Energy enhancement of the target surface electron by using a 200 TW sub-picosecond laser.

One order of magnitude energy enhancement of the target surface electron beams with central energy at 11.5 MeV is achieved by using a 200 TW, 500 fs laser at an incident angle of 72° with a prepulse intensity ratio of 5×10-6. The experimental results demonstrate the scalability of the acceleration process to high electron energy with a longer (sub-picosecond) laser pulse duration and a higher laser energy (120 J). The total charge of the beam is 400±20 pC(E>2.7 MeV). Such a high orientation and mono-energetic electron jet would be a good method to solve the problem of the large beam divergence in fast ignition schemes and to increase the laser energy deposition on the target core.

Low energy prepulse for 10 Hz operation of a soft-x-ray laser.

The influence on Nickel-like Molybdenum soft-x-ray laser performance and stability of a low energy laser prepulse arriving prior to the main laser pumping pulses is experimentally investigated. A promising regime for 10 Hz operation has been observed. A four times increase in soft-x-ray laser operation time with a same target surface is demonstrated. This soft-x-ray laser operation mode corresponds to an optimum delay between the prepulse and the main pulses and to a prepulse energy greater than 20 mJ. We also show that this regime is not associated with a weaker degradation of the target or any reduced ablation rate. Therefore the role of preplasma density gradient in this effect is discussed.

Gain lifetime measurement of a Ni-like Ag soft X-ray laser.

Experimental results of a two-stage Ni-like Ag soft X-ray laser operated in a seed-amplifier configuration are presented. Both targets were pumped applying the double-pulse grazing incidence technique with intrinsic travelling wave excitation. The injection of the seed X-ray laser into the amplifier target was realized by a spherical mirror. The results show amplification of the seed X-ray laser and allow for a direct measurement of the gain lifetime. The experimental configuration is suitable for providing valuable input for computational simulations.

Osteoclast-like cell formation in fetal and newborn long-term baboon marrow cultures is more sensitive to 1,25-dihydroxyvitamin D3 than adult long-term marrow cultures.

It is unknown if osteoclasts derived from animals at different developmental stages differ. To study this question, we used a long-term baboon marrow culture system in which osteoclast-like multinucleated cells (MNC) are formed. Fetal, newborn, or adult baboon marrow cultures were tested to determine if they differ in their responsiveness to osteotropic hormones. In fetal and newborn marrow cultures 1,25-dihydroxyvitamin D3 (1,25D3) at 10(-10) M significantly increased MNC formation with a maximal effect seen at 10(-9) M. Higher concentrations of 1,25D3 progressively decreased MNC formation. In contrast, in adult baboon marrow cultures, 10(-9) M 1,25D3 was required to significantly increase MNC formation, with a maximal affect at 10(-8) M 1,25D3. Calcitonin (25-200 ng/ml) inhibited MNC formation in fetal, newborn, or adult baboon marrow cultures treated with 1,25D3 in an identical manner. The effects of 1,25D3 on granulocyte-macrophage progenitor cells (CFU-GM), the probable precursors of MNC, were identical in fetal and adult baboon marrow cultures, with a significant inhibition of CFU-GM colony formation at 10(-8) M 1,25D3. These results suggest that 1) osteoclast precursors are more sensitive to some osteotropic hormones during the fetal and newborn periods, and 2) differences in the 1,25D3 sensitivity of osteoclast-like MNC formation in fetal, newborn, and adult baboon marrow cultures are not due to effects on early proliferating precursors but may result from effects of 1,25D3 on fusion of later precursors for MNC.

Effects of human recombinant CSF-GM and highly purified CSF-1 on the formation of multinucleated cells with osteoclast characteristics in long-term bone marrow cultures.

Several studies have suggested that the osteoclast is derived from a mononuclear precursor which is found in bone marrow. We have developed a system for studying the formation of osteoclast-like multinucleated cells in long-term bone marrow culture of baboon cells. Recombinant human CSF-GM and highly purified CSF-1, both of which stimulate the proliferation of monocyte/macrophage precursors, were found to increase the number of osteoclast-like cells formed in long-term bone marrow culture. CSF-GM stimulated multinucleated cell formation more consistently than CSF-1. The subsequent addition of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) to cultures initially treated with CSF-GM or CSF-1 further increased multinucleated cell formation. Autoradiographic studies indicate that CSF stimulated multinucleated cell formation by increasing the proliferation of the precursor cell, and that the potentiating effect of 1,25-(OH)2D3 was caused by fusion of the increased numbers of precursors. These studies suggest that the interaction of locally produced colony-stimulating factors with circulating calcium regulating hormones may be important in the control of osteoclast formation and bone resorption.

Pubertal endocrinology of the baboon: elevated somatomedin-C/insulin-like growth factor I at puberty.

Previous data suggested an increase in the rate of weight gain and linear growth in the baboon between 3 and 4 yr of age, similar to the pubertal growth spurt in man. In this cross-sectional study, radioimmunoassayable concentrations of somatomedin-C/insulin-like growth factor I(SM-C/IGF-I) were compared in prepubertal (less than 3 yr), pubertal (3-4 yr), and adult (greater than 10 yr) animals. SM-C/IGF-I concentrations in prepubertal males (0.97 +/- 0.10 U/ml) were low and were not different from those in prepubertal females (0.98 +/- 0.15 U/ml). Between 3 and 4 yr, SM-C/IGF-I increased significantly in both sexes (8.87 +/- 0.74 and 5.27 +/- 0.52 U/ml, male and female, respectively) and decreased (5.92 +/- 1.2 and 2.75 +/- 0.13 U/ml, respectively) in animals greater than 10 yr of age. Sex differences were significant in the 3- to 4-yr-old animals (male greater than female, P less than 0.001). The pubertal elevation in SM-C/IGF-I concentrations is coincident with increases in indices of somatic growth and sexual maturation in the baboon. These and other data suggest that this animal may be an appropriate model for studies to define hormonal mechanisms of pubertal growth.

Estrogen stimulates growth hormone and somatomedin-C in castrate and intact female baboons.

To evaluate the effects of physiological concentrations of estrogen on plasma concentrations of somatomedin-C (Sm-C) and GH, 16 chronic castrate female baboons were implanted either with blank Silastic capsules (n = 5) or capsules containing crystalline estradiol (E2; n = 11), which remained in place for 7 days. By day 7, serum E2 levels in treated animals rose into the physiological adult female range (mean +/- SEM, 96 +/- 9.2 pg/ml) and were greater (P less than 0.0005) than those in control animals (27.5 +/- 3.4 pg/ml). Sm-C concentrations rose significantly by day 7 in treated animals compared to those in control animals, whether assayed from unprocessed plasma (96% increase; P less than 0.01), plasma pretreated with glycine-HCl (99% increase; P less than 0.01), or plasma extracted with acid-ethanol (72% increase; P less than 0.02). GH concentrations in these animals were low and were not significantly different in E2-treated and control animals. To evaluate the effects of pharmacological doses of E2 on Sm-C and GH concentrations, six intact adult female baboons were treated with six daily injections of 1 mg E2 benzoate in oil. Serum E2 rose to a mean level of 1669 +/- 320 pg/ml on day 7. The plasma Sm-C concentration by day 7 was significantly higher than the pretreatment value whether assayed in untreated plasma (4.3-fold increase; P less than 0.01), plasma pretreated with glycine-HCl (2-fold increase; P less than 0.01), or plasma extracted with acid-ethanol (1.7-fold increase; P less than 0.01). Mean serum GH concentrations rose significantly from 3.3 ng/ml on day 0 to 23.6 ng/ml by day 7 (P less than 0.02). Evaluation of the chromatographic profile of native baboon plasma suggested a marked increase in [125I]Sm-C binding to plasma proteins after in vivo pharmacological E2 treatment; a broad peak of [125I]Sm-C binding over a size range from that of albumin to gamma-globulin was found. These results indicate that estrogen treatment of castrate or intact female baboons with both physiological and pharmacological doses results in an increase in plasma Sm-C concentrations that, at least in pharmacological doses, are mediated through an increase in GH concentrations. Although pharmacological E2 treatment results in a stimulation of plasma proteins that bind Sm-C, the effects on plasma Sm-C concentrations were found after procedures that diminish interference from circulating binding proteins. These data support the concept that estrogen may play a role in the physiological increase in plasma concentrations of Sm-C associated with normal puberty.

Characterization of HDL and lipoproteins intermediate to LDL and HDL in the serum of pedigreed baboons fed an atherogenic diet.

A lipoprotein species with ultracentrifugal flotation rates (F0(1.20) 9-28) intermediate to high density lipoproteins (HDL, F0(1.20) 0-9) and low density lipoproteins (LDL, F0(1.20) 28-56) found in the plasma of certain pedigreed baboons fed an atherogenic diet was studied by gradient gel electrophoresis (GGE) and ultracentrifugal techniques. These lipoproteins were found to be heterogeneous in size (125-220 A) and hydrated density (1.028-1.080 g/ml). The major apolipoprotein in all density subfractions of the F0(1.20) 9-28 lipoproteins exhibited the molecular weight (2.8 X 10(4) daltons) and immunochemical properties of apolipoprotein A-I (apoA-I). Protein corresponding to apolipoprotein E (apoE, 3.5 X 10(4) daltons) was observed primarily in the less dense subspecies of F0(1.20) 9-28 lipoproteins. Some low molecular weight (1.8 X 10(4), 1.3 X 10(4), and 1.1 X 10(4) daltons) apolipoproteins were also detected. At low serum F0(1.20) 9-28 lipoprotein concentrations, only the smaller, more dense, protein-rich species were present; at higher F0(1.20) 9-28 concentrations, the larger, less dense species were observed in addition to the small species. The HDL of pedigreed baboons in families with and without serum F0(1.20) 9-28 lipoproteins were also characterized. The HDL of both groups of progeny consisted of a similar set of 5 subpopulations designated HDL-I through HDL-V determined by GGE. HDL-I, consisting of material 100-125 A in size, was the major HDL subpopulation. ApoA-I was the major protein moiety in all HDL subpopulations; none contained apoE. Baboons in families with F0(1.20) 9-28 lipoproteins had more HLD-I (292 +/- 80 mg/dl vs. 235 +/- 55 mg/dl) and less HDL-II (86 +/- 22 mg/dl vs. 135 +/- 34 mg/dl) than baboons in families without F0(1.20) 9-28 lipoproteins; both groups showed identical total HDL concentrations (446 +/- 90 mg/dl and 444 +/- 49 mg/dl, respectively). Among those baboons in families with F0(1.20) 9-28 lipoproteins, there was an inverse correlation between F0(1.20) 9-28 concentration and total HDL, HDL-I and HDL-II concentrations, indicating a possible metabolic relationship between these HDL subpopulations and the F0(1.20) 9-28 species.

Effects of dietary polyunsaturated and saturated fats on lipoproteins in the baboon.

The effects of 2 different dietary fats (40% of calories from corn oil or coconut oil), in the presence of high-dietary cholesterol (1.7 mg/kcal), on the lipoprotein profiles of baboons (Papio cynocephalus sp) were studied by analytic ultracentrifugation, gradient gel electrophoresis (GGE), and heparin-manganese chloride precipitation. Relative to the corn oil (polyunsaturated fat) diet, the coconut oil (saturated fat) diet significantly increased total serum cholesterol by 43% (P less than 0.001) by increasing non-precipitable cholesterol (HDL-C) 58% (P less than 0.001) and precipitable cholesterol (VLDL + LDL-C) 35% (P less than 0.001). Analytic ultracentrifugal observations indicated that the increase in HDL-C was due to considerable increases in both HDL-I (baboon HDL of size 100-125 A and hydrated density 1.063-1.120 g/ml) and F1.20 degrees 9-28 lipoproteins (material of size 125-220 A and hydrated density 1.03-1.08 g/ml, and containing HDL apolipoproteins and apo E). Concentrations of other HDL subpopulations were unaffected by the dietary saturated rat. The increase in VLDL + LDL-C was due to increased LDL (S degree F 5-12 lipoproteins) and, to some extent, F1.20 degrees 9-28 lipoproteins because the larger, faster floating subspecies of the F1.20 degrees 9-28 lipoproteins were precipitable by heparin-manganese. In contrast, saturated fat (relative to polyunsaturated fat) induced lower concentrations of IDL (SF degree 12-20) and VLDL (SF degree 20-100). Lipoprotein size distributions by GGE indicated 5 HDL subpopulations and 2 or more LDL subpopulations in the sera of most baboons. The type of dietary fat did not affect the particle size range of each of the the HDL or LDL subpopulations. The results indicate that dietary fat markedly modulates the distribution of cholesterol between apo A-I-containing (HDL and F1.20 degrees 9-28) and apo B-containing (IDL and VLDL) lipoproteins without altering the presence of subpopulations based on particle size.

Characterization of prostaglandin E2 binding to uterine membranes from baboon, rabbit and tree shrew (Tupaia belangeri).

Membrane preparations (100,000 g pellet) of rabbit, baboon and tree shrew (Tupaia belangeri) uteri were studied for binding of [3H]prostaglandin E2 ([3H]PGE2). Unbound [3H]PGE2 was separated by filtration through Whatman GF/F filters. Non-specific binding was determined by the amount of radioactivity associated with the filters in the presence of a 100-fold excess of radioinert PGE2. PGE2 bound to membranes could be displaced by some other prostaglandin (PG) molecules: PGE1, 16,16-dimethyl-PGE2, PGA1 and PGF2 alpha, but not by 6-keto-PGF1 alpha, PGD2 or arachidonic acid. No PGE2 binding was detected using either membrane ghosts from red blood cells or liposomes. Apparent equilibrium of the binding was reached by 60 min. There was no difference in dissociation constant (Kd) values between rabbits of different reproductive stages (mean range +/- S.E.M. was from 4.6 +/- 0.3 to 5.5 +/- 1.0 nM), but pregnant baboons showed a significantly lower value (3.3 +/- 0.4 nM) than did cyclic animals (12.0 +/- 2.0 nM). Binding capacity (Bmax) values, in contrast, were different only between oestrous rabbits and other reproductive stages. The small amounts of Tupaia tissue only permitted estimates of the Kd and Bmax values to be made; these were 3.8 nM and 499 fmol/mg protein for oestrous animals and 5.4 nM and 674 fmol/mg protein for animals on day 7 of pregnancy, assuming only one class of sites. The present results demonstrate the presence of specific binding sites for PGE2 in uteri from several species.

Animal models for evaluation of drugs for use in the mature and immature newborn.

The need for a better defined and controlled approach to new therapies for possible neonatal application appears clear in light of present practice and recent history. At this conference several animal models were discussed that could be used for pharmacokinetic and pharmacodynamic studies and for evaluation of efficacy and safety prior to human newborn testing. This, coupled with a requirement for comprehensive human data collection following preliminary approval of new drugs, would, we believe, significantly improve present practice. It will, however, require pressure from the medical community and patient advocates to encourage change in current government regulations and industry policies.

[3H]Prostaglandin accumulation in vitro by baboon uterus.

Uteri from mature baboons at various stages of the menstrual cycle were collected at autopsy. Transverse slices of the uteri were incubated with [3H]prostaglandins in Tyrode's buffer. Bound and free ligands were separated by filtration. Prostaglandin (PG) accumulation by the tissue slices was evaluated as a function of incubation time, PG type and concentration, temperature, wet weight of tissue and stage of the menstrual cycle. There was no significant difference in PG accumulation in response to PG type (PGE2 or PGF2 alpha) or stage of the menstrual cycle. These results from baboon uteri were compared with those using baboon oviducts and also rabbit uteri and oviducts. Unlike the rabbit tissues, the baboon oviducts and uterine tissues did not exhibit specific net accumulation of prostaglandins.

In utero bone marrow transplantation of fetal baboons with mismatched adult marrow: initial observations.

Recent advances in prenatal diagnoses of sickle cell anemia and thalassemia permit early identification of affected fetuses. However, the only intervention possible to date is abortion of the affected fetuses. Transplantation of normal marrow into fetuses in utero could correct these life-threatening disorders, but to accomplish this techniques must be developed for fetal transplantation in man. Therefore, we have transplanted fetal baboons with mismatched adult baboon bone marrow from donors that differed at the glucose phosphate isomerase locus. Twenty-two fetuses between 60 and 160 days of gestation (term gestation is 182 days) were transplanted intraperitoneally with 10(9) marrow mononuclear cells/kg body weight using an ultrasonic technique. No immunosuppressive or preparative regimen was given prior to or after transplantation, and all fetuses tolerated the procedure well. One month after transplantation fetal blood samples were obtained to assess chimerism. Three chimeras were detected among 10 fetuses transplanted at 80 days' gestation, and no chimeras were detected in fetuses greater than 80 days' gestation at the time of transplantation. All chimeras died in utero during the third trimester of pregnancy: one of an intrauterine infection at 160 days' gestation, one at 135 days' gestation and one at 145 days' gestation. In contrast, the other 19 non-chimeric fetuses survived. These data suggest: (1) in utero fetal bone marrow transplantation is technically feasible in primates; (2) that allogeneic adult bone marrow can engraft and persist for at least 1 month in fetal baboons transplanted at 80 days of gestation; and (3) that delineation of the causes for loss of fetal chimeras should prove valuable in assessing the therapeutic potential for in utero bone marrow transplantation in man.

Mixed lymphocyte culture reactivity of fetal baboons: application for in utero bone marrow transplantation.

Bone marrow transplantation offers a potential cure for patients suffering from genetic diseases such as inborn errors of metabolism. The optimal time to transplant many of these affected individuals would be early in gestation. To date, little information is available on the cellular immune reactivity of fetal primate lymphocytes. Therefore, we tested peripheral blood lymphocytes obtained in utero from baboon fetuses (Papio sp.) for their ability to respond in mixed lymphocyte culture (MLC) against their mothers, against a pool of unrelated animals, and in the case of fetuses given unrelated bone marrow transplants in utero, against their specific bone marrow donors. The majority of fetuses as young as 80 gestational days (182-day normal gestation period) were capable of responding strongly to maternal and unrelated lymphocytes in MLC. Of six fetuses that were transplanted, three did not engraft as indicated by undetectable levels of the donor-specific type B allele of glucose phosphate isomerase in fetal blood samples 1 month post-transplant. The three fetuses that did engraft all lost their grafts before birth. These data demonstrate that fetal lymphocytes obtained in utero can be tested for MLC reactivity and suggest that MLC testing can be used to select appropriate donor-recipient combinations for in utero bone marrow transplantation.

Effect of intra-amniotic administration of Exosurf in preterm rabbit fetuses.

OBJECTIVE: Currently, treatment of respiratory distress syndrome (RDS) of the preterm newborn incorporates exogenous surfactant administration. Because fetuses make breathing motions, we proposed that intra-amniotic administration of an exogenous surfactant, Exosurf, to the preterm rabbit fetus results in uptake of Exosurf into the lungs and improves pulmonary mechanical properties compared with post-delivery treated and untreated litter mates. METHODS: Ten preterm rabbit fetuses were used in a labeling study. A mixture of iron dextran and Exosurf was given in utero, and the minimum dose required to assure delivery of the mixture into the distal airways was 5 mL. In a lung function study, 30 rabbit pups received either 5 mL Exosurf in utero, 0.2 mL Exosurf post-delivery, or no treatment. Pressure-volume curves, opening pressures, and lung volumes at 50 cm H2O were compared among the three groups. RESULTS: Those rabbit pups receiving Exosurf either in utero or after delivery had significantly better pressure-volume relationships (P less than .001) and lower opening pressures (P less than .005) than the rabbit pups with no treatment. There were no differences between the animals treated intra-amniotically and post-delivery. CONCLUSIONS: Intrauterine administration of exogenous surfactant results in uptake of the surfactant solution into the lungs and alters the pulmonary characteristics of the preterm rabbit pup. Potential adverse effects of this means of surfactant administration must be evaluated further. Intrauterine surfactant delivery may provide an additional means of RDS prophylaxis in the antepartum period.

Extending the duration of active oral contraceptive pills to manage hormone withdrawal symptoms.

OBJECTIVE: To test the hypothesis that extending the number of consecutive active oral contraceptives (OC)s given will decrease the frequency of menstrual-related problems including dysmenorrhea, menorrhagia, premenstrual-type symptoms, and menstrual migraines. METHODS: A prospective analysis was designed to track the experiences of 50 women taking OCs and experiencing menstrual-related problems. Fifty consecutive patients, who were taking OCs and had symptoms during the pill-free interval, were followed in a multispecialty clinic by an individual physician and nurse practitioner team. The patients were permitted to extend the number of consecutive active OCs to delay menstrual-related symptoms. RESULTS: Immediate outcome of the 50 patients revealed 74% (37 patients) stabilized on an extended regimen of 6 to 12 weeks of consecutive days with active OCs. Twenty-six percent (13 patients) either discontinued OCs or returned to the standard regimen with 3 weeks of active pills. Of the 37 patients who were stabilized on an extended regimen, 27 have completed thus far between five and 13 extended cycles with 6-23 months of follow-up (mean 16 months). CONCLUSIONS: Experience in a series of 50 OC users with menstrual-related symptoms demonstrated that delaying menses by extending the number of consecutive days of active pills is well tolerated and efficacious. We believe that a large prospective study is warranted to further our knowledge in this area.

Total parenteral nutrition does not improve diaphragm development in premature baboons.

We hypothesized that total parenteral nutrition accelerates growth and development of diaphragm muscle (DPH) in prematurely delivered baboons (140 days gestation). For 10 days after delivery by cesarean section, we administered parenteral nutrition containing glucose, electrolytes, and water or total parenteral nutrition containing lipids, amino acids, glucose, vitamins, and electrolytes. After 10 days of care, dorsolateral and ventrolateral (VL) costal DPH were sampled for histochemically determined mean fiber area (MFA) and fiber type percentages. We determined isolated bundle isometric tension (normalized for cross-sectional area), time to peak tension, half-relaxation time, force-frequency relationship, and fatigability. Neither sex nor nutritional treatment affected contractile properties. Differences among sexes and muscle sites, but not among nutritional treatments, were observed for histochemical characteristics. In females, the VL DPH had a lower percentage of type IIo fibers and a greater MFA of type IIc fibers than the dorsolateral DPH and a lower percentage of type IIo fibers and greater MFA of type IIc and IIo fibers than the VL DPH in males. Mean fiber cross-sectional area of VL DPH was significantly greater in females than males. The larger fibers in females than males suggest a stronger DPH in females. Earlier growth of type II fibers in females could contribute to a better outcome for female than male premature infants with hyaline membrane disease.

Hormone withdrawal symptoms in oral contraceptive users.

OBJECTIVE: To measure the timing, frequency, and severity of hormone-related symptoms in oral contraceptive (OC) users, specifically to compare active-pill with hormone-free intervals. METHODS: Using daily diaries, women recorded pelvic pain, bleeding, headaches, analgesic use, nausea or vomiting, bloating or swelling, and breast tenderness during active-pill intervals and hormone-free intervals. Participants either had no prior OC use, had taken OCs and were restarting, or had been taking OCs continuously for 12 months or longer. RESULTS: Two hundred sixty-two women, 26 with no previous OC use, 43 prior users, and 193 current users, provided daily records of hormone-related symptoms. Subjects with no prior OC use and prior users restarting were similar in no recent OC use, and because of the small sample, they were pooled for analysis as new-start OC users. Current users had patterns of symptoms that were more frequent during hormone-free intervals than during the three active-pill weeks. These included pelvic pain (70% versus 21%, P < .001), headaches (70% versus 53%, P < .001), use of pain medication (69% versus 43%, P < .001), bloating or swelling (58% versus 19%, P < .001), and breast tenderness (38% versus 16%, P < .001). Similar patterns were seen in new-start OC users after the first cycle. Among new-start OC users, menstrual flow patterns, headache, bloating or swelling, and breast-tenderness symptoms decreased during the three cycles to approach those levels of current users. CONCLUSION: Almost all symptoms assessed were significantly worse during the 7-day hormone-free interval than during the 21 days of hormone-containing pills.

Oxygen delivery rate and sufficiency of oxygenation during ECMO in newborn baboons.

Minimum acceptable O2 delivery (DO2) during extracorporeal membrane oxygenation (ECMO) remains to be defined in a newborn primate model. The right atrium, carotid artery, and femoral artery were cannulated, and the ductus arteriosus, aorta, and pulmonary artery ligated in neonatal baboons (Papio cynocephalus) under a combination of ketamine, diazepam, and pancuronium. The internal jugular vein was also cannulated retrograde to the level of the occipital ridge. We measured hemoglobin, pH, arterial and venous PO2 (both from the pump circuit and from the cerebral venous site), serum lactate and bicarbonate concentrations, and pump flow, and we calculated hemoglobin saturations, (DO2), O2 consumption (VO2), systemic O2 extraction, and cerebral O2 extraction. Six baboons were studied during each of two phases of the experiment. In the first, flow rates were varied sequentially from 200 to 50 ml.kg-1.min-1 with saturation maximized. In the second, flow was maintained at 200 ml.kg-1.min-1 and saturation was reduced sequentially from 100 to 38%. VO2 fell significantly below baseline at a flow rate of 50 ml.kg-1.min-1 and a DO2 of 8 +/- 2 (SE) ml.kg-1.min-1 in phase 1 and at DO2 of 12 +/- 5 in phase 2. Both systemic and cerebral O2 extraction rose significantly at a flow of 100 ml.kg-1.min-1 and DO2 of 17 +/- 4 ml.kg-1.min-1 in phase 1, whereas neither rose with decreasing DO2 in phase 2. In fact, cerebral extraction fell significantly DO2 of 16 +/- 6 ml.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of lung injury in the pathogenesis of hyaline membrane disease in premature baboons.

To test the hypothesis that hyaline membrane disease (HMD) has a multifactorial etiology in which barotrauma plays a major role, we compared the immediate institution of high-frequency oscillatory ventilation (HFOV; 15 Hz, n = 5) with positive-pressure ventilation with positive end-expiratory pressure (PPV; n = 7) in premature baboons (140-days gestation) with HMD. Measurements of ventilation settings and physiological parameters were obtained and arterial-to-alveolar O2 (PaO2-to-PAO2) ratio and oxygenation index [(PaO2/PAO2)-to-mean airway pressure ratio (IO2)] were calculated. At death (24 h), static pressure-volume (PV) curves were performed, and phospholipids (PL) and platelet-activating factor (PAF) were measured in lung lavage fluid. Morphological inflation patterns were analyzed using a panel of standards. By design, mean airway pressure was initially higher (19 vs. 13 cmH2O) in the HFOV animals. PaO2-to-PAO2 ratio and IO2 progressively deteriorated in the PPV animals and then stabilized at significantly lower levels than with HFOV. PV curves from HFOV animals had significant increases in lung volume at maximum distending pressure, deflation volume at 10 cmH2O, and hysteresis area compared with PPV, which showed no hysteresis. Seven of seven PPV and only one of five HFOV animals had morphological findings of HMD. PL amount and composition in both groups were consistent with immaturity, even though the quantity was significantly greater in the PPV group. PAF was present (greater than or equal to 0.10 pmol) in six of seven PPV and in the only HFOV animal with HMD. We conclude that HFOV protected PL-deficient premature baboons from changes in gas exchange, lung mechanics, and morphology typical of HMD in this model.(ABSTRACT TRUNCATED AT 250 WORDS)