OBJECTIVE:We compared responses to bolus infusion of 5% albumin (ALB) or normal saline (NS) for hypotension in neonates.STUDY DESIGN:Hypotensive infants were given 10 ml kg(-1) of NS or ALB. A second bolus was given for persistent hypotension. Dopamine therapy was started for hypotension after the second bolus. The primary response was increase in arterial blood pressure toward normal range 1 h postinfusion. Secondary measures included duration of normotension, meeting criteria for second bolus, meeting criteria for vasopressor support and cost comparison.RESULT:Those receiving ALB (N=49 ALB and 52 NS) were more likely to achieve a normotensive state (ALB=57.1%, NS=32.1% P=0.01) 1 h following the initial bolus therapy. Subsequently, the NS group was also more likely to qualify for vasopressor infusion (ALB=24.5%, NS=44.2% P=0.02). Overall cost for either therapy was equivalent.CONCLUSION:In hypotensive neonates, ALB results in a greater likelihood of achieving normotension and decreased subsequent use of vasopressors when compared to NS.

Objective. To determine the safety and efficacy of prophylaxis with palivizumab in reducing the incidence of hospitalization because of respiratory syncytial virus (RSV) infection in high-risk infants. Methods. A randomized, double-blind, placebo-controlled trial was conducted at 139 centers in the United States, the United Kingdom, and Canada. During the 1996 to 1997 RSV season, 1502 children with prematurity (less than or equal to 35 weeks) or bronchopulmonary dysplasia (BPD) were randomized to receive 5 injections of either palivizumab (15 mg/kg) or an equivalent volume of placebo by intramuscular injection every 30 days. The primary endpoint was hospitalization with confirmed RSV infection. Children were followed for 150 days (30 days from the last injection). Those with hospitalization as a result of RSV infection were evaluated for total number of days in the hospital, total days with increased supplemental oxygen, total days with moderate or severe lower respiratory tract illness, and incidence and total days of intensive care and mechanical ventilation. The incidence of hospitalization for respiratory illness not caused by RSV and the incidence of otitis media were also evaluated. The placebo and palivizumab groups were balanced at entry for demographics and RSV risk factors. Ninety-nine percent of children in both groups completed the protocol and similar to 93% received all five scheduled injections. Results. Palivizumab prophylaxis resulted in a 55% reduction in hospitalization as a result of RSV (10.6% placebo vs 4.8% palivizumab). Children with prematurity but without BPD had a 78% reduction in RSV hospitalization (8.1% vs 1.8%); children with BPD had a 39% reduction (12.8% vs 7.9%). When gender, entry age, entry weight, BPD, and gestational age were included in a logistic regression model, the effect of prophylaxis with palivizumab remained statistically significant. The palivizumab group had proportionally fewer total RSV hospital days, fewer RSV hospital days with increased oxygen, fewer RSV hospital days with a moderate/severe lower respiratory tract illness, and a lower incidence of intensive care unit admission. Palivizumab was safe and well tolerated. No significant differences were observed in reported adverse events between the two groups. Few children discontinued injections for related adverse events (0.3%). Reactions at the site of injection were uncommon (1.8% placebo vs 2.7% palivizumab); the most frequent reaction was mild and transient erythema. Mild or moderate elevations of aspartate aminotransferase occurred in 1.6% of placebo recipients and 3.6% of palivizumab recipients; for alanine aminotransferase these percentages were 2.0% and 2.3%, respectively. Hepatic and renal adverse events related to the study drug were similar in the two groups. Conclusions. Monthly intramuscular administration of palivizumab is safe and effective for prevention of serious RSV illness in premature children and those with BFD.

EXCITATORY AMINO ACIDS (NMDA) ALTER HYPOXIC PULMONARY VASOCONSTRICTION (HPV) IN THE ISOLATED SALT PERFUSED RAT LUNG. † 249

Using an in situ isolated salt-perfused rabbit lung preparation, we investigated the functional ontogeny of pulmonary vascular dopamine receptors. In rabbits from 1 to 23 d of age, we measured pulmonary vascular vasodilatory responses to the peripheral vascular dopamine receptor (DA1) agonist, fenoldopam, and sodium nitroprusside during prostaglandin F2 alpha-induced pulmonary vasoconstriction. In separate experiments, the lungs were pretreated with the DA1 receptor blocker, SCH 23390, before prostaglandin F2 alpha, fenoldopam, and sodium nitroprusside. Lungs from rabbits at one of 6 age groups (n = 6-8 per group) were ventilated and perfused. After a stabilization period, prostaglandin F2 alpha was infused into the pulmonary inflow catheter in a concentration range to yield a sustained rise in mean pulmonary artery pressure (4.9 +/- 0.2 mm Hg). Fenoldopam was injected into the pulmonary artery at doses of 0.01, 0.1, 1.0, and 10 micrograms/g after a recovery period, sodium nitroprusside (0.2 micrograms/g) was injected into the pulmonary artery, and the resultant changes in vascular pressure were recorded. Across all age groups, with and without DA1 receptor blockade, sodium nitroprusside-induced vasodilation was similar (-2.7 +/- 0.2 mm Hg) and was considered reference vasodilation. The fenoldopam vasodilation response was considered a percentage of the sodium nitroprusside reference. Response to fenoldopam varied significantly (p < 0.05 by analysis of variance) across the six age groups, with a maximum at 3-5 d of age. Pretreatment with SCH 23390, a selective DA1-blocking agent, significantly attenuated fenoldopam vasodilation in all but the youngest animals (age 0-2 d), in which no blockade effect was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular dopamine (DA1) receptors may modulate circulatory hemodynamics in lambs. We evaluated resting dopaminergic tone in lambs by pharmacologically manipulating peripheral DA1 receptors with i.v. SCH 23390, (a highly selective, competitive DA1 receptor antagonist) and i.v. fenoldopam, (a highly selective DA1 receptor agonist) in unanesthetized lambs, instrumented for circulatory studies, while measuring the systemic and pulmonary vascular changes that the manipulations induced. We examined both the independent effects of DA1 receptor stimulation and blockade as well as the effects of the agonist and the antagonist infused together (competitive interaction). SCH 23390, infused at 2.5 micrograms/kg.min-1, caused significant increases in left atrial, systemic, and pulmonary artery pressure, as well as an increase in systemic vascular resistance and a decrease in heart rate. Fenoldopam, infused at the dose of 60 micrograms/kg.min-1 caused significant decreases in mean systemic artery pressure and systemic vascular resistance while increasing cardiac index and mean pulmonary artery pressure. SCH 23390 blunted the fenoldopam-induced effects. Our data suggest that dopaminergic influence may be active in the maintenance of resting hemodynamics of the lamb.

ABSTRACT: Using an isolated salt-perfused lung model in rabbits from 1 to 21 d of age, we measured the concentration of epinephrine in the pulmonary venous drainage and the pulmonary vascular response after a single dose of intratracheal epinephrine (0.1 μg/g body weight). Lungs from 30 rabbits were isolated, ventilated, and perfused at one of four age groups (n = 7–8 per group). After ventila-tion/perfusion was judged to be stable, saline control was injected into the trachea, changes in pulmonary pressure were recorded, and perfusate was collected for 45 s. After restabilization, epinephrine was injected into the trachea, changes in pulmonary vascular pressure were recorded, and perfusate was collected for 45 s x two aliquots. Perfusate epinephrine concentrations were determined by HPLC. Littk epinephrine was detected in the perfusate after control over all age groups, and little vascular response was noted. There was a significant age-related increase hi perfusate epinephrine concentration as well as an age-related increase in vascular response (increased PAP), with the maximum epinephrine concentration and change in PAP noted at 14–21 d [group 4 = (1.72 ± 0.42) x 104 pmol/L]. Also, in rabbits less than 6 d of age, deposition of epinephrine into the pulmonary venous drainage was delayed. In the rabbit model, the concentration of epinephrine reaching the heart via pulmonary circulation after intratracheal injection is, at birth, very tow, and the pulmonary vascular response is diminished. Both increase as a function of age until 14–21 d of age. These findings may have clinical importance in human neonatal resuscitation endeavors.

Hypertension in the neonate is commonly related to renal disease. More specifically, renovascular hypertension in neonates is often associated with the placement of a umbilical artery catheter. Many medications, including angiotensin-converting enzyme (ACE) inhibitors, have been used in the treatment of neonatal hypertension. Captopril, an ACE inhibitor, is an oral agent that is effective in renovascular hypertension. We describe the use of intravenous enalapril, another ACE inhibitor, in successfully treating severe renovascular hypertension refractory to standard medical therapy in two term neonates.

Neonatal rabbits were exposed to either normoxia (21% oxygen) or hyperoxia (. 95% oxygen) for 2-4 days, and isolated ventilated perfused lung preparations from the various animals were studied. 5-Hydroxytryptamine (5HT) uptake, perfusion pressure, alveolar lavage protein and lung tissue vitamin E concentrations were measured. There was no difference in mortality between the two groups at any time point. There was no difference in perfusion pressures at any time point. There were no differences between normoxic and hyperoxic animals in alveolar lavage protein or 5 HT uptake at 2 and 3 days. At 4 days, 5HT uptake (fractional) was lower in the hyperoxia group than in controls (0.65 +/- 0.033 v. 0.75 +/- 0.013 (mean +/- SE); p less than or equal to 0.05) and alveolar lavage protein was higher compared to normoxia (1111 +/- 415 micrograms/ml v. 481 +/- 78 micrograms/ml; p less than or equal to 0.05). Lung vitamin E concentrations were higher at 3 days in rabbits exposed to hyperoxia compared to normoxia (16.5 +/- 1.8 micrograms/gm v. 12.3 +/- 0.6 micrograms/gm; p less than or equal to 0.05). In air exposed animals there was a decrease in lung vitamin E concentration after 2 days, whereas hyperoxia exposed animals had no significant decrease in lung vitamin E concentrations from 2-4 days exposure. These studies establish that the decrease in 5HT uptake, albeit delayed compared to that described previously in adult animals, is a reasonable measure of pulmonary oxygen toxicity in newborn rabbits.

Ethanol is a pulmonary vasoconstrictor in rat lungs perfused in situ with Krebs-Henseleit salt solution. Pentobarbital-anesthetized rats were tracheotomized, and an in situ recirculating isolated lung perfusion was instituted using a Krebs-Henseleit buffer with 3% bovine albumin at 37 degrees C. Changes in pulmonary arterial pressure and tracheal inspiratory pressure during intravenous ethanol infusion at four different cumulative doses were measured in normoxic (n = 6) and hyperoxic (n = 6) lungs, compared to normoxic perfusate (no ethanol infusion) controls (n = 6). Perfusate alcohol levels progressively increased in experimental groups. Perfusate gas and pH values were normal and not altered by ethanol. PAP increased by the end of ethanol infusion from 9.7 +/- 2 to 26 +/- 13 mm Hg in the normoxic group and from 10.6 to 22 +/- 9 mm Hg in the hyperoxic lungs (p less than .02); no change occurred in control lungs. Severe pulmonary edema occurred in 83% of the ethanol exposed lungs (vs. 0% of perfusate controls). Postethanol wet/dry weight ratios were twice normal (p less than .02). Pulmonary arterial pressure rose in two stages. First there was a 25-100% increase before airway pressure increased, representing pulmonary vasoconstriction. This was followed by a precipitous 100-500% transmitted pressure rise as severe pulmonary edema developed. Thus, we conclude that the vasoconstrictor effect of ethanol on the pulmonary circulation occurs in rats as well as in lambs, dogs, and humans. In isolated perfused rat lungs, the response is locally mediated.