Vaso-Excitor and -Depressor Substances as “Toxic” Experimentally Induced Shock ∗

Abstract

In our observations on the visceral circulation of animals in tourniquet and traumatic shock, capillary changes, in addition to those produced by generalized vasoconstriction, were noted remote from the site of injury. This and the fact that similar changes occurred in irreversible hemorrhagic shock led us to look for the presence in the blood of abnormal substances which would account for the observed reactions. Descriptions of the vascular reactions after these shock treatments involving fluid loss are being published. 1 They indicate that the changes are of the order of an initial hyper-reactive condition, suggesting the presence of vaso-excitors, and a subsequent hypo-reactive condition in which substances possessing vaso-depressor properties predominate in the blood.

To obtain objective evidence for this, small quantities′ of blood, taken at intervals during the shock syndrome, were introduced into the blood of normal rats and the effect noted on the vessels of the normal mesoappendix. This test proved to be a discriminating one because of the highly specific pattern of responsiveness of these vessels.

The blood from the shocked animals was either heparinized or allowed to clot and the serum collected and refrigerated for 24 hours. The test rat, under nembutal, was prepared for blood pressure measurements 2 and its mesoappendix exposed for microscopic observation. About 0.5 cc of the blood or serum to be tested was then injected into the tail vein. The effect on the capillary circulation of the test rat was transient but was found to simulate many of the changes previously observed in the shocked animals. For control, it was found that normal and hemolyzed blood or serum of dogs and rabbits after 24 hours refrigeration exerted no specific effects.

The criteria looked for were: (a) altered appearance of the capillary flow with a shift toward either an ischemic or a hyperemic flow and a change in rate of the venular flow; (b) change in responsiveness to topical application of epinephrine; and (c) augmentation or diminution of the vasomotion of arteriolar vessels.