Why the study?
Does a protease inhibitor alone or combined with a prostacyclin analogue improve anticoagulation profiles compared to heparin or no anticoagulation in a canine model of LVAD?
Does a protease inhibitor alone or combined with a prostacyclin analogue improve anticoagulation profiles compared to heparin or no anticoagulation in a canine model of LVAD?
In a canine LVAD model, combining a protease inhibitor with a prostacyclin analogue effectively prevented activation of the blood coagulation system, suggesting a potential alternative to heparin.
May support FUT + PG as heparin alternative in LVAD; hypothesis-generating in canine model, requires human trials before any practice consideration.
[Aim] Protease inhibitor (FUT) alone, and the combined administration of FUT and prostacyclin analogue (PG) were studied as anticoagulants for left LVAD instead of heparin. [Materials and Methods] On 36 mongrel dogs, LVAD was performed for 24 hours, and blood coagulative study was made before and during LVAD performance. Dogs were divided into the following 4 groups according to the type of anticoagulation. GroupI: no anticoagulation (n=9), Group II: heparin (0.25 mg/kg/hr) (n=9), Group III: FUT alone (15μ g/kg/min) (n=9), Group IV: FUT (15μ g/kg/min) + PG (1 μ g/kg/min) (n=9) [Results] In all groups, LVAD could be performed without any thrombogenic trouble. Prothrombin time showed marked prolongation in Group II (heparin), but gradual prolongation in other groups. Activated partial thromboplastin time showed gradual prolongation in all groups. Fibrinogen showed a marked decrease and reached 50 % of preoperative value (below 100 mg/dl) in 24 h in Group I (no anticoagulation): whereas, in Group II (heparin) and Group III (FUT). it showed a slight decrease till 3 h after the start, but thereafter came gradually back to the previous level. In Group IV (FUT + PG), it was almost unchanged all the time. α2-plasmin inhibitor was almost unchanged in Group II (heparin), Group III (FUT) and Group IV (FUT + PG); whereas. in Group I (no anticoagulation), it showed severe decrease and reached to 55 % of preoperative value in 24 h. Factor XII showed gradual significant decrease in all groups. [Conclusion] FUT alone can prevent the activation of blood coagulation system to some extent as low dose of heparin. PG combined with FUT can prevent the activation of intrinsic pathway of blood coagulation system to a minimal level through intense inhibition of platelet aggregatin by PG.
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Takahama et al. (2000) studied this question.
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