (n = 6). Adhesive strips were also bonded in vivo onto intact rat sciatic nerves (n = 6) in order to quantitatively assess, by counting myelinated axons, the thermal damage induced by the laser. RESULTS: The adhesive bonded well to tissue with a tensile strength of 12.5 +/- 2.6 KPa (mean +/- SD; n = 13). The in vivo anastomosed nerves were in continuity 3 d after surgery. Axon counting showed the number and morphology of myelinated axons were normal proximally ( approximately 96%) compared with intact nerves (100%). Axon demyelination was observed at the operation site ( approximately 49%) and distally ( approximately 27%), and was attributed to laser-induced thermal damage. CONCLUSIONS: Nerve anastomosis, performed by the laser-adhesive procedure, was successful 3 d postoperatively. Proximal myelinated axons were not significantly damaged by the low laser fluence.

Age, hypertension and arterial function.

1. Ageing exerts a marked effect on the cardiovascular system and, in particular, the large arteries. Using a variety of techniques to assess arterial stiffness, many cross-sectional studies have demonstrated a significant relationship between age and aortic stiffness, although the age-related changes observed in peripheral arteries appear to be less marked. 2. The relationship between arterial stiffness and hypertension is more complex. The distending, or mean arterial, pressure is an important confounder of measurements of arterial stiffness and, therefore, must be taken into consideration when assessing arterial stiffness in hypertensive subjects or investigating the effect of antihypertensive agents. Current methods for correcting for differences in distending pressure involve pharmacological manipulation, statistical correction or mathematical manipulation of stiffness indices. 3. Many studies have provided evidence that both peripheral (muscular) and central (elastic) arteries are stiffer in subjects with mixed (systolic/diastolic) hypertension compared with normotensive subjects. However, it is unclear to what extent differences in mean arterial pressure explain the observed differences in hypertensive subjects. In contrast, isolated systolic hypertension is associated with increased aortic, but not peripheral artery, stiffness, although the underlying mechanisms are somewhat unclear. 4. Traditional antihypertensive agents appear to reduce arterial stiffness, but mostly via an indirect effect of lowering mean pressure. Therefore, therapies that target the large arteries to reduce stiffness directly are urgently required. Agents such as nitric oxide donors and phosphodiesterase inhibitors may be useful in reducing stiffness via functional mechanisms. In addition, inhibitors or breakers of advanced glycation end-product cross-links between proteins, such as collagen and elastin, hold substantial promise.

A modified postural drainage position produces less cardiovascular stress than a head-down position in patients with severe heart disease: a quasi-experimental study.

QUESTION: Does a modified postural drainage position (horizontal) produce less cardiovascular and respiratory stress than a head-down postural drainage position (30 degrees) in people with severe heart disease? DESIGN: A quasi-experimental study. PARTICIPANTS: Thirty-one patients (mean age 69 years, SD 13) with severe left ventricular systolic dysfunction (mean ejection fraction 23%, SD 7) who were stable, receiving regular medication and free of acute respiratory illness. INTERVENTION: Two manoeuvres were performed--one from long sitting to a modified (horizontal) postural drainage position, and one from long sitting to a head-down (30 degrees) postural drainage position. OUTCOME MEASURES: Cardiovascular responses examined were blood pressure, sphygmocardiographic indices, and cardiac rhythm. Respiratory responses examined were respiratory rate, transcutaneous arterial oxyyhaemoglobin saturation, and dyspnoea. RESULTS: Three participants were intolerant to the postural drainage positions--two during head-down and one during modified positioning. The remaining 28 participants maintained their resting cardiac rhythm and did not complain of chest pain or dyspnoea. The changes in cardiovascular responses during the sitting to head-down postural drainage manoeuvre in the tolerant participants were significantly greater (p < 0.05) than the changes during the sitting to the modified postural drainage manoeuvre for most of the sphygmocardiographic indices. In contrast, there were no significant respiratory responses to either postural drainage manoeuvre. CONCLUSION: Modified positioning is associated with less cardiovascular stress than head-down positioning, yet for most patients with severe heart disease, both positions are generally well tolerated. For a subset of these patients, either position may be inappropriate. This suggests that modified positioning should be attempted first but that a head-down position may be attempted if the modified position proves ineffective.

Snoring-related energy transmission to the carotid artery in rabbits.

Epidemiological studies link habitual snoring and stroke, but mechanisms involved are poorly understood. One previously advanced hypothesis is that transmitted snoring vibration energy may promote carotid atheromatous plaque formation or rupture. To test whether vibration energy is present in carotid artery walls during snoring we developed an animal model in which we examined induced snoring (IS)-associated tissue energy levels. In six male, supine, anesthetized, spontaneously breathing New Zealand White rabbits, we surgically inserted pressure transducer-tipped catheters (Millar) to monitor tissue pressure at the carotid artery bifurcation (PCT) and within the carotid sinus lumen (PCS; artery ligated). Snoring was induced via external compression (sandbag) over the pharyngeal region. Data were analyzed using power spectral analysis for frequency bands above and below 50 Hz. For frequencies below 50 Hz, PCT energy was 2.2 (1.1-12.3) cmH2O2 [median (interquartile range)] during tidal breathing (TB) increasing to 39.0 (2.5-95.0) cmH2O2 during IS (P = 0.05, Wilcoxon's signed-rank test). For frequencies > 50 Hz, PCT energy increased from 9.2 (8.3-10.4) x 10(-4) cmH2O2 during TB to 172.0 (118.0-569.0) x 10(-4) cmH2O2 during IS (P = 0.03). Concurrently, PCS energy was 13.4 (8.5-18.0) x 10(-4) cmH2O2 during TB and 151.0 (78.2-278.8) x 10(-4) cmH2O2 during IS (P < 0.03). The PCS energy was greater than PCT energy for the 100-275 Hz bandwidth. In conclusion, during IS there is increased energy around and within the carotid artery, including lower frequency amplification for PCS. These findings may have implications for carotid atherogenesis and/or plaque rupture.

Cardiovascular responses to short-term head-down positioning in healthy young and older adults.

BACKGROUND AND PURPOSE: Isolated head-down postural drainage is assumed to acutely load the cardiovascular system. Consequently, it is considered a relative contraindication in the presence of severe cardiovascular disease. Evidence demonstrating that the head-down manoeuvre as used by physiotherapists does significantly load the cardiovascular system is lacking. The present study documents the cardiovascular responses t short-term 30 degrees head-down positioning in healthy subjects. The results are a point of reference for respiratory patients with and without cardiovascular disease. METHOD: A quasi-experimental research design was used, with multiple measurements obtained at rest (long sitting and in the head-down position. Twenty-one young subjects (mean age 25 years (standard deviation, (SD) 3 years)) and 19 older subjects (mean age 66 years (SD 6 years)) were studied. Applanation tonometry and sphygmocardiography were used to measure temporal and pressure variables, and indices that estimate myocardial work and coronary blood flow. RESULTS: Absolute differences existed between the two age groups for all variables at rest (p < 0.001). No age-time interaction was observed for any variable in the head-down position (p > 0.05). Serial measures in the head-down position did not vary across time (p > 0.05). Small (<9%) but significant (p < or = 0.02) decreases in heart rate, relative diastolic duration, mean arterial blood pressure and diastolic time indices, and small (<12%) but significant (p < or = 0.002) increases in cardiac cycle time, ejection duration (relative and absolute) and absolute diastolic duration were observed in the head-down position compared with rest. A small (9%) but significant (p < 0.001) fall in the sub-endocardial viability ratio occurred in the head down position. CONCLUSION: The findings have little consequence in health, but they suggest that head-down postural drainage may be of concern for chest physiotherapy recipients with reduced cardiac reserve or impaired barorefilex function.

Basal NO locally modulates human iliac artery function in vivo.

We demonstrated previously that endogenous NO influences large-artery distensibility in the ovine hindlimb. However, the role of basal NO in larger human conduit arteries is controversial. The aim of this study was to investigate whether basal production of NO, acting locally, influences iliac artery distensibility in humans. Distensibility was assessed by intra-arterial measurement of the pulse wave velocity. Eighteen subjects, free of significant coronary or iliac artery disease, were studied after diagnostic cardiac catheterization. Simultaneous pressure waveforms were recorded with a high-fidelity dual-pressure sensing catheter, placed in the common iliac artery during intra-arterial infusion of saline (baseline), glyceryl trinitrate (4 nmol/min), or NG-monomethyl-L-arginine (8 and 16 micromol/min). Drugs were infused proximally, via the catheter to perfuse the segment of artery under study, or distally, via the sheath, to control for any reflex changes in flow or sympathetic activation. Velocity was calculated using the foot-to-foot methodology. Six subjects received glyceryl trinitrate and 12 NG-monomethyl-L-arginine. There was no change in velocity after infusion of glyceryl trinitrate or NG-monomethyl-L-arginine via the sheath. However, infusion of glyceryl trinitrate via the catheter significantly reduced velocity by 31.43+/-5.80% (mean+/-SEM; P<0.01; P=0.02 for comparison). Likewise, infusion of the highest dose of NG-monomethyl-L-arginine via the catheter significantly increased velocity by 27.25+/-8.20% (P=0.001; P=0.02 for comparison). Importantly, there was no change in mean arterial blood pressure throughout the studies. These data indicate that under resting conditions, local NO production modulates human iliac artery distensibility and that exogenous NO increases arterial distensibility.

Role of natriuretic peptides in regulation of conduit artery distensibility.

Arterial distensibility, assessed by the pulse-wave velocity (PWV), is an independent predictor of cardiovascular risk. We investigated whether natriuretic peptides, acting locally, modify conduit artery distensibility in vivo. All studies were conducted in anesthetized sheep (n = 18) by using a validated ovine hindlimb model. In brief, the PWV was calculated, with the use of the foot-to-foot methodology, from two pressure waveforms recorded simultaneously with a high-fidelity dual pressure-sensing catheter placed in the common iliac artery. Drugs were infused either proximally, via the catheter to perfuse the segment of artery under study, or distally, via the sheath to control for any reflex changes in flow or sympathetic activation. First, the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP) were studied. Second, the role of endogenous ANP was investigated by infusing the natriuretic peptide receptor type A (NPRA)-selective receptor antagonist A71915. Third, A71915 was coinfused with ANP. Fourth, the NPRC-selective agonist cANF was infused. Infusion of CNP or des-[Gln18Ser19Gly20Leu21Gly22]-ANF-(4-23)-NH2 (cANF) had no effect on iliac PWV. However, infusion of ANP, and to a lesser degree BNP, resulted in a reduction in PWV (-9%; P < 0.01 and -6%; P < 0.05, respectively). A71915 increased iliac PWV from 2.97 +/- 0.13 to 3.06 +/- 0.13 m/s; P < 0.01. Coinfusion of A71915 with ANP completely abolished the effects of ANP (P < 0.01). Importantly, ANP-BNP infusion via the sheath did not alter PWV. In conclusion, ANP, and to a lesser extent BNP, modify large artery distensibility via the NPRA receptor. Neither CNP nor cANF altered PWV, suggesting that the NPRB and NPRC receptors do not acutely influence distensibility in vivo.

Endothelin-1 regulates arterial pulse wave velocity in vivo.

OBJECTIVES: The aim of this study was to investigate whether endothelin-1, acting locally, regulates arterial distensibility, assessed by measuring pulse-wave velocity in vivo. BACKGROUND: Arterial stiffness is a key determinant of cardiovascular risk. Several lines of evidence support a role for the endothelium in regulating arterial stiffness by release of vasoactive mediators. However, the role of endothelin-1 (ET-1) in the regulation of arterial stiffness has not been investigated. METHODS: All studies were conducted in anesthetized sheep. Pulse wave velocity (PWV) was calculated using the foot-to-foot methodology from two pressure waveforms simultaneously recorded with a high-fidelity, dual pressure-sensing catheter placed in the common iliac artery. RESULTS: Intra-arterial infusion of ET-1 significantly increased iliac PWV by 12 +/- 5% (mean +/- STD; p < 0.001), whereas infusion of the endothelin-A (ET(A)) receptor antagonist BQ-123 significantly reduced PWV by 12 +/- 4% (p < 0.001). After BQ-123 infusion, exogenously infused ET-1 did not significantly change PWV compared with infusion of saline (change of -0.08 +/- 0.11% vs. -0.01 +/- 0.07%; p = 0.53). Importantly, infusion of BQ-123 or ET-1 distal to the common iliac artery did not affect PWV. CONCLUSIONS: These results demonstrate, for the first time, that endogenous ET-1 production directly regulates large artery PWV in vivo. In addition, exogenous ET-1 increases PWV, and this can be blunted by ET(A) receptor blockade. These observations explain, in part, why conditions that exhibit up-regulation of ET-1 are also associated with arterial stiffening. Therefore, drugs that block ET(A) receptors may be effective in reducing large artery stiffness in humans, and thus cardiovascular risk.

Nitric oxide regulates local arterial distensibility in vivo.

BACKGROUND: Arterial stiffness is an important determinant of cardiovascular risk. Several lines of evidence support a role for the endothelium in regulating arterial stiffness by release of vasoactive mediators. We hypothesized that nitric oxide (NO) acting locally regulates arterial stiffness in vivo, and the aim of this experiment was to test this hypothesis in an ovine hind-limb preparation. METHODS AND RESULTS: All studies were conducted in anesthetized sheep. Pulse wave velocity (PWV) was calculated by the foot-to-foot methodology from 2 pressure waveforms recorded simultaneously with a high-fidelity dual pressure-sensing catheter placed in the common iliac artery. Intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA) increased iliac PWV significantly, by 3+/-2% (P<0.01). Infusion of acetylcholine and glyceryl trinitrate reduced PWV significantly, by 6+/-4% (P=0.03) and 5+/-2% (P<0.01), respectively. Only the effect of acetylcholine, however, was significantly inhibited during coinfusion of L-NMMA (P=0.03). There was no change in systemic arterial pressure throughout the studies. Importantly, infusion of L-NMMA or acetylcholine distal to the common iliac artery (via the sheath) did not affect PWV. CONCLUSIONS: These results demonstrate, for the first time, that basal NO production influences large-artery distensibility. In addition, exogenous acetylcholine and glyceryl trinitrate both increase arterial distensibility, the former mainly through NO production. This may help explain why conditions that exhibit endothelial dysfunction are also associated with increased arterial stiffness. Therefore, reversal of endothelial dysfunction or drugs that are large-artery vasorelaxants may be effective in reducing large-artery stiffness in humans, and thus cardiovascular risk.