deamino-arginine-vasopressin and Vascular-Diseases

Topics: Adrenocorticotropic Hormone; Anabolic Agents; Androgens; Clofibrate; Coronary Disease; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Fibrinolysis; Fibrinolytic Agents; Glucocorticoids; Humans; Inflammation; Male; Metformin; Phenformin; Plasminogen Activators; Postoperative Complications; Sulfonylurea Compounds; Thromboembolism; Thrombophlebitis; Vascular Diseases

We report the case of a 2-year-old female child with a pelvic vascular malformation complicated by chronic low-grade bleeding. Treatment with intranasal desmopressin significantly reduced vaginal bleeding. Therefore, we suggest that intermittent use of intranasal desmopressin may be useful in the treatment of chronically bleeding low-flow vascular malformations.

Topics: Administration, Intranasal; Child, Preschool; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Pelvis; Vaginal Diseases; Vascular Diseases

To determine the role of von Willebrand factor (vWF) in adhesion of sickle (SS) erythrocytes in microvascular flow conditions, we have perfused the ex vivo mesocecum vasculature of the rat with desmopressin, an analogue of vasopressin that causes the release of endothelial vWF. Analysis of vWF in the venous effluent of the isolated vasculature showed mainly the presence of extra-large molecular weight forms characteristic of endothelial vWF, which in the presence of desmopressin showed an average increase of 54%. Also, desmopressin induced a significant increase in adhesion of washed oxygenated (oxy) unseparated SS erythrocytes, accompanied by a persistent microvascular obstruction and a pronounced increase in the peripheral resistance (PRU). In contrast, infusion of SS deformable discocytes (SS2) in desmopressin-perfused vasculature resulted in a significant adhesion but not in persistent vasoocclusion, showing that SS2 discocytes alone are not sufficient for microvascular obstruction. Furthermore, SS4 erythrocytes (dense discocytes and irreversibly sickled erythrocytes) caused a persistent microvascular blockage and a significantly higher PRU than SS2 discocytes. However, the increase in PRU for SS4 erythrocytes following desmopressin treatment was 50% less compared with a corresponding increase for SS2 discocytes over the control values, which showed a smaller effect of desmopressin on the hemodynamic behavior of SS4 dense erythrocytes. Incubation of desmopressin-treated vasculature with anti-vWF antibodies resulted in a pronounced decrease in adhesion and significantly improved hemodynamic behavior of SS cells. Also, in untreated vasculature, similarly incubated with anti-vWF antibodies, there was almost complete inhibition of adhesion. Under the described perfusion conditions, antibodies to fibronectin and thrombospondin, as well as incubation of SS erythrocytes with anti-vWF antibodies did not affect adhesion. These results are compatible with a model for SS vasoocclusion in which extra-large vWF-mediated adhesion of deformable SS erythrocytes is the first step followed by an accelerated entrapment of dense SS erythrocytes.

Topics: Adult; Anemia, Sickle Cell; Animals; Cecum; Cell Adhesion; Deamino Arginine Vasopressin; Endothelium, Vascular; Erythrocytes; Humans; Microcirculation; Muscle, Smooth, Vascular; Rats; Reference Values; Regression Analysis; Vascular Diseases; Venules; von Willebrand Factor

Different morphologic and density classes of sickle cells (SS) may play distinct roles in the generation of vasoocclusion, explaining the complexity of this phenomena. The densest SS red blood cells (RBCs) (SS4) can induce vasoocculsion in ex vivo microcirculatory preparations as well as in an intact animal model. Previous studies of the interaction of SS deformable discocytes with endothelial monolayers or the rat ex vivo mesocecum preparation have shown adhesion that is desmopressin (dDAVP)-stimulated, von Willebrand factor (vWF)-mediated, and limited to the small venules. However, in vivo adhesion of SS RBCs to the endothelium has neither been demonstrated nor characterized; and, in particular, the relation of adhesion to vasoocclusion is unknown. Using an intact animal model that involves injecting saline-washed, density-defined SS RBCs into the femoral artery of a rat, we find that: (1) Quantitative studies of RBCs retained in the rat thigh using 99mTc-labeled RBCs and gamma camera imaging showed that dDAVP induces a threefold increase in retention of normal (AA) cells and deformable SS discocytes (SS2). (2) electron microscopy and Microfil injection show that the retention of SS2 cells is due to adhesion to the vascular endothelium with no evidence of obstruction. (3) H-1 magnetic resonance imaging showed that retention of SS4 cells induced a dose-dependent increase in tissue edema (presumable secondary to tissue hypoxia), while retention of AA or SS2 cells produced no change. We conclude that endothelial adhesion of deformable SS discocytes can be demonstrated in an in vivo animal model, that this adhesion is enhanced by dDAVP (presumably related to, but not necessarily limited to the release of vWF), and that this phenomenon per se does not lead to vasoocclusion. Nevertheless, adhesion of deformable SS discocytes may have consequences. We hypothesize that adhesion of SS discocytes could narrow the lumen of postcapillary venules and facilitate secondary trapping of SS4 cells and lead to subsequent vasoocclusion.

Topics: Anemia, Sickle Cell; Animals; Cell Adhesion; Deamino Arginine Vasopressin; Edema; Endothelium, Vascular; Erythrocytes; Female; Humans; Microcirculation; Microscopy, Electron, Scanning; Rats; Rats, Inbred Strains; Vascular Diseases

Topics: Arginine Vasopressin; Constriction; Deamino Arginine Vasopressin; Fibrinolysis; Humans; Vascular Diseases; Veins