Local and systemic effects of intra-arterial desmopressin in healthy volunteers and patients with type 3 von Willebrand disease. Role of interleukin-6.
Intra-arterial desmopressin caused dose and time dependent increases (p <0.001 for all) in forearm blood flow (all doses) and plasma tissue plasminogen activator (t-PA) concentrations (desmopressin > or = 70 ng/min). Although plasma t-PA concentrations rose in both forearms, there was a modest local release of t-PA in the infused forearm (14 ng/100 mL of tissue/min, p <0.05). At desmopressin doses > or = 300 ng/min, plasma von Willebrand factor (vWf) and Factor VIII:C concentrations rose in both forearms (p <0.001) and correlated with the rise in interleukin-6 concentrations (r = 0.92, p <0.001: r = 0.85, p = 0.002 respectively). Neither desmopressin nor substance P caused t-PA, vWf or Factor VIII:C release in the patients, although desmopressin increased plasma interleukin-6 concentrations as in healthy volunteers. We conclude that desmopressin releases t-PA, vWf and Factor VIII:C predominantly via systemic mechanisms, possibly mediated by cytokine release. Patients with type 3 vWD appear to have a generalised failure to release t-PA acutely despite a normal interleukin-6 response to desmopressin infusion.
Newby
D E
DE
Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, UK. d.e.newby@ed.ac.uk
Stewart
A
A
Witherow
F N
FN
Grieve
S
S
Dawson
P
P
Fox
K A
KA
Webb
D J
DJ
Ludlam
C A
CA
D000328:Adult; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005169:Factor VIII / Q000187:drug effects / Q000378:metabolism; D005542:Forearm; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007261:Infusions, Intra-Arterial; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000187:drug effects; D014842:von Willebrand Diseases / Q000188:drug therapy* / Q000503:physiopathology; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism
D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D013373:Substance P; D005169:Factor VIII; D010959:Tissue Plasminogen Activator; D003894:Deamino Arginine Vasopressin