Vascular Occlusive Events Research Articles

Thromboxane biosynthesis and metabolism in relation to cardiovascular risk factors

Enhanced platelet biosynthesis of thromboxane A 2 is associated with several cardiovascular risk factors, as a consequence of a direct effect on platelet biochemistry and/or some form of endothelial dysfunction. Moreover, episodic increases in thromboxane biosynthesis occur in acute coronary and cerebral ischemic syndromes. Thromboxane-dependent platelet activation represents an important mechanism that amplifies the consequences of acute vascular lesions as well as those of longstanding metabolic or hemodynamic disturbances, and results in increased risk of vascular occlusive events.

Thromboxane biosynthesis and metabolism in relation to cardiovascular risk factors.

Enhanced platelet biosynthesis of thromboxane A2 is associated with several cardiovascular risk factors, as a consequence of a direct effect on platelet biochemistry and/or some form of endothelial dysfunction. Moreover, episodic increases in thromboxane biosynthesis occur in acute coronary and cerebral ischemic syndromes. Thromboxane-dependent platelet activation represents an important mechanism that amplifies the consequences of acute vascular lesions as well as those of long-standing metabolic or hemodynamic disturbances, and results in increased risk of vascular occlusive events.

Erythrocyte-Endothelial Cell Adherence in Sickle Cell Disorders

Detachment of individual sickle erythrocytes from cultured endothelial cell monolayers has been evaluated by a fluid-shearing technique in an effort to quantitate adherence at shear forces that would be anticipated in the in vivo circulation. Nonirreversibly sickled cells (non-ISC) were more adherent at normal oxygen tensions than control cells. More than 1% non-ISC remained attached to the monolayer at forces greater than physiologic shear stresses in capillary and venous circulations, and many of the most avidly attached cells, once separated, immediately reattached to adjacent endothelial cells. These data suggest that hemoglobin S-containing erythrocytes may have a higher frequency of adherence in vivo in regions of low shear stress where prolonged erythrocyte-endothelial cell contact could occur. Some of these cells detached by shear force would subsequently reattach in in vivo conditions. Plasma-enhanced attachment frequency and plasma from blood in a case of sickle crisis caused further increase. These observations further support the concept that sickle erythrocyte-endothelial cell interaction may be a significant factor in initiation of vascular occlusive events in sickle cell disease.

Erythrocyte-endothelial cell adherence in sickle cell disorders

Detachment of individual sickle erythrocytes from cultured endothelial cell monolayers has been evaluated by a fluid-shearing technique in an effort to quantitate adherence at shear forces that would be anticipated in the in vivo circulation. Nonirreversibly sickled cells (non-ISC) were more adherent at normal oxygen tensions than control cells. More than 1% non-ISC remained attached to the monolayer at forces greater than physiologic shear stresses in capillary and venous circulations, and many of the most avidly attached cells, once separated, immediately reattached to adjacent endothelial cells. These data suggest that hemoglobin S-containing erythrocytes may have a higher frequency of adherence in vivo in regions of low shear stress where prolonged erythrocyte-endothelial cell contact could occur. Some of these cells detached by shear force would subsequently reattach in in vivo conditions. Plasma-enhanced attachment frequency and plasma from blood in a case of sickle crisis caused further increase. These observations further support the concept that sickle erythrocyte- endothelial cell interaction may be a significant factor in initiation of vascular occlusive events in sickle cell disease.

The factor VIII complex in atherosclerosis: Effects of aspirin

Sixty patients with well-documented previous myocardial infarction were treated with either 1 gm of aspirin daily or a placebo (AMIS trial). The factor VIII-von Willebrand factor complex was measured at 3–4-month intervals during the first 12–16 months of the trial. The levels of the complex did not change appreciably during this period, and the mean values for all but seven patients fell within 2 S.D. of the mean values obtained in normal laboratory controls. The concentrations of the factor VIII-von Willebrand complex in patients with a variety of vascular occlusive events did not differ from those in patients without such events. Finally, the mean values in patients treated with aspirin were virtually identical to those receiving placebo. We conclude that plasma levels of the factor VIII-von Willebrand factor complex are not altered in patients with atherosclerotic vascular disease, and are unaffected by aspirin therapy.

1120 MOYA-MOYA IN AMERICAN CHILDREN

Recurring cerebrovascular disease is extremely rare in children. Moya-moya (supraclinoid carotid stenosis with multiple cerebral telangiectasias) may be the vascular pathology underlying many such instances. Initially described as a congenital anomaly in the Japanese literature, it is uncommonly recognized in occidentals. We have cared for two Caucasian children in whom several factors strongly suggest moya-moya can be an acquired process and in whom the course was much more benign that commonly described. A 4½ year old boy with transposition of the great vessels developed a right hemiparesis after a total corrective operation. Six and one-half years later he had a subarachnoid hemorrhage (SAH). Computed tomography and cerebral angiography demonstrated a left frontal intracerebral hematoma and subadjacent brain atrophy and moya-moya. He has been well for 2½ years. A girl with sickle cell disease had a right hemiparesis at age 8. Six years later she had a SAH. Computed tomography and cerebral angiography demonstrated left parietal atrophy, intracerebral hematoma, and moya-moya. She has been normal for 2 years. Presentation of moya-moya in children as SAH has been noted only once previously. Moreover, our two children had a basic disease process not associated with cerebral telangiectasia but occasionally associated with cerebrovascular occlusive disease. The demonstration of moya-moya six years after a single presumably vascular occlusive event strongly suggests moya-moya can be a tenuous physiologic compensation to an acquired phenomenon.