David Berry

Clearance of natural surfactant phosphatidylcholine from 3-day-old rabbit lungs: effects of dose and species.

ABSTRACT: Surfactants were labeled in vivo with [3H] choline and the large aggregates of the surfactant were recovered by alveolar wash and centrifugation. The labeled natural surfactants from rabbit, sheep, cat, and pig were injected into the airways of 3-day-old rabbits, and the percent recoveries of the labeled surfactant-associated phosphatidylcholine were measured in alveolar washes, lung tissue after alveolar wash, and in the lungs (alveolar wash plus lung tissue). The rabbit surfactant-associated phosphatidylcholine was cleared from the lungs at a constant 15.6 ± 1.8% per 24 h (mean ± SE) of the injected doses of surfactant that contained from 0.41 to 10.2 µmol phosphatidylcholine. At all times following injection, approximately 50% of the labeled phosphatidylcholine remaining within the lungs was recovered in the alveolar wash and 50% with the lung tissue. The percent clearances for sheep, cat, and pig surfactant phosphatidylcholine in rabbits were 12.5, 16.6, and 16.3% per 24 h, respectively, values not different from that measured for rabbit surfactant. The results documented a slow clearance of exogenously administered surfactant phosphatidylcholine as a fixed percent of the injected dose that was unchanged by species source of the surfactant.

Hemodynamic and hormonal responses to atrial distension in the ovine fetus

OBJECTIVEnOur purpose was to evaluate the hemodynamic and endocrine responses to elevations of atrial pressure in fetal sheep.nnnSTUDY DESIGNnBy use of a randomized block design, 10 ovine fetuses underwent pulmonary artery constriction proximal to the ductus arteriosus with and without propranolol pretreatment.nnnRESULTSnAtrial 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.nnnCONCLUSIONSnThe 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.

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. 1-4 The absence of this anti-atelectasis factor2,3 was proposed by Avery and Mead in 1959 to be the cause of hyaline membrane disease of premature infants.5 An indepth historical review of pulmonary surfactant by Tierney 6 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 issues of surfactant replacement.

PULMONARY FUNCTION TESTS IN VERY LOW BIRTH INFANTS RANDOMIZED TO A DOUBLE-BLIND PLACEBO-CONTROLLED DEXAMETHASONE TRIAL. † 1158

PULMONARY FUNCTION TESTS IN VERY LOW BIRTH INFANTS RANDOMIZED TO A DOUBLE-BLIND PLACEBO-CONTROLLED DEXAMETHASONE TRIAL. † 1158

1420 PULMONARY SURFACTANT (PS): WHAT PROPERTIES ARE IMPORTANT?

PS can lower surface tension (ST) to <10 dynes/cm (d/c). This is believed to be essential for normal lung function. We tested a detergent, Tween 20 (T), which cannot lower ST to less than 25 d/c, for its effect on the respiratory failure due to respiratory distress syndrome (RDS) in lambs (L) at 120-124 days gestation. L were delivered by cesarean section and each received one of three solutions intratracheally prior to the 1st breath: 1) 0.45% saline (saline); 2) 5% in 0.45% saline; or 3) PS in 0.45% saline. Each L was mechanically ventilated using 100% O2. Only the peak inspiratory pressure (PIP) was adjusted in an attempt to maintain a normal arterial pCO2. Values given are mean ± SEM at 30 min of age. N = 5 to 7 in each group.Gas exchange in L given T was much better than in L given saline and at a lower PIP. It approached that in L given PS. This occurred while the AW ST of L given T was the same as the AW ST of L given saline. Thus the ability of PS to lower ST to <10 d/c is less critical than previously believed.

DISTRIBUTION OF PULMONARY BLOOD FLOW AND PROTEIN LEAK IN PREMATURE LAMBS

We studied 10 premature lambs with RDS to assess pulmonary blood flow (PBF) and protein leak distribution relative to aerated and atelectatic lung volumes. The lambs were delivered by C-section, intubated, paralyzed and ventilated so as to maintain normal blood gases. At 3.5 hrs, 125I ovalbumin (OA) was injected into an umbilical artery. At 4 hrs, radiolabeled microspheres were injected into the right ventricle to assess PBF distribution. The animals were sacrificed at 4 hrs of age, the lungs were removed, and divided into approximately 60 1 gm pieces, separating the lung into 3 categories: collapsed (C), partially aerated (P), and fully aerated (A). Each piece was assayed for 125I and microspheres. Results: 1) There was more flow to A than C regions, p<.01 in 8/10 lambs. By weight A was 36.7-70.1% (56.1%) and C was 14.9-52.1 (26.4%), while the % of total blood flow was 49.6-77.7% (64.0%) and 8.0-39.1% (19.2%), respectively. Without autoregulation there would be a mean shunt of 26.4% instead of the 19.2% measured, which could make a significant difference in the FiO2 needed to maintain normal oxygenation. Including P with C does not significantly change these results. 2) There was a relatively uniform protein leak throughout the lung but more in A than C in 4/5 animals that received OA, p<.05. 3) There was no correlation between blood flow and protein leak. Conclusions: Premature lambs with RDS have a small but significant ability for autoregulation of PBF, and intravascular protein tends to leak more in A than C regions.

HEMODYNAMIC EFFECTS OF HIGH FREQUENCY OSCILLATORY VENTILATION |[lpar]|HFOV|[rpar]| PRETERM LAMBS

The effects of (HFOV) on the preterm cardiovascular system have not been evaluated. We studied 14 surfactant-treated preterm twin lambs (120 days gest. age) after occlusion of the ductus arteriosus with a balloon catheter. Left ventricular (LV) performance was evaluated using cineangiocardiography and radionuclide labeled microspheres. Studies were obtained after 2 and 3 hrs of conventional ventilation [CV] (Grp A, n=7) or HFOV (Grp B, n=7). HFOV was fixed at 15 Hz (900/min) and settings were adjusted to maintain similar blood gases in both groups. The following measurements were obtained: cardiac output (CO) ml min−1. kg−1, organ flows (% distribution,); LV ejection fraction (EF %), end diastolic volume (EDV); aortic:pulmonary mean (AO/PA) and mean airway pressures (MAP); ratio PaO2/FiO2.At similar end diastolic pressures and systemic resistances, and at comparable MAP and blood gases, there were no significant differences of LV performance or blood flow distribution with HFOV or CV (Wilcoxon test). Oxygenation (PaO2/FiO2) was similar in the groups. HFOV is an equally effective mode of ventilation and has no apparent deleterious effects upon the preterm cardiovascular system.