The multiple organ failure (MOF) in association with the disseminated intravascular coagulation syndrome (DIC) has long been thought to arise mainly from multiple microthrombi that disturb the microciruculation. In this report, we attempted to see whether or not shit hypothesis still holds true, and also to see whether vasoactive substances such as nitric oxide and its metabolites (NOX), and endothelin (ET) are involved in the development and propagation of DIC by utilizing animal DIC models induced in rats. Namely, the Wistar strain rats were intravenously infused either with 50 mg/kg of lipopolysaccharide (LPS) or 3.75 units/kg of tissue factor (TF) via the tail vein over a period of 4 hours, and the levels of D-dimer, NOX and ET in plasma were measured, and the kidney specimens were examined microscopically. In the LPS-induced DIC animalsm, a significant increase was noted in the plasma level of ET but not in the D-dimer, and marked fibrin deposition was observed in the renal glomeruli. On the other hand, marked increased in both the D-dimer and NOX in plasma were noted in the TF-induced DIC animals without any fibrin deposition in the renal glomeruli. Our data seem to indicate that involvement of vasoactive substances may vary in the development of MOF, i.e., ET disturbing the microcirculatin in the LPS-induced DIC, while NOX retaining the vascular integrity in the TF-induced DIC.

View full abstract

Plasma concentrations of VWF may serve as an indicator of certain endothelial functions. We measured plasma VWF concentrations in patients with heart failure accompanied by increased pulmonary venous pressure, and in those with pulmonary hypertension i.e., elevated pulmonary arterial pressure. We also measured plasma VWF concentrations before and after volume overloading with injection of contrast media, and stimulation by acetylcholine in patients with angina pectoris to test the effects of acute hemodynamic overloading and biochemical stimulation on plasma VWF concentrations. VWF concentrations in patients with heart failure of 23.1±9.2 (μg/ml) and in patients with pulmonary hypertension of 21.2±5.3 (μg/ml) were significantly higher than the value in age-matched controls of 10.3±3.7 (μg/ml), suggesting that the increased plasma VWF concentrations serves as an indicator of chronic hemodynamic stimulation in pulmonary circulation. Since plasma VWF concentrations rather decreased after acute volume overloading with contract media and after injection of achetylcholine, we suggest that the VWF plasma concentration is not significantly influenced by these acute stimulations.

View full abstract

Nitric Oxide (NO) is known to have a variety of functions, and among them are vasodilatation and neurotransmission as favorable functions, and cytotoxicity and hypotension as unfavorable functions. Although NO produced in sepsis has been reported to exhibit an antithrombotic effect, little is known whether or not NO exerts this antithrombotic function under physiological conditions. We have therefore attempted to see whether or not NO manifests any functions against thrombus formation in normal Wistar rats injected with various amounts of L-NAME (N(omega)-nitro-l-arginine methyl ester) an NO synthase inhibitor, i.e. 0.8, 4.0, 20.0 and 100 mg/kg/4hr via the tail vein. Plasma levels of fibrinogen and D-dimer were found to be significantly increased in all rats regardless of the amounts of L-NAME given to the rats, but the thrombin-antithrombin complex was significantly increased in those given 20.0 mg/kg/4hr or more of L-NAME. Fibrin deposition in the glomerulus appeared to become distinct dose-dependently of the drug given to the animals. The finding that administration of L-NAME alone was able to induce the appearance in plasma of the parameters of thrombus formation and fibrin deposition in the glomerulus seems to suggest that NO is involved in the regulation of thrombus formation under physiological circumstances, although its mechanism remains to be clarified.

View full abstract

We compared the sensitivity and specificity of two methods to detect platelet activation, i.e., the spontaneous platelet aggregation of small aggregates (SPA) and the flow cytometric method, and determined the correlation between these two methods. Thirty-five patients with chronic cerebral infarction (CCI) and 19 age-matched control subjects were enrolled in this study. Platelet activation was first determined by SPA using laser light scattering. Platelet activation was also measured by flow cytometry and two activation-dependent monoclonal antibodies (MoAbs), a MoAb against CD62P (MoAb-CD62P) and a MoAb against the platelet fibrinogen receptor (PAC-1). When cut off points were set at the mean+2SD (standard deviation) of the control subjects, the SPA, MoAb-CD62P and PAC-1 methods demonstrated sensitivity of 37.1%, 60% and 60%, and specificity of 100%, 100% and 94%, respectively. When ROC (Receiver Operating Characteristics) curves were drawn based on these methods, however, the differences in AUC were not statistically significant. There was a statistically significant correlation between the SPA value and the CD62P positive rate, and also between the SPA value and the PAC-1 positive rate. The PAC-1 and the MoAb-CD62P methods were more sensitive than the SPA method in detecting platelet activation in CCI patients.

View full abstract