R. A. Huggins

Protective Action of N-Allyl-Normorphine Against Respiratory Depression Produced by Some Compounds Related to Morphine.∗†

Conclusions 1. N-allyl-normorphine prevents or antagonizes the respiratory depression produced by codeine, Dilaudid, Metopon and Methadon. 2. It did not provide protection against the respiratory depression caused by Demerol.

Effects of Hypertonic Glucose and Mannitol on Plasma Volume.

Summary The influence of hyper tonic glucose and mannitol on blood volume was tested in normovolemic-normotensive and hypovo-lemic-hypotensive dogs. Neither glucose nor mannitol had any effect on the blood volume of normovolemic dogs. In hypovolemic-hypo-tensive dogs, mannitol produced a significant increase in the plasma volume by mobilizing fluid from the extravascular spaces. The fluid entering the circulation was accompanied by a significant amount of protein. Also, plasma volume increased after hemorrhage with glucose, but the increase was small and was not accompanied by protein. Thus, both glucose and mannitol, but particularly the latter, increased the blood volume in hypovolemia.

Conjugation of N-Allylnormorphine by Liver Slices∗

Conclusions 1. N-Allylnormorphine can be estimated by the use of the Snell and Snell reagent, for a change in the alkyl group on the nitrogen does not change the intensity of the color produced. 2. N-Allylmrmorphine is oonjugated by surviving liver slim at the same rate as is morphine. In two and onehalf hours, about 75% of the two compounds is conjugated. 3. Because conjugation of the two compounds proceeds at essentially the same rate and the effective blocking dose of N-allylnormorphine is small, the latter compound must be more firmly fixed to the receptor site than is morphine.

Blood Flow Determinations and Cardiodynamic Effects of a Venous Shunt in Pulmonary Hypertension.

Conclusion 1. In acute experiments producing increased pulmonary vascular pressure in dogs, the capacity of a pulmonary vein-azygous vein shunt was found to be up to 8% of the total cardiac output. 2. There was no consistent evidence that the presence of the shunt produced or added to the strain on the right ventricle or interfered with the filling pressure of the left ventricle.

Effects of certain anesthetics on distribution of red cells in the dog.

The animals were anesthetized with either sodium pentobarbital or morphine alone or in combination and the effects of these drugs were determined on the cell and plasma volumes and hematocrits on unsplenectomized and splenectomized groups. ‘Circulatory’ hematocrit is used to designate the distribution of cells and plasma throughout the circulatory system rather than ‘body’ hematocrit or over-all cell percentage; and BVR cells is used in place of the term F cells . In unsplenectomized dogs with pentobarbital alone the venous hematocrit is significantly lower than the morphinized or morphine-pentobarbitalized dogs, and the BVR cells (circ. hemat/venous hemat.) is 1.02. The latter figure is significantly different from 0.89 with morphine alone or 0.90 with the combined drugs. Removal of the spleen affected neither the variability of individual dogs nor significantly changed the BVR cells . The action of morphine when given alone, markedly increased the plasma volume and when combined with pentobarbital resulted in a redistribution of red cells; thus the BVR cells was decreased for these groups compared to pentobarbital alone. These data imply that cell and plasma volume should be measured simultaneously and independently for determining the blood volume with the utmost accuracy.

Determination of Cell Volume in Massive Transfusions Using Fe59 and Cr51

When dogs are injected with either or both Fe59 and Cr51-labeled cells (initial tag) prior to a series of transfusions (up to 20.0–25.0 cc % body weight) the measured blood and cell volume closely approach and may exceed the expected. After the series of transfusions are completed, if an additional isotope (final tag) is injected the blood and cell volumes are much less than the expected. The difference between the blood and cell volumes determined by the initial and final tag can be explained by the ‘trapping’ of red blood cells. The volume of red blood cells ‘trapped’ after multiple transfusion (up to 10.0–14.9% body weight) can equal or exceed the added cell volume.

A Comparison of Cardiac Outputs, Determined by Direct Fick and Pressure Pulse Methods

A method of determining cardiac output that is more rapid than the standard procedures, and with less dependence on skilled technical help has long been needed. With the publication by Hamilton and Remington 1 of a method for determining stroke volume from a pressure pulse this need has been met if their results are reproducible by others. In addition, their method has the added advantage, for the pharmacologist, of being able to follow the actions of a drug on the output from stroke to stroke. Using the dye method as their basis of comparison, they found a correlation of r = +0.994 with an average variation between the two measurements of ±8.2% with a range of +35 to −13%. While the dye method has been shown to give compara-able to the Fick method 2 within ± 10%, it seemed essential that a comparison be made between the Fick and the pressure pulse method not only to compare the accuracy of the pressure pulse method but to check our own calculations of cardiac output by that method. Methods. A total of 8 dogs were used and 15 outputs were determined under a variety of conditions. The dogs were anesthetized with sodium barbital 300 mg/kg administered orally or intraperitoneally. Pressure pulses were obtained by means of a Hamilton manometer 3 of adequate frequency. A No. 9 ureteral catheter was passed down the right jugular to the right ventricle and the position verified by fluoroscopy. A slow, heparinized saline drip was maintained through the catheter. Oxygen consumption was measured by connecting the dog to a McKesson Recording Metabolor, with a tracheal cannula. Blood samples were taken under oil simultaneously from the right ventricle and a femoral artery and promptly iced.