We examined the effects of nitric oxide (NO)/endothelium-derived relaxing factor (EDRF) on platelet surface glycoproteins (GP). As determined by flow cytometry, in both a washed platelet system and platelet-rich plasma, the EDRF congener (S-nitroso-N-acetylcysteine) markedly inhibited both the thrombin-induced and the (stable thromboxane A2 analogue) U-46619-induced upregulation of P-selectin (alpha-granule protein), CD63 (lysosomal protein), and the GPIIb-IIIa complex (fibrinogen receptor) but minimally inhibited downregulation of the GPIb-IX complex (von Willebrand factor receptor). The inhibitory effects of EDRF were markedly reduced in whole blood or by the addition of washed erythrocytes. Platelets in whole blood were still responsive to guanosine 3',5'-cyclic monophosphate (cGMP), as shown by complete inhibition of P-selectin upregulation by the stable analogue N6,2'-O dibutyryl cGMP. These data suggests that 1) cGMP negatively regulates the platelet surface expression of P-selectin, CD63, and the GPIIb-IIIa complex but not the platelet surface expression of the GPIb-IX complex and 2) hemoglobin within erythrocytes inhibits the effects of EDRF/NO on platelet surface glycoproteins.

Two hundred five patients who underwent elective abdominal aortic aneurysm repair were divided into two groups: those who underwent infrarenal cross-clamping alone (n = 166) and those who underwent suprarenal cross-clamping alone or combined with infrarenal cross-clamping (n = 39). Mortality was comparable between groups (1.2% for infrarenal cross-clamping vs 2.6% for suprarenal cross-clamping). Transient renal insufficiency was more frequent in the suprarenal group than in the infrarenal group (28% vs 10%), but dialysis rates (3% for suprarenal vs 2% for infrarenal) were similar. Cardiac morbidity was comparable between groups as well. Operating room data reflected the technical challenge of complex aneurysm repairs. The retroperitoneal approach was the preferred exposure in the suprarenal group since better access to the suprarenal aorta may be achieved with this technique. While abdominal aortic aneurysm repairs requiring suprarenal cross-clamping remain a technical challenge, the risks are not formidable and suprarenal cross-clamping should be considered when confronted with difficult periaortic dissection.

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Platelet degranulation has been implicated in the pathophysiology of acute arterial thrombosis, intimal hyperplasia, and atherogenesis. Most previous studies that examined the effect of heparin on platelet function have used platelet aggregometry. These studies have resulted in contradictory data and, by the nature of the assay, reveal no information with regard to platelet degranulation. In contrast, flow cytometry allows accurate quantification of the extent of platelet degranulation by measurement of the platelet surface binding of a GMP-140 specific monoclonal antibody (S12). GMP-140 is only expressed on the platelet surface after platelet alpha granule release. In the present study increasing concentrations of heparin were added to whole blood anticoagulated with sodium citrate. Platelets were activated with a panel of agonists, and the extent of platelet degranulation was quantified by whole blood flow cytometry. Heparin concentrations as high as 100 units/ml were found to suppress platelet alpha granule release induced by either a thromboxane A2 analog (U46619) or a combination of adenosine diphosphate and epinephrine. Heparin suppressed alpha granule release induced by thrombin both in whole blood and in washed platelets. The addition of heparin after platelet activation had no effect on S12 binding. In summary, heparin in high concentrations is a potent inhibitor of platelet degranulation, an action that is unrelated to its effect on the coagulation cascade. Although the heparin concentrations used in this study exceed those used clinically by a factor of 10 or more, future studies of heparin fractions may allow the separation of the anticoagulant and antiplatelet properties of the molecule and allow the administration of an agent that selectively suppresses platelet degranulation without the humoral anticoagulant effect.