Protective effects of a PGI2 analogue OP-2507 on hemorrhagic shock in rats--with an evaluation of the metabolic recovery using near-infrared optical monitoring.

Abstract

The protective effects of the PGI2 analogue, OP-2507 against hypoxic tissue injury were investigated in a 60-70 min acute hemorrhagic shock model in 29 rats. To assess the metabolic recovery of mitochondria after tissue injury induced by hemorrhagic hypotension with a mean arterial pressure of 30 mmHg, we have non-invasively monitored changes in the brain tissue parameters of cyt. aa3 redox state, blood oxygenation and relative blood volume by spectrophotometry through the closed skull and intact skin. Pretreatment with 0.1 mg/Kg s.c. of OP-2507 at 30-40 min before induction of shock was performed on 14 rats (OP-treated group). The remaining 15 rats were used as a control (control group). There was a consistent prolongation of survival time and a significant improvement in survival rate after reinfusion of the shed blood in the OP-treated group. In this group there was a rapid and complete reoxidation of cyt. aa3 with a mean overshoot of 9 +/- 5.5% above the baseline value after reinfusion. On the other hand, in the control group the extent of reoxidation was significantly lower, with a minimal 11 +/- 3.2% below the base line. In order to evaluate the mechanisms involved 10 mg of NaCN i.v. was administered to the living rats at 60-70 min after reinfusion of the blood in both groups. In the OP-treated group, brain Hb saturation increased up to 20% above the pre-cyanide infusion level. However in the control group there was a non-significant increase in the Hb oxygenation level. These observation indicate that in the OP-treated group oxygen consumption by mitochondria is significantly higher than that in the control group. Thus, enhanced oxygen utilization could lead to the active restoration of injured tissue by promoting oxidative phosphorylation. Under these experimental conditions the oxidative response of cyt. aa3 is concluded to correlate closely with the prognosis of shock animals in both groups. These results indicate the potential usefulness of OP-2507 in protecting the brain and other organs from oxygen insufficiency as a result of tissue ischemia and anoxia.