sodium-oxybate and Coronary-Disease

To determine the influence of gamma-hydroxy-butyrate (GHB) on spontaneous and lipopolysaccharide (LPS)-stimulated release of tumour necrosis factor-alpha (TNF), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interleukin-10 (IL-10) in whole blood from patients undergoing coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC). In addition, the pharmacological modulation on lipopolysaccharide (LPS)-stimulated cytokine release by GHB (GHB-Na and GHB-ethanolamide) was characterized in a separate in vitro-assay.. In a prospective, randomized, double-blinded study, 12 patients undergoing elective CABG were assigned to receive either saline (control) or GHB-Na (25 mg/kg as loading dose followed by 25 mg/kg/h) intraoperatively. Blood samples were obtained (A) preoperatively, (B) 20 min after ECC and (C) 24 h after ECC. Plasma levels (spontaneous release) as well as LPS-stimulated cytokine secretion were measured in a whole blood culture system ex vivo and correlated with mRNA-expression in peripheral blood mononuclear cells (PBMC). In addition, the dose-response characteristics of modulation of the cytokine response by GHB was studied in vitro in the same assay.. Plasma IL-6 and IL-10 levels were significantly elevated after CABG, while TNF and IL-1 beta were detectable only occasionally in both groups. Expression of all cytokines studied was significantly reduced upon ex vivo LPS-stimulation at time point B. Despite maintained expression of TNF and IL-1 beta mRNA-transcripts upon ex vivo LPS-stimulation in patients treated with GHB, release of the cytokines in the supernatant was decreased to a similar degree as in the control group. Cytokine response upon LPS-stimulation was restored 24 h after CABG for the group mean, however, with substantial individual heterogeneity. In vitro, pharmacological doses of GHB-Na (2 mg/ml) attenuated LPS-induced IL-1 beta release. However, application of the GHB-receptor antagonist NCS-382 caused a nearly complete cessation of IL-1 beta release in vitro (to 2.5% of control). GHB-ethanolamide (LK 544) did not influence the LPS-stimulated release of the cytokines studied.. The results suggest a biphasic response of stimulated PBMC cytokine gene expression during CABG with an initial tolerance to LPS-stimulation shortly after termination of ECC. However, whether or not PBMC express functional GHB receptors remains unclear in light of contradictory effects of the different ligands. In spite of the ex vivo and in vitro results, application of GHB-Na in doses which are primarily based on its use as an anesthetic agent do not seem to modulate the release of the cytokines studied.

Topics: Adult; Aged; Coronary Artery Bypass; Coronary Disease; Cytokines; Double-Blind Method; Extracorporeal Circulation; Female; Gene Expression; Humans; In Vitro Techniques; Inflammation; Interleukin-1; Interleukin-15; Interleukin-6; Lipopolysaccharides; Male; Middle Aged; Prospective Studies; RNA, Messenger; Sodium Oxybate; Tumor Necrosis Factor-alpha

The method of quantitative evaluation of blood supply of ischemic myocardial focus was suggested, it consists in measuring the venous blood outflow from the ischemic area with the help of ultrasonic technique. In experiments on anaesthetized dogs with coronary artery occlusion the rate of blood flow and dynamics of its changes in the ischemic focus were determined. It was shown that sodium oxybutyrate improves the blood supply of myocardial ischemic area.

Topics: Animals; Coronary Circulation; Coronary Disease; Dogs; Drug Evaluation, Preclinical; Rheology; Sodium Oxybate; Time Factors; Transducers

Topics: Animals; Coronary Disease; Dogs; Heart Arrest, Induced; Humans; Intraoperative Complications; Mitral Valve; Myocardium; Sodium Oxybate

It was shown in experiments on cats anesthesized with nembutal that sodium hydroxybutyrate given in doses of 100 and 200 mg/kg increases the coronary blood flow in the intact myocardium. At the same time oxygen consumption by the heart rises to a far less degree. The drug provokes negligible hypertension, raises the systolic and cardiac outputs, and enhances myocardial contractility. It was discovered in experiments on dogs with the ischemized heart that sodium hydroxybutyrate in a dose of 200 mg/kg increases the blood supply both to the intact and ischemized myocardium areas. Changes in myocardial ischemia duration and in the hemodynamics produced by sodium hydroxybutyrate are similar to those caused by the drug in experiments with the intact heart.

Topics: Animals; Cats; Coronary Disease; Coronary Vessels; Dogs; Heart; Hemodynamics; Hydroxybutyrates; Myocardial Contraction; Myocardium; Oxygen Consumption; Sodium Oxybate