Human endothelial impairment in sepsis Vaudo, Gaetano; Marchesi, Simona; Siepi, Donatella ...
Atherosclerosis,
04/2008, Letnik:
197, Številka:
2
Journal Article
Recenzirano
Abstract The onset of sepsis is often non-specific, and its severity is cryptic. The pathophysiological mechanism of sepsis development involves vascular alteration and, in particular, the impairment ...of endothelial function. Aim of the study was to evaluate the potential implications of brachial endothelial function assessment in patients affected by Gram-negative sepsis. Forty-five young patients (mean age 41 ± 8 years, 18 males) with Gram-negative sepsis were included; at admission time (T0) signs and symptoms, clinical and laboratory data were collected; the Sequential Organ Failure Assessment (SOFA) score was assessed at the time of the access along with the evaluation of brachial flow-mediated vasodilation (FMV). The same parameters were repeated 3 days after hospitalization (T1). Study population at the hospitalization time was divided on the basis of a brachial FMV cut off: at the T0 subjects with FMV < 7.5% had lower white blood cell count in comparison to subjects with FMV ≥ 7.5% (6693 ± 1559 mmc versus 14,270 ± 2399 mmc); subjects with FMV < 7.5% had a significant increase in SOFA score at T1 (4 ± 1 versus 6 ± 1) and a significant reduction of brachial FMV at T1 (4.8 ± 2.7% versus 3.7 ± 2.6%) (all p < 0.05). FMV at the admission time was predicted by white blood cells ( β = 0.65; p < 0.001) and brachial diameter ( β = −0.292; p < 0.05); Δ changes in FMV were predicted by changes in SOFA score ( β = −0.41; p < 0.05). In conclusion, the present study indicates that in the initial phase of sepsis an impairment of brachial FMV anticipated the progression in organ failures; these considerations support the potential utility of brachial FMV in clinical practice in acute pathologies as septic state.
To determine the effects of capillary rarefaction on cardiovascular reactivity and microcirculatory functioning in essential hypertension.
Hypertension is associated with abnormal cardiovascular ...reactivity and increased vasoconstriction. Capillary rarefaction amplifies these abnormalities, which modify microcirculatory hemodynamics. Hence this study of the hemorheological pattern and the veno-arteriolar reflex in hypertensive patients and normotensive control subjects.
Sixty-one men with never-treated essential hypertension and capillary rarefaction (< 80 capillaries per field) and 20 age-matched and sex-matched controls underwent a strenuous cycle ergometer test to monitor, during exercise and recovery, the blood pressure profile and the hemorheological pattern: blood viscosity at low shear, hematocrit and leukocyte counts, soluble P-selectin levels, and red and white blood cell filterability rates. The veno-arteriolar reflex was determined by laser-Doppler flowmetry before exercise and at recovery.RESULTS Hypertensive men with < or = 72 capillaries per field had an abnormal hemorheological profile before exercise. The physiological response to exercise was observed only in the controls and in hypertensives with > or = 73 capillaries per field. Abnormal responses to exercise worsened as capillaries were more rarefied. At recovery, hemorheological parameters in hypertensives with 65-72 capillaries per field returned to baseline, remaining significantly (P < 0.05) different to control values. Variations in the hemorheological pattern in hypertensives with < 64 capillary per field persisted at recovery. The veno-arteriolar reflex followed the same pattern.
A reduced microvascular network may contribute to abnormal cardiovascular reactivity and to exercise-induced rheological abnormalities in hypertension.
Abstract There is much evidence to suggest the existence of racial differences between blacks and whites in the behaviour of endothelial function. Infective state, sustained by viral or bacterial ...agents, may injure the endothelial surface favouring the onset and progression of atherosclerotic process, mainly by an inflammatory mechanism. The aim of the study was to investigate endothelial function, expressed as brachial flow-mediated vasodilation (FMV), in black and white healthy subjects, along with antibody titer to cytomegalovirus, hepatitis virus (B, C), herpes virus-1 and 2, Epstein-Barr, Chlamydia pneumoniae and the expression of adhesion molecules. We enrolled 22 young (mean age 27 ± 8 years) healthy subjects of black race (10 males) and 20 healthy young subjects (10 males, mean age 28 ± 9 years) of white race. Total infectious burden (TIB) was defined as the number of serological positive infections. Black subjects have a reduced brachial FMV (6.9 ± 3.5% versus 11.6 ± 3.0%, p < 0.01) and increased values of hsCRP (0.35 ± 0.15 mg/dL versus 0.07 ± 0.08 mg/dL, p < 0.05), white cells (8578 ± 1041/mmc versus 5833 ± 998/mmc, p < 0.01) and adhesion molecules (respectively: sVCAM-1 945 ± 142 versus 779 ± 93, sICAM-1 534 ± 107 ng/mL versus 325 ± 80 ng/mL; both p < 0.01) in comparison to white subjects. The total infectious burden in black race was significantly higher than in white race (5 ± 1 versus 2 ± 1, p < 0.01). At the univariate analysis, brachial FMV was significantly related to the levels of adhesion molecules (respectively: sVCAM-1 r = −0.49; sICAM-1 r = −0.50, both p < 0.05), hsCRP ( r = −0.47, p < 0.05) and white blood cells ( r = −0.43, p < 0.05). TIB was associated with brachial FMV ( r = −0.64, p < 0.05), sVCAM-1 ( r = 0.55, p < 0.05) and hsCRP ( r = 0.47, p < 0.05). At the multivariate analysis the only predictive variables for brachial FMV were hsCRP, TIB and brachial diameter (respectively: β = −0.49, −0.19, −0.54, all p < 0.05). This study confirms that endothelial reactivity is impaired in young African black patients; moreover its behavior is strictly related to the inflammatory state and to the total infectious burden.
Atherosclerosis is increasingly recognized as an inflammatory vascular disease, and high blood pressure (BP) has been suggested to exert a proinflammatory action. Whether plasma viscosity (PV), a ...major determinant of blood flow in microcirculation and a marker of systemic inflammation and cardiovascular risk, is increased in elderly subjects with isolated systolic hypertension is not known. In addition, the correlation of BP and its pulsatile component (ie, pulse pressure PP), with PV levels independent of the confounding effect of other cardiovascular risk factors has not been investigated. To this aim, we measured PV in 108 elderly men with never treated, uncomplicated isolated systolic hypertension, and in 60 healthy matched normotensive control subjects.
The PV values were higher in hypertensive subjects than in controls (1.39 ± 0.11 v 1.34 ± 0.09 cP, P < .01). The PV showed a significant direct relation with both systolic BP (r = 0.32) and PP (r = 0.37, both P < .01), but not with diastolic BP (r = −0.03, P = .68). The PV was also directly associated with serum low-density lipoprotein cholesterol and triglycerides. In a multivariate analysis, PP was a significant predictor of PV levels when a consistent number of cardiovascular risk factors were simultaneously controlled for.
In conclusion, PV is elevated in elderly subjects with isolated systolic hypertension. Systolic BP and PP appear to be major determinants of PV levels in these patients, independent of the potential proinflammatory action of traditional cardiovascular risk factors.
Chronic inflammatory stimulus seems to contribute to atherosclerotic process. Several studies have established a relationship between infective agents as
Chlamydia pneumoniae, herpes virus and ...cytomegalovirus and atherosclerotic lesions. Aim of this study was to investigate the effects of influenza infective state on endothelial function of healthy young subjects, expressed as brachial flow-mediated vasodilation (FMV) and soluble form of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1). In 10 male subjects (mean age 35
±
14 years) exhibiting influenza symptoms for 3 days, we determined total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, sVCAM-1, sICAM-1 and brachial FMV. All subjects had an antibody pattern characteristic of influenza A or B virus infection. After 3 months brachial FMV was significantly increased (8.6
±
2.3% versus 11.5
±
3.2%;
p
<
0.001), while HDL (46
±
10
mg/dL versus 49
±
9
mg/dL;
p
<
0.05), sICAM-1 and sVCAM-1 were reduced (respectively: 488
±
105
ng/mL versus 340
±
127
ng/mL;
p
<
0.001, 1710
±
80
ng/mL versus 1216
±
63
ng/mL;
p
<
0.001). Univariate analysis showed a positive correlation between changes in CRP and sICAM-1 levels (
r
=
0.95,
p
<
0.001), a negative one between changes in sICAM-1 and brachial FMV (
r
=
−0.65,
p
<
0.05) and between CRP and brachial FMV (
r
=
−0.64,
p
<
0.05). This small study suggested that inflammatory state determined by viral agents may transitorily alter endothelial function in healthy subjects.
Prostaglandin E1 (PGE1) may relieve rest pain and heal ulcers in critical limb ischemia, but its mechanism of action is still incompletely understood. To investigate the effects of PGE1 treatment on ...endothelial function evaluated as brachial artery flow-mediated vasodilation (FMV) and on soluble adhesion molecule plasma levels (vascular adhesion molecule-1 sVCAM-1 and intercellular adhesion molecule-1 sICAM-1), 12 patients with critical limb ischemia were treated with daily PGE IV infusion (alprostadil 60 microg) for 2 weeks. FMV and plasma sICAM-1 and sVCAM-1 concentrations were determined at baseline, after the first infusion, and after 1 and 2 weeks. Compared with 30 healthy control subjects, patients had higher baseline sVCAM-1 (2.402 +/- 296 ng/ml vs 972 +/- 117 ng/ml) and sICAM-1 levels (464 +/- 51 ng/ml vs 206 +/- 37 ng/ml, both p < 0.05) and lower FMV (1.0 +/- 1.1% vs 5.6 +/- 1.6%, p < 0.05). sICAM-1 concentration progressively decreased with treatment (from 464 +/- 51 ng/ml to 326 +/- 56 ng/ml, 288 +/- 42 ng/ml, and 279 +/- 44 ng/ml after the first dose and, respectively, after 1 and 2 weeks; all p < 0.05). sVCAM-1 showed a reduction after 2 weeks (from 2.402 +/- 296 ng/ml to 1.916 +/- 176 ng/ml; p < 0.05). FMV improved after 1 and 2 weeks (from 1.0 +/- 1.1% to 3.1 +/- 0.6% and 5.2 +/- 2.1%, both p < 0.05). In conclusion, treatment with PGE1 determines a significant improvement in endothelial function in patients with critical limb ischemia.
This double-blind pilot study observed the effects of a twenty-one day oral ticlopidine treatment (250 mg/twice daily) on the neurologic outcome and the hemorheologic pattern of 15 patients and 15 ...placebo-treated controls. Patients and controls (age range sixty-six to eighty-six years) were included in the study within twelve hours of the onset of ischemic stroke, confirmed clinically and by computerized tomography. Scores on Hachinski's Scale and the following hemorheologic parameters were monitored weekly for twenty-one days: fibrinogen levels, the whole blood, unfractionated white and red blood cell filterability rates (through 5-micron-pore-diameter filters using a constant-flow positive-pressure system), and the leukocyte count and activation (by microscopic observation). The results showed treatment with ticlopidine improved the neurologic outcome (Hachinski's Score +36%, p less than 0.03) slightly but significantly (p less than 0.001) increased the average values of the whole blood (+19%) and red cell (+17%) filterability rates and decreased fibrinogen levels (-17%).
The usefulness of Clopidogrel as inhibitor of platelet aggregation has been demonstrated, but its effect on hemoreological parameters, such as whole blood viscosity at low and high shear rate, red ...cell aggregation and deformability indexes, filterability rate and and deformability of red blood cells has not been studied. This study revealed that, in subjects with impaired blood rheology and ultrasound evidence of atherosclerosis, 3-weeks treatment with clopidogrel (75 mg daily) improved blood viscosity at high shear rate and other hemorheological parameters, including red cell filterability rates and dynamic red cell deformability index (p<0.01 for all), without any unwanted side effect. Blood viscosity at low shear rate and red cell aggregation index improved after only 1-week treatment, and the reductions were mantained after two and three weeks (p<0.01). These results indicate that, similarly to another thienopyridine such as ticlopidine, Clopidogrel may have a positive influence on several hemorheological parameters, thus exerting its protection not only through inhibition of platelet function, but also through changes in the hemorheological profile.
In peripheral vascular disease (PVD), impaired blood viscosity (BV) plays a major role in residual microvascular perfusion. Indeed, during acute leg ischaemia factors influencing microvascular BV ...include the plasma fibrinogen concentration, red and white blood cell rheology, as well as platelet aggregation and activation.
To assess the effects of Iloprost in patients with PVD.
The effects of an infusion of a single dose of Iloprost (from 0.5 up to a maximum of 2 ng/kg/min. over 6 hours) in 16 patients with stage II peripheral vascular disease on blood rheology and tissue perfusion were determined in a double-blind placebo-controlled study, using repeated treadmill exercise test to stress leg circulation. Blood viscosity at low shear, soluble P-selectin levels (expression of platelet activation), unfractionated leukocyte and erythrocyte filterability rates, plasma fibrinogen concentration, haematocrit, leukocyte and platelet counts and transcutaneous oxygen pressure (TcPO(2)) were measured in two matched groups of 8 PVD patients before and after Iloprost infusion.
Controlled peripheral ischaemia generated an impaired haemorheological profile; Iloprost reduced the impairments in BV and the filterability rates of unfractionated leukocytes and erythrocytes, inhibited platelet activation, and improved erythrocyte deformability. These changes were associated with significant shortening of the TcPO(2) half recovery time (the drop of TcPO(2) occurs because the ischaemic skeletal muscle steals oxygen from the skin), indicating that ischaemic damage had been contained.
Our results show that the infusion of a single dose of Iloprost in patients with PVD is associated with a significant improvement in microvascular functioning
Abstract Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis associated with impaired endothelial function and intermittent claudication is the hallmark symptom. ...Hypothesizing that osteopathic manipulative treatment (OMT) may represent a non-pharmacological therapeutic option in PAD, we examined endothelial function and lifestyle modifications in 15 intermittent claudication patients receiving osteopathic treatment (OMT group) and 15 intermittent claudication patients matched for age, sex and medical treatment (control group). Compared to the control group, the OMT group had a significant increase in brachial flow-mediated vasodilation, ankle/brachial pressure index, treadmill testing and physical health component of life quality (all p < 0.05) from the beginning to the end of the study. At univariate analysis in the OMT group there was a negative correlation between changes in brachial flow-mediated vasodilation and IL-6 levels ( r = −0.30; p = 0.04) and a positive one between claudication pain time and physical function score ( r = 0.50; p = 0.05). In conclusion, despite the relatively few patients in our study, these results suggest that OMT significantly improves endothelial function and functional performance in intermittent claudication patients along with benefits in quality of life. This novel treatment combined with drug and lifestyle modification might be an effective alternative to traditional training based on exercise.
PDF
