title: S-nitrosoglutathione preserves platelet function during in vitro ventricular assist device circulation.
abstract: Complications (severe bleeding/thromboembolism) may occur during ventricular assist device (VAD) circulation, caused mainly by platelet dysfunction from platelet activation. We hypothesized that S-nitrosoglutathione (GSNO), having platelet activity preservation properties like nitric oxide (NO), may be a titratable agent to diminish platelet activation and thus preserve platelet function. Dose-response measurement of platelet aggregation by GSNO was performed using an aggregometer. GSNO (1,000 microM) caused inhibition of collagen and ristocetin induced aggregation by approximately 50%. Next, in vitro ventricular assist device (VAD) circulation was performed (over 48 hours using human whole blood), both without (control) and with GSNO (1,000 microM), and the aggregability of perfusate was measured at 0, 0.5, 1, 3, 6, 12, 24, and 48 hours. In control VAD circuits, collagen induced platelet aggregability gradually decreased and became significantly lower after 3 hours of circulation. With GSNO, platelet function did not significantly decrease until after 12 hours. Similar results were seen for ristocetin induced aggregation; control aggregation dropped significantly after 6 hours, but not until after 24 hours with GSNO. Liquid phase measurement of total nitrogen oxides (NO(T)) confirmed added GSNO maintained high perfusate NO(T) compared with control. GSNO is effective in preserving platelet aggregation during the first 12 to 24 hours in vitro and may be effective in preserving platelet function by inhibiting platelet activation during in vivo VAD circulation.
authors.affiliation: Department of Medicine, University of California Irvine Medical Center, Orange, USA.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Aledia
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Tran
authors.forename: Bryan O
authors.initials: BO
authors.lastname: King
authors.forename: Dan L
authors.initials: DL
authors.lastname: Serna
authors.forename: Jamie
authors.initials: J
authors.lastname: Eng
authors.forename: Blanding U
authors.initials: BU
authors.lastname: Jones
authors.forename: John C
authors.initials: JC
authors.lastname: Chen
authors.forename: James H
authors.initials: JH
authors.lastname: Roum
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006353:Heart-Assist Devices; D006801:Humans; D066298:In Vitro Techniques; D009589:Nitrogen Oxides / Q000032:analysis; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012310:Ristocetin / Q000494:pharmacology; D026422:S-Nitrosoglutathione / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D009589:Nitrogen Oxides; D010975:Platelet Aggregation Inhibitors; D012310:Ristocetin; D026422:S-Nitrosoglutathione; D003094:Collagen