8 research outputs found
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Effects of severe, uncontrolled hypertension on endothelial activation: soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1 and von Willebrand factor
OBJECTIVES The molecular mechanisms whereby severe, uncontrolled hypertension (SHT) is translated into acute vascular target organ dysfunction have not been completely defined. We sought to determine whether SHT is associated with pressure-dependent endothelial activation as assessed by soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and von Willebrand Factor (vWF).
METHODS We determined sVCAM-1, sICAM-1 and vWF in three groups(i) untreated patients referred specifically for treatment of SHT [diastolic blood pressure (DBP) ≥ 120 mmHg;n = 24]; (ii) untreated patients with established mild hypertension (MHT; DBP 95–100 mmHg;n = 19); and (iii) normotensive volunteers (DBP ≤ 90;n = 16).
RESULTS By analysis of variance, sVCAM-1 (P = 0.002), sICAM-1 (P = 0.02) and vWF (P = 0.009) were greater in SHT and MHT than in normotensives but did not differ between SHT and MHT. We observed a significant positive correlation between blood pressure and soluble activation markers at lower blood pressures (normotensives and MHT considered together) that was not present in SHT.
CONCLUSIONS Even mild elevation of blood pressure may be sufficient to activate the expression of adhesion molecules. Mechanisms other than the endothelial expression of adhesion molecules may be important in mediating the accelerated target organ injury produced by SHT in humans. Concentrations of soluble adhesion molecules and vWF may depend more strongly upon factors in the hypertensive microenvironment other than the absolute level of blood pressure
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Elevated platelet P-selectin expression and platelet activation in high risk patients with uncontrolled severe hypertension
Uncontrolled severe hypertension is associated with alarming rates of cardiovascular events but the mechanisms of vascular injury are not well understood. Recent investigative interest has focused on platelet activation and platelet P-selectin (CD62P) as direct mediators of vascular inflammation and injury. We investigated the association of extreme blood pressure (BP) elevation with platelet P-selectin and fibrinolytic markers in high risk patients with severe hypertension.
Cross-sectional comparison of platelet CD62, tissue plasminogen activator antigen (tPA), and plasminogen activator inhibitor-1 activity (PAI-1) among 3 BP groups: untreated severely hypertensive patients (SHT; n=18), untreated mildly hypertensive patients (MHT; n=19), and normotensive controls (NT; n=16).
Platelet CD62 was greatest in SHT (p=0.00008) and showed a strong correlation with both systolic (p=0.0002, r=0.52) and diastolic (p=0.0003, r=0.52) BP. tPA was greater in SHT than MHT or NT (ANOVA; p=0.02) and correlated with diastolic BP but not SBP. PAI-1 did not correlate with either SBP or DBP but was related to body mass index, diabetes, and dyslipidemia.
Platelet CD62 demonstrated a strong and graded association with both systolic and diastolic BP that persisted in the presence of multiple concomitant risk factors. The association of BP with CD62P was stronger than with either PAI-1 or tPA-Ag. Platelet activation and platelet CD62 increase in a BP-dependent manner and this relationship persists at extreme levels of BP. Platelet activation and platelet CD62 may participate in the accelerated target organ injury observed in high risk patients with severe hypertension
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P-680: Endothelial and platelet activation in severe, uncontrolled hypertension: Absolute effect of extreme blood pressure elevation on soluble adhesion molecules and CD62 (P-selectin)
Introduction: Although patients with extreme elevations of blood pressure (BP) are at especially high risk for acute target organ injury, the molecular mechanisms by which severe uncontrolled hypertension (HT) is translated into acute target organ injury are not established. Whether adhesion molecules and CD62 (P-selectin) are mediators of acute target organ injury in patients with severe uncontrolled hypertension is not known. The aim of our study is to ascertain the effect of extreme elevation of BP on endothelial and platelet injury/activation as measured by expression of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and CD62. Methods: Comparison of sVCAM-1, sICAM-1, and CD62 among 3 groups: Untreated severe hypertensives (Severe HT; n=24) with diastolic blood pressure (DBP)≥120 mm Hg, mild hypertensives (Mild HT; n=19) with DBP≤100 mm Hg, and normotensive control subjects (NT; n=15). Results [Expressed as mean (SD)]: sVCAM-1 (p=.0001), sICAM-1 (p=.006), and CD62(p=.0006) were greater in Severe HT and Mild HT than NT but did not differ between Severe HT and Mild HT. By regression analysis, there appeared to be no relationship between the absolute level of BP and the concentrations of sVCAM-1 and sICAM-1. CD62 showed a significant but weak relationship with systolic (p=.001, R squared=.19), diastolic (p=.006, R squared=.14), and pulse pressure (p=.003, R squared= .16). Conclusion: Our results suggest that concentrations of soluble adhesion molecules and CD62 may depend more strongly upon factors in the hypertensive microenvironment other than the absolute level of BP. There does not seem to be a dose-response between these markers and BP per se. Even mild elevation of BP may be sufficient to activate the expression of adhesion molecules and CD62. Other mechanisms than endothelial cell and platelet activation/injury may be important in producing target organ injury in severe uncontrolled hypertension. (See Table) Severe HT Mild HT Normotensive SBP (mm Hg) 195 (26) 145 (10) 121 (9) DBP (mm Hg) 127 (7) 96 (1) 79 (6) Pulse Pressure 68 (23) 46 (10) 42 (7) sVCAM-1 (ng/ml) 635 (237) 690 (215) 389 (72) sICAM-1 (ng/ml) 234 (88) 262 (74) 179 (45) CD62 (Mabs/plt) 977 (371) 978 (234) 604 (194
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Early injection of high-dose recombinant factor VIIa decreases blood loss and prolongs time from injury to death in experimental liver injury
Treatment of von Willebrand disease with a high-purity factor VIII/von Willebrand factor concentrate: a prospective, multicenter study
Among patients with von Willebrand disease (VWD) who are unresponsive to desmopressin therapy, replacement with plasma-derived concentrates is the treatment of choice. Because prospective studies are lacking, such treatment has been largely empirical. A multicenter, prospective study has been conducted in 81 patients with VWD (15 patients with type 1, 34 with type 2, and 32 with type 3 disease) to investigate the efficacy of a high-purity factor VIII/von Willebrand factor (FVIII/VWF) concentrate for treatment of bleeding and surgical prophylaxis. Two preparations of the concentrate-one virally inactivated with solvent detergent, the other with an additional heat-treatment step--were evaluated. Pharmacokinetic parameters were similar for both preparations. Using pre-established dosages based on the results of pharmacokinetic studies, 53 patients were administered either preparation for the treatment of 87 bleeding episodes, and 39 patients were treated prophylactically for 71 surgical or invasive procedures. Sixty-five (74.7%) and 10 (11.5%) of the bleeding episodes were controlled with 1 or 2 infusions, respectively. Patients with severe type 3 VWD typically required more infusions and higher doses, at shorter time intervals, than did patients with generally milder types 1 and 2. Among patients undergoing surgical procedures, blood loss was lower than that predicted prospectively, and losses exceeding the predicted value did not correlate with the postinfusion skin bleeding time. In conclusion, the concentrate effectively stopped active bleeding and provided adequate hemostasis for surgical or invasive procedures, even in the absence of bleeding time correction