Dose response effect of diaspirin crosslinked hemoglobin (DCLHb) on systemic hemodynamics and regional blood circulation in rats

Diaspirin crosslinked hemoglobin (DCLHb(TM), Baxter Healthcare Corporation) a hemoglobin-based blood substitute has been found to increase mean arterial pressure (MAP) in a dose limiting manner. The present study was undertaken to determine dose-dependent effects of DCLHb on systemic hemodynamics and regional blood circulation. DCLHb (10% solution) in doses of 133, 400 and 1200 mg/kg i.v. was given to urethane anaesthetized rats. Normal saline(12 ml/kg) served as a control. Cardiovascular parameters were determined using a radioactive microsphere technique. DCLHb in the doses of 133, 400 and 1200 mg/kg i.v. produced a 46%, 67% and 65% increase in MAP, respectively. Total peripheral resistance (TPR) increased significantly with 133 and 400 mg/kg dose, while cardiac output increased significantly with 400 and 1200 mg/kg dose. There was no change in heart rate. A dose of 133 mg/kg of DCLHb produced a significant decrease in blood flow to the musculoskeletal system, kidney and liver. DCLHb in the dose of 400 and 1200 mg/kg significantly increased blood flow to the heart, gastrointestinal tract (GIT), mesentery & pancreas and skin. All doses of DCLHb produced a significant increase in vascular resistance to the musculoskeletal system and liver. DCLHb in the dose of 133 mg/kg increased resistance to the GIT. heart, skin and kidneys, while the dose of 400 mg/kg increased resistance to the kidneys. A dose of 1200 mg/kg decreased coronary vascular resistance. It is concluded that cardiovascular effects appear to be different with higher (1200 mg/kg) and lower (133 mg/kg) doses of DCLHb.