PubMed HealthSearch

Biomedical subjects

W A Carlo

Publications and source records attributed to W A Carlo.

At least 19 recordsLinked to original sources

Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome.

OBJECTIVES: To examine the safety and pharmacokinetics of multiple intratracheal (IT) doses of recombinant human CuZn superoxide dismutase (rhSOD) in premature infants with respiratory distress syndrome who are at risk for developing bronchopulmonary dysplasia (BPD). Methods. Thirty-three infants (700 to 1300 g) were randomized and blindly received saline, 2.5 mg/kg or 5 mg/kg rhSOD IT within 2 hours of surfactant administration. Infants were treated every 48 hours (as long as endotracheal intubation was required) up to 7 doses. Serial blood and urine studies, chest radiographs, neurosonograms, SOD concentration and activity measurements, and tracheal aspirate (TA) inflammatory markers were assessed throughout the 28-day study. RESULTS: SOD concentrations in serum (0.1 [0.05/0.15] microg/mL-geometric mean with lower/upper confidence intervals), tracheal aspirates (TA) (0.2 [0.1/0.3] microg/mL) and urine (0.3 [0.2/0.4] microg/mL) were similar at baseline in all 3 groups and did not change significantly in the placebo group. In the rhSOD treatment groups, SOD concentrations were increased on day 3 and did not change significantly thereafter over the 14-day dosing period (also measured on days 5, 7, and 13). SOD concentrations averaged 0.4 [0.3/0.5] microg/mL in serum, 0.8 [0.6/1.2] microg/mL in TA and 1.1 [1.0/1.3] microg/mL in urine for the low-dose group and 0.6 [0.5/0.7] microg/mL in serum, 1.1 [0.9/1.5] microg/mL in TA, and 2.2 [1.6/2.9] microg/mL in urine for the high-dose group over the 14-day dosing period. Enzyme activity directly correlated with SOD concentration and rhSOD was active even when excreted in urine. TA markers of acute lung injury (neutrophil chemotactic activity, albumin concentration) were lower in the rhSOD agroups compared with placebo. No significant differences in any clinical outcome variable were noted between groups. CONCLUSIONS: These data indicate that multiple IT doses of rhSOD increase the concentration and activity of the enzyme in serum, TA and urine, reduce TA lung injury markers and are well-tolerated. Further clinical trials examining the efficacy of rhSOD in the prevention of BPD are warranted.

Analysis of Variance

Comparison of Infasurf (calf lung surfactant extract) to Survanta (Beractant) in the treatment and prevention of respiratory distress syndrome.

OBJECTIVE: To compare the relative safety and efficacy of Infasurf (calf lung surfactant extract; ONY, Inc, Amherst, NY, IND #27169) versus Survanta (Beractant, Ross Laboratories, Columbus, OH) in reducing the acute severity of respiratory distress syndrome (RDS) when given at birth and to infants with established RDS. DESIGN: A prospective, randomized, double-blind, multicenter clinical trial. SETTING: Thirteen neonatal intensive care units participated in the treatment arm: seven of these concurrently participated in the prevention arm. PATIENTS: The treatment arm enrolled infants of </=2000 g birth weight with established RDS, and the prevention arm enrolled infants of </=29 weeks' gestation with birth weights <1250 g. INTERVENTION: Infants were randomly assigned to receive Infasurf (n = 303, treatment arm; n = 180, prevention arm) or Survanta (n = 305, treatment arm; n = 194, prevention arm) in accordance with the Survanta package insert instructions. OUTCOME MEASURES: We projected a 25% reduction between groups in the need for a third dose of surfactant for infants with established RDS, and a 25% reduction in the need for a second dose of surfactant for infants who received prophylactic surfactant. Secondary outcomes included the severity of RDS measured by inspired oxygen concentrations and mean airway pressure, air leaks, complications associated with surfactant administration, and survival to 36 weeks' postmenstrual age without the need for oxygen supplementation. RESULTS: In the treatment arm, there was no difference between groups in the number of infants requiring more than two doses of surfactant. The interval between doses was significantly longer for Infasurf, suggesting an increased duration of treatment effect. The inspired oxygen concentration and mean airway pressure were lower in the Infasurf infants during the first 48 hours in the treatment arm. In the prevention arm, there were no differences with respect to the number of surfactant doses. The dosing intervals were longer for Infasurf infants after the second dose. No difference in inspired oxygen or mean airway pressure was noted during the first 72 hours. There were no significant differences in the incidence of air leaks, complications associated with dosing, complications of prematurity, mortality, or survival without chronic lung disease in the prevention or treatment arm. CONCLUSIONS: Infants treated with Infasurf have a modest benefit in the acute phase of RDS. Infasurf seems to produce a longer duration of effect than Survanta.

Age Factors

Inhaled nitric oxide in term infants with hypoxemic respiratory failure.

OBJECTIVE: To determine whether inhaled nitric oxide (NO) administered during conventional mechanical ventilation could produce improvements in oxygenation and reduce the incidence of meeting extracorporeal membrane oxygenation (ECMO) criteria in infants with hypoxemia. DESIGN: Prospective, randomized, controlled trial. Enrolled infants were assigned to conventional treatment with or without adjunctive inhaled NO. Control infants meeting failure criteria (partial pressure of arterial oxygen (PaO2)<80 mm Hg (10.7 kPa)) were allowed to cross over. Caregivers were not masked to group assignment. SETTING: Neonatal intensive care units at the University of Alabama Hospital and the Children's Hospital of Alabama, October 1993 to May 1994. PATIENTS: Newborn infants, both term and near-term, with PaO2 less than 100 mm Hg (13.3 kPa) who were receiving mechanical ventilation with 100% oxygen. Exclusion criteria included major congenital anomalies, diaphragmatic hernia, profound asphyxia, and significant bleeding. INTERVENTIONS: Inhaled NO was initiated in the NO group at a dose of 20 to 40 ppm and advanced stepwise to 80 ppm if PaO2 remained less than 100 mm Hg (13.3 kPa). OUTCOME MEASURES: Primary outcome variables were treatment failure and meeting of ECMO criteria before crossover. Improvement in oxygenation and ultimate use of ECMO or high-frequency oscillatory ventilation were secondary outcome variables. RESULTS: Seventeen neonates with hypoxemia were enrolled; 16 had echocardiographic evidence of pulmonary hypertension, and eight had extrapulmonary shunting. At 1 hour of treatment, two infants in the NO group responded with increases in PaO2 of more than 100 mm Hg (13.3 kPa); after crossover, two had increases in PaO2 of more than 10 mm Hg (1.3 kPa) and one control infant had an increase in PaO2 of more than 10 mm Hg (1.3 kPa). All control infants met failure criteria and crossed over to receive NO; two had increases in PaO2 of more than 10 mm Hg (1.3 kPa) with NO treatment. Despite initial responses, all subjects in both groups eventually met failure criteria. There were no differences between groups in primary outcome variables. CONCLUSIONS: Although inhaled NO produced a transient improvement in oxygenation in some infants, it did not reduce the incidence of meeting ECMO criteria in this population.

Administration, Inhalation

The role of nitric oxide in the treatment of neonatal pulmonary hypertension.

Nitric oxide production appears to be decreased in infants with persistent pulmonary hypertension (PPHN). Inhaled nitric oxide may improve oxygenation by two mechanisms: increased pulmonary blood flow and improved ventilation-perfusion matching. Nitric oxide inhalation has been tested in newborns with PPHN, congenital heart diseases, and bronchopulmonary dysplasia. We present a review of the articles concerning inhaled nitric oxide for infants with PPHN. Overall, 59% of the neonates had an initial improvement in oxygenation in response to nitric oxide inhalation. A sustained response was observed in 60% of the infants. Patients with extrapulmonary shunting, clear chest radiographs, and adequate lung volume seem to have a better response, whereas patients with congenital diaphragmatic hernia, severe sepsis, and alveolar capillary dysplasia are more likely to fail. To define the benefit-risk ratio, six prospective randomized trials are currently in progress.

Animals

Clinical surfactant preparations mediate SOD and catalase uptake by type II cells and lung tissue.

Pulmonary surfactant mixtures are rapidly taken up by alveolar type II cells and thus may serve as vectors for the pulmonary delivery of antioxidant enzymes to the alveolar epithelium. We prepared emulsions of Survanta with superoxide dismutase (CuZn-SOD) and catalase and quantified their cellular uptake both in vitro and in vivo. Incubations of fetal lung epithelial cells with an emulsion of Survanta plus SOD and catalase mixtures resulted in significant augmentation of SOD and catalase activities (12.8 +/- 4.6 U SOD/microgram DNA; 7.49 +/- 2.21 U catalase/microgram DNA). These numbers were significantly greater than those obtained in controls (1.8 U SOD/microgram DNA; 0.55 +/- 0.52 U catalase/microgram DNA, Survanta alone (0.43 U SOD/microgram DNA; 0.16 U catalase/microgram DNA), and SOD and catalase alone (3.47 +/- 5.2 U SOD/microgram DNA; 4.24 +/- 3.0 U catalase/microgram DNA). Intratracheal instillation of the Survanta plus SOD and catalase mixture resulted in significant augmentation of enzymes by the rat lung homogenates. Confocal microscopic analysis revealed the presence of antioxidant enzymes in the cytoplasm of epithelial cells. We concluded that Survanta supplementation, in addition to replenishing surfactant stores, can also enhance the delivery of antioxidant enzymes to alveolar epithelium both in vitro and in vivo.

Animals

Carotid bodies and ventilatory response to hypoxia in aminophylline-treated piglets.

Peripheral chemoreceptors may be immature in neonatal animals, exhibiting maturational changes in the perinatal period. Even though methylxanthines are respiratory stimulants, many premature neonates do not respond to them. Thus, we hypothesized that carotid body activity is necessary for aminophylline to reverse hypoxia-induced respiratory depression. We exposed 16 anesthetized newborn piglets (age 2-7 days) to hypoxia (inhalation of 12% oxygen) for 5 min. Aminophylline (15 mg/kg iv) was administered either prior to (11 piglets) or following (5 piglets) carotid body denervation (CBD). Before CBD, hypoxia elicited transient initial increases in tidal volume (from 79 +/- 4 to 99 +/- 1% of maximum, mean +/- SE), minute ventilation (from 64 +/- 5 to 93 +/- 4%), and peak phrenic electroneurogram (from 63 +/- 8 to 91 +/- 6%, all P < 0.05). This was followed by a decrease in tidal volume, minute ventilation and phrenic electroneurogram (all P < 0.05). Prior to CBD, aminophylline pretreatment prevented the decrease in all the measures of respiratory output during late hypoxia. After CBD, hypoxia induced an initial and sustained depression of ventilation (tidal volume from 100 to 33 +/- 14%; frequency from 94 +/- 4 to 42 +/- 17%; minute ventilation from 100 to 32 +/- 14%, all P < 0.05) and phrenic electroneurogram (peak phrenic from 100 to 47 +/- 18%; minute phrenic from 85 +/- 6 to 55 +/- 21%, both P < 0.05). Administration of aminophylline after CBD did not prevent the profound respiratory depression elicited by hypoxia in the chemodenervated piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline

Interaction of surfactant mixtures with reactive oxygen and nitrogen species.

Increased concentrations of partially reduced oxygen and nitrogen reactive species damage the alveolar epithelium and either cause or exacerbate surfactant deficiency. For this reason, there is a quest to identify surfactant replacement mixtures, which in addition to repleting depleted surfactant stores can also reduce the steady-state concentrations of reactive species in the alveolar space. Herein, we evaluated the ability of natural lung surfactant (NLS) and two mixtures (Exosurf and Survanta) used clinically for the correction of surfactant deficiency to scavenge hydroxyl radical-type species (.OH), generated either by the decomposition of peroxynitrite or by Fenton reagents (FeCl3 + H2O2). Exosurf or Survanta decreased .OH only when present at high lipid concentrations (6.5 mM). On the other hand, 40 microM of NLS decreased .OH concentrations from 75 +/- 2 to 53 +/- 2 microM (P < 0.05), most likely because of the interaction of .OH with protein sulfhydryl groups. Similarly, 40 microM of NLS incubated with a bolus of H2O2 (400 microM) decreased the H2O2 concentration in the supernatant by approximately 50%, due to the presence of catalase-type activity. In contrast to NLS, neither Exosurf nor Survanta scavenged H2O2, even when present at millimolar lipid concentrations. We concluded that Exosurf and Survanta contain limited antioxidant activity compared with NLS.

Animals

Access to neonatal intensive care for low-birthweight infants: the role of maternal characteristics.

OBJECTIVES: This study assessed the impact of mother's race, insurance status, and use of prenatal care on very low birthweight infant delivery in or transfer to hospitals with neonatal intensive care units (ICUs). METHODS: Multivariate analysis of Alabama vital statistics records between 1988 and 1990 for infants weighing 500 to 1499 g was conducted, comparing hospital of birth and maternal and infant transfer status, and controlling for infant birthweight and for maternal pregnancy history and demographic characteristics. RESULTS: With other factors adjusted for, non-White mothers with early prenatal care were more likely than White mothers to deliver their very low birthweight infants in hospitals with neonatal ICUs without transfer. Among the mothers who presented first at hospitals without such facilities, those who had late prenatal care were less likely than those with early care to be transferred to hospitals with neonatal ICUs before delivery. Medicaid coverage increased the likelihood of antenatal transfer for White women. Likelihood of infant transfer was not associated with these maternal characteristics. CONCLUSIONS: Maternal race, prenatal care use, and insurance status may influence the likelihood that very low birthweight infants will have access to neonatal intensive care. Interventions to improve perinatal regionalization should address individual and system barriers to the timely referral of high-risk mothers.

Adolescent

Comparison of perceived and actual rates of survival and freedom from handicap in premature infants.

OBJECTIVE: Our goal was to learn whether physicians delivering obstetric care accurately estimated rates of survival and freedom from handicap in premature infants. STUDY DESIGN: We surveyed by mail 409 obstetricians and general and family physicians reported to perform deliveries in Alabama to identify their perceptions regarding survival and handicap-free rates of infants born at gestational ages between 23 and 36 weeks, inclusive. Responses were compared with published national rates of survival and freedom from handicap by means of unpaired t tests. RESULTS: A total of 224 physicians responded (55%), and 183 were still practicing obstetrics. They significantly underestimated survival rates from 23 through 34 weeks' gestation (p < 0.05) and freedom from serious handicap from 23 through 36 weeks' gestation (p < 0.05). They advocated early treatment of preterm labor, but < 50% would perform cesarean delivery for fetal distress before 26 weeks' gestation. CONCLUSION: We conclude that physicians delivering obstetric care significantly underestimate survival and freedom from handicap in preterm infants. Perinatal care may be adversely affected by these misperceptions.

Persons with Disabilities

Response of upper airway and chest wall muscles to selective brain stem hypoxia in the newborn.

In animals with intact peripheral chemosensory afferents, hypoxia differentially affects upper airway (UA) and chest wall muscles. To determine the contribution of brain stem (BS) hypoxia to the response of UA and chest wall muscles during early life, we perfused the BS through a vertebral artery intermittently with blood from an extracorporeal circuit in nine newborn piglets (age 1-5 days). BS perfusions were performed with hypoxemic blood (arterial PO2 32 +/- 6 to 38 +/- 8 Torr) with different levels of BS PCO2 (28 +/- 2, 37 +/- 4, and 56 +/- 5 Torr) while systemic normocapnic hyperoxia was maintained (arterial PCO2 36 +/- 3 to 40 +/- 6 Torr, arterial PO2 345 +/- 73 to 392 +/- 37 Torr). Electromyograms (EMGs) of alae nasi (AN), external intercostal (EI), and diaphragm (DIA) were recorded. Normocapnic hypoxia of the BS induced a sustained increase in AN EMG (P < 0.01, analysis of variance) and depression of EI and DIA EMGs without a transient increase. These contrasting responses were also observed during hypocapnic and hypercapnic hypoxia of the BS and were not affected by inputs from the peripheral chemoreceptors or rostral cerebral structures that were not exposed to hypoxia. We conclude that, despite eliciting the known central respiratory depression, BS hypoxia causes an increase in the respiratory drive to an UA airway muscle. Thus, BS hypoxia elicits a selective rather than a generalized respiratory muscle depression. The respiratory muscles with high energy expenditure (DIA and EI) are depressed while UA muscles are stimulated or disinhibited. This response is independent of the level of BS arterial PCO2.

Animals

Regulation of expiratory muscles during postnatal development in anesthetized piglets.

We compared maturation of the responses of the rib cage [triangularis sterni (TS)] and abdominal [transversus abdominis (TA)] expiratory muscles with each other and with the responses of the diaphragm (DIA) during hypercarbic and hypoxic stimulation. Studies were performed in anesthetized (urethan and chloralose) piglets of two age groups (< 6 days, n = 10; 14-21 days, n = 11) before and after bilateral cervical vagotomy. Hypercarbia (7% CO2-93% O2) was associated with comparable sustained increases in the minute electromyograms (EMGs) of both TS and TA, which were closely coupled to the DIA responses in both age groups. Hypoxia (12% O2-88% N2) caused a biphasic response of the minute EMG of both expiratory muscles and DIA; these biphasic responses were less prominent at 14-21 days than at < 6 days. Vagotomy caused an increase in the amplitude of both TS and TA (38 +/- 30 and 27 +/- 21%, respectively) as well as the DIA (45 +/- 16%) but did not affect their relative responses to chemostimulation. We conclude that during postnatal development 1) the rib cage and abdominal expiratory muscle responses to chemostimulation are coupled to each other and parallel those of the DIA and 2) the presence of vagal afferents attenuates the drive to both inspiratory and expiratory motoneurons under the current experimental conditions but does not influence the relative responses of expiratory muscles and DIA to hypercarbia or hypoxia. We speculate that comparable activation of inspiratory and expiratory pumping muscles serves to stabilize respiratory control in the face of altered chemosensory or vagal inputs during early postnatal life.

Afferent Pathways

PEEP does not improve pulmonary mechanics in infants with bronchiolitis.

Positive end-expiratory pressure (PEEP) may improve pulmonary mechanics, work of breathing, and gas exchange in some patients with respiratory failure. These beneficial effects do not occur consistently, however, and side effects, such as gas trapping due to expiratory flow limitation, may be exacerbated. We determined the effects of PEEP (0, 3, 6, and 9 cm H2O applied in random order) on the expiratory airway resistance and static compliance of nine infants mechanically ventilated for acute bronchiolitis. We also noted the presence of inadvertent PEEP (PEEPi) to determine its influence on the response to applied PEEP. Applied PEEP at any level failed to consistently improve passive expiratory airway resistance or increase compliance from baseline (PEEP = 0 cm H2O, resistance = 92 +/- 32 cm H2O/L/s; compliance = 0.71 +/- 0.19 ml/cm H2O/kg). Increases in end-expiratory lung volumes ranged from 18 to 40% of the tidal volume at maximal PEEP. Although all infants had PEEPi (5 +/- 2 cm H2O), PEEPi had no influence on the response of mechanics to applied PEEP other than that peak inspiratory pressures increased when PEEP > PEEPi. We conclude that the routine use of PEEP in infants with bronchiolitis does not consistently improve passive expiratory pulmonary mechanics and may increase the risk of barotrauma from gas trapping.

Airway Resistance

Early ABRs in infants undergoing assisted ventilation.

ABR was performed on 42 preterm infants undergoing assisted ventilation with conventional or high-frequency oscillatory ventilation (HFOV). ABRs from these very young neonates were evaluated to further detail the emerging response and to determine if type of ventilation or other perinatal factors had effects on the ABR. While responses were present down to 26 weeks gestational age, the only factors which appeared related to absent ABRs were birthweight and gestational age.

Auditory Cortex

Measurement of interrupter resistance in rabbits exposed to methacholine aerosols.

We studied the effect of increasing airway resistance on equilibration of airway and alveolar pressure during passive expiratory airflow interruption. In 10 anesthetized and paralyzed rabbits, airway and alveolar pressures were compared before and after airway resistance was increased with methacholine. In all studies, airway pressure rose to equilibrate with alveolar pressure immediately after the interruption (delta Pinit) regardless of increases in airway resistance. The pressures then remained equal during the interruption while gradually increasing to plateau (delta Pdiff). Before methacholine exposure, delta Pdiff was small (0.6 +/- 0.3 cmH2O). Steady-state resistance calculated from the sum of delta Pinit and delta Pdiff was similar to airway resistance calculated from delta Pinit alone. After methacholine, increased airway resistance was accompanied by increased delta Pdiff (2.0 +/- 0.5 cmH2O), causing disproportionate increase in steady-state resistance. delta Pdiff increases were equal in the airway and alveoli, implying resistive changes distal to the sampled alveoli. Thus increasing airway resistance did not delay pressure equilibration across airways. However, increases in airway resistance were accompanied by tissue resistive changes that were greater than the increases in airway resistance.

Aerosols

Alae nasi activation in preterm infants during oral feeding.

Preterm infants may demonstrate impaired ventilation during oral feeding with resultant hypoxemia and hypercarbia. This study was designed to determine whether infants activate a representative upper airway muscle, the ala nasi, in response to these ventilatory changes. Ten preterm infants (postconceptional age at study 35 +/- 4 wk, weight 2.2 +/- 0.1 kg) were studied during a control period, continuous feeding, subsequent intermittent feeding, and a period of nonnutritive sucking. Nasal airflow was measured with a pneumotachometer to quantify minute ventilation. The alae nasi electromyogram (EMGAN) was recorded with surface electrodes, and sucking pressure was detected by a catheter in the feeding nipple. End-tidal CO2 and O2 saturation were also recorded during each period. The percentage of breaths associated with EMGAN activity increased from 41 +/- 13% during the control period to 95 +/- 5% and 93 +/- 7% during continuous and intermittent sucking, respectively (p < 0.05). Eighty-seven +/- 5% of EMGAN activity occurred during inspiration. During continuous and intermittent sucking, the amplitude of EMGAN activity also increased (6.8 +/- 5.2 and 6.7 +/- 4.0 arbitrary units/breath, respectively) compared with the control period (2.4 +/- 2.8 units/breath, p < 0.05). In association with the increase in EMGAN activity, O2 saturation fell from 98 +/- 1% in the control period to 95 +/- 1% during both continuous and intermittent feeding (p < 0.05), and minute ventilation fell from 274 +/- 80 mL/min/kg during the control period to 190 +/- 81 and 208 +/- 57 mL/min/kg during continuous and intermittent feeding, respectively (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide

Oxygen desaturation complicates feeding in infants with bronchopulmonary dysplasia after discharge.

Recurrent episodes of hypoxemia may affect the growth, cardiac function, neurologic outcome, and survival of infants with bronchopulmonary dysplasia (BPD). As oral feeding might stress these infants by compromising pulmonary function even after hospital discharge, we measured oxygen saturation (SaO2) via pulse oximetry before, during the initial 10 minutes of, and immediately after oral feeding in 11 patients with BPD, 12 very low birth weight infants, and 23 healthy full-term infants. All infants with BPD had been previously discharged from the hospital after weaning from supplemental oxygen. Studies were done at a mean postconceptional age of 43 weeks while the infants were fed at home by one of their parents. Levels of SaO2 for the three groups were comparable before and during feeds. After feeding, the infants with BPD had significantly lower mean levels of SaO2 (84 +/- 8% [SD] vs 93 +/- 4% and 93 +/- 3%, respectively; P less than .01). They also spent more time after feeding with an SaO2 less than 90% (64 +/- 34% of time vs 27 +/- 33% for the very low birth weight and 22 +/- 20% for the term group; P less than .01) and greater time with an SaO2 less than 80% (37 +/- 28% vs 4 +/- 10% and 4 +/- 8%, respectively; P less than .01). Desaturation in infants with BPD was related to larger volume and faster oral intake during feeding. Thus, the data indicate that desaturation after feeding remains a recurrent problem for survivors of BPD after discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight

Effect of ventilatory strategy on cardiac output during high frequency jet ventilation.

STUDY OBJECTIVE: The aim was to study the effects of changes in ventilation variables on cardiac function during high frequency jet ventilation. DESIGN: Controlled changes in mean airway pressure (2-10 cm H2O), tidal volume (4 and 8 ml), and frequency (4-8 Hz) were used to assess the effects of ventilatory variables on cardiac output in cats with normal and reduced lung compliance during high frequency jet ventilation. Cardiac output was continuously measured with an electromagnetic flow probe placed around the aorta. Respiratory compliance was reduced by lung lavage. EXPERIMENTAL MATERIAL: Seven anaesthetised adults cats, weight 3.0(SEM 0.2) kg, were used in the study. MEASUREMENTS AND MAIN RESULTS: Cardiac output fell as mean airway pressure was raised from 2 to 10 cm H2O at all frequencies and tidal volumes. At identical levels of minute ventilation and mean airway pressure, cardiac output was improved with combinations of smaller tidal volumes and higher frequencies. Reducing respiratory compliance by lung lavage dampened the effect of mean airway pressure on cardiac output, but maintained the relationship between ventilatory variables observed before lavage. CONCLUSION: At identical settings of minute ventilation and mean airway pressure, cardiac output may be improved with smaller tidal volumes during high frequency jet ventilation.

Airway Resistance

Maturation of respiratory reflex responses in the piglet.

Stimulation of chemo-, irritant, and pulmonary C-fiber receptors reflexly constricts airway smooth muscle and alters ventilation in mature animals. These reflex responses of airway smooth muscle have, however, not been clearly characterized during early development. In this study we compared the maturation of reflex pathways regulating airway smooth muscle tone and ventilation in anesthetized, paralyzed, and artificially ventilated 2- to 3- and 10-wk-old piglets. Tracheal smooth muscle tension was measured from an open tracheal segment by use of a force transducer, and phrenic nerve activity was measured from a proximal cut end of the phrenic nerve. Inhalation of 7% CO2 caused a transient increase in tracheal tension in both age groups, whereas hypoxia caused no airway smooth muscle response in either group. The phrenic responses to 7% CO2 and 12% O2 were comparable in both age groups. Lung deflation and capsaicin (20 micrograms/kg iv) administration did not alter tracheal tension in the younger piglets but caused tracheal tension to increase by 87 +/- 28 and 31 +/- 10%, respectively, in the older animals (both P less than 0.05). In contrast, phrenic response to both stimuli was comparable between ages: deflation increased phrenic activity while capsaicin induced neural apnea. Laryngeal stimulation did not increase tracheal tension but induced neural apnea in both age groups. These data demonstrate that between 2 and 10 wk of life, piglets exhibit developmental changes in the reflex responses of airway smooth muscle situated in the larger airways in response to irritant and C-fiber but not chemoreceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals