Mechanical pressure versus intrinsic effects of hypertension on large arteries in humans

Brachial artery diameter and compliance were measured in 23 normotensive control subjects and 49 hypertensive patients. The results were compared in isobaric conditions by a modeling analysis extrapolating from the measured data a short segment of the pressure-diameter and pressure-compliance curves in the artery. A logarithmic diameter-pressure function was used as well as measurements of brachial artery blood pressure and lumen diameter (by pulsed Doppler), and of brachial-to-radial pulse wave velocity (by mechanography). The measured values of diameter and compliance in the hypertensive patients were 109% and 63%, respectively, of the control group values. By extrapolating the data via the model at the same pressure level in all subjects (the average level of mean blood pressure of the two groups), the isobaric values of diameter and compliance in the hypertensive patients were 107% and 81%, respectively, of the control group values. Overall, measured isobaric diameters and measured compliance correlated with systolic, diastolic, and mean blood pressure values (p less than 0.001), whereas isobaric compliance correlated only with systolic (p less than 0.05) and pulse (p less than 0.01) pressure values. Thus, the increased diameter and reduced compliance of the brachial artery observed in hypertensive humans cannot be attributed solely to the stretching effect of elevated blood pressure, but also to intrinsic alteration of the arterial walls. These could represent either adaptative structural or functional changes secondary to the chronic increase in arterial pressure, or primary abnormalities of the vessel wall.     

Effect of hypertension on viscoelasticity of large arteries in humans

Two traditional methodologic approaches, the analysis of the arterial pressure waveform in the time domain and the measurement of pulse wave velocity along the arterial tree, have been extensively used to determine the distensibility of large arteries in humans. They have shown that large artery walls are stiffened in the presence of hypertension. However, several methodologic limitations, especially the noncapability of these methods to take into account the physiologic pressure-dependence of arterial distensibility, have led to the development of new approaches for characterizing more in depth the elastic and viscous properties of large arteries. The noninvasive recording of instantaneous pressure and diameter waveforms in superficial arteries (carotid or femoral) by means of tonometry and ultrasonography allows, via appropriate model of the arterial wall, determination of the pure elastic properties as well as the wall viscosity of the vessel. Using case (hypertensive)-control (normotensive) studies it has been found that elastic alteration (stiffening) was preferential in the femoral artery rather than in the carotid artery and that viscous alteration (increased wall viscosity) was relatively uniform in both arteries. This topographic dissociation between elastic and viscous responses of the arterial wall to hypertension suggests that the elastic alteration might be a local phenomena dependent on the singularities of the arterial system, whereas abnormal wall viscosity may reflect a more general influence of hypertension on large artery smooth muscle, the likely determinant factor of viscosity. Therefore, the elastic and viscous components of the arterial walls should be considered independently when assessing the development of hypertensive vascular change and its response to antihypertensive treatment.     

Adrenergic mechanisms and remodeling of subcutaneous small resistance arteries in humans

BACKGROUND: Vascular structural alterations in small resistance arteries of patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. In fact, no difference in the smooth muscle cell volume (CV) between normotensive subjects (NT) and essential hypertensive patients was observed. However, experimental models of hypertension with chronic infusion of agonists of adrenergic receptors were characterized by the presence of smooth muscle cell hypertrophy or hyperplasia. Recently, we have observed the presence of vascular smooth muscle cell hypertrophy in patients with renovascular hypertension. OBJECTIVE: The aim of the study to investigate the structural characteristics of subcutaneous small resistance arteries of NT, of EH, and of patients with phaeochromocytoma (Phaeo). PATIENTS AND METHODS: Thirty Phaeo, 30 NT and 30 EH were included in the study. A biopsy of subcutaneous fat was taken from all subjects. Small resistance arteries (relaxed diameter 160-280 microm) were dissected and mounted on a micromyograph and the media : lumen ratio was calculated. In nine Phaeo, nine NT and 13 EH the cell volume was measured by an unbiased stereological principle, the 'disector' method.RESULTS No difference in smooth muscle cell volume was observed between groups. However, inward remodeling in Phaeo was less marked than in EH, although the increase in media : lumen ratio was similar compared with NT. However, the lack of changes in media cross-sectional area, compared with NT, suggest that there has been little hypertrophy, the changes observed thus being eutrophic. CONCLUSIONS: Our data show, based on a reasonably large sample, that a pronounced activation of the adrenergic system is not associated with vascular smooth muscle cell hypertrophy or hyperplasia in humans. It is therefore possible that adrenergic mechanisms may have a relevant role in the development of eutrophic remodeling in small vessels.     

Serial evaluation of segmental esophageal reconstruction using a polyurethane scaffold in a pig model

BackgroundMany esophageal pathologies are clinically treated by resection and reconstruction of the esophagus. Surgical esophagectomy remains a morbid procedure and despite minimally invasive advances, has changed little in decades. Novel approaches to esophageal segmental resection and reconstruction are an unmet need.MethodsCircumferential thoracic esophageal transection was performed in both male and female pigs and the defects reconstructed using 5 or 10 cm polyurethane (PU) tubular grafts and stented. A subset were treated with stent only. Animals were survived to 14, 30, 60, and 399 days. Tissues were evaluated histologically, and via non-invasive serial endoscopy and contrast swallowing studies in long-term animals.ResultsLuminal patency was achieved in all animals with no clinical evidence of leak. In short-term animals, there was healing noted in all cases with a variably sized region of ulceration remaining at the most central part of the repaired tube (between the proximal and distal anastomosis). In four long-term animals following stent removal, two resumed normal diet and thrived, while two animals were euthanized prior to the proposed endpoint because of stricture formation and inability to tolerate a normal diet. Re-epithelialization was observed in all groups, and more complete over time.ConclusionsThe PU scaffold provides a matrix across which formation of new tissue can occur. The mechanisms through which this happens remain unclear, but likely a combination of fibrosis and tissue contraction, in conjunction with new tissue formation.     

Constriction of resistance arteries determines l-NAME-induced hypertension in a conscious hamster model

The influence of infusion of a nitric oxide (NO) synthase inhibitor, N(omega)-nitro-l-arginine methyl ester (l-NAME), on resistance arteries (diameter, 150 +/- 8 microm) and its relationship with hypertension were examined in conscious hamsters fitted with a dorsal skinfold window. After infusing l-NAME (10 and 30 mg/kg), hamsters showed immediate hypertension of +13 +/- 9 and +21 +/- 9 mm Hg, respectively, relative to basal values, and a maximum of +44 +/- 4 mm Hg at 30 min for the high-dose group. There was simultaneous significant vasoconstriction of the resistance arteries (A(0)) which reduced to 60 +/- 5% of baseline diameter at 3 h; however, there was no significant vasoconstriction in large and small arterioles with diameters diameters less than 70 microm. Blood flow rate in all the vessels decreased in consonance with the vasoconstriction of the resistance artery, irrespective of microvessel classification. These results indicate that the resistance artery plays a key role as a regulator and microvascular resistance in determining blood flow distribution and hypertension when a NO synthase inhibitor is infused.     

The evaluation of radiolabeled artesunate on tissue distribution in rats and protein binding in humans

The present study reports the tissue distribution, pharmacokinetics, mass balance, and elimination of [(14)C] artesunate (AS) following single intravenous administration in rats. Protein binding was performed with rat and human plasma. Radioactivity and drug levels in blood, plasma, tissues, urine, and feces up to 192 hours were collected and measured. The mean terminal half-life of plasma (76 h) and blood (105 h) radioactivity was prolonged compared with that of unchanged AS (0.43 h) and dihydroartemisinin (0.75 h), an active metabolite of AS. Drug was widely distributed after 1 hour in select tissues. After 24 hours, the radioactivity rapidly declined in all tissues except spleen until 96 hours. Only 1% of total radioactivity was detected in brain tissue. AS revealed a higher binding capacity with human and rat plasma proteins (73-81%). The radioactivity in whole blood was higher (two to fourfold) than that in plasma throughout the period of the treatment, suggesting that AS binding to RBCs may relate to its powerful antimalarial activity.     

Physiologic evaluation of translesion pressure gradients in peripheral arteries: comparison of pressure wire and catheter-derived measurements

BACKGROUND: Catheter-derived pressure gradient (CPG) measurements across vascular lesions are used to determine the hemodynamic significance of a stenosis prior to peripheral vascular intervention. We tested the hypothesis that CPGs overestimate the true translesion gradient during hemodynamic interrogation. METHODS: We evaluated 20 lesions (iliac, subclavian, or renal) in 16 patients undergoing angiography for peripheral vascular disease. Mean arterial pressure gradients were measured across each lesion using a 4- or 5-Fr fluid-filled catheter and compared to gradients measured with a 0.014' pressure wire (PWG). RESULTS: In all lesions, the CPG was higher than the PWG (28.3 +/- 4.5 mmHg vs 11.6 +/- 1.8 mmHg; P < 0.05). Both CPG and PWG correlated with diameter stenosis (CPG = 0.78 [DS]- 29; r(2)= 0.44; P < 0.05 and PWG = 0.30 [DS]- 10.5; r(2)= 0.43; P < 0.05), but the CPG overestimated the pressure gradient compared with the PWG. CONCLUSION: Peripheral arterial vascular lesion pressure gradients assessed with large diameter catheters consistently overestimate the actual PG. Although both CPG and PWG correlated with anatomic stenosis, the overestimation of the physiologic significance of these lesions may lead to inappropriate intervention. Use of a pressure wire for hemodynamic interrogation may be a better tool for assessment of the hemodynamic significance of a peripheral vascular lesion.     

The effect of prostaglandin E1 on nailfold capillary blood pressure and red blood cell velocity in humans

PGE(1) or PGI(2) acutely increase total skin perfusion in healthy volunteers. This study investigated whether skin nutritive perfusion and capillary pressure were increased by acute infusion of PGE(1). In a double blind randomised placebo controlled study the effect of Alprostadil (PGE(1), Prostavasin, intra-venous, infusion rate: 0.38 microg/h/kg,) on skin nailfold capillary blood pressure (CP) and capillary red blood cell velocity (CBV) was investigated in 16 healthy volunteers (placebo: 5 male, 3 female, age: 27.7, range: 22-29 years; Alprostadil: 5 m, 3 f, age 27.1, 22-38 y), using the electrical impedance servo nulling technique and spatial shift alignment method, respectively. Initial finger tip temperature, systemic blood pressure, heart rate, CP, capillary pulse pressure amplitude (CPPA) and CBV showed no significant differences between the two groups (placebo: 23.6 +/- 3.0 degrees C, 123 +/- 13/83 +/- 5 mmHg, 63 +/- 11 beats/min, 15.6 +/- 3.9 mmHg, 1.5 +/- 1.8 mmHg, and 425 microm/s (290-800); Alprostadil: 23.4 +/- 2.7 degrees C, 121 +/- 9/82 +/- 10 mmHg, 65 +/- 9 beats/min, 14.4 +/- 3.7 mmHg, 1.8 +/- 1.3 mmHg, and 680 (140-1090 microm/s)). Twenty minute infusion with either Alprostadil or placebo had no significant effect on any of the parameters measured. Thus, in healthy volunteers, skin capillary blood pressure, capillary pulse pressure amplitude and capillary blood velocity are unaltered by acute administration of PGE(1) at ambient temperatures.     

Vasopeptidase inhibition has potent effects on blood pressure and resistance arteries in stroke-prone spontaneously hypertensive rats

The antihypertensive agent omapatrilat represents a novel approach to antihypertensive therapy, namely vasopeptidase inhibition. Omapatrilat (BMS-186716) concomitantly inhibits neutral endopeptidase and angiotensin-converting enzyme, leading to protection from degradation of natriuretic and other hypotensive peptides in addition to interruption of the renin-angiotensin system. Although the potency of omapatrilat on reduction of blood pressure has been reported, its effects on resistance artery structure and function were unknown. We tested omapatrilat in stroke-prone spontaneously hypertensive rats (SHRSP), a malignant model of hypertension, with the hypothesis that it would improve the structure and endothelial function of mesenteric resistance arteries. Ten-week-old SHRSP were treated orally for 10 weeks with omapatrilat (40 mg/kg per day). Mesenteric arteries (lumen <300 microm) were studied on a pressurized myograph. After 10 weeks, untreated SHRSP had a systolic blood pressure of 230+/-2 mm Hg that was significantly reduced (P<0.05) by omapatrilat (145+/-3 mm Hg). Omapatrilat treatment improved endothelium-dependent relaxation of resistance arteries as elicited by acetylcholine (10(-5) mol/L) but had no significant effect on endothelium-independent relaxation produced by a nitric oxide donor (sodium nitroprusside). This suggested that there existed endothelial dysfunction in SHRSP that was corrected by vasopeptidase inhibition, probably in part caused by the potent blood pressure-lowering effect of omapatrilat. Media width and media/lumen ratio were significantly decreased (P<0.05) by omapatrilat, and a trend (P=0.07) to increase lumen diameter was observed. Vascular stiffness (slope of the elastic modulus versus stress curve) was unaltered by omapatrilat. In conclusion, omapatrilat, acting as a potent antihypertensive agent, may improve structure and endothelial function of resistance arteries in SHRSP, a severe form of genetic hypertension.     

A model of the vascular resistance and compliance distribution in a lung lobe

The arterial and venous pressure curves obtained after occluding the venous outflow from a dog lung lobe perfused with constant flow contain information about the intralobar longitudinal distribution of vascular resistance (R) and compliance (C). To utilize this information, a lumped model consisting of four parallel C's separated by three serial R's was used. Solutions of the governing differential equations yield a nonlinear system of four algebraic equations in the seven unknowns and the measured data. Three of the equations form a linear subsystem in which the unknowns are the three R's and the coefficients are functions of the four C's. This is an underdetermined system, but when nonnegativity and boundedness constraints are adjoined, the solution set falls within a narrow band of distributions of cumulative R relative to cumulative C. The shape of this band changes when data are obtained from lobes influenced by various vasoactive stimuli revealing the changes in the longitudinal distribution of the vascular resistance relative to the vascular compliance.     

体外循环动脉微栓过滤器性能离体实验研究

目的:通过离体实验评价成人型动脉滤器(QUART)、米道斯动脉滤器(MEDOS)和宁波动脉微栓滤器的跨滤器压差和气泡去除能力。方法:分别选用QUART、MEDOS和宁波3种动脉过滤器各15个,依次为QG组、MG组和NG组,连接模拟体外循环管路,使用1 000 mL0.9%氯化钠预充环路,并在管路上连接Stockert气泡捕捉器。同时在动脉滤器的入口端、出口端和排气管处连接电子测压仪,使用管钳维持动脉滤器出口处压力为80 mmHg(1 mmHg=0.133 kPa),测定动脉滤器入口端、出口端和排气管处的压力。在流量为5.0 L/min时,于动脉滤器入口处每隔1 min加入10 mL空气,最多不超过80mL。结果:预充后NG组中9个(9/15,60.0%)动脉微栓滤器发出报警音,明显高于QG组和MG组,差异具有统计学意义(P<0.05);首次倒排时,QG、MG和NG组分别有1/15(6.7%)、13/15(86.7%)和15/15(100.0%)发出报警音,QG组明显低于MG组和NG组,差异具有统计学意义(P<0.05)。随着主泵流量的增加,3种动脉滤器入口端压力、出口端压力及压差均逐渐升高。相同流量下,3种动脉滤器入口端压力、出口端压力和压差差异均无统计学意义(P>0.05);流量为5 L/min,3组动脉滤器分别加入气体至80 mL时均未发出报警音。结论:使用动脉滤器时,排气需要2遍以上,才能安全使用。正常转机流量下,3种动脉滤器跨滤器压差基本相同。3种动脉滤器均有较强的气泡隔离能力。     

Lack of effect of a single oral dose of cyclosporine on systemic blood pressure and on forearm blood flow and vascular resistance in humans

The acute hemodynamic effect of cyclosporine in man is controversial. A randomized, double blind, placebo-controlled, cross-over study was undertaken to evaluate the effect of a single oral dose of cyclosporine (20 mg/kg body weight) on mean blood pressure (MBP), heart rate (HR), forearm blood flow (FBF), and vascular resistance (FVR) in 16 healthy adult subjects. Subjects were studied twice, with an intervening period of 2 weeks, before and after the administration of either cyclosporine or the vehicle olive oil. Blood pressure was measured on brachial and digital arteries. After 30 min of rest, basal measurements were obtained and individuals were randomly assigned to receive either cyclosporine or the vehicle, and the same measurements were repeated 2 h later. Mean whole blood levels of cyclosporine were 1542 ± 387 ng/mL (range 1000 to 2550) 2 h after the administration of a single oral dose of cyclosporine. Cyclosporine did not cause any significant change in the hemodynamic parameters when compared with vehicle. Pre- and post–cyclosporine data were as follows (means ± SD): MBP (determined by Finapres on the digital artery), 92 ± 10 v 95 ± 11 mm Hg; HR, 66 ± 10 v 68 ± 11 beats/min; FBF, 3.9 ± 1.3 v 3.8 ± 1.8 mL/100 mL/min; and FVR, 28 ± 9 v 33 ± 18 units, respectively. For the vehicle the results were: MBP, 94 ± 9 v 94 ± 9; HR, 67 ± 9 v 67 ± 11; FBF, 3.3 ± 1.6 v 3.2 ± 2.0; FVR, 35 ± 14 v 37 ± 15, respectively. These figures did not differ from those obtained with the auscultatory method applied to the brachial artery among 10 selected subjects studied with Finapres. In conclusion, we found no evidence that at supratherapeutic doses cyclosporine causes acute increase in blood pressure or peripheral vasoconstriction in humans.     

Menopause and the characteristics of the large arteries in a population study

In previous cross-sectional and longitudinal population studies, we found that the slope of systolic pressure on age was steeper in postmenopausal than in premenopausal women. We hypothesised that this observation could be due to a specific effect of menopause on the elasticity of the large arteries. We investigated 315 randomly selected women, aged 30 to 70 years. Based on 5.2 years of follow-up, 166 women were premenopausal and 149 menopausal (44 reaching menopause and 105 postmenopausal). These women were matched on age and body mass index with 315 men. We used a wall-tracking ultrasound system to measure the diameter, compliance and distensibility of the brachial and the common carotid and femoral arteries as well as carotid-femoral pulse wave velocity. Pulse pressure was determined from 24-h blood pressure recordings. Both in menopausal women (r = 0.37; P < 0.001) and in matching male controls (r = 0.16; P = 0.04), pulse pressure widened with increasing age. The slope of the 24-h pulse pressure on age was steeper in menopausal women than in their premenopausal counterparts (0.428 vs -0.066 mm Hg per year; P = 0.003) and than in the male controls (0.428 vs 0.188 mm Hg per year; P = 0.06). After adjustment for age, 24-h mean pressure, body mass index, antihypertensive drug treatment, smoking and the use of oral contraceptives or hormonal replacement therapy, postmenopausal women showed a higher carotid-femoral pulse wave velocity (7.77 vs 6.71 m/s; P = 0.02) and had a slightly greater diameter of the common carotid artery (7.09 vs 6.79 mm; P = 0.07) than their premenopausal counterparts. After similar adjustments, menopausal class was not significantly associated with other vascular measurements in women or with any vascular measurement in control men. In conclusion, menopause per se may increase aortic stiffness. We hypothesise that this phenomenon may contribute to the rise in systolic pressure and pulse pressure in women beyond age 50 and, in turn, may lead to a slight dilatation of the common carotid artery.