Arginine vasopressin increases plasma levels of von Willebrand factor in sheep

Introduction

The V1a/V2 receptor dual-agonist arginine vasopressin (AVP) is increasingly used in catecholamine-resistant septic shock [1]. While V1a receptor stimulation results in vasoconstriction, V2 receptor stimulation promotes coagulation, at least in part through an increase in plasma von Willebrand factor antigen (vWF:Ag) activity. We hypothesized that, at an intravenous infusion rate representative of the requirements for the treatment of sepsis-induced vasodilatory hypotension in sheep [2], AVP provides procoagulant activities. We tested this hypothesis by measuring vWF:Ag activity in unanesthetized healthy sheep during administration of AVP in comparison with the vWF:Ag activity increase induced by the selective V2 receptor agonist desmo-pressin (dDAVP).

Methods

After two to four measurements of vWF:Ag activity and hemoglobin (Hb) over a 1-hour baseline (BL) period, 13 female sheep were randomly administered one of two treatments: an intravenous bolus of dDAVP (1 nmol/kg; n = 7) or a 2-hour intravenous infusion of AVP (3 pmol/kg/min; n = 6). vWF:Ag activity and Hb were measured every 30 minutes over 2 hours from the time of dDAVP administration or the initiation of AVP administration. For each sheep, vWF:Ag activity was corrected for plasma volume by calculating the vWF:Ag activity/Hb ratio and was expressed as percentage of the mean BL value. Data are expressed as the mean ± SEM.

Results

Following dDAVP bolus injection and during AVP infusion, the vWF:Ag activity/Hb ratio increased to a maximum of 135 ± 4% (n = 7) and 135 ± 6% (n = 4) of mean BL value, respectively (P < 0.001 and P = 0.002 vs. BL, respectively). The vWF:Ag activity/Hb ratio did not increase beyond the maximal fluctuation range of BL measurements in two out of the six sheep treated with AVP (maximum increases of 96% and 101%).

Conclusion

At an intravenous infusion rate representative of the requirements for the treatment of sepsis-induced vasodilatory hypotension in sheep [2], the V1a/V2 receptor dual-agonist AVP increased vWF:Ag activity to the same extent as the selective V2 receptor agonist dDAVP. Because of its V2 receptor agonist activity, the use of AVP may potentially amplify the microcirculation impairment caused by sepsis-induced coagulopathy.