Further Experimental and Early Clinical Observations Concerning the Protective Action of Low Molecular Weight Dextran Upon Intravenous Hypaque Toxicity

Rapid intravenous injection of large amounts of concentrated diatrizoates results in a syndrome which includes the prompt development of systemic hypotension, bradycardia, pulmonary hypertension, and pulmonary edema and hemorrhage. Read (9) demonstrated the simultaneous development of diffuse red blood cell aggregation following such injections, and Sobin (10) has confirmed this finding in man. Low molecular weight dextran has been employed by Gelin (4) and other Swedish investigators in the prevention and treatment of the red blood cell aggregation seen following burns, fractures, and muscle trauma and by Long and Lillehei (8) in preventing similar aggregations after prolonged cardiopulmonary bypass. Earlier experiments from this laboratory (2) indicated that such premedication approximately doubles the LD 50 and LD 100 of rapidly injected intravenous Hypaque-90 in dogs. Experimental Studies: Further animal experiments have been carried out in an effort to determine whether other common parenteral agents are also capable of affording this protective action, and to inquire into some aspects of the mechanism of the protection afforded. Mongrel dogs were anesthetized with pentobarbital and subjected to single intravenous doses of 5 c.c.∕kg. Hypaque-903 with the aid of a steel syringe and hand-lever injector. This dose has proved almost uniformly lethal in the unpremedicated animal in our experience (3). Premedication, with a standard dosage of 10 c.c.∕kg., was administered intravenously over a two-minute period, following which a ten-minute control period was permitted for equilibration. In addition to the low molecular weight dextran used in the majority of these studies, injections of equal amounts of normal saline, 5 per cent dextrose in water, dog plasma, 6 per cent human serum albumin, and 6 per cent commercial dextran have been evaluated. Aortic blood hematocrit, sedimentation rate, and whole blood and plasma viscosity have been measured and, in addition, the blood pressure, electrocardiogram, respiratory rate and depth, and microcirculation of the bulbar conjunctiva were monitored. While all of the premedication solutions resulted in some decrease in mortality, none approached the activity of the low molecular weight dextran solution. The component of blood viscosity due to the red cells is here called “apparent RBC viscosity,” and was calculated with the measurements of blood and plasma viscosity and the formula: where μ viscosity and h hematocrit. Low molecular weight dextran was capable of maintaining an essentially normal apparent RBC viscosity (Fig. 1). In marked contrast, in the animals without premedication, the apparent RBC viscosity is more than doubled.