Biomedical subjects

G J Redding

Publications and source records attributed to G J Redding.

At least 37 records · Page 2Linked to original sources

PubMed1991

Group B streptococcus induces tumor necrosis factor in neonatal piglets. Effect of the tumor necrosis factor inhibitor pentoxifylline on hemodynamics and gas exchange.

Group B streptococcus (GBS), a common neonatal gram-positive pathogen, causes similar pathophysiologic features in human newborns and neonatal animal models of sepsis. Previous reports suggest that mediators in addition to TxA2 and PGI2 contribute to the late effects of GBS infusion (2 to 4 h), which include persistent increases in Ppa, hypoxemia, systemic hypotension, and a progressive fall in CO. Tumor necrosis factor (TNF) infusion in animals produces several of the late GBS effects. We hypothesized that GBS causes increased serum TNF levels 2 to 4 h into infusion in neonatal piglets. We also postulated that the TNF inhibitor, pentoxifylline (PTF), would attenuate both GBS-induced TNF production and late GBS effects. In piglets infused with 1.25 x 10(9) cfu/kg/h of GBS, serum TNF levels (pg/ml, ELISA assay) significantly increased at 2 h (231 +/- 41) and at 4 h (1,047 +/- 290, n = 9). In piglets infused with concomitant GBS + PTF, serum TNF levels at 4 h (208 +/- 39, n = 8) were reduced compared to GBS alone piglets (p less than 0.02). Control piglets infused with 0.9% saline or PTF alone for 4 h had no detectable serum TNF (less than 35). GBS alone and GBS + PTF infusion caused similar increases in serum TxB2 levels at 1, 2, and 4 h. Serum 6-keto-PGF1 alpha levels (pg/0.1 ml) significantly increased at 4 h (85 +/- 18) with GBS alone, and were more elevated at 4 h (306 +/- 75) with GBS + PTF infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Predictive value of oropharyngeal cultures for identifying lower airway bacteria in cystic fibrosis patients.

Identifying lower respiratory pathogens in young, non expectorating cystic fibrosis (CF) patients has been problematic. Bronchial secretions are difficult to obtain, and little is known about lower airway flora in these patients. We collected simultaneous bronchial and oropharyngeal specimens in 43 CF patients in optimal respiratory status, including both expectorating (17) and nonexpectorating (26) patients, to determine the predictive value of oropharyngeal cultures for identifying lower airway pathogens. An additional goal was to characterize the lower respiratory flora of these patients. Predictive values were defined as the proportion of oropharyngeal culture results that accurately reflected the results of bronchial cultures. Predictive values of positive oropharyngeal cultures in nonexpectorating patients were 83% (95% confidence interval 36 to 100%) for Pseudomonas aeruginosa and 91% (59 to 100%) for Staphylococcus aureus. Predictive values of negative oropharyngeal cultures were lower: 70% (48 to 86%) for R aeruginosa and 80% (52 to 96%) for S. aureus. A relatively high proportion of nonexpectorating CF patients less than 10 yr old had R aerusginosa (11 of 24, 46%) or Klebsiella species (5 of 24, 21%) in their lower airways. The isolation of Klebsiella was associated with younger age (p = 0.03) and recent administration of antistaphylococcal antibiotics (p = 0.05). Our results suggest that oropharyngeal cultures yielding R aeruginosa or S. aureus are highly predictive, but such cultures lacking these organisms do not rule out the presence of these pathogens in the lower airways of CF patients.

Bacterial Infections↗

PubMed1990

Lung function in children following empyema.

Spirometry was performed and response to exercise was measured in 15 children following recovery from empyema to evaluate the impact of pleural infection on subsequent lung function. Seven children underwent chest tube drainage; eight did not. The two groups were similar in age (mean +/- SD, 6 +/- 5 years), sex distribution, bacterial pathogen-producing empyema, and age at follow-up evaluation (12 +/- 5 years). Only one child reported recurrent respiratory symptoms. No child had restrictive spirometric changes (total lung capacity, less than 80%; vital capacity, less than 80% predicted) but seven of 15 had a reduced forced expiratory volume in 1 second (less than 80% predicted) or forced expiratory flow during the middle half of the vital capacity (less than 75% predicted), suggesting mild airway obstruction. No child demonstrated reduced exercise tolerance due to restrictive ventilatory limitations. Mild obstructive abnormalities in lung function were identified with equal frequency in children treated with and without chest tube drainage.

Child↗

PubMed1990

Regional pulmonary blood flow in piglets during group B streptococcal bacteremia.

Shunt fraction (QS/QT) and perfusion to hypoxic lung regions increase when pulmonary vascular driving pressure (PVDP) is raised by increasing pulmonary blood flow or enlarging the size of the hypoxic region. We hypothesized that perfusion to collapsed areas would similarly increase when PVDP was increased by a circulating pulmonary vasoconstrictor. Group B streptococci (GBS) were infused into 10 young piglets with left lung atelectasis to produce pulmonary vasoconstriction and determine if perfusion to collapsed regions (QL/QT) and intrapulmonary QS/QT increased as pulmonary vascular resistance (PVR) increased. Left lung collapse alone increased PVR from 11 +/- 3 to 18 +/- 10 mm Hg/L/min and QS/QT from 1.9 +/- 1.4% to 8.3 +/- 6.4%; QL/QT decreased from 44 +/- 1% to 10 +/- 7% of total pulmonary blood flow (p less than 0.02). Intravenous GBS increased PVDP from 11 +/- 3 to 27 +/- 4 mm Hg and further increased PVR from 18 +/- 10 to 33 +/- 12 mm Hg/L/min (p less than 0.02) but did not change cardiac output, QS/QT, or QL/QT. Changes in QL/QT and QS/QT are not predicted by changes in PVDP alone but also depend upon the site and nature of pulmonary vasoconstriction in infants with regional lung disease.

Animals↗

PubMed1990

Tumor necrosis factor-induced neonatal pulmonary hypertension: effects of dazmegrel pretreatment.

The endogenously produced cytokine, tumor necrosis factor-alpha (TNF-alpha), has been shown in adult animal models to be associated with many of the pathophysiologic effects of sepsis, including systemic hypotension and hemorrhagic necrosis. TNF-alpha can induce the release of various vasoactive arachidonic acid metabolites, suggesting that TNF-alpha may act either directly or via intermediary substances in producing its effects. The pathophysiologic role of TNF-alpha in neonatal sepsis, especially its potential effect on pulmonary vascular tone, is presently unknown. To assess the role of TNF-alpha in neonatal sepsis, 19 piglets (19 +/- 5 d old) were anesthetized, intubated, paralyzed, mechanically ventilated, and catheterized to assess pulmonary and systemic vascular hemodynamics and pulmonary gas exchange. The multiple inert gas elimination technique was used to assess ventilation perfusion matching. A 30-min infusion of human recombinant TNF-alpha (250 micrograms/kg total dose) was administered to animals pretreated with either 10 mg/kg dazmegrel, a thromboxane synthase inhibitor (n = 9) or placebo (n = 10). TNF-alpha alone induced a prompt and sustained rise in pulmonary arterial pressure and pulmonary vascular resistance that continued at least for 2 h after onset of the infusion. In contrast, the animals pretreated with dazmegrel demonstrated no rise in pulmonary vascular resistance until 2 h after the onset of the infusion. Neither group of animals demonstrated a significant decline in arterial PO2 or evidence from inert gas analysis of VA/Q mismatching or increase in intrapulmonary shunt.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

The effect of respiratory viral infections on patients with cystic fibrosis.

We examined, in a 2-year prospective study, the frequency of respiratory viral infections in 19 school-age patients with cystic fibrosis and their unaffected siblings. At 2-month intervals throughout the study period, pulmonary function tests, oropharyngeal cultures, and serologic tests for respiratory viruses were performed in all subjects. Quantitative sputum cultures for bacteria were performed in subjects with cystic fibrosis. The same laboratory specimens were also collected at the time of all acute respiratory illnesses. Over the 2-year period, 398 viral cultures and serum samples were collected, 210 from patients with cystic fibrosis and 188 from their siblings. The frequency of culture-documented and seropositive viral infections was not significantly different between patients with cystic fibrosis and their siblings. The patients with the highest frequency of viral infection were younger and had the lowest rate of decline in lung function and severity score. We conclude that school-age patients with cystic fibrosis are no more susceptible to viral infections than their unaffected siblings. We were unable to demonstrate any significant adverse effect of respiratory viral infections on pulmonary function in 19 patients with cystic fibrosis aged 5 to 21 years.

Acute Disease↗

PubMed1989

Safety of aerosol tobramycin administration for 3 months to patients with cystic fibrosis.

To determine the potential toxicity of prolonged aerosol tobramycin administration, 22 patients with cystic fibrosis were monitored while receiving inhaled tobramycin three times a day for 12 weeks. Prior to, four times during administration and approximately 6 weeks after discontinuation of treatment, we assessed pulmonary function, weight, height, body temperature, eighth cranial nerve function, serum creatinine, blood urea nitrogen, urinary creatinine clearance, plasma iothalamate clearance, urinary beta-2 microglobulin concentration, and Pseudomonas aeruginosa density in sputum. There was no detectable laboratory evidence of nephrotoxicity. Neither a decrease in auditory acuity (range 250-20,000 Hz) nor vestibular dysfunction was detected. Pulmonary function tests significantly improved during the first month in all subjects (P less than 0.05) but returned to enrollment values by the end of the 12th week of administration of tobramycin aerosol. Sputum P. aeruginosa density initially decreased from a mean of 10(7) cfu/gm to a mean of 10(4) cfu/gm after 2 weeks of aerosol tobramycin administration and remained significantly below the enrollment value throughout. Coincident with the reduced bacterial density, a reduction in cough frequency and sputum production, as well as a weight gain was observed. Seventy-three percent of the patients with sputum P. aeruginosa isolates susceptible to tobramycin on enrollment yielded resistant organisms during aerosol administration. However, 1 year later all sputum P. aeruginosa isolates obtained from patients were susceptible to tobramycin. We conclude that thrice daily aerosol tobramycin administration for 3 months is not associated with detectable eighth cranial nerve or renal toxicity. Transient emergence of tobramycin resistant P. aeruginosa may occur.

Administration, Inhalation↗

PubMed1989

Isogenic group B streptococci devoid of capsular polysaccharide or beta-hemolysin: pulmonary hemodynamic and gas exchange effects during bacteremia in piglets.

Group B beta-hemolytic streptococcus (GBS) causes thromboxane (Tx)-associated pulmonary hypertension and hypoxemia in neonatal animals and human infants. The components of GBS that induce these features of sepsis are incompletely characterized. The capsular polysaccharide has been implicated based on the effects of GBS extracts. We used isogenic mutants of a parent GBS strain (COH 31 r/s) devoid of capsular polysaccharide or beta-hemolysin to determine if these components caused the acute features of GBS bacteremia. In neonatal piglets, we observed a similar increase in pulmonary vascular resistance (PVR, mm Hg/L/min) during a 1 h infusion at 5 x 10(8) colony-forming unit/kg/h of COH 31 r/s (n = 5, 11.6 +/- 1.4 to 67.1 +/- 17.9), an isogenic GBS mutant devoid of type III CP (n = 5, 12.5 +/- 1.4 to 56.9 +/- 5.0), and an isogenic GBS mutant devoid of beta-hemolysin (n = 4, 11.0 +/- 1.9 to 51.9 +/- 7.9). All three GBS strains caused increases in blood TxB2 levels, mild arterial hypoxemia, mild reduction in mixed venous PO2, and a 30-40% reduction in cardiac output after a 1 h infusion. The Tx-synthase inhibitor, dazmegrel, completely reversed pulmonary hypertension, and partially reversed arterial hypoxemia and TxB2 levels to baseline values for all GBS strains. In six additional piglets, infusion of polystyrene beads of similar size to GBS at a dose of 5 x 10(8) beads/kg/h caused no changes in gas exchange or blood TxB2 levels, but a mild increase in PVR (13.3 +/- 2.0 to 17.7 +/- 3.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Bronchopulmonary dysplasia. Survival after prolonged mechanical ventilation.

We reviewed the records of 4778 infants who were admitted to the affiliated intensive care nurseries at the University of Washington in Seattle from Jan 1, 1980, through Dec 31, 1983. We evaluated the outcome for patients with bronchopulmonary dysplasia who required mechanical ventilation and supplemental oxygen for at least six months. Eight (53%) of 15 study patients were alive at 3 years of age. Preselected indexes measured during the first six months of life that were not associated with death before 3 years of age included growth measurements, fraction of inspired oxygen at 6 months of age, mean airway pressure, arterial partial pressure of carbon dioxide, and right ventricular hypertrophy. In contrast, recurrent cyanotic episodes requiring intermittent muscle paralysis or long-term sedation therapy to maintain gas exchange occurred in six of seven nonsurvivors and only one of eight survivors. The survivors have reactive airway disease and recurrent lower respiratory tract infections.

Body Height↗

PubMed1988

Hypoxic pulmonary vasoconstriction during and after infusion of group B Streptococcus in neonatal piglets. Vascular pressure-flow analysis.

Hypoxic pulmonary vasoconstriction (HPV) is attenuated after endotoxin infusion into adult dogs and sheep. High dose infusions of Group B Streptococcus (GBS), a neonatal pathogen, into newborn animals produce pulmonary hypertension, hypoxemia, and reduced cardiac output similar to high dose endotoxin infusions in adult animals. To avoid the compounding effects of reduced arterial and mixed venous PO2, HPV was studied after low dose endotoxin in adult animals. We hypothesized that HPV would be attenuated in piglets after a low dose GBS infusion. Both PVR and pressure-flow (P/Q) relationships were measured in piglets to characterize the neonatal pulmonary vascular response to alveolar hypoxia before and after GBS infusion. Hemodynamic measurements were made under Zone 3 conditions in 5 piglets breathing room air and 13% FIO2: (1) prior to GBS, (2) 20 min into a 1-h infusion of 3 +/- 1 x 10(8) cfu/kg/h live GBS, (3) 1 h, and (4) 3 h after completion of the GBS infusion. Prior to GBS, alveolar hypoxia increased PVR (14 +/- 1.3 to 33 +/- 3.6 mm Hg/L/min) and P/Q slope (12 +/- 2.3 to 41 +/- 6.8 mm Hg/L/min). During all subsequent exposures to 13% FIO2, the PVR and P/Q slopes were similar to pre-GBS values. When animals breathed room air, the PVR and P/Q slopes were greater than pre-GBS values during but not after the GBS infusion. We conclude that HPV is not altered 1 and 3 h after a 1-h low dose GBS infusion in neonatal piglets. Infusion of GBS and alveolar hypoxia independently increase pulmonary vascular resistance.

Animals↗

PubMed1988

Neonatal group B streptococcal sepsis: effects of late treatment with dazmegrel.

Neonatal group B streptococcal (GBS) sepsis produces pulmonary arterial hypertension and hypoxemia that are preventable by pretreatment with the selective thromboxane A2 synthase inhibitor, dazmegrel. In the present experiment we administered dazmegrel (8 mg/kg) 2 h after the initiation of a 2 1/2 h infusion of 5 X 10(8) GBS/kg/h in ten 2- to 3-wk-old piglets. The multiple inert gas elimination technique was used to measure intrapulmonary shunt and alveolar ventilation to pulmonary perfusion mismatching. Thromboxane B2, the stable metabolite of thromboxane A2, and 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin, were assayed in arterial blood. Pulmonary arterial pressure increased immediately after initiation of the GBS infusion, rising from 12 +/- 2 to 34 +/- 4 torr (p less than 0.02); pulmonary vascular resistance increased by 400% (p less than 0.01). Arterial hypoxemia developed (p less than 0.02) in association with an increase in the low ventilation-perfusion ratio index but without a significant increase in intrapulmonary shunt. Thromboxane B2 levels increased 10-fold. Infusion of the carrier substance for dazmegrel after 2 h of GBS infusion produced no change in any variables. In contrast, infusion of the drug resulted in the return to pre-GBS infusion baseline values for both pulmonary arterial pressure and pulmonary vascular resistance. However, no improvement in arterial pO2 or in the low ventilation-perfusion ratio index occurred. Both pulmonary vascular resistance and pulmonary arterial pressure remained normal for 0.5 h after dazmegrel administration despite continued GBS infusion. Thromboxane B2 levels were decreased 30 min after dazmegrel (p less than 0.02), but remained greater than pre-GBS levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Thromboxane-associated pulmonary hypertension during three types of gram-positive bacteremia in piglets.

Thromboxane-associated pulmonary hypertension occurs in animals during intravenous infusion of group B streptococcus (GBS), a gram-positive neonatal pathogen. We postulated that other gram-positive neonatal pathogens, such as Streptococcus fecalis (ENT) and Staphylococcus epidermidis (S. epi) would also induce increased thromboxane synthesis and pulmonary hypertension when infused into piglets. We observed similar hemodynamic and gas exchange abnormalities during stepwise increases in the dose of GBS, Ent, and S. epi (n = 3, 4, and 4 piglets receiving each bacteria, respectively). Pulmonary vascular resistance increased significantly in the absence of acidosis or reduced arterial or mixed venous pO2 at a dose of 2.5 x 10(8) cfu/kg/h for Ent and S. epi. In 14 additional piglets, pulmonary vascular resistance increased markedly after 60 min of intravenous infusion of 4 +/- 1 x 10(8) cfu/kg/h for each organism (p less than 0.05, GBS: 11.7 +/- 1.8 to 75.6 +/- 18.4 mm Hg/liter/min, Ent: 12.7 +/- 1.7 to 64.9 +/- 10.6 mm Hg/liter/min, S. epi: 10.5 +/- 0.8 to 56.9 +/- 6.0 mm Hg/liter/min), and blood thromboxane B2 levels increased (p less than 0.05, GBS: 30 +/- 10 to 1830 +/- 330 pg/ml, Ent: 20 +/- 7 to 1110 +/- 300 pg/ml, S. epi: 31 +/- 9 to 1260 +/- 350 pg/ml). This dose of each bacteria caused a similar degree of mild arterial hypoxemia (57-66 mm Hg). The thromboxane synthetase inhibitor, dazmegrel, completely reversed pulmonary hypertension, reduced TxB2 levels to near baseline values, and partially reversed arterial hypoxemia despite ongoing bacterial infusion. We conclude that thromboxane-associated pulmonary hypertension occurs in piglets during infusion of different gram-positive neonatal pathogens.

Animals↗

PubMed1988

Effects of respiratory alkalosis on thromboxane-induced pulmonary hypertension in piglets.

Acute hypoxic pulmonary vasoconstriction is attenuated by respiratory alkalosis. It is unknown if alkalosis similarly reduces pulmonary vasoconstriction produced by thromboxane A2. Respiratory alkalosis does not always attenuate persistent pulmonary hypertension in newborns, some of whom have elevated serum thromboxane B2 levels. We hypothesized that alkalosis attenuates thromboxane-induced pulmonary vasoconstriction less than it does hypoxic pulmonary vasoconstriction in infants. Hemodynamic responses to respiratory alkalosis during pulmonary vasoconstriction produced in random order by breathing 12% inspired oxygen and by infusing 0.1 micrograms/kg/min of the thromboxane-mimetic U46,619 were compared in eight 2-wk-old piglets. Hypoxia increased mean pulmonary artery pressure from 12 +/- 3 to 29 +/- 2 mm Hg and pulmonary vascular resistance (PVR) from 11 +/- 4 to 25 +/- 8 mmHg/L/min; U46,619 increased pulmonary artery pressure from 16 +/- 5 to 37 +/- 6 mm Hg and PVR from 14 +/- 5 to 51 +/- 17 mm Hg/liter/min. U46,619 also decreased cardiac output accounting in part for the greater increase in PVR compared to hypoxia-induced vasoconstriction. Respiratory alkalosis decreased PVR to 14 +/- 6 mm Hg/liter/min during exposure to hypoxia and to 28 +/- 9 mm Hg/liter/min during infusion of U46,619. In six additional piglets with U46,619-induced pulmonary vasoconstriction, the effects of lung stretch and hypocapnic alkalosis were separated by doubling tidal volume and then adding inspired CO2 to return PaCO2 to prehyperventilation levels. Respiratory alkalosis decreased PVR from 52 +/- 36 to 35 +/- 21 mm Hg/liter/min. Despite the increased tidal volume, PVR increased to 53 +/- 35 Hg/liter/min when PaCO2 returned to 44 +/- 5 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkalosis, Respiratory↗

PubMed1987

Effects of hyperoxia on vasoconstriction and VA/Q matching in the neonatal lung.

Exposure of adult animals to 48-72 h of 100% O2 breathing is associated with a blunting of hypoxic pulmonary vasoconstriction (HPV) (Newman et al. J. Appl. Physiol. 54: 1379-1386, 1983). It is unknown whether HPV is also diminished in neonates after hyperoxic exposure and if so to what extent such suppression might interfere with pulmonary gas exchange during hypoxic gas breathing. We tested the possibility that hyperoxia would suppress HPV and interfere with ventilation-perfusion (VA/Q) matching and therefore gas exchange in neonatal piglets. Twelve 2- to 4-wk-old piglets were exposed for an average of 68 h to greater than 90% inspired O2. A control group of eight piglets was exposed to room air for a similar period of time. Immediately after exposure the animals were anesthetized and instrumented. Pulmonary hemodynamics and respiratory and inert gas exchange were assessed while the animals inspired an O2 fraction of 1.0, 0.21, and 0.12. After 20 min of hypoxic gas breathing, pulmonary arterial pressure rose to a lesser degree in the hyperoxia (H)-exposed animals than in the control (C) animals (P less than 0.02). The increase in pulmonary vascular resistance was similarly blunted. Venous admixture of the insoluble inert gas, sulfur hexafluoride, an index of extremely low VA/Q areas, was increased during hypoxic gas breathing compared with room air breathing in the H-preexposed animals (P less than 0.02). Standard deviation of pulmonary blood flow was increased (P less than 0.02), indicating an increase in mismatching of VA/Q during hypoxic breathing in the H-preexposed animals compared with the C animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Effects of the thromboxane synthetase inhibitor, dazmegrel (UK 38,485), on pulmonary gas exchange and hemodynamics in neonatal sepsis.

Group B streptococcal (GBS) sepsis produces arterial hypoxemia in newborns. In piglets we previously found that hypoxemia develops because of increased ventilation perfusion heterogeneity, and reduced mixed venous pO2 occurring in association with decreased pulmonary blood flow. We hypothesize that increased thromboxane A2 (TxA2) synthesis mediates the immediate alterations in gas exchange found in GBS sepsis. We studied 18 anesthetized, ventilated piglets before, during, and after a 30-min infusion of 2 X 10(9) colony forming units/kg of GBS. Nine piglets were pretreated with 8 mg/kg of dazmegrel (DAZ), a TxA2 synthetase inhibitor, and nine animals received GBS without DAZ pretreatment. Pulmonary and systemic arterial pressures, pulmonary vascular resistance, pulmonary blood flow, respiratory gas tensions, intrapulmonary shunt, and SD of pulmonary blood flow, an index of ventilation perfusion mismatching, were measured. Systemic and pulmonary arterial levels of thromboxane B2 and 6-keto-PGF1 alpha were also measured. The sham-treated animals showed the expected rise in pulmonary arterial pressure from 12 +/- 3 to 29 +/- 7 torr, (p less than 0.02). By comparison, the animals pretreated with DAZ did not demonstrate pulmonary arterial hypertension and had a delay in the fall in pulmonary blood flow until 2 h postinfusion. Arterial PO2 did not decline significantly after the GBS infusion in the DAZ-pretreated animals; the untreated animals showed a significant fall in pO2 from baseline. There was no significant change in intrapulmonary shunt or SD of pulmonary blood flow compared to baseline in the DAZ-pretreated animals. The elevation in thromboxane B2 occurring with GBS sepsis did not occur in the DAZ-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Isolated deafness following recovery from neurologic injury and adult respiratory distress syndrome. A sequela of intercurrent aminoglycoside and diuretic use.

We report two children who survived neurologic injury (near-drowning and Reye's syndrome) and adult respiratory distress syndrome and who required prolonged ventilatory support. Follow-up examination in both children showed steady neurologic recovery, but five months following discharge from their acute illness, profound hearing loss was diagnosed in both children. A review of the literature is reported and the hypothesis that combined aminoglycoside antibiotic and loop diuretic therapy caused the hearing loss is presented. Recommendation is made for audiologic assessment within six months of recovery from critical illness of pediatric patients in whom therapy has included loop diuretic and aminoglycoside antibiotic therapy.

Aminoglycosides↗

PubMed1985

Alterations in gas exchange associated with lobar atelectasis in young piglets.

Lobar atelectasis is common among infants and children with obstructive lung diseases. However, the effect of lobar collapse in the presence of diffuse lung disease on gas exchange in the pediatric age group has not been described. We developed an infant model of lobar atelectasis using piglets and tested the hypothesis that diffuse alveolar hypoxia increases shunt fraction (Qs/QT) associated with lobar atelectasis by redirecting pulmonary blood from the well-ventilated portion of the lung into the collapsed region. Shunt fraction was determined using the multiple inert gas elimination technique. The proportion of pulmonary blood flow perfusing the left lower lobe was measured with microspheres. Qs/QT increased significantly but by a variable amount to an average value (+/- SD) of 5.9 +/- 4.2% following lobar collapse. The percentage of cardiac output perfusing the left lower lobe fell by an average of 70 +/- 17% in response to lobar collapse. When animals were ventilated with 12% oxygen, shunt fraction increased to 18.7 +/- 7.1% and blood flow to the collapsed left lower lobe increased from 9 +/- 3 to 22 +/- 3% of cardiac output. Lobar atelectasis in conditions where diffuse alveolar hypoxia is present may be associated with a significantly greater intrapulmonary shunt than lobar atelectasis in children with otherwise normal lungs.

Animals↗

PubMed1985

Mechanisms of pulmonary gas exchange abnormalities during experimental group B streptococcal infusion.

Group B streptococcal sepsis in newborns produces pulmonary arterial hypertension and hypoxemia. The purpose of this study was to investigate the mechanisms by which hypoxemia occurs. Ten anesthetized, ventilated piglets were infused with 2 X 10(9) colony forming units/kg of Group B streptococci over a 30-min period. Pulmonary arterial pressure rose from 14 +/- 2.8 to 38 +/- 6.7 torr after 20 min of the bacterial infusion (p less than 0.01). During the same period, cardiac output fell from 295 to 184 ml/kg/min (p less than 0.02). Arterial PO2 declined from 97 +/- 7 to 56 +/- 11 torr (p less than 0.02) and mixed venous PO2 fell from 39.6 +/- 5 to 28 +/- 8 torr (p less than 0.05). The multiple inert gas elimination technique was used to detect increases in shunt and alterations in ventilation-perfusion matching. Intrapulmonary shunt did not increase during or after the infusion with group B streptococci. However, there was a significant increase (p less than 0.05) in the SD of pulmonary blood flow, an index of VA/Q mismatching, 20 min after initiation of the infusion of bacteria. All the above changes reverted toward baseline during the 2-h period following discontinuation of the infusion. We conclude that the hypoxemia occurring in the early phase of group B streptococcal sepsis does not develop solely because of increased shunt, but rather is produced by a decline in cardiac output in conjunction with mismatching of pulmonary perfusion to alveolar ventilation.

Animals↗