Maria Cristina D'Adamo

Morphological and hemostatic changes in rats with abdominal arterial prosthesis.

We evaluated the changes over time in hemostatic factors during ongoing arterial thrombosis in rats, as induced by a loop-shaped aortic prosthesis. Moreover, we investigated this condition by inspecting in parallel local thrombus growth, systemic vascular prostacyclin and t-PA production. One minute after loop insertion, activated platelets spread on the internal surface of the prosthesis and 24 hrs later numerous platelet aggregates supported by a fibrin network could be observed. However, no evidence for platelet activation could be concomitantly found in peripheral blood. A sustained increased in PGI2 formation was detected together with a progressive increase in plasma fibrinolytic activity during thrombus growth. The levels of fibrinogen as well as antithrombin III (ATIII) and heparin cofactor II (HCII) activities were steadily increased in loop-bearing animals. In conclusion, the dynamic phases of thrombus formation, in an aortic prosthesis, produce changes in vascular function and in hemostatic factors at the level of systemic blood.

Different response of vascular fibrinolysis to adrenergic stimulation in young and aged rats

We have studied the vascular response to epinephrine infusion in an experimental model of vascular perfusion in young (3 ± 1 months) and old (18 ± 3 months) rats. Five min epinephrine infusion induced a dosedependent (0.15–25 μM) increase in t-PA release and in perfusion pressure in both young and old rats. However, in old rats, the basal levels of t-PA were higher than in young rats (0.24 ± 0.06 vs 0.08 ± 0.01 IU/ml; p < 0.01, means ± SE, n = 6) and epinephrine infusion induced a significantly higher increase in t-PA activity levels (0.78 ± 0.06 vs 0.47 ± 0.08 IU/ml, p < 0.01, for 625 μM epinephrine). The response, however, was characterized by a delayed onset. An opposite tendency was observed in the increase of the perfusion pressure, which was significantly lower in old than in young rats. In young rats venous stasis induced in young rats, a rapid and significant increase in t-PA activity (from 020 ± 0.03 to 0.68 ± 0.02 IU/ml; p < 0.01; n = 6). The response rapidly decreased, reaching the basal level at 5 minutes of wash-out. In aged rats, however, the increase in t-PA activity triggered by thirty minute venous stasis was less pronounced, delayed and long-lasting. Our data show a different vascular response to adrenergic stimulation in young and aged rats.

Effect of aspirin on the fibrinolytic response in perfused rat hindquarters

The role of aspirin on tissue plasminogen activator (t-PA) release was studied in rats after experimental venous occlusion. For this purpose, we developed a new experimental model which combines a vascular perfusion system (isolated rat hindquarters) with vascular stimulation, namely the application of venous stasis. Application of venous stasis for 30 min induced the release of t-PA from the vascular endothelium into the perfusate (from 0.19 +/- 0.05 to 0.39 +/- 0.05 UI/ml), reaching a peak 90 s after reperfusion. Aspirin administered to rats 60 min before the experiments (100 mg/kg i.v.), or dissolved in Tyrode solution (100 microM), suppressed 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) synthesis (0.38 +/- 0.09 in control and < 0.01 and 0.15 +/- 0.09 ng/ml, respectively, in aspirin-treated groups) but did not prevent the increase in fibrinolytic activity after venous occlusion (from 0.20 +/- 0.04 to 0.38 +/- 0.06 and from 0.07 +/- 0.03 to 0.27 +/- 0.03 IU/ml, respectively, in the aspirin-treated group). Our results suggest that the increase in fibrinolytic activity after experimental venous occlusion in isolated rat hindlegs is modulated by mechanism(s) other than the cyclooxygenase pathway in the vascular wall.