K. Riegel

Stroke Volume and Left Ventricular Output in Preterm Infants with Patent Ductus Arteriosus

ABSTRACT: To assess the effect of patent ductus arteriosus (PDA) on left ventricular output (LVO) we studied stroke volume (SV), LVO, and heart rate (HR) in 21 very low birth wt preterm neonates with clinically symptomatic PDA before and after surgical ligation. Six additional infants were also studied before PDA with left-to-right shunt was detectable by the pulsed Doppler technique. Gestational age (median and range) was 28 (24–32) wk. SV was measured by duplex Doppler and M-mode echocardiography, and LVO was calculated as product of SV and HR. LVO was 419 (305–562) mL/min/kg during symptomatic PDA. It decreased to 246 (191–292) mL/min/kg after ligation (n = 21, p < 0.001). SV was 2.69 (1.98–4.10) mL/kg during symptomatic PDA decreasing to 1.63 (1.22–1.98) mL/kg after ductal closure (n = 21, p < 0.001). HR did not change after ductal closure. In the six infants with three examinations, LVO and SV were normal before detectable ductal left-to-right shunt and after ligation, but LVO was increased by 59.5 ± 23% (mean ± SD) (p < 0.05), and SV by 60 ± 32% (p < 0.05) during symptomatic PDA. In conclusion, preterm neonates with RDS, requiring mechanical ventilation, increased LVO during symptomatic PDA by increasing their SV, and not by changing their HR.

Die sogenannte Standard-O2-Dissoziationskurve des gesunden erwachsenen Menschen

SummaryIn-vitro oxygen dissociation curves were constructed for 14 subjects. To uncover individual variations, at least 3 curves were drawn for most subjects over a period of several weeks. In 5 subjects they were drawn over a period of 2 years. The resultant individual characteristics are constant for years. The maximum variation of oxygen partial pressure necessary to produce 50% saturation in our subjects amounted to 5.4 mm Hg. The mean partial pressure of oxygen for half saturation from all experiments was 26.8 mm Hg, standard deviation ±2.6. A new „Standard Oxygen Dissociation Curve“ is presented.

Über den Einfluß der Kationenkonzentration im Erythrocyten auf die Lage der Sauerstoff-Dissoziationskurve des Blutes

SummaryThe interrelationship between oxygen affinity and cation concentration within the erythrocyte has been investigated, using blood samples from healthy adults, anemic children and erythrocyte suspensions whose cation concentration had been altered. It is shown that the position of the oxygen dissociation curve depends in part upon the cation concentration of the red blood cells; with a high intracellular cation concentration the dissociation curve shifts to the right, the opposite shift is seen with low cation concentration. The substitution of intracellular potassium by sodium does not influence the oxygen affinity unless the total cation concentration is changed.

Oxygen Transport in Congenital Heart Disease: Influence of Fetal Hemoglobin, Red Cell pH, and 2,3-Diphosphoglycerate

Extract: In 48 individuals (age 1 day to 13 years) with congenital heart disease, blood oxygen transport function was studied in order to evaluate adaptive changes in shunt hypoxemia and to investigate the in vivo regulation of erythrocyte 2,3-diphosphoglycerate concentration (RBC 2,3-DPG) in the presence of fetal hemoglobin (HbF). Arterial pO2 and oxygen content, oxygen capacity, acid base status, oxygen affinity, HbF fraction, plasma pH, red cell pH, and RBC 2,3-DPG were determined. During the first 50 days of life values of standard P50 (stdP50) (37°, pH7.4), actual in vivo P50 (actP50), RBC 2,3-DPG, O2 capacity, arterial plasma pH, and red cell pH were scattered around the normal range, although tending to low values for stdP50 and arterial plasma pH and to high values for O2 capacity. After the third month, stdP50 actP50, RBC 2,3-DPG, O2 capacity, and red cell pH were found to be elevated. Plasma pH and actP50 were scattered around the normal range (Figs. 1 and 2).Intraerythrocytic pH in hypoxemic infants was increased compared with normal children when related to plasma pH (Fig. 3). A close to normal intraerythrocytic pH was therefore found in the hypoxemic infants with low plasma pH, and an increased intraerythrocytic pH in the hypoxemic children with normal plasma pH (Fig. 1). A significant negative correlation exists between erythrocyte H+ ion and 2,3-DPG concentration (Fig. 5); regression constants derived from data at high (mean 47%) and low (mean 9%) fractions of HbF are not significantly different (Regression Equations 8 and 11 in Table 1). Thus, the known difference in 2,3-DPG binding to fetal or adult deoxyhemoglobin does not measurably influence the erythrocyte 2,3-DPG concentration, indicating that in vivo the 2,3-DPG synthesis in hypoxia is virtually regulated by the erythrocyte pH, which in turn is determined by plasma pH and the oxygenation state of hemoglobin.Speculation: In young infants and older children with cyanotic heart disease an identical negative correlation between the concentrations of 2,3-DPG and hydrogen ions within the erythrocyte was found. The in vivo regulation of 2,3-DPG synthesis thus appears to be controlled by the erythrocyte pH which, in turn, is determined by plasma pH and oxygen saturation of hemoglobin. Apparently the well established difference of 2,3-DPG binding to fetal or adult deoxyhemoglobin does not measurably influence the erythrocyte 2,3-DPG concentration, indicating that in vivo a relief of product inhibition of the diphosphoglycerate mutase does not contribute significantly to the regulation of 2,3-DPG synthesis in hypoxemia.

Blood Volume and Hematocrit in Various Organs in Newborn Piglets

Summary: Plasma volume and red cell mass of various organs in piglets aged 24 hr (n = 7) and 7 (n = 6), and 14 (n = 6) days were measured using 99mTc-labeled albumin and 51Cr-labeled red blood cells. Organ activities were counted in a whole-body counter. Blood volume and hematocrit were calculated. The blood volumes in μl/g varied markedly between various organs. The lowest blood volumes at 24 hr of age were found in skin (21.9 ± 5.0 μl/g), brain (33.3 ± 8.4), and skeletal muscle (35.5 ± 7.4). The highest values at this age were noted in liver (670.0 ± 89.1), lung (533.8 ± 80.7), spleen (332.0 ± 82.8), and kidney (300.6 ± 55.5). Blood volumes of about 150 μl/g were observed in heart muscle and thyroid gland and those of about 100 μl/g in thymus and gastrointestinal tract. The total blood volume was 100.2 ± 3.9 μl/g at 24 hr and remained unchanged during the first 2 wk of life. A significant decrease in relative blood volume with growth was noted in liver and lung (P ≤0.01), and in skeleton (P ≤0.05). The blood volume, contained in the great vessels outside the organs, increased from 29.5 ± 5.5% of total blood volume at 24 hr to 31.2 ± 5.7% at 7 days and to 38.2 ± 7.5% at 14 days of life. The total body/venous hematocrit ratio was about 0.84. Accordingly, tissue hematocrits of most organs were below the venous hematocrit. Only in spleen was the tissue/venous hematocrit ratio (TH/VH) higher than 1.0. TH/VH of brain, gastrointestinal tract, thyroid gland, and thymus approached unity. The lowest TH/VH was found in kidney (0.54 ± 0.08 at day 1). In skin, the TH/VH decreased from 0.98 ± 0.10 to 0.82 ± 0.07 during the first 2 wk of life.Speculation: Marked decrease of blood volume per of tissue in liver, skeleton, and gastrointestinal tract with growth indicate high metabolic activity shortly after birth, which diminishes later on. Low blood content of the great vessels at day I Should mean disminished tolerence to acute blood loss. Low organ hematwrits may be due to a more rapid flow of red blood cells than of plasma and to plasma skimming.

Blood oxygen affinity in infancy: the interaction of fetal and adult hemoglobin, oxygen capacity, and red cell hydrogen ion and 2,3-diphosphoglycerate concentration.

In 86 infants postnatal changes of oxygen half saturation pressure (P50) of blood and erythrocytes, oxygen capacity, fetal hemoglobin, and plasma and red cell hydrogen ion concentrations have been reexamined considering, in addition, age-related changes of red cell 2,3-diphosphoglycerate (2,3-DPG). The results obtained indicate that 1) the well known differences of P50, of newborn and adult blood as well as 2) the increasing P50 after birth depend on both the relationship between fetal and adjilt hemoglobin and red cell 2,3-DPG. Mean red cell 2,3-DPG concentration, which is similar in the newborn and the adult (4 β mol/ml RBC), has been found increased by 25 percent after the third day of extrauterine life. This increase is neither due solely to changes in red cell H+ ion concentration nor to changes of oxygen capacity, both of which correlate inversely with 2,3-DPG. Although later on mean red cell 2,3-DPG surpasses the normal adult level, a gradual decrease between the third and ninth week could be observed followed by another increase in the third month.

Comparative studies of the respiratory functions of mammalian blood. II. Marsupialia: great grey kangaroo and Tasmanian devil.

Abstract Blood samples from two marsupials (the great grey kangaroo and the Tasmanian devil) were used to construct oxygen dissociation curves at pH 7.4 and 37 °C. Erythrocyte morphology was studied and hemoglobin was subjected to electrophoresis, potassium ferricyanide oxidation and alkali denaturation. The glucose-6-phosphate dehydrogenase activity in the erythrocytes was determined. These studies showed high oxygen-carrying capacities in the blood of both marsupials. The Tasmanian devil has small erythrocytes. Hemoglobin from the Tasmanian devil migrates slowly when subjected to starch block electrophoresis and contains an alkali-stable fraction of 55.7 %. Hemoglobin from both animals when subjected to oxidation by potassium ferricyanide showed slow and fast components.

Comparative studies of the respiratory functions of mammalian blood. I. Gorilla, chimpanzee and orangutan.

Abstract Blood samples from a chimpanzee, two gorillas and an orangutan were used for the construction of oxygen dissociation curves at pH 7.4 and 37 °C. The morphology of the erythrocytes was also studied. Hemoglobin from each species was subjected to starch block electrophoresis. The rate of hemoglobin oxidation by potassium ferricyanide was determined as was the amount of alkaliresistant hemoglobin. The glucose-6-phosphate dehydrogenase activity in the erythrocytes was measured. With regard to all these parameters the blood of these members of the family Pongidae was essentially similar to that of the human adult except that the hemoglobin of each of these animals showed a slow rate of methemoglobin formation when exposed to potassium ferricyanide. The orangutan has large red blood cells and hemoglobin which travels slowly when subjected to starch block electrophoresis.

Comparative studies of the respiratory functions of mammalian blood. III. Fetal and adult dromedary camel blood

Abstract Blood samples were obtained from two adult camels and one fetal camel of approximately 7 months gestational age. As in other mammalian species, fetal blood has a higher oxygen affinity than adult blood and there was a higher hemoglobin concentration in fetal blood than in the mothers blood. Fetal erythrocytes are larger than adult erythrocytes. Methemoglobin concentration is somewhat higher in fetal blood than in adult blood but seems to be in the normal range. Camel erythrocytes have a greater resistance to hemolysis by hypotonic saline than human erythrocytes. Analysis of the characteristics of camel hemoglobin showed no difference between the pigment of adults and that of a 7 months fetus with regard to hemoglobin electrophoresis, alkali denaturation or the rate of oxidation by potassium ferricyanide. On the other hand, red cells from the fetal camel had a higher activity in reducing methemoglobin and a lower activity of carbonic anhydrase than that found in the blood of the adult animal.

Blood Volume in Newborn Piglets: Effects of Time of Natural Cord Rupture, Intra-Uterine Growth Retardation, Asphyxia, and Prostaglandin-Induced Prematurity

Summary: Blood volume (BV), red cell mass (RCM; Cr-51) and plasma volume (125I-labeled albumin) were measured in 205 piglets from 28 litters shortly after birth. Spontaneous cord rupture in healthy piglets occurred during delivery (n = 25) or within 190 sec of birth (n = 82). Spontaneous and induced delay of cord rupture resulted hi a tune-dependent increase hi BV and RCM. BV (± S.D.) at birth was 72.5 ± 10.5 ml/kg (RCM, 23.6 ± 4.6 ml/kg) in the 25 piglets with prenatal cord rupture and 110.5 ± 12.9 ml/kg (RCM, 38.4 ± 7.0 ml/kg) hi 17 piglets with late spontaneous cord rupture. The mean blood volume of all the 107 healthy piglets with spontaneous cord rupture was 90.2 ± 12.7 ml/kg (RCM, 30.1 ± 4.8 ml/kg). RCM was significantly (P < 0.05) increased hi nine piglets with intra-uterine growth retardation (RCM, 35.8 ± 11.2 ml/kg) and hi 13 with metabolic acidosis but without signs of asphyxia (RCM, 35.8 ± 6.7 ml/kg). In five piglets with cord wrapping, prenatal cord rupture, and acute asphyxia, BV (57.8 ± 7.3 ml/kg) was significantly decreased. In five other piglets with prenatal cord rupture and acute asphyxia, BV (67.9 ± 10.0 ml/kg) corresponded to that of the normal piglets with prenatal cord rupture. However, delay of cord rupture to 60 sec after birth did not increase BV (66.0 ± 11.8 ml/kg) in four piglets with acute asphyxia. Forty-one premature piglets delivered 6 days before normal term had their cords ruptured prenatally or within 5 sec of birth. Their hematocrit at birth (0.337 ± 0.028 liters/liter) was significantly decreased compared to the normal full-term piglets with corresponding tune of cord rupture (0.384 ± 0.033 liters/liter). RCM in 18 piglets with prostaglandin-induced prematurity (18.9 ± 3.4 ml/kg) was significantly lower than hi 23 piglets whose births had been induced by ovarectomy of their mothers (RCM, 22.1 ± 3.2 ml/kg).Speculation: There is a great variability of placental transfusion in piglets (average, 24%; range, 0 to 60% of fetal blood volume) because natural cord rupture occurred at any time from sub partu to 3 nun after birth. This implies that hypo- or hypervolemia per se, hi the otherwise well adapted newborn, must not represent a pathologic condition. On the other hand, hi the newborn with abnormal adaptation to extra-uterine life, abnormal blood volume may be carefully considered as either cause or consequence of maladaptation requiring appropriate treatment.