PubMed Health⌕ Search

Biomedical subjects

T A Merritt

Publications and source records attributed to T A Merritt.

At least 19 recordsLinked to original sources
PubMed1999

Oxidative inactivation of surfactants.

Reactive oxygen species (ROS) may play an important role in the chronic pulmonary morbidity of preterm infants. We therefore studied the magnitude and mechanisms of oxidative inactivation of a natural lung surfactant (NLS) and of two surfactants used for treatment of respiratory distress syndrome, beractant and KL4 surfactant (KL4). Incubation with Fenton reagents, 2-4 mM peroxynitrite (ONOO-) or 0.5 mM hypochlorous acid (OCl-), resulted in an increased minimum surface tension (MST) of all surfactants; the order of effect on MST was beractant > KL4 > NLS. After incubation with Fenton reagents, NLS contained a higher concentration of conjugated dienes (p < 0.01) but lower concentration of malondialdehyde (p < 0.001) than beractant. Protein carbonyl concentrations after treatment with Fenton reagents were higher in NLS and KL4 than in beractant (p < 0. 05). Surface area cycling for 24 h with 2 mM ONOO- or 0.5 mM OCl- caused both beractant and KL4 to increase the proportion of light subtypes from 8-10% to 26-29%; with Fenton reagents, there was disappearance of the light subtype and formation of ultraheavy subtype 74-91% with poor MST. Natural and therapeutic surfactants differ markedly in their sensitivity to ROS, which may be important for surfactants in therapeutic use because oxidative inactivation may limit their effect. Oxidation of natural surfactant may result in reduced function and contribute to chronic lung disease.

Animals↗
PubMed1999

A critical evaluation of clinical practice guidelines in neonatal medicine: does their use improve quality and lower costs?

Clinical practice guidelines and care pathways have become a focus of quality improvement efforts in Neonatology. Health care administrators believe that using clinical practice parameters reduces health care costs, improves quality of care, and limits malpractice liability. Practice guidelines and surveys of consumer satisfaction have grown in use partly because third-party payers, insurers, and health maintenance organizations, as well as hospital administrators bent on reducing variable costs of care and contracting for capitated care have championed their development, implementation, and monitoring. Overall there is minimal evidence-based medicine to support that neonatal outcomes have benefitted from their implementation, although some studies show affirmative effects in limited populations or in a limited number of centres. For highly autonomous physicians and nurses this standardization of medical decision making may represent a difficult transition into efforts to improve quality, based on evidence-based care, and in some instances into corporate medicine. By realigning the traditional values of patient relationships, including parent involvement, the implementation of guidelines has been fast-tracked in some institutions, without appropriate audit to determine their effectiveness in achieving their goals. However, because guidelines and clinical pathways are here to stay, neonatologists need to think critically about how their content and method of implementation, monitoring and modification may influence medical and nursing teaching and decision making in the future. If guidelines are introduced primarily as a cost savings or containment tool that ignores their impact on the quality of medical care and thereby restricts needed care, then neonatologists must be quick to challenge the potentially damaging and inappropriate use of guidelines and care pathways. Several international efforts are underway to study both the impact of evidence-based guidelines and to determine if they can be imported from one care system into another. Furthermore, there are many medico-legal implications of guideline and clinical pathway implementation that may not favour physicians and other neonatal care practitioners, and leave to hospitals, insurers, and ultimately the courts, decisions regarding evidence-based care. Neonatologists and other practitioners in neonatal care centres should critically analyse the goals of guideline development, implementation and monitoring and should restrict themselves to guideline directed care only at those practices for which there is evidence supporting their implementation and continuous monitoring.

Consumer Behavior↗
PubMed1998

Intensive lifestyle changes for reversal of coronary heart disease.

CONTEXT: The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year. OBJECTIVES: To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes (without lipid-lowering drugs) on coronary heart disease. DESIGN: Randomized controlled trial conducted from 1986 to 1992 using a randomized invitational design. PATIENTS: Forty-eight patients with moderate to severe coronary heart disease were randomized to an intensive lifestyle change group or to a usual-care control group, and 35 completed the 5-year follow-up quantitative coronary arteriography. SETTING: Two tertiary care university medical centers. INTERVENTION: Intensive lifestyle changes (10% fat whole foods vegetarian diet, aerobic exercise, stress management training, smoking cessation, group psychosocial support) for 5 years. MAIN OUTCOME MEASURES: Adherence to intensive lifestyle changes, changes in coronary artery percent diameter stenosis, and cardiac events. RESULTS: Experimental group patients (20 [71%] of 28 patients completed 5-year follow-up) made and maintained comprehensive lifestyle changes for 5 years, whereas control group patients (15 [75%] of 20 patients completed 5-year follow-up) made more moderate changes. In the experimental group, the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year (a 4.5% relative improvement) and by 3.1 absolute percentage points after 5 years (a 7.9% relative improvement). In contrast, the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year (a 5.4% relative worsening) and by 11.8 percentage points after 5 years (a 27.7% relative worsening) (P=.001 between groups. Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up (risk ratio for any event for the control group, 2.47 [95% confidence interval, 1.48-4.20]). CONCLUSIONS: More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group. In contrast, in the control group, coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred.

Aged↗
PubMed1998

Inhibitory effects of oxyradicals on surfactant function: utilizing in vitro Fenton reaction.

The inhibitory effects of reactive oxygen species (ROS) on the surface tension-lowering abilities of three surfactants were compared: natural lung surfactant (NLS), KL4 surfactant containing synthetic peptide resembling the hydrophobic/hydrophilic domains of SP-B in an aqueous dispersion of phospholipids, and Survanta (SUR) containing SP-B and SP-C. The inhibitory concentrations of Fenton reactants (i.e. 0.65 mM FeCl2, 0.65 mM EDTA, 30 mM H2O2), deduced from dose-response plots of FeCl2 on minimum surface tension (MST) of SUR, were used to assess the Fenton effect on biophysical properties of various surfactants. Neither H2O2 (30 mM) nor FeCl2 with EDTA (both 0.65 mM) alone affected surfactant function, but when mixed together significantly increased (p < 0.01) the MST of SUR compared with KL4 (p < 0.05) in a FeCl2 concentration-dependent manner. This effect on NLS was not significant (p = 0.05) at similar phospholipid concentrations. Also, the range of increases in surface adsorption in mN/m at equilibrium surface tension (EST) was 27-40 for SUR, 36-44 for KL4, and 24-25 for NLS. We speculate that the presence of SP-A and the catalase content in NLS may have protective effects on inactivation of NLS by ROS. We conclude that the in vitro Fenton effect could be a valuable test system for comparing the inactivation range of surfactants by oxyradicals.

Animals↗
PubMed1998

Bronchoalveolar lavage with KL4-surfactant in models of meconium aspiration syndrome.

As a model of the meconium aspiration syndrome (MAS) of human infants, adult rabbits and newborn rhesus monkeys received intratracheal instillation of human meconium to induce pulmonary injury. Injured rabbits were ventilated with 100% O2 and divided into four treatment groups, receiving: 1) bronchoalveolar lavages (BAL) with dilute KL4-Surfactant; 2) lavages with equal volumes of sterile saline; 3) a single intratracheal bolus of KL4-Surfactant, 100 mg/kg; and 4) no treatment. The untreated rabbits developed atelectasis, a fall in pressure-volume levels and in partial pressure of O2 in arterial blood (PaO2) from approximately 500 to < 100 mm Hg, and severe pulmonary inflammation between 3 and 5 h after instillation of meconium. Rabbits treated by BAL with dilute KL4-Surfactant showed rapid and sustained recovery of PaO2 to approximately 300 mm Hg within minutes, a return toward normal pressure-volume levels, and diminished inflammation. Rabbits receiving BAL with saline failed to show recovery, and rabbits treated with a bolus of surfactant intratracheally exhibited a transient response by 1-2 h after treatment, but then returned to the initial atelectatic state. Newborn rhesus monkeys, after receiving human meconium intratracheally before the first breath, developed severe loss of pulmonary function. Treatment of these monkeys 1-5 h after birth with BAL with dilute KL4-Surfactant produced clearing of chest radiographs and a rapid improvement in pulmonary function with ratios of partial pressure of O2 in arterial blood to the fraction of O2 in the inspired air rising into the normal range where they remained through the 20-h period of study. The studies indicate that pulmonary function in two models of severe meconium injury respond rapidly to BAL with dilute KL4-Surfactant.

Animals↗
PubMed1998

Early discharge of premature infants. A critical analysis.

Although significant advances in the medical management of acutely ill preterm infants have resulted in unprecedented rates of survival, issues surrounding the convalescent care, discharge preparation, and readiness of parents or other caregivers have been less well studied and represent the art of medicine. Recent consensus statements provide a degree of content validity; however, important areas of scientific inquiry remain. Much is left to understand about the pathophysiology, management, and outcomes of apnea, bradycardia, and oxygen desaturation episodes continuing at term. Why do the most immature infants have a delay in the maturation of respiratory control? Do breathing studies really provide information that predicts subsequent respiratory control abnormalities? If methylxanthines are used at discharge, what criteria should be adhered to regarding their discontinuation? How is nutrition best provided while transitioning to home? In infants whose mothers desire exclusive breast-feeding, should gavage feeds be used to supplement in order to avoid bottle-feedings? How long should breast milk be fortified, and when should supplemented artificial milks be used and for what period of time postdischarge should these more expensive special-discharge artificial milks be used? What other supplements, such as inositol, vitamins, or antioxidants, should be provided in order to achieve optimal growth and development? Technology-dependent infants pose even greater complexities. Some infants and families adapt to extensive use of technology in the home. In other situations, basic infant care is difficult to achieve. What are the essential components for successful early discharge, and how can the studies involving selected families be made universal? How can NICUs better prepare fathers and mothers for premature parenthood? To what extent are we overwhelming families with additional responsibilities and expectations that may compromise their competency in basic parenting? Furthermore, the degree of provider variation in evaluating and providing for discharge planning is now being more carefully studied. In some circumstances, integrated teams in the NICU have facilitated the discharge process saving days of hospitalization, whereas in others adherence to discharge planning guidelines has lengthened the stay in the NICU and resulted in higher costs. What is the ideal system for achieving coordination of care without co-opting parental choices in assuming more care responsibility than is comfortable? In the design of tertiary care facilities, more attention to space for rooming-in experiences needs to receive greater priority. Furthermore, because of intensity of care, adverse environmental stimuli, and for issues of better resource utilization, should not most previously ill infants be discharged from level II or intermediate care centers? Finally, issues of increasing decision-making responsibility placed on parents (with the reassurance and guiding hand of dedicated physicians and nurses focused on individual infants) must never be made subservient to the economic whims of insurers to decrease costs without understanding the value of the entirety of the care process for critical illness, through convalescence, to it is hoped a supportive and nurturing environment in the home. Our patients deserve no less. The questions posed present a sample of issues yet to be scientifically addressed. These and many other questions need to be answered before we fully understand the optimal process of discharge for the preterm infant.

Humans↗
PubMed1997

Characterization of surfactant subtypes of beractant and a synthetic peptide containing surfactant KL4 following surface area cycling and addition of fibrinogen.

Surfactant is not a homogeneous material and can be separated into subtypes. Subtype conversion is clinically important because it is thought to occur naturally and because surface activity varies depending on the subtype. Fibrinogen, a naturally occurring serum protein, is known to affect this conversion. In this study we studied two surfactants, beractant and KL4, to examine their subtype characteristics. Surface area cycling, an in vitro method, was used in conjunction with sucrose gradient ultracentrifugation to separate subtypes in both surfactants. Activity, expressed as minimum surface tension of these subtypes, was measured using a pulsating bubble surfactometer. The effect of fibrinogen on subtype conversion and subsequent change in activity was elucidated. Our results indicate that following surface area cycling, beractant and KL4 have different subtypes and different responses to fibrinogen. Cycling of beractant resulted in two bands, representing a heavy and a light subtype. In the presence of fibrinogen, cycling resulted in two separate heavy subtypes. Cycling of KL4 surfactant also yielded light and heavy subtypes. However, in the presence of fibrinogen, cycling of KL4 resulted in ultraheavy subtypes. These ultraheavy subtypes retained minimum surface tension comparable to that of native KL4 surfactant. We conclude that these two surfactant preparations have different subtype conversions when subjected to surface area cycling and in the presence of fibrinogen. These conversions result in different activities toward lowering surface tension. We speculate that endogenous fibrinogen will also affect these two surfactants differently in vivo and thus affect their clinical effectiveness.

Biological Products↗
PubMed1997

Recombinant human superoxide dismutase reduces lung injury caused by inhaled nitric oxide and hyperoxia.

We previously demonstrated that 48 h of 100 ppm inhaled nitric oxide (NO) and 90% O2 causes surfactant dysfunction and pulmonary inflammation in mechanically ventilated newborn piglets. Because peroxynitrite (the product of NO and superoxide) is thought to play a major role in the injury process, recombinant human superoxide dismutase (rhSOD, a scavenger of superoxide) might minimize this insult. Four groups of newborn piglets (1-3 days of age) were ventilated with 100 ppm NO and 90% O2 for 48 h. Piglets received no drug, 5 mg/kg rhSOD intratracheally at time 0, 5 mg/kg rhSOD intratracheally at 0 and 24 h, or 10 mg/kg rhSOD by nebulization at time 0. At 48 h, bronchoalveolar lavage (BAL) was performed, and lung tissue was analyzed for markers of inflammation, oxidative injury, acute lung injury, and surfactant function. There were significant differences between rhSOD-treated piglets and untreated controls with respect to BAL neutrophil chemotactic activity, cell counts, and protein concentration as well as lung tissue malondialdehyde concentrations. Minimum surface tension of BAL surfactant from all groups studied was increased, with no differences found among groups. These data suggest that rhSOD, at the doses used, mitigated the inflammatory changes, oxidative damage, and acute lung injury from exposure to 100 ppm NO and 90% O2 but did not appear to improve surfactant function. This has important clinical implications for infants treated with hyperoxia and NO for neonatal lung disorders.

Administration, Inhalation↗
PubMed1997

Clinical practice guidelines in pediatric and newborn medicine: implications for their use in practice.

Clinical practice guidelines are becoming pervasive in pediatrics and newborn medicine. They have spanned a wide range of primary care practice parameters from treating otitis media with effusion, to performing complex surgery for congenital heart disease, and management of respiratory distress syndrome and coordinating discharge from the neonatal intensive care unit. Administrators believe that using clinical practice parameters reduces health care costs, improves quality of care, and limits malpractice liability. Practice parameters and guidelines have grown in use because powerful interests-third-party payers, insurers, and health maintenance organizations, as well as hospital administrators bent on reducing variable costs of care and contracting for capitated care-champion their development, implementation, and monitoring. Economic credentialing of physicians with excessive variances without risk-adjusting for other than average patients is problematic and remains unchecked partly because of the fundamental characteristics of the evolving health care industry in which costs are more easily measured than quality. For highly autonomus physicians this standardization of medical decision making may represent a difficult transition into corporate practice by realigning traditional values of the doctor-patient relationship. However, because guidelines are almost certainly here to stay, pediatricians and neonatologists need to think critically about how their content and method of implementation, monitoring, and modification may influence medical teaching and decision making in the future. If guidelines are introduced primarily as a cost savings or containment tool that ignores the impact on the quality of care and restricts necessary care for infants and children, especially those with chronic illness or who are developmentally at risk, then neonatologists and pediatricians must be quick and determined to challenge the potentially damaging use of practice parameters or guidelines. Furthermore, there are many medicolegal implications of guideline implementation that may not favor physicians and leave to hospitals, insurers, and ultimately the courts decisions regarding evidence-based practice. In this review article, we pay special attention to the guidelines developed in newborn medicine. We discuss why and how guidelines are developed and critically evaluate the available evidence describing potential benefits and drawbacks of guidelines in general. There are legal implications to the implementation of guidelines, and guidelines may increase provider susceptibility to malpractice allegations. Neonatologists and pediatricians should critically analyze the following questions when guidelines are being developed: Are clinical practice parameters the most effective means to reduce the costs of health care, or improve the quality of health care services while reducing the need for and protecting physicians from malpractice suits? Or do clinical practice guidelines more closely resemble an audit system developed by health care organizations, insurers, and others including government-sponsored health care to appease powerful interests-with limited evidence for promise and perhaps potential negative cost, quality, and malpractice liability implications? In pediatric and newborn medicine there is limited evidence that guidelines have achieved the desired goals and further analysis of their process of care and the costs of implementation is warranted.

Health Services↗
PubMed1997

High endothelin-1 in the airways of preterm infants is associated with less severe respiratory distress during the early postnatal period.

OBJECTIVE: To study the relationship between endothelin-1 (ET-1) in the airways and respiratory distress in preterm infants. METHODS: ET-1 was determined in 60 tracheal aspirates from 11 preterm intubated infants (gestational age 28.0 +/- 2.5 weeks) during the first week of life. RESULTS: The concentration of ET-1 of the aspirates was 6 to 2760 pg/mL (median 293 pg/mL). Negative correlations existed between mean log ET-1 and mean airway pressure (R2 = .812) and fraction of inspired oxygen (R2 = .591), whereas a positive correlation was found between the arteriolar/alveolar oxygenation ratio within 3 hours of birth and mean log ET-1 on the first day (R2 = .555). CONCLUSION: The association of high ET-1 in the airways with less severe respiratory distress in the early postnatal period may be attributable to effects of ET-1 on surfactant secretion or development of airway epithelium.

Endothelin-1↗
PubMed1996

Effect of N-nitroso-N-methylurethane on gas exchange, lung compliance, and surfactant function of rabbits.

OBJECTIVES: To define the effect of N-nitroso-N-methyl-urethane (NNNMU) on pulmonary gas exchange, compliance and the biochemical and functional properties of the lung surfactant system. DESIGN: Four days after inducing lung injury, gas exchange and pulmonary compliance were studied and a bronchoalveolar lavage was taken. SETTING: Experimental laboratory of a university department of medicine, division of pulmonary and critical care medicine. ANIMALS: Ten rabbits after they had received an injection of NNNMU and five control animals. INTERVENTIONS: Controlled mechanical ventilation and bronchoalveolar lavage. MEASUREMENTS AND RESULTS: Measurements of gas exchange (using the multiple inert gas elimination technique), hemodynamics and pulmonary compliance were performed during ventilatory and hemodynamic steady state. A bronchoalveolar lavage (BAL) was taken after sacrificing the animal. BAL samples were processed for cell count and biochemical and functional surfactant analysis. Animals injected with NNNMU developed mild, but significant reduction in PaO2, while maintaining eucapnia during spontaneous air breathing. V/Q distributions and arterial blood gases were similar in all animals when ventilated mechanically with a fixed tidal volume. Compliance of the lung and phospholipid levels in lavage of NNNMU animals was significantly lower than in control animals (CON). Function of surfactant recovered from animals receiving NNNMU was decreased significantly where compared to CON. Thus, NNNMU resulted in a lowered lavage surfactant phospholipid content, impaired surfactant function, decreased compliance and hypoxemia during spontaneous ventilation. However, gas exchange was similar to that of control animals during mechanical ventilation. CONCLUSION: We conclude that NNNMU-induced gas exchange abnormalities present after 4 days are mild and are reversed by fixed volume mechanical ventilation despite marked alteration in surfactant function and lung compliance. These observations further define properties of a lung injury model that is of value in the study of surfactant replacement.

Animals↗
PubMed1996

Adrenocortical function in the very low birth weight infant: improved testing sensitivity and association with neonatal outcome.

OBJECTIVE: To evaluate adrenocortical function in ill preterm infants and investigate potential relationships between plasma cortisol concentrations and major neonatal outcomes. STUDY DESIGN: Randomized trial of adrenocorticotropic hormone (1-24ACTH) stimulation testing, followed by a chart review. SETTING: Two level III neonatal intensive care units, Sacramento, Calif. PARTICIPANTS: Sixty-seven very low birth weight infants, born at 32 weeks of gestation or earlier weighing 1500 gm or less, who had endotracheal intubation and indwelling arterial access. RESULTS: Most infants (76%) had baseline cortisol concentrations < 414 nmol/L (15.0 micrograms/dl), and of those, only 36% responded to stimulation with 1-24ACTH, 0.1 microgram/kg. Raising the 1-24ACTH dose to 0.2 microgram/kg resulted in a response rate of 67% (p = 0.09) but decreased the sensitivity of the test. An elevated mean 11-deoxycortisol/cortisol ratio indicated that decreased 11 beta-hydroxylase activity may limit cortisol production in some infants. Infants with baseline cortisol concentrations less than 414 nmol/L (15.0 micrograms/dl) were more likely to have chronic lung disease (p < 0.002) and less likely to have severe intraventricular hemorrhage (p < 0.02). Response to 1-24ACTH was not associated with a detectable difference in outcome. CONCLUSION: Many very low birth weight infants have low cortisol and ACTH concentrations and are unable to mount a cortisol response to physiologic doses (0.1 microgram/kg) of 1-24ACTH. These findings suggest that delayed maturation of adrenal response may result in physiologically inadequate cortisol concentrations in stressed very low birth weight infants. This delayed maturation may contribute to the development of chronic lung disease.

Adrenocorticotropic Hormone↗
PubMed1996

The efficacy and safety of KL4-surfactant in preterm infants with respiratory distress syndrome.

The present study was undertaken to determine if a synthetic peptide, KLLLLKLLLLKLLLLKLLLLK (KL4), in which K = lysine and L = leucine, in an aqueous dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and improve gas exchange in premature human infants with respiratory distress syndrome (RDS). The KL4 peptide was synthesized to resemble the amino acid pattern of surfactant protein B (SP-B). Forty-seven infants with RDS were treated within 4 h of birth with the KL4-peptide/phospholipid mixture, called KL4-Surfactant. The average arterial-to-alveolar oxygen tension ratios (a/A O2) of 39 patients included in efficacy analyses rose from pretreatment values of 0.14 +/- 0.02 (mean +/- SEM) to 0.40 +/- 0.04 (normal value > or = 0.40) by 12 h of age. Mean airway pressures and oxygenation index values fell concomitantly, and expansion of the lungs was observed on radiographs. The median duration of mechanical ventilation was 5.0 d. Of the 39 included infants, 29 required only a single dose. Radiographic data indicate that those patients requiring a second instillation of KL4-Surfactant but not showing a sustained rise in a/A O2 ratios did, in fact, exhibit expansion of alveoli in the lung. There were no RDS-related deaths; the incidence of complications was no higher than found in other comparable published studies. The data demonstrate that the synthetic peptide, KL4, which mimics the hydrophobic and hydrophilic pattern of SP-B, when formulated in an aqueous dispersion with the phospholipids DPPC and POPG, creates a strong and durable surfactant activity as judged by expansion of pulmonary alveoli and improvement of gas exchange in infants with RDS.

Age Factors↗
PubMed1996

Efficacy of synthetic peptide-containing surfactant in the treatment of respiratory distress syndrome in preterm infant rhesus monkeys.

Studies were conducted to assess the efficacy and safety of a synthetic peptide-containing surfactant in the treatment of respiratory distress syndrome (RDS) in preterm (approximately 80% of normal gestation) infant rhesus monkeys. Surfactant was prepared consisting of the phospholipids dipalmitoylphosphatidyl choline and palmitoyl-oleoyl phosphatidyl glycerol and a synthetic peptide modeled after surfactant protein B (SP-B), "KL4-Surfactant" contained a peptide having the sequence KLLLLKLLLLKLLLLKLLLLK, where "K" is lysine and "L" is leucine. The peptide was selected because it mimics the repeating stretches of hydrophobic residues with intermittent basic hydrophilic residues seen in SP-B. KL4-Surfactant was shown to have biophysical activity assessed as the ability to lower surface tension at an air-liquid interface in a pulsating bubble surfactometer. Thirty premature rhesus monkeys were treated shortly after birth with one dose of KL4-Surfactant. The arterial to alveolar oxygen partial pressure ratio (a/A) was found to rise from a pretreatment level of 0.11 +/- 0.01 (mean +/- SEM), indicative of severe RDS, to 0.40 +/- 0.02 at 12-13 h post-treatment. The improvement in oxygenation persisted throughout the study period, with a mean a/A at 22-23 h of 0.45 +/- 0.07. Chest radiographs and gross and microscopic examination of the lungs all confirmed the reversal of the atelectasis seen before treatment. Animals treated with a dose of 200 mg/kg showed a faster, more consistent, and greater response than did a group treated with an average dose of 127 mg/kg. There was no evidence of toxicity after treatment with the higher dose as demonstrated by physiologic, hematologic, biochemical, and pathologic data. The importance of the peptide in the synthetic surfactant was apparent from the results obtained with a control group of nine premature monkeys treated with a non-peptide-containing surfactant; the a/A of this group was 0.15 +/- 0.03 at nine hours of age as compared with a value of 0.38 +/- 0.02 for 30 comparable animals receiving KL4-Surfactant.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Comparative effects of some serum components and proteolytic products of fibrinogen on surface tension-lowering abilities of beractant and a synthetic peptide containing surfactant KL4.

The serum components of C-reactive protein, lysophosphati-dylcholine, fibrinogen, and fibrinogen proteolytic products have been shown to reduce surface tension-lowering abilities of lung surfactant. The inhibitory effects of these serum components were compared among four different surfactants: natural lung surfactant, a phospholipid mixture that had no surfactant proteins, KL4 surfactant which has a synthetic surfactant protein B (SP-B)-like peptide, and beractant (BER) which has both SP-B and SP-C. The pulsating bubble surfactometer was used to measure the surface tension of these surfactants after the addition of inhibitors. Inhibition of BER and KL4 surfactant was observed with some serum components within 1 min of pulsation, but was reversed after 3 min of pulsation for KL4 surfactant and to a lesser extent with BER. The surface tension of phospholipid mixture alone was significantly increased and did not improve with further pulsations. Natural lung surfactant was least inhibited and was affected only at very high fibrinogen concentrations (5 mg/mL). At identical concentrations of these inhibitors, KL4 surfactant was inhibited less compared with BER. We conclude that the response of a lung surfactant to inhibitory agents may depend on the presence or absence of surfactant-related protein(s) in the surfactant and the concentration of exogenous surfactant used. KL4 surfactant, which has a synthetic peptide in lieu of SP-B, resists inhibition to these serum components more than BER at similar phospholipid concentrations.

Amino Acid Sequence↗