Complement C5A Antagonist Treatment Improves the Acute Circulatory and Inflammatory Consequences of Experimental Cardiac Tamponade

OBJECTIVE:Cardiogenic shock often leads to splanchnic macro- and microcirculatory complications, and these events are linked to local and systemic inflammatory activation. Our aim was to investigate the consequences of complement C5a antagonist treatment on the early circulatory and inflammatory changes in a clinically relevant large animal model of cardiac tamponade. DESIGN AND SETTING:A randomized, controlled in vivo animal study in a university research laboratory. SUBJECTS:Anesthetized, ventilated, and thoracotomized Vietnamese mini pigs (24 ± 3 kg). INTERVENTIONS:Group 1 (n = 6) served as sham-operated control. In group 2 (n = 7), cardiac tamponade was induced for 60 minutes by the administration of intrapericardial fluid, while the mean arterial pressure was kept in the interval 40 to 45 mm Hg. Group 3 (n = 6) was treated with a complement C5a antagonist compound (the peptide acetyl-peptide-A, 4 mg/kg) after 45 minutes of tamponade. MEASUREMENTS AND MAIN RESULTS:The macrohemodynamics, including the superior mesenteric artery flow, was monitored; the average red blood cell velocity in the small intestinal mucosa was determined by an intravital orthogonal polarization imaging technique. The whole blood superoxide production, the plasma level of high-mobility group box protein-1 and big-endothelin and the small intestinal myeloperoxidase activity were measured. One hundred eighty minutes after the relief of tamponade, the mean arterial pressure was decreased, while the plasma levels of superoxide, high-mobility group box protein-1, and big-endothelin, and the intestinal myeloperoxidase activity were increased. The administration of acetyl-peptide-A normalized the mean arterial pressure and preserved the cardiac output, while the superior mesenteric artery flow and mucosal average red blood cell velocity were increased significantly, and the plasma superoxide, high-mobility group box protein-1, big-endothelin, and intestinal myeloperoxidase levels were reduced. CONCLUSIONS:These results provide evidence that blockade of the C5a effects significantly influences the acute splanchnic macro- and microhemodynamic complications and decreases the potentially harmful inflammatory consequences of experimental cardiogenic shock.