Hypoxic Newborns Research Articles

Heat shock protein 70 expression in neonatal rats after hypoxic stress

Objectives: The tissue damage due to hypoxia in newborns is to some extent age-dependent; organs of premature babies are more vulnerable to hypoxic insult than full-term neonates. The of thisimmunohistochemical study was to investigate the role of heat shock protein 70 (HSP70), a stress-inducible protein, in developing the response to hypoxia in premature newborns.Methods: Postnatalday-7 rats (corresponding to a human fetus of 32-34 weeks' gestation) and day-12 rats (corresponding to a full-term newborn infant) (n = 7) were subjected to mild hypoxia at 33°C. Control rats(n = 7) for each group breathed room air for 4 h. After 4 h of recovery, the animals were killed, and brains, hearts and kidneys were removed for immunohistochemical staining.Results:Immunohistochemically, HSP70 expression was found to be induced in the hippocampus and myocardium after exposure to hypoxia. The level of HSP70 expression in the hippocampus after hypoxic stress was significantlyhigher in the 12-day rats than in the 7-day rats (p = 0.03). However, HSP70 expression in the myocardium did not show any significant difference between the two groups. In addition, no significantinduction of HSP70 expression was apparent in the kidney of rats exposed to hypoxia or in any organ of the control animals.Conclusions: We conclude that diminished HSP70 expression in the hippocampusof premature newborns may play a critical role in developing the response to hypoxic stress. However, HSP70 expression in the heart and the kidney after exposure to hypoxia did not appear to be relatedto fetal maturity.

Intraerythrocyte nonprotein-bound iron and plasma malondialdehyde in the hypoxic newborn

Intraerythrocyte nonprotein-bound iron (INPBI), malondialdehyde (MDA), and hypoxanthine plasma levels (HxPL), were determined by high-pressure liquid chromatography in 138 randomly selected newborn infants with gestational ages ranging from 23 to 42 weeks at birth and on fourth day of life. MDA plasma levels were significantly higher in cord and fourth-day blood samples of preterm babies than term infants as well as babies born by emergency Caesarean section than babies born by vaginal delivery and in intubated than in nonintubated newborns. Highly significant correlations both in cord blood and fourth-day blood samples were observed between MDA plasma levels and gestational age, birth weight, Apgar score at 1 min and 5 min, HxPL, pH, base deficit, and INPBI content. Multiple regression analysis identified HxPL as the best single predictor of MDA plasma levels in cord blood, and INPBI content in fourth-day blood as the best single predictor of MDA plasma levels in fourth-day blood. The results indicate that red cells and plasma lipoproteins are a common target of free radical-induced oxidative stress during hypoxia.

Oxygen transport in conscious newborn dogs during hypoxic hypometabolism.

We questioned whether the decrease in O2 consumption (VO2) during hypoxia in newborns is a regulated response or reflects a limitation in O2 availability. Experiments were conducted on previously instrumented conscious newborn dogs. VO2 was measured at a warm ambient temperature (30 degrees C, n = 7) or in the cold (20 degrees C, n = 6), while the animals breathed air or were sequentially exposed to 15 min of fractional inspired O2 (FIO2): 21, 18, 15, 12, 10, 8, and 6%. In normoxia, VO2 averaged 15 +/- 1 (SE) and 25 +/- 1 ml . kg-1 . min-1 in warm and cold conditions, respectively. In the warm condition, hypometabolism (i.e., hypoxic VO2 < normoxic VO2) occurred at FIO2 </=10%, whereas in the cold condition, hypometabolism occurred at FIO2 </=12%. The same results were obtained in a separate group (n = 14) of noninstrumented puppies. For all levels of FIO2 with hypometabolism, the relationships between measures of O2 availability (arterial O2 saturation or content, venous PO2 or saturation, x-axis) vs. VO2 (y-axis) had lower slopes in warm than in cold conditions. Hence, VO2 during hypometabolism in the warm condition was not the maximal attainable for the level of oxygenation. The results do not support the possibility that the hypoxic drop in VO2 in the newborn reflects a limitation in O2 availability. The results are compatible with the idea that the phenomenon is one of "regulated conformism" to hypoxia.

Experimental study of the possibility of metabolic correction of maternal, fetal, and newborn hypoxia in rats using a new amino acid composition MR-33

The status of pregnant rats, their fetuses, and progeny exposed to oxygen insufficiency are compares. By the end of pregnancy the resistance to hypoxia markedly decreases. Newborn rats during nursing are highly resistant to hypoxia. When nursing period is over, the resistance to hypoxia drops, but later is gradually restored. MR-33 preparation produces a pronounced antihypoxic effect. Administration of the drug to pregnant rats not only appreciably improves their resistance to oxygen insufficiency, but also promotes adaptation and compensatory mechanisms in the progeny, thus helping the progeny to better tolerate hypoxia, particularly when its probability is particularly high.

Effect of hypoxia on blood glucose, hormones, and insulin receptor functions in newborn calves.

At between 7 and 11 h after delivery, 14 fasted calves were randomly divided into two groups to examine the effects of neonatal hypoxia on blood glucose metabolism and its mechanisms. One group was subjected to breathe a gas mixture containing 4.8-5.9% oxygen in nitrogen from a hood for 2 h. The second control group breathed atmospheric gas. Several possible causes of changes in blood glucose were assessed, including insulin, glucagon, and hydrocortisone as prereceptor factors, insulin binding as a receptor factor, and insulin receptor tyrosine kinase (IR-TK) activity as a postbinding factor. The hypoxic animals exhibited increased concentrations of blood glucose (from 5.47 +/- 1.61 mmol/L to 7.97 +/- 1.30 mmol/L), plasma insulin, and hydrocortisone, but decreased concentrations of glucagon. The percentage of specific binding activity decreased in the hypoxic group compared with the control group (12.71 +/- 1.25% versus 15.14 +/- 1.27%, p < 0.01). Several parameters of insulin receptor binding, i.e. affinity constants, high and low binding capacities, and numbers of binding sites, showed a tendency to decrease after hypoxia. Only lower affinity binding sites decreased significantly. At the postreceptor level, IR-TK activity was decreased in the hypoxic group compared with controls. It is concluded that hypoxia induced insulin resistance in these newborn calves. The results suggest that the primary mechanism for insulin resistance in the hypoxic newborn was reduced insulin receptor responsiveness with attenuated activity of IR-TK at the postreceptor level.

Nifedipine Prevents Pulmonary Hypertension But Does Not Prevent Decreased Endothelial Nitric Oxide Synthase in Lungs of Newborn Pigs Exposed to Chronic Hypoxia. † 1792

Decreased production of nitric oxide (NO) might contribute to the development of neonatal pulmonary hypertension. We previously showed that pulmonary hypertension develops when newborn pigs are exposed to chronic hypoxia (JAP 77:2853, 1994) and provided evidence that NO production is decreased in lungs of chronically hypoxic newborn pigs (FASEB J 10: A307, 1996). We also showed that treatment with the calcium channel blocker nifedipine prevents the development of pulmonary hypertension in chronically hypoxic newborn pigs (Ped. Research 39:332A, 1996). We wondered (a) whether the decreased NO production in lungs of chronically hypoxic newborn pigs is due to a decreased amount of endothelial nitric oxide synthase (eNOS), the enzyme responsible for basal NO production and if so (b) whether treatment with nifedipine during chronic hypoxia prevented the decrease in eNOS. To answer these questions we maintained 1-3 day old pigs in a chamber filled with either room air (Control) or 11% O2 (Chronic Hypoxia) for 10 days. Some of the Chronic Hypoxia piglets were given nifedipine, 3-5 mg/kg sublingually tid (Nifedipine-treated). We applied an immunoblot analysis to whole lung homogenates of piglets from all groups. A monoclonal antibody to eNOS detected eNOS protein in the lung homogenates at a molecular mass of approximately 135 kDa. eNOS protein amounts did not differ between lung homogenates from Chronic Hypoxia piglets (n=5) as compared to Nifedipine-treated chronically hypoxic piglets (n=4). For both the Chronic Hypoxia and Nifedipine-treated chronically hypoxic piglets, eNOS protein amounts were decreased by 60% (p<0.05) as compared to Controls (n=5). Thus, eNOS decreased in lungs of chronically hypoxic newborn piglets both with and without nifedipine-treatment. Preventing decreased eNOS is not the mechanism by which nifedipine prevents pulmonary hypertension during chronic hypoxia in newborns. Supported by Children's Hospital of WI Foundation

Cardiovascular and respiratory consequences of body warming during hypoxia in conscious newborn cats.

Acute hypoxia in newborns of various species including humans is associated with decreased thermogenesis and a fall in body temperature. We have investigated the cardiorespiratory consequences of correcting the fall in colonic temperature (Tc) during acute hypoxia in newborn cats. Experiments were conducted on 21 unanesthetized kittens (12 +/- 1 d SEM, 244 +/- 8 g) instrumented with catheters in the left common carotid artery and superior vena cava for measurements of systemic arterial pressure, central venous pressure, heart rate, arterial blood gases, arterial O2 saturation (SaO2) and mixed venous O2 saturation. Oxygen consumption (VO2) and CO2 production (VCO2) were also measured. Alveolar ventilation (VA), cardiac index (CI), and systemic vascular resistance index (SVRI) were calculated. These determinations were made in 21% O2 at an ambient temperature (Tamb) of 25 degrees C, and after 80 min of exposure to Fio2 = 0.10. In one group Tamb was maintained at 25 degrees C (n = 8) during hypoxia and Tc fell by 2.7 +/- 0.4 degrees C whereas in a second group Tamb was increased to 35 degrees C for the second 40 min of hypoxia to raise Tc the prehypoxic level (n = 13). VO2, VCO2, VA, SaO2, and systemic arterial pressure during hypoxia did not differ between the animals which were warmed and those which were not. However, CI and heart rate were greater (452 +/- 23 versus 346 +/- 30 mL.min-1.kg-1 p < 0.05, 279 +/- 8 versus 228 +/- 12 beats.min-1 p < 0.05) and SVRI lower (0.115 +/- 0.022 versus 0.153 +/- 0.014 mm Hg.mL-1.min.kg, p < 0.05) during hypoxia in the warmed animals compared with the unwarmed group. Thus, artificially raising Tc during hypoxia resulted in peripheral vasodilation, whereas systemic arterial pressure was maintained by the increase in cardiac output. We conclude that, in the hypoxic kitten, raising Tc to normoxic values elicits a response that may reflect a condition of relative hyperthermia.

Acute hypoxia does not increase bacterial translocation in newborn rabbits

Purpose: We have previously demonstrated that spontaneous bacterial translocation (BT) occurs, in newborn rabbits and correlates strongly with small bowel colonization (BC). Birth stress, specifically hypoxia, is believed to increase this pathologic process and thus lead to sepsis. This study investigated the relationship between BT and acute hypoxia in newborn rabbits. Methods: Four hundred seventeen rabbit pups (aged 0, 2 to 4, 6, and 28 days) were divided into four groups according to the type of hypoxic stress: 9% O 2 for 1 hour, 9% O 2 + 12% CO 2 for 1 or 4 hours, and 21% O 2 (control animals). The animals were killed 1.5 or 20 hours after the stress. Sterile specimens of mesenteric lymph nodes (MLN), spleen, liver, small bowel, and large bowel were incubated aerobically at 37°C for 24 hours in thioglycolate broth, and subsequently plated on both MacConkey and Colistin Naladixic Acid media. After 24 hours, the growth on both plates was recorded. χ 2 analysis was used, and P values of less than .05 were considered significant. Results: BC of the small bowel and BT to the MLN were low in the first 4 days of life in the hypoxic groups (range, 0% to 21% BC, 0% to 6% BT) and the control group (range, 4% to 30% BC, 3% to 12% BT). After an increase in BC at 6 days of age, the rate of BT increased to 25% to 29% in control animals. The rate of BT in the hypoxic groups (25%) did not differ significantly from that of the controls ( P > .05). Additionally, killing at 20 hours ( v 1.5 hours) was not associated with an increase in the incidence of BT. None of the stress groups had a significant increase in BT compared with the controls. Importantly, although 4 hours of 9% O 2 + 12% CO 2 resulted in a 30% mortality rate, the incidence of BT was no higher than that of the control animals (13% v 29%; P > .05). Conclusion: Severe hypoxic stress in newborn rabbits does not increase the incidence of BT. Because the incidence of BT correlates with that of BC, and because BC is the same in the control and hypoxic animals, the sepsis observed in hypoxic newborns probably is not related to an increased incidence of BT.

NIFEDIPINE PREVENTS PULMONARY HYPERTENSION BUT DOES NOT PREVENT IMPAIRED ENDOTHELIUM DEPENDENT PULMONARY DILATION IN NEWBORN PIGS EXPOSED TO CHRONIC HYPOXIA. † 1976

Pulmonary hypertension developed and pulmonary dilation to the endothelium dependent agent acetylcholine (Ach) was blunted when newborn pigs were exposed to alveolar hypoxia (J. Appl. Physiol. 77:2853, 1994 and Ped. Res. 30:391A, 1994). To see if treatment with the calcium channel blocker nifedipine would prevent the development of pulmonary hypertension and prevent impaired pulmonary dilatory responses to Ach, we maintained 1-3 day old pigs in a chamber filled with either room air (Control) or 11% O2 (Chronic Hypoxia) for 10 days. Some of the Chronic Hypoxia piglets were given nifedipine, 3-5 mg/kg sublingually tid (Nifedipine). The pigs were anesthetized and catheters placed for in vivo measurement of pulmonary arterial pressure (Ppa), pulmonary wedge pressure (Pw), and determination of cardiac output by the thermodilution technique. Lungs were then excised and perfused with a mixture of blood and 3% albumin-saline. We maintained flow constant at 50 (ml/min)/kg and measured Ppa responses to Ach (10-5 M). PVR was greater in Chronic Hypoxia pigs than in either Control or Nifedipine treated chronic hypoxia pigs. The decrease in Ppa with Ach was less in isolated lungs from both Chronic Hypoxia and Nifedipine treated chronic hypoxia pigs than from Control pigs. Thus, nifedipine treatment prevented the development of pulmonary hypertension during chronic hypoxia in newborn pigs. However, responses to the endothelium dependent vasodilator Ach were blunted in lungs of both chronica hypoxia and nifedipine-treated chronic hypoxia pigs. Nifedipine treatment may prevent pulmonary hypertension but may not prevent all of the functional pulmonary vascular changes that occur with chronic hypoxia in newborns. Supported by Am Heart Assoc.Table

BASAL AND ACETYLCHOLINE STIMULATED NITRIC OXIDE PRODUCTION ARE DECREASED IN LUNGS OF CHRONICALLY HYPOXIC NEWBORN PIGS. † 1977

Decreased production of vasodilators such as nitric oxide might contribute to the development of pulmonary hypertension. We previously found that pulmonary hypertension developed and that pulmonary vasodilation to the endothelium-dependent agent acetylcholine was blunted when newborn pigs were exposed to alveolar hypoxia (J. Appl. Physiol. 77:2853, 1994 and Ped. Res. 30:391A, 1994). The purpose of this study was to determine whether basal and acetylcholine stimulated production of nitric oxide are decreased in lungs of chronically hypoxic newborn pigs. We maintained 1-3 day old pigs in a chamber filled with either room air (Control) or 11% O2 (Chronic Hypoxia) for 10-12 days. Each pig was anesthetized and its lungs excised and perfused with 5% dextran at a constant flow of 50 (ml/min)/kg. Perfusate samples were collected at 15 min intervals for 90 min for measurement of basal nitrites and nitrates (NOx). Next, acetylcholine (10 μg/min) was infused and perfusate samples were collected at 10 min intervals for 30 min for measurement of acetylcholine stimulated NOx. Nitrate reduction and the Greiss reaction were used for NOx determination. Values intable are mean ± SE, *different from Control, unpaired t test, p<0.05. Both basal and acetylcholine stimulated rates of perfusate accumulation of NOx were lower in chronically hypoxic than in control lungs. These findings suggest that basal pulmonary production of nitric oxide and the ability to increase pulmonary production of nitric oxide in response to acetylcholine are decreased in newborn pigs exposed to chronic hypoxia. An impaired ability to increase nitric oxide production could explain why dilation to endothelium dependent agents such as acetylcholine are blunted in lungs of chronically hypoxic newborn pigs. It is possible that decreased basal pulmonary production of nitric oxide contributes to the development of pulmonary hypertension during chronic hypoxia in newborns. Supported by the American Heart Association and the Dept. of VA.

INITIATION OF MITOCHONDRIAL PROTEIN SYNTHESIS AT BIRTH † 1293

We have observed that oxidative phosphorylation (OXPHOS) by isolated mitochondria (MITO) increases at birth in liver and kidney (Ped. Res. 37,214), but not heart (this meeting), and that newborn hypoxia prevents increased OXPHOS. To determine whether initiation of MITO biogenesis is also regulated by oxygen availability pre-term rabbit pups (30-31 days gestation, term=32 days) delivered by C-section were either sacrificed at birth (time zero) or maintained under normoxic (21% O2, NOX) or hypoxic(10% O2, HYPOX) conditions for 4 hours at 35° C. MITO were isolated and in-vitro protein synthesis (PS) determined by measuring 35S methionine incorporation. PS was greater in heart MITO from NOX vs HYPOX or time zero pups (113 ± 18 vs 55.2 ± 20 or 60.0 ± 13 CPM/ mg Prot / 30 min respectively, n=6, p < 0.05) while PS rate was similar for liver (48 ± 13 vs 47 ± 10 or 51.3 ± 11) and kidney (44.1± 15 vs 37.5 ± 20 or 39.5 ± 13) MITO. Nucleotide regulation of PS in NOX and HYPOX pups was also evaluated. PS was reduced by 40-50% (p < 0.05) when isolated MITO from heart, liver and kidney were incubated with 5 mM ATP + 1 mM GTP. Inhibition was similar in MITO from NOX and HYPOX pups. In summary, MITO biogenesis at birth is modulated by nucleotides in all organs and oxygen availability in heart, but not liver or kidney. Taken together these data demonstrate that metabolic adaptation at birth involve increased MITO OXPHOS or biogenesis, changes which are modulated by oxygenation in an organ specific manner.

RESUSCITATION OF HYPOXIC NEWBORNS WITH ROOM AIR OR OXYGEN

To study the short term effects of resuscitation of hypoxic newborn babies with room air, a randomized multicenter study was initiated. Here the data from one center is reported. Entry criteria were: birth weight > 1000 gram, heart rate at birth < 80 per min and or apnoe justifying resuscitation. This was performed with bag and mask or after endotracheal intubation when needed. Babies were enrolled into a group treated with room air (RA, N=36) or 100% oxygen (O2, N=42). Babies in RA group who did not respond within 90 seconds were treated with supplementary oxygen. Heart rate from birth to 10 minutes and Apgar scores from 1 to 20 minutes were identical in both groups as well as pH, BE, paO2 and paCO2 at 10 and 30 minutes post partum. Neonatal mortality was 2/36 in RA and 4/42 in O2 groups (NS) respectively. The study shows that judged by short term follow up hypoxic newborn infants may be resuscitated with room air just as well as with 100% O2.

Diaphragmatic and ventilatory responses to alveolar hypoxia and hypercapnia in conscious kittens.

Ventilation and electromyographic (EMG) activity of the diaphragm were recorded in unanesthetized kittens 2 and 10 wk of age during normoxia, hypercapnia (2 and 4% CO2), and hypoxia (12 and 10% O2). We measured integrated diaphragmatic EMG activity at end inspiration (DIAI) and end expiration (DIAE); the difference (DIAI-E), which represents the phasic change of the diaphragmatic activity, was considered responsible for a given tidal volume (VT). During hypercapnia, the 2-wk-old kittens increased minute ventilation (V) by increases in both VT and respiratory frequency (f), whereas the 10-wk-old kittens increased V primarily by an increase in VT. At both ages, DIAI and DIAI-E increased during hypercapnia, whereas DIAE did not change significantly. During hypoxia, in the young kittens, V and VT decreased while f increased markedly; in the older kittens, V, VT, and f did not change significantly. In kittens of both ages, DIAI increased during hypoxia; because diaphragmatic activity persisted into expiration, DIAE also increased. DIAI-E, as well as VT, was decreased in the young kittens, whereas in the older ones DIAI-E was slightly increased despite an unchanged VT. Finally, the ventilatory and diaphragmatic response to hypoxia changes with maturation in contrast to the response to hypercapnia. It is concluded that 1) the hypoxia-induced reduction of VT may result from prolongation of diaphragmatic activity into expiration, inasmuch as it induces a reduction of the phasic change of the diaphragmatic activity, and 2) because DIAI-E indirectly reflects central inspiratory output, a central mechanism should be involved in the reduced VT and V in response to hypoxia in newborns.

Lymphocyte Beta-2-Adrenoceptors and Plasma Catecholamines in Fetal Hypoxia

Conclusive evidence has been furnished that the beta 2-adrenoceptor density in circulating lymphocytes is related to that of beta 2-adrenoceptors in tissues from the same subjects. This study was designed to evaluate the effect of fetal hypoxia on lymphocyte beta 2-adrenoceptor density. The material consisted of 8 hypoxic newborns, 4 delivered by vacuum extraction and 4 by Caesarean section, after approximately 10 h parturition. The control group consisted of 8 vaginally delivered newborns without hypoxia. Umbilical plasma adrenaline and noradrenaline were significantly elevated in the hypoxic newborns. Their lymphocyte beta 2-adrenoceptor density was lower (p less than 0.01) than that in the controls. A plausible explanation for this finding might be downregulation of beta 2-adrenoceptors because of elevated plasma catecholamine level.

Effects of ischemia on cholinergic neurotransmission and electrolyte content in newborn pig lumbar spinal cord

The biochemical changes of the elements of cholinergic neurotransmission (choline acetyltransferase, ChAT; acetylcholinesterase, AChE; butyrylcholinesterase, BuChE; and muscarinic cholinergic receptors, mAChR) as well as the electrolyte content were studied in ischemic lumbar spinal cord segments of newborn pigs. Ischemia was elicited by ligating the aorta for 30 min. Although no significant changes were observed in the sodium, potassium and calcium content of ischemic spinal cords, the calcium content was slightly elevated, to 119.3% of the control value. Whereas significant depletions were observed in both AChE and ChAT activities (to 69.1 and 87.7% of the control value, respectively), there was no significant change in BuChE activity as compared to the control value. The mAChR were also decreased, from 33.25 ± 2.2 to 27.18 ± 1.9 fmol/mg protein, while the K d value was not significantly altered. It is concluded that even a relatively brief interruption of the oxygen supply can cause severe damage in the lumbar spinal cord of the newborn pig, affecting the cholinergic neurotransmission elements. This animal model might be suitable for studying the effects of hypoxia in newborns and children during chest operations involving the descending aorta.

Adenylate kinase activity in the cerebrospinal fluid of hypoxic newborns

Adenylate kinase (AK) activity in the cerebrospinal fluid (CSF), described as a marker of brain edema and lesions in adults, was studied in 79 newborns with severe respiratory distress within 24 h after admission to the Intensive Care Unit (ICU). The CSF-AK activity was compared with CSF lactate concentration, CSF lactate dehydrogenase activity (LDH), and CSF and serum creatine kinase isoenzyme BB (CK-BB) activity. Newborns were divided into Group I with moderate to severe brain dysfunction and Group II with mild or no detectable brain dysfunction on discharge from the ICU. Mean CSF-AK activity (11.31 U/L) in Group I was significantly (p less than 0.001) higher than in Group II (2.82 U/L). Correlation between CSF-AK and CSF lactate was r = 0.714, p less than 0.01 and between CSF-AK activity and CSF-LDH activity was r = 0.550, p less than 0.01 in Group I. Preliminary data indicate that CSF-AK activity within 24 h after ischaemia is an indicator of hypoxic brain lesions in newborns. Its prognostic value for the infant's development remains to be determined by further study.

Clinical Correlates Do Not Predict PaO2 Response After Tolazoline Administration in Hypoxic Newborns

In an attempt to determine which hypoxic newborns might benefit from administration of tolazoline hydrochloride (Tz), we identified all neonates known to have received Tz at four Chicago area perinatal centers over a 4-yr period. For each of 41 infants, five statistical analyses were used to correlate 31 clinical and ventilatory variables with PaO2 values before and after Tz administration. Fourteen neonates responded to Tz infusion with more than a two-fold increase in PaO2. None of 31 clinical variables successfully predicted a positive Tz response in these infants, and a positive response (increased PaO2) was not associated with increased likelihood of survival. BP fell after Tz in 72% of patients, while heart rate rose after Tz treatment in 66% of cases. These data suggest a need to re-evaluate the administration of Tz to hypoxic newborn infants.

The Relationship Between Perinatal Hypoxia and Newborn Encephalopathy

LOW, J. A.; GALBRAITH, R. S.; MUIR, D. W.; KILLEN, H. L.; PATER, E. A.; KARCHMAR, E. J. Author Information

Clinical correlates do not predict PaO2 response after tolazoline administration in hypoxic newborns.

In an attempt to determine which hypoxic newborns might benefit from administration of tolazoline hydrochloride (Tz), we identified all neonates known to have received Tz at four Chicago area perinatal centers over a 4-yr period. For each of 41 infants, five statistical analyses were used to correlate 31 clinical and ventilatory variables with PaO2 values before and after Tz administration. Fourteen neonates responded to Tz infusion with more than a two-fold increase in PaO2. None of 31 clinical variables successfully predicted a positive Tz response in these infants, and a positive response (increased PaO2) was not associated with increased likelihood of survival. BP fell after Tz in 72% of patients, while heart rate rose after Tz treatment in 66% of cases. These data suggest a need to re-evaluate the administration of Tz to hypoxic newborn infants.

HAEMODYNAMIC EFFECTS OF BETA-2-RECEPT0R STIMULATION IN CHILDREN

Terbutalin (Te) increases PaO2 in hypoxic newborns with respiratory disorders. The haemodynamic effects of Te have not been investigated in infants previously. The hypothesis that Te reduces pulmonary vasoconstriction and increases cardiac output was investigated in infants with symtomatic ventricular septal defect (VSD) and postoperative children (PO) with suspicion of persistent pulmonary hypertension. Methods: During diagnostic heart catheterization main pulmonary artery (MPA), left atrium and systemic artery (BP) pressures as well as pulmonary flow (Qp) by thermodilution technique were determined before and after the injection of 10 ug/kg Te in the right atrium. Pulmonary vascular resistance (Rp) was expressed in UM2 (mean pressure gradient over pulmonary vascular bed divided by Qp in L/min per M2BSA) Results: In the VSD group (n=21) all but one had pulmonary hypertension. After Te systolic and mean MPA pressure decreased slightly (p< <0,05). Qp increased (p<0,01). Heart rate increased markedly and stroke volume decreased. Mean Rp decreased (p<0,01). BP dropped at 2 min and was restituted at 5 min. In the PO group all 12 had pulmonary hypertension. After Te MPA systolic pressure increased slightly (p<0,05) while diastolic and mean pressures were unchanged. Qp increased (p< <0,01). Mean Rp fell after Te (p<0,02). BP dropped at 2 and 5 min and was back to initial level at 10 min. No complications of Te injection were detected. Conclusion: The betareceptor stimulator Terbutalin reduces pulmonary as well as systemic vascular resistance and increases cardiac output. The drug may have diagnstic and therapeutic usefulness in conditions with pulmonary vasoconstriction and low cardiac output in early life.