Blood Coagulation and Fibrinolysis in SART-Stressed (Repeated Cold-Stressed) Rats and Drug Effects on the Altered Hemostatic Parameters.

Abstract

Blood coagulation and fibrinolytic activity was studied in SART (spe cific alternation of rhythm in temperature)-stressed animals found to exhibit thrombo cytopenia and prolonged bleeding time, and drug effects on the abnormalities were evaluated. 1) SART-stressed rats revealed prolongation of activated partial thrombo plastin and thrombin time, no change in prothrombin time, decreased plasma fibrino gen levels, and shortened euglobulin clot lvsis time (ELT). Antithrombin III and a, plasmin inhibitor activity remained constant following stress exposure. 2) During stress, fibrinogen levels declined from day 5 and remained depressed up to day 14. Reduction in ELT developed in a similar manner to fibrinogen. 3) Decreased fibrino gen levels were prevented by consecutive doses of tranexamic acid, an antifibrinolyt ic, and Neurotropin, a sedative analgesic. Shortened ELT was counteracted by chron ic treatment with Neurotropin and alprazolam, an anxiolytic. Single administrations of the above agents failed to affect either change. These results indicate that SART stressed animals exhibit suppressed intrinsic coagulability and enhanced fibrinolytic activity, but normal extrinsic coagulability. Considering the previous report together with the above results, the hemostatic system under SART stress tends uniformly toward hemorrhage.Moreover, Neurotropin appears to improve and normalize hemostatic imbalance due to SART stress, a chronic form of stress.

Induction of Hypercoagulability Condition by Chronic Localized Cold Stress in Rabbits

“…Chohan et al, (19) reported that rats exposed to noise over a long period showed complex hemostatic abnormalities, such as a prolonged bleeding time, increased level of fibrinogen and shortened aPTT. In contrast, rats subjected to specific alternation of rhythm in temperature (SART) stress, exhibited decreased fibrinogen level and prolongation of aPTT, indicating suppressed activity of the intrinsic coagulation cascade (2). Thus, the hemostatic changes resulting from chronic cold stress present a complicated picture and appear to vary according to the type, severity and duration of stress.…”

“…Many investigators have suggested that alteration in the hemostatic system occurs in stress situation, which is involved with diseases related to abnormal hemostasis including myocardial infarction, cerebrovascular ischemia, thrombosis and disseminated intravascular coagulation (1)(2)(3)(4). Activation of coagulation factors is secondary to endothelial injury that could result from repeated transient vasospasm induced by catecholamine (5,6).…”

Attenuation by prolonged nitric oxide synthase inhibition of the enhancement of fibrinolysis caused by environmental stress in the rat

“…Each rat was anaesthetized by subcutaneous administration of pentobarbitone at 40 mg kg-', and 5 ml of citrated blood (containing 1/10 volume of 3.8% sodium citrate) was withdrawn from the abdominal aorta. Blood examinations were carried out as reported previously (Hata et al, 1991;Kawabata & Hata, 1993b). Briefly, after the visual estimation of platelet count in whole blood, platelet-poor plasma was obtained by centrifuging the citrated blood at 1700 g and 40C for 10 min, and plasma fibrinogen and protein levels were determined by the thrombin time method and by Lowry's method, respectively.…”

“…Briefly, after the visual estimation of platelet count in whole blood, platelet-poor plasma was obtained by centrifuging the citrated blood at 1700 g and 40C for 10 min, and plasma fibrinogen and protein levels were determined by the thrombin time method and by Lowry's method, respectively. Euglobulin clot lysis time (ECLT) was measured essentially according to Gallimore et al, (1971), using the euglobulin fraction prepared by the method of Kluft et al (1976), as described previously (Hata et al, 1991). The activity of blood coagulation factor VIII:coagulant and of plasminogen activator inhibitor (PAI) in plasma was determined spectrophotometrically, with commercially available assay kits using chromogenic substrates (Chmielewska et al, 1983;Kawabata & Hata, 1993b).…”

Role of adrenocorticotropic hormone in the activation of heparin secretion by mast cells in stressed rats

“…These processes include, first and foremost, the release of heparin, a direct-acting anticoagulant, into the circulation. Enhanced heparin release from mast cells and heightened anticoagulant potential of the blood during stress have been described [1,[6][7][8].Since the body's adaptation to stimulants begins at the neuroendocrine level, namely with excitation of the sympathoadrenal and hypothalamus-hypophysis-adrenal cortex systems, it is logical to assume that the excitation of these systems is causally related to the intensity of heparin secretion. Indeed, as our previous studies showed [3], the activation of heparin secretion by mast ceils in stress involves the participation of circulating catecholamines, primarily epinephrine.…”