title: The anti-inflammatory effect of diazoxide in coronary artery bypass grafting.
abstract: Many therapeutic strategies have been designed to suppress the inflammatory response in patients undergoing coronary artery bypass grafting (CABG). Pharmacological preconditioning with diazoxide is an alternative in effective cardioprotective strategies, but more evidence is required to show its effect on the inflammatory response. Forty patients with stable angina who were scheduled for isolated elective CABG operations were randomized into control and diazoxide (DZX) groups. In the DZX group, 1.5 mg/kg diazoxide was infused intravenously in 5 min followed by a 5-min washout before commencing the cardiopulmonary bypass. In the control group, placebo infusion was given similarly. Blood samples for cytokine measurement were collected from the radial artery and coronary sinus perioperatively, and hemodynamic data were recorded. Thirty-six patients fulfilled the data collection. Cardiac index (CI) increased in both groups over time as compared with baseline. In the DZX group, the increase of CI was greater than that in the control group (P = 0.002). Systemic and coronary sinus plasma levels of IL-6, IL-8, and IL-10 increased significantly after reperfusion in both groups as compared with baseline (P < 0.05). IL-6 and IL-8 both reached the peak value at 6 h after cardiopulmonary bypass. IL-10 reached peak level at 20 min after reperfusion in both groups. There was significantly higher IL-10 in DZX groups (P = 0.015). The ratios of IL-6 to IL-10 and IL-8 to IL-10 were significantly lower in DZX groups than in controls (P = 0.025 and P = 0.041 for each, respectively). Pharmacological preconditioning with DZX in CABG patients shifts the circulating inflammatory cytokine balance toward the anti-inflammatory direction.
authors.affiliation: Division of Cardiothoracic Surgery and Anaesthesia, Heart Center, Tampere University Hospital, Fin-33521 Tampere, Finland.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Minxin
authors.initials: M
authors.lastname: Wei
authors.forename: Jari
authors.initials: J
authors.lastname: Laurikka
authors.forename: Pekka
authors.initials: P
authors.lastname: Kuukasjärvi
authors.forename: Timo
authors.initials: T
authors.lastname: Rinne
authors.forename: Eva-Liisa
authors.initials: EL
authors.lastname: Honkonen
authors.forename: Riina
authors.initials: R
authors.lastname: Nieminen
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
authors.forename: Matti
authors.initials: M
authors.lastname: Tarkka
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001794:Blood Pressure; D001026:Coronary Artery Bypass; D003981:Diazoxide / Q000627:therapeutic use*; D005260:Female; D006334:Heart Function Tests; D006339:Heart Rate; D006801:Humans; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D014655:Vascular Resistance
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003981:Diazoxide