thromboxane-b2 and Respiration-Disorders

Cardiopulmonary bypass induces respiratory dysfunction postoperatively, with activation of both the complement system and white cells implicated. This study compared the effects of bubble and membrane oxygenators for cardiopulmonary bypass in terms of respiratory dysfunction and markers of white cell activation and endothelial damage.. Fifty patients undergoing cardiopulmonary bypass were randomly allocated either membrane or bubble oxygenation. Respiratory function was assessed serially by arterial oxygen tension and alveolar-arterial oxygen gradient. Complement activation was measured by serial sampling of serum C3a levels. White cell activation was assessed by serial measurement granulocyte elastase; other markers investigated were levels of thromboxane B2, von Willebrand factor and malondialdehyde. All sample measurements were made preoperatively, early and late during bypass, 4-6 h postoperatively and then on the 1st, 2nd and 6th postoperative day. All samples were corrected for haemodilution, and differences between groups tested non-parametrically.. In both groups of patients there was a highly significant fall (P < 0.001) in arterial oxygen tension accompanied by a highly significant rise (P < 0.0001) in aleveolar-arterial oxygen gradient at 18 h compared to preoperative values persisting until 6 days postoperatively. Levels of C3a increased significantly in both groups at 10 min post bypass, increased further at 60 min peaking at 4-6 h post bypass. Granulocyte elastase serum levels increased significantly at 10 min postoperatively in both groups compared to control levels, remaining elevated till 48 h, but returning to control levels by 6 days. There was a small difference (P < 0.04) between the groups at 4-6 h only. Levels of von Willebrand factor increased significantly at 60 min post bypass in both groups, remaining elevated 6 days postoperatively. Levels of malondialdehyde increased at 10 min post bypass, remaining elevated until 6 days post bypass. Thromboxane levels showed no significant changes. For all markers measured, there were no significant differences between the groups other than those already indicated.. This study demonstrated marked respiratory dysfunction, complement activation and white cell activation in patients undergoing cardiopulmonary bypass with either bubble or membrane oxygenators. There was marked variability in the response of individual patients with either oxygenation technique, but overall no significant differences between the groups.

Topics: Blood Gas Analysis; Cardiopulmonary Bypass; Complement Activation; Complement C3a; Humans; Leukocyte Elastase; Malondialdehyde; Middle Aged; Oxygenators; Respiration Disorders; Thromboxane B2; Time Factors; von Willebrand Factor

Dobutamine, a beta-adrenoceptor agonist that is often used to treat myocardial dysfunction in asphyxiated neonates, may act on the adrenoceptors of platelets resulting in activation. Little information is available on the effect and mechanistic pathway of dobutamine on the platelet aggregatory function in neonatal asphyxia. Newborn piglets were acutely instrumented and exposed to hypoxia for 2 h and reoxygenation for 4 h. Piglets were randomized to receive dobutamine infusion (5, 10, or 20 microg/kg per min) or saline (hypoxic-control) at 2 to 4 h of reoxygenation (n = 8 each), and sham-operated animals were not exposed to hypoxia and reoxygenation (n = 6). Platelet number, collagen-stimulated whole blood aggregation, and plasma concentrations of thromboxane B2 were studied. The effects of alpha- and beta-adrenoceptor antagonists (phentolamine and propranolol, respectively) on platelet aggregation to in vitro administration of dobutamine (3 microM) were also examined. Shock and metabolic acidosis developed similarly in all hypoxia-reoxygenated groups. At 4 h of reoxygenation, platelet numbers in all groups decreased, with no differences among groups. Platelet aggregation deteriorated significantly with a rightward shift of concentration-response curve in piglets receiving 10 and 20 microg/kg per min of dobutamine. The group that received 20 microg/kg per min of dobutamine had increased plasma thromboxane B2 concentrations from baseline (P < 0.05). The platelet aggregatory response induced by 3 microM of dobutamine was improved by the coadministration of the beta-but not the alpha-adrenoceptor antagonist. We observed platelet aggregatory dysfunction in hypoxic-reoxygenated newborn piglets treated with high-dose dobutamine. Further investigation is needed to examine the differential effects of dobutamine and hypoxia-reoxygenation in platelet aggregation in newborns.

Topics: Adrenergic beta-Agonists; Animals; Animals, Newborn; Blood Platelets; Collagen; Dobutamine; Heart Rate; Hydrogen-Ion Concentration; Hypoxia; Models, Biological; Oxygen; Platelet Aggregation; Respiration Disorders; Swine; Thromboxane B2