Stroke volume and left ventricular output in preterm infants with patent ductus arteriosus.

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 less than 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 less than 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 less than 0.05), and SV by 60 +/- 32% (p less than 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.

Contributions of red cells and plasma to blood viscosity in preterm and full-term infants and adults.

In preterm infants, plasma and red blood cells display several specific properties (eg, RBC size, plasma composition) that could influence blood flow behavior. Hemorheologic properties of blood from 20 preterm infants (24 to 36 weeks of gestation), ten full-term neonates, and ten adults were studied by means of a cone-plate viscometer adapted with a Couette-type chamber allowing viscometry at a wide range of shear rates (1.15 to 230/s). Blood viscosity (at given hematocrit of 60%), plasma viscosity, and RBC aggregation were very low in the smallest preterm infants, increased with gestational age, and reached the highest values in the adults. Whole blood viscosity increased directly with increasing plasma viscosity, plasma fibrinogen, and total plasma protein concentration, with the strongest correlations at the lowest shear rate of 1.15/s. The viscosity of RBCs suspended in a nonaggregating buffer solution was similar in all groups, thereby indicating that RBC deformability is similar in preterm infants, full-term neonates, and adults. Because mixing of neonatal and adult blood components occurs in most small preterm infants as a result of the transfusion of adult blood products, viscosities of cross suspensions (neonatal RBCs in adult plasma and adult RBCs in neonatal plasma) were measured. The exchange of neonatal plasma for adult plasma increased blood viscosity values in the neonates to adult values. On the other hand, the exchange of neonatal RBCs for adult RBCs did not affect blood viscosity. These results indicate that viscosity of blood with given hematocrit is lower in preterm infants than in term neonates and adults as a result of low plasma viscosity and low RBC aggregation, and that neonatal RBCs do not possess specific properties that influence blood viscosity.

The effect of moderate hypoxaemia on cardiac performance in the newborn during anaesthesia and surgery - experimental studies in newborn and two-week-old piglets.

Circulatory adaptation to hypoxaemia was studied under anaesthetic and surgical conditions in 10 newborn (age 8-42 h, weight 850-1800 g) and 8 two-week-old piglets (12-16 days, 1400-3600 g). Arterial PO2 was lowered from 60-100 mmHg to 30-40 mmHg by reducing FiO2 (concentration of oxygen during inspiration) at otherwise constant conditions; control studies were performed under the same standard conditions maintaining normoxaemia during the whole experiment in 8 newborn and 8 two-week-old piglets of comparable weight. In both hypoxic groups a prompt compensatory, statistically significant increase of cardiac performance defined by aortic blood pressure, cardiac output, peak aortic flow, stroke volume and cardiac power appeared within a few minutes of hypoxaemia, reaching a maximum half an hour later. Thereafter cardiac performance decreased steadily leading to cardiac failure. Newborns survived 197 +/- 96 min and two-week-old animals 172 +/- 128 min. Peripheral vascular resistance decreased significantly at the time of compensatory increase of cardiac performance, but increased subsequently to a maximum shortly before cardiac failure. Compensatory increase of cardiac performance was more distinct in newborn than in two-week-old piglets. Heart rate increased steadily during exposure to hypoxaemia in both groups reaching a maximum 110 min later and falling back to pre-experimental levels at the end of study. The newborn normoxic controls tolerated the experimental model significantly longer (461 +/- 167 min; P less than 0.001) than the newborn hypoxic piglets. Their response pattern, however, was basically similar. Increase of cardiac performance reached its maximum not before 130 min after the end of the pre-experimental period with subsequent fatal decrease of cardiac performance leading to cardiac failure. Two-week-old normoxic control animals responded qualitatively identically compared with the two-week-old hypoxic animals. Despite normoxaemia their average survival time did not differ significantly (209 +/- 86 min). In all four groups severe metabolic acidosis appeared in most instances during the study, irrespective of hypoxaemia or normoxaemia. Failure of stress tolerance depended on the decrease of pH per hour. This relation was more distinct in normoxic animals. In both hypoxic groups survival time correlated well with the increase of heart rate during hypoxaemia (R = 0.71 in newborn, P less than 0.05; R = 0.86 in two-week-old piglets, P less than 0.01, respectively). This correlation could not be found in the normoxic piglets.

Blood volume in newborn piglets: effects of time of natural cord rupture, intra-uterine growth retardation, asphyxia, and prostaglandin-induced prematurity.

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 in a time-dependent increase in BV and RCM. BV (x +/- 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) in 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 less than 0.05) increased in nine piglets with intra-uterine growth retardation (RCM, 35.8 +/- 11.2 ml/kg) and in 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 time 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 in 23 piglets whose births had been induced by ovarectomy of their mother (RCM, 22.1 +/- 3.2 ml/kg).

Blood volume and hematocrit in various organs in newborn piglets.

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 microliters/g varied markedly between various organs. The lowest blood volumes at 24 hr of age were found in skin (21.9 +/- 5.0 microliter/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 microliters/g were observed in heart muscle and thyroid gland and those of about 100 microliters/g in thymus and gastrointestinal tract. The total blood volume was 100.2 +/- 3.9 microliters/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 less than 0.01), and in skeleton (P less than 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.

Tc-99m-labeled red blood cells for the measurement of red cell mass in newborn infants: concise communication.

In vitro and in vivo investigations were performed to examine the binding of Tc-99m to neonatal red blood cells (RBC). Labeling efficiency was about 90%, and unbound Tc-99m less than 3% after one washing, in premature and full-term newborns and in children. Thus presence of high percentages of fetal hemoglobin (Hb F) did not influence the labeling of RBCs with Tc-99m. RBCs of 11 newborns were hemolysed and the distribution of Tc-99m on RBC components was analyzed. Although Hb F percentage averaged (60.0 +/- 8.1)% (s.d.), only (11.9 +/- 3.7)% of Tc-99m was bound by Hb F, whereas (45.0 +/- 6.1)% was associated with Hb A. RBC membranes bound (13.7 +/- 4.3)% and (29.3 +/- 4.0)% were found unbound in hemolysates. These results indicate that Tc-99m preferentially binds to beta chains. In vivo equilibration of Tc-99m RBCs and of albumin labeled with Evans blue was investigated in five newborn infants. Tc-99m RBCs were stable in each case during the first hour after injection. Elution of Tc-99m from RBCs was (3.4 +/- 1.5)% per hour. Body-to-venous hematocrit ratio averaged 0.86 +/- 0.03.

Intraarterial vs. transcutaneous PO2 monitoring in newborn infants. Indications and limitations.

For continuous PO2 monitoring as a valuable diagnostic tool in intensive care of newborn infants two methods are available, namely transcutaneous and intravascular monitoring. Both methods have advantages and limitations, but they are rather complementary than competing. The necessity of these new methods and the clinical implications are described.

Skin oxygen permeability in premature infants.

While 24 newborn infants (ages, 2 to 48 hours; gestational ages, 24 to 42 weeks) breathed various concentrations of oxygen, the PO2 values on their unheated skin surface were measured by an unheated microcathode electrode for transcutaneous PO2 monitoring. In infants with arterial PO2 values in the range of 50 to 100 torr and with similar skin temperatures, the mean surface PO2 of unheated skin was inversely related to birth weight: 27.2 torr in infants weighing less than 1,500 gm, 14.3 torr in infants weighing 1,500 to 2,500gm, and 2.9 torr in infants weighing more than 2,500 gm. In the smallest infants, the skin surface PO2 was significantly related to arterial PO2: it was about one third of arterial PO2 as estimated by a second electrode for transcutaneous PO2 monitoring heated to 44 degrees C. Phototherapy, crying, or blood transfusion increased the surface PO2 of unheated skin, but not the tcPO2 measured at 44 degrees C. These findings suggest that blood flow to the skin in excess of its metabolic needs due to immature control of cutaneous circulation, along with low resistance to oxygen diffusion, determines the high oxygen permeability of skin in premature infants.

Association of neonatal respiratory distress with birth asphyxia and deficiency of red cell mass in premature infants.

Red cell mass (RCM) was estimated using 125I-labelled human serum albumin in 128 premature infants born after 26 to 36 weeks gestation. Infants of three different gestational periods (26--29, 30--32, and 33--36 weeks) with respiratory distress (RD) averaged lower one-minute Apgar scores and lower RCM than infants without RD (P less than 0.05). The incidence of RD was significantly (P less than 0.05) higher in infants with Apgar scores below 6 and in infants with RCM of less than 35 ml/kg than in the infants with greater values. The highest incidence of RD and the highest mortality rate were found in the infants with low Apgar scores and low RCM values. Prematures with similar Apgar scores showed a higher incidence of RD when RCM was low, and infants with similar RCM showed a higher incidence of RD when Apgar scores were low. Our results suggest that both birth asphyxia and deficiency of red cell mass interfere with postnatal cardio-respiratory adaptation. In high-risk premature infants, erythrocytes should be transfused when the venous haematocrit is below 0.459

Peripheral circulation in the newborn: interaction of peripheral blood flow, blood pressure, blood volume, and blood viscosity.

Peripheral blood flow and systolic blood pressure (strain-gauge plethysmograph), blood volume (Evans blue) and whole blood viscosity (cone-plate viscometer) have been measured in 66 premature and full-term infants 6 to 144h of age. Blood flow and blood volume were moderately decreased in the infants with respiratory distress. Highly significant (P less than 0.001) correlations were found between blood flow and blood volume (r = 0.77), blood pressure and blood volume (r = 0.50), peripheral resistance and blood volume (r = -0.44), blood flow and blood pressure (r = 0.50), blood flow and peripheral resistance (r = -0.67), peripheral resistance and blood viscosity (r = 0.45), and blood viscosity and haematocrit (r = 0.86). There was no correlation between peripheral blood flow and blood viscosity. However, at given blood volume, peripheral blood flow decreased with increasing blood viscosity. These results indicate that in newborn infants peripheral blood flow, blood pressure and peripheral resistance are influenced by blood volume, but also depend on blood viscosity.

The influence of vitamin B-6 on cystathioninuria in premature infants.

The amount of cystathionine excreted in the urine of premature infants, ages 10 to 17 days, decreases after oral administration of 40 mg vitamin B-6 daily. Thus, it can be speculated that in vivo cystathionase of premature infants may be induced or activated by pyridoxine.

Blood volume of children with leukemia.

Blood volume was measured using 125iodinated human serum albumin in 27 children with acute lymphoblastic leukemia, and in 7 children with various types of leukemia. Total blood volume was normal in patients without marked enlargement of spleen and liver, and increased progressively as spleen and liver size increased. The hypervolemia was entirely due to expansion of plasma volume. In the children with marked hepatosplenomegaly, only hematocrit (but not red cell mass) was below the normal range in most cases. Both hematocrit and red cell mass were subnormal in the majority of patients without considerably enlarged spleen and liver. Therefore, anemia in children with marked hepatosplenomegaly may be partly caused by hemodilution of red blood cells in expanded plasma volume.

Stress at birth: plasma noradrenaline concentrations of women in labour and in cord blood.

Radioenzymatically measured plasma noradrenaline concentrations, present at birth in umbilical veins of 19 healthy, 17 acutely asphyxiated, and 9 chronically distressed newborn infants were found to be elevated above maternal values proportional to the degree of distress and to plasma H ion concentrations.

In vivo vs in vitro response time of trancutaneous PO2 electrodes. A comparison of four devices in newborn infants.

Four devices for transcutaneous PO2 (tcPO2) monitoring have been applied simultaneously in 16 infants. Both during a maximal change in PaO2 and during physiological PO2 variations, the in vivo response time of the electrodes did not show the differences observed in vitro. We compared A, a prototype of the electrode by Huck, Lübbers and Huch (25 micrometer Telfon membrane) ; B, the commercial version of A by Hellige--Draeger (25 micrometer Telfon); C, the Radiometer TCM I oxygen monitor (25 micrometer polypropylene); and D, the Roche macrocathode electrode (6 micrometer Mylar), at 44 degree C. In vitro the 50% response times were 2.9 (A), 4.4 (B), 3.7 (C), and 7.4 (D) sec. The rates of tcPO2 changes at the midpoint of the response curves were 3.8(A) 2.0 (B), 3.0 (C), and 1.7 (D) kPa/sec. In vivo during a sudden change from hyperoxemia (FIO2 1.0) to normoxaemia the respective rates were 0.6 (A), 0.8 (B), 1.1 (C), and 1.0(D) kPa/sec. The in vivo 50% response times were 53.3 (A), 51.1 (B), 46.2 (C) and 45.3 (d) kPa/sec. The in vivo 50% response time were 53.3 (A), 51.1 (B), 46.2 (C), and 45.3 (d) kPa/sec. The in vivo 50% resonse time were 53.3 (A), 51.1 (B), 46.2 (C), and 45.3 (D) sec. The lag time between PaO2 and tcPO2 was about one third of this overall response time. The response to more physiological variations of PaO2 (periodic breathing) was not different among the tested electrodes in terms of damping and of delay of the tcPO2 deflections. In a steady state the correlation of tcPO2 44 degree C vs PaO2 was close (r = 0.98) with all devices up to 6.1 kPa (456 torr).

Capillary-venous hematocrit differences in newborn infants. I. Relationship to blood volume, peripheral blood flow, and acid base parameters.

Venous and capillary hematocrit, acid base values, and circulatory parameters were measured simultaneously in 92 newborn infants within six hours of birth. Gestational age ranged from 26 to 41 weeks. The capillary/venous hematocrit ratio (Hctc/Hctv) was greater than 1.00 in 89 infants. We found significant inverse correlations between Hctc/Hctv and several parameters, such as pH (r = -0.82), standard bicarbonate (r = -0.73), systolic blood pressure (r = -0.51), and peripheral blood flow (r = -0.70). Most of the infants with a Hctc/Hctv of 1.20 and above had red cell mass values of less than 35 ml/kg. However, blood volume apparently did not influence the Hctc/Hctv. Gestational age appeared to affect Hctc/Hctv only before 30 weeks, when compared with the Hctc/Hctv of term infants. Our results indicate that disturbed circulation, and in particular, disturbed microcirculation is involved in the development of high Hctc/Hctv ratios. We strongly advise that hematocrits obtained by skin prick from a sick newborn infant should not be relied on as they may give misleading information on oxygen carrying capacity to vital organs.