BENEFICIAL EFFECTS OF OLIGOTIDE, A NOVEL OLIGODEOXYRIBONUCLEOTIDE, IN MURINE TRAUMATIC SHOCK

Abstract

The effects of oligotide, an oligodeoxyribonucleotide analog, were investigated in an experimental model of traumatic shock. Pentobarbital-anesthetized rats subjected to Noble-Collip drum trauma and receiving only the vehicle (i.e., Krebs-Henseleit solution) developed a severe form of traumatic shock characterized by marked hypotension (61 +/- 6 mmHg), a survival time of 115 +/- 21 min, endothelial dysfunction, significant increases in plasma free amino-nitrogen concentration (p < .001) as well as elevated intestinal myeloperoxidase activity. In contrast, oligotide given intravenously (15 mg/kg bolus + 10 mg/kg/h infusion for 5 h) resulted in a significant prolongation of survival time to 209 +/- 31 min (p < .01), a significant and sustained increase in mean arterial blood pressure, a significant attenuation of plasma free amino-nitrogen concentration (p < .01), and intestinal myeloperoxidase activity (p < .05). Furthermore, oligotide significantly preserved superior mesenteric artery (SMA) endothelial function as seen by the relaxation response of isolated SMA rings to acetylcholine (71 +/- 5% vs. 36 +/- 5%, p < .01 compared to untreated trauma rats). Moreover, oligotide in a concentration-dependent manner attenuated unstimulated human neutrophil adherence to either thrombin or trauma-activated SMA endothelium in vitro (p < .001). Thus, our data suggest that the mechanism of the protective effect of oligotide in traumatic shock is improving endothelial function and diminishing neutrophil accumulation leading to reduced tissue injury.