The effects of naloxone on endotoxic and hemorrhagic shock in horses

The effects of naloxone on the cardiovascular, hematologic and metabolic derangements associated with endotoxic and hemorrhagic shock were studied in unanesthetized horses. In the first of 3 experiments blood glucose and lactate levels, hematocrit, white, red and differential white cell counts, rectal temperature and clinical signs were obtained before and after endotoxin (10 μg/kg) administration in 5 horses. In the second experiment, two groups of 3 horses received either intravenous naloxone (0.04 mg/kg) or saline, 7 minutes prior to endotoxin. In a third experiment two groups of 4 horses received either saline or naloxone (0.20 mg/kg) immediately following acute hemorrhage. In the second and third experiments, pulse, mean arterial and right ventricular pressures, and heart rate were also observed. Endotoxin and acute hemorrhage produced hypothermia, leukopenia, lymphopenia, neutropenia, elevations in hematocrit, blood glucose and blood lactate, and clinical signs of shock. Naloxone (0.040 mg/kg IV) significantly lowered endotoxin-induced increases in right ventricular pressure and heart rate, and at a higher dose (0.20 mg/kg) antagonized the decrease in pulse and heart rate, and tachycardia observed after acute hemorrhage. These results suggest endogenous opioids are involved in the pathogenesis of shock. Naloxone appeared to attenuate some of the cardiovascular responses associated with shock and thus may be of therapeutic value in shock management.