Recombinant human diamine oxidase prevents hemodynamic effects of continuous histamine infusion in guinea pigs

Recombinant human diamine oxidase prevents hemodynamic effects of continuous histamine infusion in guinea pigs Author: Weiss-Tessbach, Matthias (Contact person) Department of Clinical Pharmacology, Medical University of Vienna, Austria DescriptionData from: Recombinant human diamine oxidase prevents hemodynamic effects of continuous histamine infusion in guinea pigsRelated publication: Inflammation Research (2023), DOI: 10.1007/s00011-023-01783-3 Description of the data and file structureExperimental data from 38 female Dunkin-Hartley guinea pigs studied in an anaesthetised, continuous intravenous histamine-infusion model of histamine-induced shock, testing whether recombinant human diamine oxidase with a mutated heparin-binding motif (rhDAO_mHBM) prevents histamine-induced haemodynamic effects. The study comprised rhDAO pharmacokinetics (2 mg/kg), endogenous diamine oxidase release after heparin, histamine dose-finding, a main experiment at 8 µg/kg/min histamine with buffer / rhDAO 2 mg/kg / rhDAO 4 mg/kg, and urinary metabolite measurements. Data are in tidy (long) format: one measurement per row. time_min is minutes from the start of the histamine infusion (0 = start); in the main experiment histamine was infused from 10 to 40 min. An empty cell means not measured. Units are given in each column header. Files and variables File: GP_rhDAO_histamine_dataset_FWF_P36105.xlsxDescription: A single Excel workbook containing a README sheet, an Animals metadata sheet, six measurement sheets, and a Figure_map sheet linking each sheet to the corresponding published figure. Variables Sheet: Animals - GP_ID — animal identifier (GP1–GP42) - sex — female - strain — Dunkin-Hartley - body_weight_g — body weight in g - experiment_role — role in the study (heparin, method/urine, dose-finding, PK/pilot, pilot, main, cohort) - treatment_group — treatment received (buffer, rhDAO 2 mg/kg, rhDAO 4 mg/kg, NaCl, histamine only, etc.) - histamine_dose_ug_kg_min — histamine infusion rate in µg/kg/min (a range for dose-finding animals) - rhDAO_dose_mg_kg — rhDAO dose in mg/kg, if given - in_publication — whether the animal contributes to a published figure (Yes/No) - figures — figures in which the animal appears - notes — fate / experimental notes Sheet: Hemodynamics - GP_ID — animal identifier - treatment_group — treatment received - phase — experiment phase (main, dose-finding, pilot, rhDAO PK) - time_min — minutes from start of histamine infusion (0 = start) - HR_bpm — heart rate in beats/min - MAP_mmHg — mean arterial pressure in mmHg - body_temp_C — core body temperature in °C Sheet: Plasma_histamine - GP_ID — animal identifier - treatment_group — treatment received - time_min — minutes from infusion start - histamine_ng_mL — plasma histamine in ng/mL - assay — assay method (Immunotech immunoassay; main experiment) Sheet: Plasma_rhDAO - GP_ID — animal identifier - treatment_group — treatment received - phase — Fig 1a PK or Fig 3c main experiment - time_min — minutes from infusion start - rhDAO_ug_mL — plasma recombinant human diamine oxidase in µg/mL - assay — DAO antigen ELISA Sheet: Endogenous_DAO_heparin - GP_ID — animal identifier (GP1–GP4) - time_min — 0 = baseline; 5 = 5 min after 500 IU/kg heparin i.v. - DAO_activity_ng_mL — endogenous diamine oxidase in ng/mL - note — sampling context Sheet: Blood_gas - GP_ID — animal identifier - treatment_group — treatment received - time_min — 0 or 60 min - lactate_mmol_L — arterial lactate in mmol/L - pO2_mmHg — arterial oxygen partial pressure in mmHg - pCO2_mmHg — arterial carbon dioxide partial pressure in mmHg Sheet: Urine - GP_ID — animal identifier - group — group annotation from the source records - time_min — collection time in min - creatinine_mg_dL — urinary creatinine in mg/dL - histamine_ng_mL — urinary histamine in ng/mL - methylhistamine_ng_mL — urinary 1-methylhistamine in ng/mL - His_per_Krea — histamine / creatinine ratio - MHis_per_Krea — 1-methylhistamine / creatinine ratio Sheet: Figure_map - figure — published figure - description — what the figure shows - animals — animals included - sheet — sheet (and filter) that reproduces the figure Abbreviations: rhDAO = recombinant human diamine oxidase; DAO = diamine oxidase; MAP = mean arterial pressure; HR = heart rate; His = histamine; 1-MH/MHis = 1-methylhistamine; Krea = creatinine; EIA/ELISA = enzyme immunoassay; HTRF = homogeneous time-resolved fluorescence; i.v./i.a. = intravenous/intra-arterial. Note on assays: main-experiment plasma histamine (GP21–32) was measured by the Immunotech immunoassay; dose-finding/pilot plasma histamine was measured by Cisbio HTRF, so absolute values between methods are not directly comparable. Urinary metabolites were measured using LC-MS/MS. Code/softwareData can be opened in Microsoft Excel or LibreOffice Calc, or imported into R or Python (e.g., readxl, pandas/openpyxl). Animal welfare and ethicsAll animal procedures were approved by the Austrian Federal Ministry of Education, Science and Research (BMBWF) and performed at the Division of Biomedical Research, Medical University of Vienna, under animal protocol GZ 2021-0.209.778. The study used 38 female Dunkin-Hartley guinea pigs. Funding: Austrian Science Fund (FWF), award P36105 (Hertha-Firnberg programme T1135).