William M. Parkins

Effects of increased osmolality and correction of acidosis on blood flow and oxygen consumption in hemorrhagic shock

Hypertonic NaHCO3 or NaCl given to an animal in hemorrhagic shock with the blood pressure maintained at the shock level by an open reservoir produced marked increases in cardiac output and oxygen consumption. This occurred in spite of large volumes of blood which were removed to maintain the same low blood pressure and decreased arterial oxygen content. Hematocrit was greatly decreased, which would reduce blood viscosity, and plasma osmolality was increased. The increased survival rate and reduced tissue damage found in other studies with hypertonic infusions during hemorrhagic shock would seem to be the result of this hemodynamic improvement. Cellular overhydration may occur with shock, but because of changes in blood flow and oxygenation, experiments such as this yield no information about the possibility of its occurrence or reversal by increased osmolality. The hemodynamic and oxygenation changes with NaCl and NaHCO3 in hemorrhagic shock were comparable and indicate that the improvement after NaHCO3 was due to an osmotic effect rather than to pH correction. This suggests that circulatory depression by metabolic acidosis either was not present at the time and levels studied or could not be separated from the extensive osmotic effects of these solutions.

Various plasma expanders in animals.

In the process of evaluating the merits of a plasma expander, its safety and efficacy under various experimental situations must be determined. Attention is focused particularly upon the following: (a) storage, or retention in any particular organ system; (b) blood retention and urinary excretion; (c) metabolic fate; (d) pharmaco-dynamic effects upon the various elements of the circulatory system; and (e) oncotic efficacy as exemplified by its ability to maintain an adequate plasma volume. I n each category, animal experimentation is a necessary precursor of extensive clinical trial. Only in such manner can the potential value or hazards of a suggested plasma expander be assessed. In certain instances, there may be peculiar species-sensitivities to individual substances which limit the usefulness of certain tests. This occurrence, however, is of interest, and may throw light upon unsuspected pharmacologic properties of the material being studied. At present, there are several types of substances available as suggested plasma expanders, some of which have had extensive experimental study. These include (a) gelatin, prepared from bone ossein or pork skin; (b) oxypolygelatin, a gelatin preparation chemically treated to reduce the gelation temperature of the product; (c) dextran, a polysaccharide elaborated by a micro-organism (Leuconostoc mesenferoides) which, after purification, is hydrolysed and fractionated to give a suitable molecular size; (d) polyvinypyrrolidone, a synthetic polymer produced by the controlled polymerization of vinylpyrrolidone with subsequent fractionation. Two materials that have had only preliminary experimental trials are: (a) pectin, a polyuronide, fractionated and purified from natural sources; (b) polyglucose, a product produced by the chemical polymerization of glucose. In our own investigations, attention has been focused particularly upon the efficacy of the various plasma expanders in maintaining the plasma volume after two types of shock procedures involving hemorrhage in the dog. Besides observing their oncotic effect, ancillary data upon a variety of physiologic reactions have been obtained. Investigations have also been made of the plasma retention, urinary excretion, and metabolic fate of certain of the expanders. Two procedures for evaluating plasma expanders in hemorrhagic-shocked dogs have been employed. They were developed during the period 1942 to 1945, and had an extensive trial in our laboratories by Drs. Parkins and HamilCarefully selected, healthy dogs are bled, under light nembutal anesthesia, at a standard uniform rate to a mean blood pressure of 20 mm. Hg, and are infused immediately with a volume of and in the laboratory of Dr. Lawson.4

A self-contained method for the administration of fluids at regular rates.

Summary 1. Various combinations of self-contained delivery units for the administration of fluid at regular rates are described, and the limits of usefulness of these units are delineated. 2. Combinations of such units to permit the administration of various types of fluids, including those likely to destroy the elasticity of rubber, are described.