title: Local and systemic effects of intra-arterial desmopressin in healthy volunteers and patients with type 3 von Willebrand disease. Role of interleukin-6.
abstract: 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.
authors.affiliation: Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, UK. d.e.newby@ed.ac.uk
authors.forename: D E
authors.initials: DE
authors.lastname: Newby
authors.forename: A
authors.initials: A
authors.lastname: Stewart
authors.forename: F N
authors.initials: FN
authors.lastname: Witherow
authors.forename: S
authors.initials: S
authors.lastname: Grieve
authors.forename: P
authors.initials: P
authors.lastname: Dawson
authors.forename: K A
authors.initials: KA
authors.lastname: Fox
authors.forename: D J
authors.initials: DJ
authors.lastname: Webb
authors.forename: C A
authors.initials: CA
authors.lastname: Ludlam
mesh_terms: 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
chemical_list: 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