Depression of cardiac function after deep hypothermic circulatory arrest in deeply anesthetized neonatal lambs.

Cardiac dysfunction is common after neonatal cardiac operations. Previous in vivo studies in neonatal animal models however, have failed to demonstrate decreased left ventricular function after ischemia and reperfusion. Cardiac dysfunction may have been masked in these studies by increased endogenous catecholamine levels associated with the use of light halothane anesthesia. Currently, neonatal cardiac operations are often performed with deep opiate anesthesia, which suppresses catecholamine surges and may affect functional recovery. We therefore examined the recovery of left ventricular function after ischemia and reperfusion in neonatal lambs anesthetized with high-dose fentanyl citrate (450 micrograms/kg administered intravenously). Seven intact neonatal lambs with open-chest preparation were instrumented with left atrial and left ventricular pressure transducers, left ventricular dimension crystals, and a flow transducer. The lambs were cooled (< 18 degrees C) on cardiopulmonary bypass (22 +/- 6 minutes), exposed to deep hypothermic circulatory arrest (46 +/- 1 minutes), and rewarmed on cardiopulmonary bypass (30 +/- 10 minutes). Catecholamine levels and indexes of left ventricular function were determined before (baseline) and 30, 60, 120, 180, and 240 minutes after termination of cardiopulmonary bypass. Levels of epinephrine, norepinephrine, and dopamine were unchanged from baseline values. Left ventricular contractility (slope of end-systolic pressure-volume relationship) was depressed from baseline value (31.7 +/- 9.3 mm Hg/ml) at 30 minutes (15.7 +/- 6.4 mm Hg/ml) and 240 minutes (22.7 +/- 6.4 mm Hg/ml) but unchanged between 60 and 180 minutes. Left ventricular relaxation (time constant of isovolumic relaxation) was prolonged from baseline value (19.0 +/- 3.0 msec) at 30 minutes (31.4 +/- 10.0 msec) and 240 minutes (22.1 +/- 2.8 msec) but unchanged between 60 and 180 minutes. Afterload (left ventricular end-systolic meridional wall stress) was decreased at 30, 60, and 240 minutes. Indexes of global cardiac function (cardiac output, stroke volume), preload (end-diastolic volume), and left ventricular compliance (elastic constant of end-diastolic pressure-volume relationship) were unchanged from baseline values. In deeply anesthetized neonatal lambs exposed to ischemia and reperfusion, left ventricular contractility, relaxation, and afterload are markedly but transiently depressed early after reperfusion and mildly depressed late after reperfusion.

Hemodynamic and hormonal responses to atrial distension in the ovine fetus.

OBJECTIVE: Our purpose was to evaluate the hemodynamic and endocrine responses to elevations of atrial pressure in fetal sheep. STUDY DESIGN: By use of a randomized block design, 10 ovine fetuses underwent pulmonary artery constriction proximal to the ductus arteriosus with and without propranolol pretreatment. RESULTS: Atrial pressure doubled (p < 0.05), whereas mean arterial pressure remained unchanged (p > 0.05), in response to pulmonary artery constriction in both groups. Atrial natriuretic peptide tripled (p < 0.01), arginine vasopressin tripled (p < 0.05), and plasma renin activity doubled (p < 0.05) in both the constriction and constriction plus propranolol groups. No changes in fetal hematocrit values were demonstrated in any group. CONCLUSIONS: The fetal sheep responds to increased atrial pressure with not only increased levels of atrial natriuretic peptide but also with arginine vasopressin and plasma renin activity over time. These changes occur in spite of increases in both atrial pressure and atrial natriuretic peptide. We speculate that the fetal heart may participate in redistribution of cardiac output by releasing atrial natriuretic peptide and augmenting secretion of arginine vasopressin and plasma renin activity.

Effect of atrial natriuretic factor on release of arginine vasopressin and renin in fetal lambs.

The purpose of this study was to determine the effect of increased plasma atrial natriuretic factor (ANF) concentrations on the arginine vasopressin (AVP) and renin response to arterial hypotension in fetal sheep. Lamb fetuses at 123-133 days of gestation were infused intravascularly with 0.9% NaCl and ANF at 25 ng.kg-1.min-1 (low dose) or NaCl and ANF at 250 ng.kg-1.min-1 (high dose) for 115 min. After 45 min, sodium nitroprusside was infused for 10 min to yield a 25% decrease in mean arterial blood pressure. ANF infusions resulted in plasma concentrations of 150-200 and 500-800 pg/ml in the low-dose and high-dose groups, respectively. In both the low-dose and high-dose ANF groups, AVP and renin concentrations increased in response to hypotension. In the low-dose ANF group, there was no difference in this response between ANF and control lambs. Compared with controls, a high dose of ANF resulted in an elevated basal level of AVP (1.6 +/- 0.04 vs. 12.3 +/- 6.7 pg/ml) and an 11-fold increase of AVP at 10 min of hypotension (12.2 +/- 5.6 vs. 134.9 +/- 36.1 pg/ml). Basal and stimulated renin concentrations were unchanged by the high-dose ANF infusion. This study demonstrates that in the fetal lamb, ANF concentrations of 500-800 pg/ml augment the basal and stimulated release of AVP but do not affect the renin response.

Comparison of the effect of three doses of a synthetic surfactant on the alveolar-arterial oxygen gradient in infants weighing > or = 1250 grams with respiratory distress syndrome. American Exosurf Neonatal Study Group II.

The effect of a 50% increment or decrement in the recommended 5 ml/kg dose of a commercially available surfactant (Exosurf Neonatal) on the alveolar-arterial oxygen gradient was investigated in a multicenter, double-blind, placebo-controlled rescue trial conducted at 15 hospitals in the United States. Two doses of three different volumes (2.5, 5.0, and 7.5 ml/kg) were compared with two 5.0 ml/kg doses of air in 281 infants weighing > or = 1250 gm who had respiratory distress syndrome requiring mechanical ventilation and an arterial/alveolar oxygen ratio < 0.22. The first dose was given between 2 and 24 hours of age, and the second dose was given 12 hours later to all infants who still required mechanical ventilation. Infants were stratified at entry by gender and the magnitude of the arterial/alveolar oxygen ratio. The air placebo arm of the study was terminated early when reductions in mortality rates were proved in another rescue trial of this surfactant in infants with the same birth weights. For the first 48 hours, administration of a 2.5 ml/kg dose of surfactant provided less improvement in the alveolar-arterial oxygen gradient than doses of 5.0 and 7.5 ml/kg, which were equivalent. Similar results were observed in mean airway pressure (p < 0.05). There were no significant differences among the three dosage groups in mortality rate, air leak, bronchopulmonary dysplasia, and other complications of prematurity. There were no pulmonary hemorrhages in any group. Reflux of surfactant occurred more frequently in the 5.0 and 7.5 ml/kg groups. These results indicate that more sustained improvements in oxygenation are provided, with equal safety, by the standard two 5.0 ml/kg rescue doses of this surfactant than by the 2.5 ml/kg dose. No further benefit is gained from two larger doses given 12 hours apart.

Neonatology in the 1990's: surfactant replacement therapy becomes a reality.

It has been more than 35 years since the lung was discovered to be lined with a layer of surface-active material that is important in lung stability and mechanics of respiration. The absence of this "anti-atelectasis" factor was proposed by Avery and Mead in 1959 to be the cause of hyaline membrane disease of premature infants. An indepth historical review of pulmonary surfactant by Tierney was recently published. In the years since 1959, there has been an exhaustive amount of research aimed at elucidating the structure and function of pulmonary surfactant, the ultimate goal being a safe and effective exogenous surfactant for the treatment of the Respiratory Distress Syndrome (RDS). The days of surfactant research are far from over, but the era of surfactant replacement therapy is now upon us. The practitioner needs to be knowledgeable about surfactant and aware of his or her role in surfactant therapy for premature infants. The following is intended to clarify some of the important issue of surfactant replacement.

Effects of maternal treatment with corticosteroids, T3, TRH, and their combinations on lung function of ventilated preterm rabbits with and without surfactant treatments.

Pregnant does were treated with betamethasone, T3, TRH, or combinations of betamethasone plus T3 or TRH using doses of each agent known to effect lung maturation. Preterm rabbits were then delivered at 27 days gestational age, half of each group was treated with Surfactant TA, and the rabbits were ventilated in a ventilator-plethysmograph system such that tidal volumes were regulated to mean values of 12 to 13 ml/kg. At 30 min of age when mean PCO2 values for the study groups were between 33 and 42 mm Hg, lung function of each rabbit was evaluated by the peak inspiratory pressure needed to achieve the desired tidal volume, by compliance, and by the ventilation efficiency index. These measures of lung function showed no benefit of corticosteroids or T3 in the absence of surfactant, whereas TRH significantly improved lung function. Although surfactant treatment improved lung function in all groups, the best effect after a single hormone treatment was with corticosteroids. The combined use of corticosteroids and TRH in surfactant-treated animals resulted in the best overall responses. The leak of protein into and out of the lungs was measured with radiolabeled albumins. The leak decreased as peak ventilatory pressures decreased in all groups and decreased with surfactant treatments of all groups. Corticosteroids decreased the protein leak into the airways more than could be accounted for by the effects of corticosteroids on ventilatory pressures alone (p less than 0.01). None of the hormone treatments significantly increased the saturated phosphatidylcholine pool sizes from the low values noted in the control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Normalization of arterial blood gases after treatment of surfactant-deficient lambs with Tween 20.

Pulmonary surfactant (PS) is capable of lowering surface tension at an air-water interface to less than 10 dynes/cm. This property of PS is believed to be important for normal lung function. We tested the detergent Tween 20, which cannot lower surface tension at an air-water interface to less than 25 dynes/cm, for its ability to promote reasonable gas exchange in surfactant-deficient lambs delivered prematurely at 120 to 124 days gestation. Lambs were treated at birth with 75 mM NaCl (control), 5% Tween 20 in 75 mM NaCl, or PS in 75 mM NaCl and placed on infant ventilators. Control lambs had poor oxygenation and were in respiratory failure at 30 min of age (arterial PCO2 of 75.8 +/- 11 mmHg (mean +/- SE)) despite peak inspiratory pressures (PIP) of 32 +/- 0.7 cm H2O. Pulmonary surfactant treatment allowed adequate ventilation with a PIP of 23.8 +/- 1.2 cm H2O. Tween treatment also allowed adequate ventilation with a PIP of only 27 +/- 1.3 cm H2O. Minimal surface tensions in alveolar washes of control and Tween-treated lambs were 28.7 +/- 1.3 and 26.7 +/- 2.3 dynes/cm, respectively, compared with less than 10 dynes/cm for PS-treated lambs. Thus, Tween 20 did not alter the alveolar wash minimal surface tension when compared with that of the control animals but it did significantly improve gas exchange and lung compliance.

Reutilization of surfactant phosphatidylcholine in adult rabbits.

32P-saturated phosphatidylcholine was added to [3H]choline-labeled natural surfactant and the mixture was injected intratracheally into 87 adult rabbits. The rabbits were also given [14C]palmitate intravenously at the same time. Rabbits were killed in groups from 10 min to 72 h after injection. In each rabbit we measured the total recovered [3H]phosphatidylcholine (PC) in the alveolar wash, the ratio of [3H]PC to [32P]PC in the alveolar wash, and the specific activity of [14C]PC in the alveolar wash and lamellar bodies. Values were averaged for all rabbits killed at the same times and smooth curves were fit to the data by computer. From the intravenous [14C]palmitate data we calculated a turnover time for alveolar PC of 6.0 h. From the intratracheal labeling data, we calculated a turnover time for alveolar PC of 5.7 h and determined that alveolar PC was reutilized at an efficiency of only 23%. We also concluded that this reutilization occurred as intact molecules.

Adverse reactions to parenteral lincomycin.

Lincomycin use has not been reported exclusively in children and inasmuch as it has been extensively used at our institution, a chart review of 265 patients who received parenteral lincomycin at a dose of 100 mg/kg/day in four divided doses for five days or longer was undertaken. The following conditions were diagnosed: cellulitis, 39%; septic arthritis, 21%; osteomyelitis, 16%; abscess, 13%; lymphadenitis, 9%; and pneumonia, 1%. Cures were achieved in all. The majority of organisms cultured were Staphylococcus aureus and Streptococcus pyogenes. Duration of therapy ranged from five to 63 days, with a mean of 15 days. The lincomycin dose ranged from 75 to 2,400 mg every six hours. The majority of patients received the drug intravenously, but 25.7% received it only intramuscularly. There were no adverse reactions at the administration sites. Only 3% of the patients developed diarrhea, which was not felt to be secondary to the drug. There were no cases of pseudomembranous colitis. Therefore parenteral lincomycin in children appears to be a safe and effective antibiotic when used for infections due to Gram-positive cocci.