Influence of ACTH-(1-24) and plasma hyperviscosity on free radical production and capillary perfusion after hemorrhagic shock.

Objective: The authors investigated the effects of ACTH-(1-24) and a high-viscosity solution in the restoration of microvascular function during resuscitation. They injected NG-monomethyl-L-arginine (L-NMMA) and superoxide dismutase (SOD) before ACTH-(1-24) in hamsters resuscitated with the hyperviscous solution to determine the role of ROS and NO in ACTH-(1-24) protective mechanism in the cheek pouch. Hemorrhagic shock (HS) was induced by withdrawing blood to reduce mean arterial pressure (MAP) to 30 mm Hg for 45 min.

Methods: Animals were injected with ACTH-(1-24) and resuscitated with dextran of low molecular weight (70 kDa) and a small amount (4%) of dextran of high molecular weight (500 kDa) plus ACTH-(1-24), or autologous (shed) blood withdrawn during HS. Microvascular effects were characterized by measuring blood flow, perfused capillary length (PCL), arteriolar diameter, and red blood cell (RBC) velocity. ROS were assayed at the beginning and after 45 min of HS and after 10 and 90 min of resuscitation.

Results: Resuscitation with either shed blood or dextrans 70/500 resulted in the restoration of MAP, whereas PCL, RBC velocity, and arterial diameter decreased significantly. ROS increased significantly after HS, 10 and 45 min of resuscitation. ACTH-(1-24) plus dextrans 70/500 increased MAP immediately; it increased vasodilation and PCL, and attenuated significantly ROS production and leukocyte adhesion during resuscitation. L-NMMA injected after 30 min of HS did not change the protection exerted by ACTH-(1-24) and dextrans 70/500, while SOD increased their protective effects.

Conclusions: ACTH-(1-24) appears to enhance the protective effects on the endothelium exerted by increased plasma viscosity by significantly decreasing the oxidative stress and the leukocyte adhesion during resuscitation.