Complement C5A antagonist treatment improves the acute circulatory and inflammatory consequences of experimental cardiac tamponade.
2013
Objective:
Cardiogenic shockoften leads to
splanchnicmacro- 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 tamponadewas induced for 60 minutes by the administration of intrapericardial fluid, while the
mean arterial pressurewas 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 arteryflow, 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 groupbox protein-1 and big-
endothelinand the small intestinal
myeloperoxidaseactivity were measured. One hundred eighty minutes after the relief of
tamponade, the
mean arterial pressurewas decreased, while the plasma levels of superoxide,
high-mobility groupbox protein-1, and big-
endothelin, and the intestinal
myeloperoxidaseactivity were increased. The administration of acetyl-peptide-A normalized the
mean arterial pressureand preserved the cardiac output, while the
superior mesenteric arteryflow and mucosal average red blood cell velocity were increased significantly, and the plasma superoxide,
high-mobility groupbox protein-1, big-
endothelin, and intestinal
myeloperoxidaselevels were reduced. Conclusions: These results provide evidence that blockade of the C5a effects significantly influences the acute
splanchnicmacro- and microhemodynamic complications and decreases the potentially harmful inflammatory consequences of experimental
cardiogenic shock.
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