Kinetics and characteristics of an acute phase response following cardiac arrest

Objective: Inflammation and hypoxia are frequently associated, but their in teraction is poorly understood. In vitro studies have shown that hypoxia st imulates the genes of acute phase proteins (APP) and cytokines known to ind uce APP. We decided to determine kinetics and potential determinants of an acute phase response after cardiac arrest and to assess whether isolated mo derate hypoxia can induce APP in humans in vivo. Design: Prospective, observational study in patients and human experiment, Setting: Tertiary care university hospital. Patients and participants: 22 patients after primarily successful cardiopul monary resuscitation (CPR) and 7 healthy volunteers. Interventions: None in patients; exposure of volunteers to simulated altitu de (460 torr/6 h). Results: Following CPR, type-1 APP (C-reactive protein, alpha(1)-acidglycop rotein, serum amyloid A) and type 2 APP (haptoglobin, alpha(1)-antitrypsin) increased consistently within 1-2 days and the 'negative' APP transferrin was downregulated. This APP response occurred irrespective of the cause of arrest, the estimated time of anoxia, clinical course or patient outcome an d was not different in patients with and without infectious complications. Exposure of healthy volunteers to less severe but more prolonged hypoxia di d not induce APP, although a time dependent increase of serum erythropoieti n (EPO) was measurable under these conditions, indicating the activation of oxygen dependent gene expression. Conclusions: (i) A marked acute phase response occurs regularly after cardi ac arrest, but within the complexity of this situation the severity of hypo xia is not a predominant determinant of this response. (ii) Despite in vitr o evidence for similarities in the oxygen dependent regulation of APP and E PO production, the oxygen sensitivity of these proteins in vivo is differen t. (iii) Measurements of APP are not revealing regarding infectious complic ations in the early phase after CPR.