Heart rate and blood pressure were measured in anesthetized rats after the intraperitoneal administration of radioprotective doses of 5-hydroxytryptamine (5-HT), 2-mercaptoethylamine (MEA), 2-aminoethylisothiouronium (AET), and their mixtures. All of the chemicals produced a slowing of the heart rate in most of the animals. Both doses of 5-HT (7 and 14 mg/kg) consistently elicited a marked depressor response. While a low dose of AET (100 mg/kg) had little effect, higher doses (175 and 250 mg/kg) tended to increase blood pressure. On the other hand, low doses of MEA (60 and 120 mg/kg) tended to lower blood pressure, while a high dose (165 mg/kg) produced no significant change. The blood pressure response after the administration of the mixtures of the chemicals appeared to be the resultant effect of the action of each component. The mixture of all three chemicals (7 mg/kg 5-HT, 100 mg/kg AET, 60 mg/kg MEA) elicited the most consistent response in all animals, slowing the heart rate by 20% and decreasing the blood pressure by 35%. The blood pressure reached its nadir 5 minutes after injection and remained relatively low for an additional 10 minutes.

A triple treatment, including (1) preirradiation protection by a chemical mixture (7 μmoles of AET, 25 μmoles of MEA, and 2 μmoles of serotonin, injected intraperitoneally, 0.4 ml/mouse), (2) postirradiation administration of 5× 10 5 nucleated homologous bone marrow cells intravenously, and (3) daily subcutaneous injections of the antibiotic streptomycin (5 mg in 0.5 ml of saline), for 10 days after irradiation, was used in CF No. 1/ANL mice exposed to single supralethal whole-body doses (400 to 600 rad) of either fission neutrons (CP-5 Reactor) or 900 to 1700-R doses of 250-kVp x-rays. Irradiations of each group of mice were completed in less than an hour. In the x-irradiated mice this multiple treatment elevated the ${\rm LD}_{50(30)}$ from approximately 675 R to more than 1700 R, a dose-reduction factor (DRF) in excess of 2.5. In comparison, the ${\rm LD}_{50(30)}$ for neutron-exposed animals was increased by a factor of less than 1.3. When the pre-x-irradiation treatment with the chemical mixture was used alone, the ${\rm LD}_{50(30)}$ of female CF No. 1/ANL mice was raised from 675 R to 1200 R or more (DRF = 1.8). With a similar chemical mixture, the ${\rm LD}_{50(30)}$ of neutron-irradiated mice, was increased less than 10%. These results indicate the value of a multiple approach in protecting against the deleterious effects of either x-irradiation or neutron irradiation. The data further imply that greater injury and/or less recovery occurred in the neutron-exposed mice.

The oxygen tensions in the spleen of mice forced to breathe 10%, 7%, and 4.6% oxygen were, respectively, 0.36, 0.27, and 0.10 of normal. The dose reduction factors at the corresponding levels were 1.24, 1.73, and 1.96. Serotonin reduced the oxygen tension to 0.53 of normal and gave a dose reduction factor of 1.77. PAPP reduced the oxygen tension to 0.35 of normal and gave a dose reduction factor of 1.74. A combination of serotonin and an atmosphere of 4.6% oxygen, where the oxygen tension in the vena cava declined to 0.06 of normal, gave a dose reduction factor of 2.92. If one plots the relative effectiveness of the radiation (y = 1/DRF) versus the relative oxygen tension (x) of the spleen and vena cava for each of the experimental situations, there exists an approximate linear relationship for values of x not greater than 1. The results indicate that there is a small amount of protection by both serotonin and PAPP which is independent of hypoxia. This relationship can be given as <tex-math>$F_{i}y$</tex-math> = 0.42 + 0.60x, in which the values of F i are 1.4, 1.2, and 1.12, where i refers, respectively, to serotonin, sodium nitrite, and PAPP.