Minerva Morse

THE POSITION OF THE OXYGEN DISSOCIATION CURVE OF THE BLOOD IN NORMAL CHILDREN AND ADULTS

Oxyhemoglobin dissociation curves were determined in normal children and adults as a preliminary to a study of such curves in patients with cyanotic congenital heart disease. A comparison of the curves of normal children with those of normal adults showed that the dissociation curves of children tend to lie to the right of those of the adult. In order to confirm this observation, the study was extended to include more cases and a wide range of ages. Thi-s report presents the results of the study. The report consists of a comparison between the positions of the oxyhemoglobin dissociation curves of the child and the adult in a group of 21 children two to ten years of age and 22 adults 21 to 45 years of age. In addition, it includes oxygen dissociation data for six newborn infants less than one day old, for a group of 15 older infants varying in age from 11 days to two years, and for a group of nine pre-adolescents, adolescents and post-adolescents from 11 to 20 years of age. The older infants were included in order to determine whether the slight shift of the curve to the right in childhood is greater in infancy. The older children were studied in the hope of determining the approximate age at which the leftward shift to the normal adult position occurs.

THE POSITION OF THE OXYGEN DISSOCIATION CURVE OF THE BLOOD IN CYANOTIC CONGENITAL HEART DISEASE

The similarity of the blood picture in patients with cyanotic congenital heart disease and in residents at high altitudes suggested the investigation of the position of the oxygen dissociation curve as a possible compensatory mechanism for reducing tissue hypoxia. In studies by the International High Altitude Expedition to Chile in 1935, Keys, Hall and Barron (1) found a small and questionably significant displacement of the curve to the right in the blood of residents at 5.34 km., in contrast to a displacement to the left as reported by Barcroft and his collaborators (2) from observations at 4.33 km. in 1922. With one exception, other expeditions to higher altitudes have found no changes in the position of the dissociation curve with decreasing barometric pressures (3, 4). However, a displacement of the curve to the right was given added confirmation by the finding by Aste-Salazar and Hurtado (5) that ten of the 12 native residents at altitudes of 4.5 km. had PO2 values at 50 per cent saturation which were higher than the corresponding mean level for a group of residents at sea level.2 Such a displacement, even though slight, would have advantage in that it would increase the capacity for oxygen transport by decreasing the venous saturation level for a given PO2 level. The present report describes the results of a study of the positions of the dissociation curve of the blood in 29 patients with cyanotic congenital heart disease 8 as compared with those of 43 normal individuals.

The lung volume and its subdivisions in normal boys 10-17 years of age.

disease. Because the absolute values obtained have no meaning for children varying so greatly in size, except as they can be referred to some standard of reference, such as height, weight, and other measurements of body size, the results were analyzed by statistical methods in order to determine the relation of the lung volume and its subdivisions to various physical characteristics of the child. These relationships were then expressed in the form of regression equations which can be used to predict the lung volume and its subdivisions for a given individual and, by means of the standard error of estimate, can give a measure of the amount of variation that may be expected in the normal child. Of the various subdivisions of the lung volume

Blood volume and exercise

Summary 1. The increase of serum protein concentration has been determined following both moderate and vigorous exercise in experiments on eighty-five healthy boys. The blood pressure changes have also been observed. 2. In nineteen of these subjects, the increase of the concentration of the blue dye, T-1824, following exercise has also been determined. 3. In twelve of these subjects there was evidence of circulatory collapse.

THE ARTERIAL BLOOD GASES, THE OXYGEN DISSOCIATION CURVE, AND THE ACID-BASE BALANCE IN POLYCYTHEMIA VERA

Studies of the circulation and pulmonary function in normal children and in patients with polycythemia related to cyanosis in congenital heart disease raised questions concerning the extent to which polycythemia itself might be responsible for some of the abnormalities observed in the blood in cyanotic congenital heart disease. These questions concerned the possibility that the increased viscosity of polycythemic blood might prevent proper diffusion of oxygen in the alveolarcapillary system, resulting in arterial oxygen unsaturation, the characteristics of the oxyhemoglobin dissociation curve in polycythemia vera, since this has been found shifted to the right in the blood of patients with cyanotic congenital heart disease (1), and the relation of a low CO2 content and combining power to polycythemia, since these were observed to be low in the secondary polycythemia of congenital heart disease (2-4). Studies of the blood in polycythemia vera were made and compared with similar studies in cyanotic congenital heart disease. These included determinations of the oxygen content, oxygen capacity and oxygen saturation of arterial blood, the effect of breathing oxygen on the oxygen content of such blood, the oxyhemoglobin dissociation curve and the carbon dioxide content, combining

ARTERIAL BLOOD GASES AND ACID-BASE BALANCE IN CYANOTIC CONGENITAL HEART DISEASE

The purpose of this report is to present data concerning the arterial blood gases and the acidbase balance in patients with cyanosis due to congenital heart disease. Since the study is related to cyanosis and abnormalities of the blood consequent to this, no distinction is made between the various anatomical defects producing cyanosis. Compensatory or adaptive mechanisms in the presence of cyanosis related to congenital heart disease have been the subject of a number of studies (1-6). The present study was undertaken to obtain further information concerning the arterial blood gases in this disease, especially in relation to age and in respect to the influence of arterial unsaturation on the acid-base balance. Sixty cyanotic patients were studied, varying in age from 1 to 36 years. The methods used have been described in a preceding report (7).

Blood volume in congenital heart disease

Summary The abnormal circulation in congenital heart disease is in many respects similar to the abnormal circulation in a peripheral arteriovenous fistula, although the vascular paths of the shunted blood are shorter. This communication is continuous in an extracardiac fistula, as the patent ductus arteriosus, and intermittent in intracardiac shunts, the septal defects. The abnormal communication initiates an accessory circulation which, in relation to dynamics and volume, is independent of the systemic or pulmonary circulation upon which it is parasitic. The accessory or “third” circulation in several simple congenital cardiac defects is illustrated. The relation of the abnormal circulation to the circulating blood volume is considered. The volume of the circulation was determined by the blue dye method in three categories of congenital heart disease, (1) intracardiac acyanotic shunts, (2) patent ductus arteriosus, and (3) cyanotic congenital heart disease. The values obtained were compared with the blood volume of normal children. The blood volume in patients with a patent ductus arteriosus was found to be increased, and the volume diminished following surgical ligation of the open ductus. The blood volume in acyanotic intracardiac arteriovenous shunts was elevated by a smaller amount. The volume in the cyanotic type of congenital heart disease was greatly increased, due to an increase of red blood cells. The plasma was usually below the expected amount. It was concluded that the abnormal circulation in the three categories ofcongenital heart disease requires an elevation of circulating blood volume. It could not be determined whether this increase is a direct measure of the abnormal shunt.

The influence of fruit and vegetable feeding upon the iron metabolism of the infant

Summary 1. A study of the iron metabolism of three normal infants, ranging in age from five weeks to seven months, has shown that vegetable (spinach) or fruit (apricots) feeding in addition to the milk formula exerts no significant effect upon the amount of iron retained by the infant. Such feeding increased the iron intake 60 to 171 per cent. The hemoglobin concentration and the number of erythrocytes in the blood were within or above the normal range for infants of this vicinity and age, and were not raised by the vegetable or fruit feeding. 2. A study of the effect of such feeding upon an anemic infant, twenty-three months old, who had been living on an almost exclusive milk diet, has shown a lack of effect in the case of dried spinach, but a marked increase in retention of iron when apricots were added to the diet, an effect which disappeared again after wheat germ extract was also included. The effect in each case is related to the amount of fecal matter eliminated in the metabolism period. We prefer to with-hold interpretation until more data are available. The hemoglobin concentration and erythrocyte count of the blood were not improved during the course of such feeding. 3. A very large increase in the concentration of soluble iron in the diet of the anemic infant, brought about by adding ferric ammonium citrate, resulted in a large increased retention of iron, but up to the end of three weeks on the diet, only a very slight increase in the number of erythrocytes had occurred and practically no change in hemoglobin concentration. 4. When the diet of the anemic infant was further supplemented by liver, the retention of iron was increased still more. The retention in this instance was accompanied by a rise in hemoglobin from 6.0 to 9.1

Some responses of the child to exercise.

Summary The effects of exercise have been studied intensively in twelve children from 11 to 13 years of age. The study has included determinations of the changes in heart rate and systolic and diastolic pressures, resulting from both moderate and maximal work on the bicycle ergometer, and determinations of the changes in many of the blood components under the two conditions of work. An attempt has also been made to relate these changes to the nutritive status and to the physical capacity of the child. The nutritive status of each child has been established by clinical examination, by the weight and fat indices of McCloy, and by creatinine indices. Physical capacity has been measured by performance on the bicycle ergometer. With the exception of serum pH and sodium during moderate work and diastolic pressure, blood sugar, serum chloride, and CO2 tension during maximal work, all of the factors measured showed significant changes as the result of exercise. Pulse rate and systolic pressure increased with exercise, but as work was changed from a moderate to a maximal character little further increase occurred, as a rule. Diastolic pressure showed great variability of response under either condition of work, decreasing in the majority of children during moderate exercise, but showing an increased tendency to rise during maximal exercise. Hemoglobin, red cell volume, and serum protein increased with both moderate and maximal exercise. With one exception (R. W.), the magnitude of the rise was greater during maximal exercise, the maximum increase for an individual child reaching 8.2 per cent for protein, 8.6 per cent for cell volume, and 10.4 per cent for hemoglobin. The sodium and chloride concentration of the serum showed little change, although an increase of approximately 0.7 meq. in chloride during moderate exercise appears to be significant. Serum phosphate increased during both moderate and maximal exercise by a small amount not exceeding 0.3 meq. The rise in phosphate tended to be higher during maximal work. Blood sugar showed small variable responses to exercise but increased slightly in the majority of persons. Serum lactate increased, on the average, by 3.5 meq. during moderate exercise, and by 7.8 meq. during maximal exercise. Serum bicarbonate, corrected to initial pH, showed a corresponding, but slightly greater, fall. The pH did not change appreciably during moderate exercise but decreased on the average, by 0.09 during maximal work. Greater variations in response occurred during moderate work in pulse rate and serum lactate, bicarbonate, CO2 tension, sugar, and phosphate, and during maximal work in systolic, diastolic and pulse pressures. These factors would, therefore, appear to offer more fruitful fields for investigation of individual differences and their relation to physical capacity. The present investigation was limited to too small a number of children and too heterogenous a group to enable us to draw conclusions, but a few relationships appear suggestive. Superior physical capacity is indicated in the child, as well as in the adult, by the lack of a significant rise in serum lactic acid and a corresponding fall in bicarbonate when a fixed moderate task is performed. Those children showing the smaller, often insignificant, rises in phosphate during moderate exercise possess good or superior physical capacity. These children also show little change or a slight fall in blood sugar under such conditions while the others exhibit a rise which may become marked. The children showing the higher cardiovascular responses to moderate work are only fair or poor in physical capacity. While nutritive status undoubtedly has some effect upon the physical response of the child, many other factors complicate the problem. Many more children will have to be studied and the various factors interrelated in some statistical manner before much progress can be made in the solution of the problem. We feel, however, that the methods used in the present investigation offer valuable tools for its solution.

The effect of various supplements to the diet on the iron balance of the anemic infant

Summary The effect of various supplements to the diet on the iron retention and hemoglobin of three cases of secondary anemia has been shown. Additional iron, when supplied by pureed spinach, was not utilized by these infants. The iron of apricots, although utilized somewhat better than that of spinach, affected no change in hemoglobin and only a slight increase in retention. Iron salts, when given in large amounts either in the form of ferrous sulphate or ferric ammonium citrate caused a marked increase in the retention and a rise in hemoglobin. There was no evidence shown that the ferrous salt was more efficacious than the ferric salt. Copper salts, given in conjunction with either a low or a high iron intake, did not seem to have any effect on the iron retention or the hemoglobin level. The copper contents of the previous diets were apparently adequate. The introduction of liver into a diet of low iron content caused a slight increase in retention, but no gain in hemoglobin. With a high iron intake, a decreased retention of iron occurred coincident with the addition of liver to the diet. It is suggested that this lowered retention was due not to the liver per se, but to a lessened need of the infant for iron at that time.