Experimental Pulmonary Embolism Due to Red Cell Aggregation.

The effect of clumping or aggregation of red blood cells on flow has recently become of increasing interest. Unimpeded flow through the capillaries depends to a great extent upon the red cells remaining separate in the plasma. Clumping causes blockage of the blood vessels, the extent of which is governed by the rate of flow and perfusion pressure, and the relative size of the clumps and lumen of the vessel. This blocking is manifest as an increase in resistance, as in pulmonary hypertension, and can, combined with other factors such as low perfusion pressure, vasoconstriction, and a low oxygen saturation, cause widespread tissue ischaemia, especially in the brain and kidney, which are sensitive to lack of oxygen (Knisely, Eliot, and Bloch, 1945; Heimbecker and Bigelow, 1950). Intravascular aggregation of red cells occurs naturally in many clinical conditions, especially where tissue damage is a feature. These include traumatic shock, burns, cardiac infarcts, and during extra-corporeal circulation (Gelin, 1956). This can be observed in the conjunctival vessels and is reflected by a high sedimentation rate. It can also be caused in vivo and in vitro by the injection of certain substances into the blood. These include high molecular weight dextran, some radio-opaque dyes, and other large molecules such as hexadimethrine bromide ('polybrene', Abbott). We have chosen the latter to produce experimental red cell aggregation and to study its effects on the circulation for two reasons. It is a powerful and reliable agent for causing aggregation; and it is an efficient neutralizer of heparin (Preston, Hohf, and Trippel,\ 1956) and as such is used at the end of cardiopulmonary by-pass. We have studied its circulatory effects in detail in order to isolate the effects of red cell aggregation that cause pulmonary hypertension. There is no general agreement as to the effects of this drug on the circulation if given other than extremely slowly and in small amounts. A prolonged systemic hypotension has been reported (Weiss, Gilman, Catenacci, and Osterberg, 1958; Kimura, Young, Stein, and Richards, 1959; Egerton and Robinson, 1961). On the other hand, an early rise in pulmonary artery pressure has been found by others (Rothnie and Kinmonth, 1960; Holemans and Adamis, 1962). The latter put forward the suggestion that the changes in pressure could be due to blocking of the pulmonary vessels by red cell aggregates seen in vitro. Other substances causing pulmonary hypertension on intravenous injection were also studied and their actions compared. The results show how red cell aggregation can produce pulmonary hypertension due to mechanical blocking of the pulmonary vessels.' The circulatory effects described in this paper may help in the investigation of such clinical conditions as pulmonary embolism and pulmonary hypertension of the obliterative type, as well as in stressing the danger of substances likely to cause aggregation.