VASO-based calculations of CBV change: accounting for the dynamic CSF volume

The goal of the vascular space occupancy (VASO) imaging technique is to use selective nulling of the blood signal to infer relative changes in cerebral blood volume (CBV). In accordance with recent work, we show that changes in the local CSF fraction (x(c)) with activation can significantly impact the VASO signal, thereby limiting our ability to infer DeltaCBV from DeltaVASO alone. Here we calculate CBV change using a VASO-based method which ACcounts for the Dynamic Cerebrospinal (ACDC) fluid fraction. By combining data from two separate VASO acquisitions that eliminate either the blood signal (VASO(b)) or the CSF signal (VASO(c)), a nonlinear least-squares optimization may then be used to simultaneously solve for the relative changes in CBV and CSF with activation. The method is applied across the whole brain during a breath-holding task, offering insight into the relationship between changes in CBV and x(c) associated with global vasodilatation. Calculations of mean changes in CBV in different volumes of interest obtained from the proposed method compare much better with previous (gold-standard) PET data than traditional VASO methods that do not account for a nonzero Deltax(c) with activation. This confirms the necessity of incorporating the dynamic CSF volume into VASO-based calculations of DeltaCBV.     

Effects of insulin infusion on endothelium-derived vasoactive substances

Summary An association between insulin resistance and hypertension has been reported in several studies. In apparent contradiction, insulin infusion in healthy volunteers is associated with vasodilatation. Furthermore, there is evidence that some insulin effects may differ between the sexes. We performed three-step hyperinsulinaemic-euglycaemic clamp studies in six men and six women to test the hypotheses that: 1) insulin might affect the release of vasoactive substances by the endothelium, and 2): this putative effect on vasoactive substances might differ between men and women. Six other women and six men served as control subjects, receiving 154 mmol/l NaCl (saline) infusion. Plasma levels of insulin, immunoreactive endothelin, l-arginine (precursor of nitric oxide), l-citrulline (by-product of nitric oxide synthesis) and cyclic GMP (second messenger of nitric oxide) were measured during infusion of insulin or 154 mmol/l NaCl (saline), respectively. We also assessed urinary excretion of 6-keto PGF-1α (a degradation product of prostacyclin reflecting prostacyclin production). Blood pressure was monitored in all subjects throughout the experiment. In women plasma levels of immunoreactive endothelin decreased from (mean ± SD) 2.58 ± 0.96 to 1.7 ± 0.72 pmol/l during insulin infusion (p < 0.01), while remaining constant in female control subjects (p < 0.02). No changes in levels of endothelin were observed in men during infusion of insulin or saline. In women levels of cGMP rose and levels of l-arginine decreased significantly during insulin infusion, consistent with an increase in nitric oxide production. Excretion of 6-keto PGF-1α also increased significantly in women during insulin infusion. No such effects were observed in men, or in women during infusion of saline. Blood pressure remained constant in all subjects during hyperinsulinaemia. We conclude that sex differences exist in the effects of insulin on the endothelium. Short-term hyperinsulinaemia in women is associated with a decline in levels of immunoreactive endothelin, and possibly with a rise in production of nitric oxide and prostacyclin. In contrast, levels of vasoactive substances remained constant in men during hyperinsulinaemia. Our findings may partly explain insulin's vasodilatory effects in healthy individuals. It remains to be investigated whether these effects are lost in insulin-resistant states. Our observation that there is a sex difference in insulin effects on the endothelium may help explain why the link between hyperinsulinaemia and cardiovascular disease appears to be clearer in men than in women. [Diabetologia (1996) 39: 1284–1292] Received: 30 April 1996 and in revised form: 18 July 1996     

Diagnosis of hepatopulmonary syndrome with contrast transthoracic echocardiography and histological confirmation

ABSTRACT— We report a patient with cirrhosis and hepatopulmonary syndrome. This syndrome is an entity characterized by anomalies in the arterial oxygenation in patients with chronic hepatic disease and/or portal hypertension and demonstration of pulmonary vasodilatation (PV) in absence of primary cardiac or pulmonary disease. We show that the finding of PV with transthoracic contrast enhanced echocardiography (TCEE) in the diagnosis of PV is real and corresponds to direct measurement of capillary diameter by morphometry.     

Pulmonary Arterial Endothelial Dysfunction Potentiates Hypercapnic Vasoconstriction and Alters the Response to Inhaled Nitric Oxide

Background. Pulmonary hypertensive crisis can be initiated by episodes of hypercapnic acidosis. Hypercapnic vasoconstriction in the newborn pulmonary arterial circulation may be modulated by endogenous production of nitric oxide (NO) by the endothelial cell and effectively treated with inhalation of NO.

Methods. Sixteen 48-hour-old piglets were randomized to receive a hypercapnic challenge after administration of either saline vehicle or the NO synthase inhibitor N-ω-nitro-

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-arginine (L-NA). Pulmonary arterial pressure, flow, and radius measurements were taken at baseline, after infusion of vehicle or L-NA, during hypercapnia (inspired fraction of carbon dioxide, 0.15), and during inhalation of NO (100 ppm). Fourier analysis was used to calculate input mean impedance, reflecting distal arteriolar vasoconstriction, and characteristic impedance, reflecting proximal arterial geometry and distensibility.

Results. Input mean impedance was increased with L-NA administration. Animals pretreated with L-NA also underwent a much larger increase in input mean impedance with exposure to hypercapnia than untreated animals. Characteristic impedance increased in the treated animals, but not in the controls.

Conclusions. In the newborn pulmonary arterial circulation, endogenous NO production by the endothelial cell modulates resting tone distally, but not proximally. In addition, lack of a functional endothelium markedly potentiates the distal vasoconstrictor response to hypercapnia and produces proximal vasoconstriction. Despite impaired endothelial function, inhaled NO remains an effective vasodilator in hypercapnic pulmonary vasoconstriction.     

老年2型糖尿病大血管病变与血管内皮依赖性舒张功能的相关性

目的　探讨老年 2型糖尿病大血管病变与血管内皮依赖性舒张功能的关系。方法　采用高分辨超声以肱动脉反应性充血前后血管内径变化百分比反映血管内皮依赖性舒张功能 ,对 4 5例老年 2型糖尿病患者 (2 4例合并大血管病变 ,2 1例无大血管病变 )及 2 0例对照组进行血管内皮依赖性舒张功能测定 ,同时测定血糖、血脂及血压水平。结果　老年 2型糖尿病患者肱动脉内径变化率明显低于对照组 [(1 97± 1 75 ) %vs (7 18± 1 6 1) % ,P <0 0 1],并与患者的年龄、血糖、低密度脂蛋白、收缩压水平负相关 ,且大血管病变组肱动脉内径变化率较无大血管病变组更低[(0 4 2± 0 36 ) %vs (3 5 6± 3 2 1) % ,P <0 0 1]。结论　老年 2型糖尿病大血管病变的发生与血管内皮依赖性舒张功能紊乱密切相关。     

Effect of nifedipine on superior mesenteric artery impedance in humans

Objective: In a randomized, double-blind placebo-controlled study the acute effect of sublingual nifedipine (10 mg) on the superior mesenteric artery pulsatility index (PI) was studied over 60 min in 12 healthy subjects (Age 43 y). Methods: PI was considered as a parameter of vascular resistance and was calculated as the peak-to-peak amplitude of the waveform divided by the mean amplitude. PI measurements were performed with the subject resting and fasting and were made 5, 10, 15, 30, 45 and 60 min for 1 hour after nifedipine (10 mg) or placebo. Arterial blood pressure and heart rate were measured at the same times. Results: Placebo administration failed to change arterial blood pressure, heart rate or PI. 5 min after 10 mg sublingual nifedipine, PI had significantly decreased from 5.0 to 3.8, with a nonsignificant decrease in arterial blood pressure and an increase in heart rate. By 15 min after nifedipine administration PI had further decreased to 3.1, and there was a concomitant significant decrease in mean arterial blood pressure and increase in heart rate. Sixty minutes after drug intake PI and arterial blood pressure were still below baseline not significant but the heart rate remained significantly increased. Conclusion: Our data indicate that in healthy subjects sublingual administration of nifedipine had a vasodilator effect (decrease in PI) on the superior mesenteric vascular bed. Received: 1 August 1995/Accepted in revised form: 2 March 1996     

Potential neurogenic and vascular roles of nitric oxide in migraine headache and aura

It has long been known that nitrate and nitrite medications consistently cause significant headache as a side effect. Classical research has shown that cerebral vasodilation accompanies the use of these medications. More modern studies suggest that these vasodilators exert their action on blood vessels via nitric oxide and its second messenger, cyclic guanosine monophosphate. This paper reviews research studies and theoretical articles which address the concept that nitric oxide plays a major role in the vasodilation associated with the headache phase of migraine with aura. A brief discussion of nitric oxide biochemistry and pharmacology follows.
In addition, there is a review of evidence examining the possible contributions of nitric oxide to the neurogenic and vascular events associated with spreading cortical depression, an animal model of migraine aura. The paradoxical hypotheses that nitric oxide may contribute to both the propagation of spreading cortical depression and its limitation are presented. Finally, a rationale for the experimental use of nitric oxide agonists and antagonists in the abortion of migraine aura is introduced.     

Enhanced external counterpulsation improves skin oxygenation and perfusion

BACKGROUND: Enhanced external counterpulsation (EECP) augments diastolic and reduces systolic blood pressures. Enhanced external counterpulsation has been shown to improve blood flow in various organ systems. Beneficial effects on skin perfusion might allow EECP to be used in patients with skin malperfusion problems. This study was performed to assess acute effects of EECP on superficial skin blood flow, transdermal oxygen and carbon dioxide pressures. MATERIALS AND METHODS: We monitored heart rate, blood pressure, transdermal blood flow as well as oxygen and carbon dioxide pressures in 23 young, healthy persons (28 +/- 4 years) and 15 older patients (64 +/- 7 years) with coronary artery disease before, during and 3 min after 5 min EECP. Friedman test was used to compare the results of 90-s epochs before, during and after EECP. Significance was set at P < 0.05. RESULTS: Enhanced external counterpulsation increased heart rate and mean blood pressure. During EECP, transdermal oxygen pressure and concentration of moving blood cells increased while transdermal carbon dioxide pressure and velocity of moving blood cells decreased significantly in both groups. After EECP, transdermal carbon dioxide pressure was still reduced while the other parameters returned to baseline values. CONCLUSIONS: Improved skin oxygenation and carbon dioxide clearance during EECP seem to result from the increased concentration and reduced flow velocity, i.e. prolonged contact time, of erythrocytes. The increased concentration of moving blood cells and the decreased velocity of moving blood cells at both tested skin sites indicate peripheral vasodilatation.     

Brachial artery pulsatility index change 1 minute after 5-minute forearm compression: comparison with flow-mediated dilatation.

OBJECTIVE: Endothelial impairment evaluation by sonographic measurement of flow-mediated dilatation (FMD) has become broadly used. However, this method has 2 main caveats: the dilatation depends on the baseline arterial diameter, and a high precision level is required. Vasodilatation leads to an amplified fall in impedance. We hypothesized that assessment of the pulsatility index change (PI-C) 1 minute after 5-minute forearm compression might evaluate that fall in impedance. The aim of this study was to compare the PI-C with FMD. METHODS: Flow-mediated dilatation and the PI-C were assessed in 51 healthy women aged between 35.1 and 67.1 years. We correlated both FMD and the PI-C with age, body mass index, waist circumference, cholesterol level, high-density lipoprotein level, glucose level, systolic and diastolic blood pressure, pulse pressure, brachial artery diameter, simplified Framingham score, intima-media thickness, and carotid stiffness index. Intraclass correlation coefficients between 2 FMD and PI-C measurements were also examined. RESULTS: Only FMD correlated with baseline brachial diameter (r = -0.53). The PI-C had a high correlation with age, body mass index, waist circumference, cholesterol level, systolic blood pressure, pulse pressure, simplified Framingham score, and intima-media thickness. The correlation between FMD and the PI-C was high (r = -0.66). The PI-C had a higher intraclass correlation coefficient (0.991) than FMD (0.836) but not brachial artery diameter (0.989). CONCLUSIONS: The PI-C had a large correlation with various markers of cardiovascular risk. Additionally, PI-C measurement does not require offline analysis, extra software, or electrocardiography. We think that the PI-C could be considered a marker of endothelial function. However, more studies are required before further conclusions.     

Effects of fluvastatin, an HMG-CoA reductase inhibitor, on serum levels of interleukin-18 and matrix metalloproteinase-9 in patients with hypercholesterolemia

BACKGROUND: Interleukin-18 (IL-18), a novel proinflammatory marker, and matrix metalloproteinase-9 (MMP-9) represent the indices of plaque stability. It is unknown whether hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), which provide anti-inflammatory and endothelium protection effects, have the property of stabilizing plaque in patients with hypercholesterolemia. HYPOTHESIS: The study was designed to investigate the influence of statin therapy in circulating IL-18, MMP-9, and endothelial function. METHODS: We investigated the effects of a 12-week therapy with fluvastatin on IL-18, MMP-9, and endothelial function in patients with hypercholesterolemia. RESULTS: Compared with placebo, fluvastatin significantly improved flow-mediated vasodilatation to hyperemia, a hallmark of endothelial function [from 3.8% (-3.9 approximately 15.2) to 5.9% (-0.3 approximately 13.2), p = 0.001], and attenuated plasma levels of high sensitivity C-reactive protein (hsCRP) [from 1.3 (0.3 approximately 7.7) to 1.1 mg/l (0.2 approximately 3.5), p = 0.018], IL-18 [from 247.6 (145.4 approximately 378.4) to 196.4 pg/dl (90.7 approximately 380.2), p <0.001], total MMP-9 (from 58 +/- 46.3 to 39.4 +/- 22.4 ng/dl, p = 0.023), and MMP-9 activity [from 6.4 (3.6 approximately 27) to 5.6 ng/dl (3.1 approximately 13.7)]. However, no significant correlation was found between the degree of changes in lipid profile and flow-mediated dilatation (FMD) and plasma concentration of IL-18 and MMP-9. CONCLUSIONS: Fluvastatin reduced plasma concentrations of IL-18 and MMP-9, and improved endothelial function in patients with hypercholesterolemia independent of its lipid-lowering effect.