Beneficial effects of oligotide, a novel oligodeoxyribonucleotide, in murine traumatic shock.
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.
Skurk
C
C
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Nuss
C
C
Lefer
A M
AM
D000818:Animals; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects; D009584:Nitrogen / Q000097:blood; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D019007:P-Selectin; D009195:Peroxidase / Q000032:analysis; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012774:Shock, Traumatic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013917:Thrombin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D015415:Biomarkers; D009838:Oligodeoxyribonucleotides; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D014665:Vasodilator Agents; D009195:Peroxidase; D013917:Thrombin; D009584:Nitrogen