Biomedical subjects

A Kugelman

Publications and source records attributed to A Kugelman.

24 records · Page 2Linked to original sources

PubMed1995

Intratracheal pulmonary ventilation versus conventional mechanical ventilation in a rabbit model of surfactant deficiency.

Intratracheal pulmonary ventilation (ITPV) enhances the clearance of CO2 from dead space and lungs by a bias flow of gas administered in the distal trachea. ITPV flow is continuously administered through a separate catheter placed within an endotracheal tube (ETT). After exiting from catheter's tip in the distal trachea, the flow of gas is redirected outward away from the lungs. We hypothesized that, compared with conventional mechanical ventilation (CMV), ITPV may increase minute CO2 clearance (VCO2), reduce the partial pressure of CO2 dioxide in arterial gas (PaCO2), and reduce distal tracheal peak inspiratory pressure (dPIP). We induced surfactant deficiency in 15 adult rabbits by lung lavage with 10 mL/kg normal saline. Animals were ventilated through a double-lumen 4.0 ETT, inserted through a tracheotomy incision. dPIP, distal positive end expiratory pressure, and distal mean airway pressure were monitored, and the mean exhaled CO2 concentration was measured. For ventilator rates (respiratory rate) of 30, 45, and 70 breaths/min, the study included two phases: phase I compared CO2 clearance and PaCO2 between ITPV and CMV using similar ventilatory pressures; phase II evaluated the effectiveness of ITPV in reducing dPIP and tidal volume (Vt), compared with CMV, while maintaining eucapnea. When comparing ITPV and CMV, the following results (mean +/- SD) were achieved at respiratory rate of 30, 45, and 70 breaths/min, respectively. Phase I ITPV resulted in mean percent reduction of PaCO2 by 31.4 +/- 10%, 37.1 +/- 9.7% and 38.3 +/- 9%; mean percent increase in VCO2 by 61.3 +/- 29%, 56 +/- 23, and 98 +/- 40%, compared with CMV. Phase II ITPV resulted in mean percent reduction of dPIP by 35.5 +/- 14%, 38 +/- 10.8%, and 37.2 +/- 13.7%, and mean percent reduction in Vt by 34.7 +/- 12.9%, 36.4 +/- 15%, and 52.7 +/- 10.7%, compared with CMV. The changes in PaCO2, VCO2 (phase I), and dPIP and Vt (phase II) were all significantly more than 25% (p < 0.05). Oxygenation and pH were not significantly different between ITPV and CMV. We conclude that, in a surfactant deficiency rabbit model, ITPV is an efficient mode of assisted ventilation that increases CO2 clearance and reduces ventilator pressures required for adequate ventilation. We speculate that ITPV can minimize lung barotrauma associated with mechanical ventilation.

Animals↗

PubMed1994

Quinone-induced oxidative stress elevates glutathione and induces gamma-glutamylcysteine synthetase activity in rat lung epithelial L2 cells.

Glutathione (GSH) is one of the most important physiological antioxidants involved in detoxification of hydrogen peroxide and lipid hydroperoxide. Previous studies have shown that cells can maintain and even increase cellular GSH content in response to sublethal oxidative stress. We hypothesized that gamma-glutamylcysteine synthetase (gamma GCS), the rate-limiting enzyme in de novo GSH synthesis, could be induced by oxidative stress. Rat lung epithelial L2 cells were challenged with 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), generates O2.- and H2O2 continuously through redox cycling. Exposure of confluent L2 cells with sublethal doses of DMNQ caused sustained elevation of cellular GSH levels over a 24-h period (to 2.5-fold with 10 microM). DMNQ caused increases in gamma GCS activity (70% at 24 h with 10 microM), the gamma GCS catalytic heavy subunit (gamma GCS-HS) protein level, and gamma GCS-HS mRNA content (approximately 4-fold after 6 h with 10 microM). The elevation of gamma GCS-HS mRNA by DMNQ was eliminated by co-incubation with actinomycin D. Nuclear run-on experiments demonstrated that the transcriptional rate of the gamma GCS-HS gene was increased by 3- or 6-h exposure to 10 microM DMNQ. Our results suggested that the induction of de novo GSH synthesis by naphthoquinone-induced oxidative stress is associated with the transcriptional activation of the gamma GCS-HS gene and the subsequent elevation in gamma GCS activity. Unlike simpler quinones, DMNQ cannot form a GSH conjugate. Thus, the induction of gamma GCS-HS gene transcription does not require formation of an electrophile-glutathione conjugate.

Animals↗

PubMed1994

Relationship between the parachute reactions and standing and walking in normal infants.

Assumption of the vertical position and independent walking are potentially hazardous motor milestones in the developing infant. It has been presumed that the parachute reactions evolved to protect infants from injury during this developmental stage. To determine the relationship between the appearance of the upper and lower parachute reactions and the developmental milestones of unsupported standing and independent walking, 190 normal infants were prospectively studied. The upper parachute reaction was found to precede the lower by less than a month (mean age of appearance: 8.9 and 9.2 months, respectively). More than one-half of the cohort achieved standing without either the upper (49%) or lower parachute reaction (57%); however, no independent walking occurred without the upper parachute reaction, and only 2 of 190 infants (1%) walked independently without the lower parachute reaction. Onset of walking occurred about 4 months after the appearance of the upper parachute reaction. The significance of these findings is discussed.

Accidental Falls↗

PubMed1994

gamma-Glutamyl transpeptidase is increased by oxidative stress in rat alveolar L2 epithelial cells.

The tripeptide glutathione (GSH) is used by cells to detoxify hydroperoxides, produced during oxidative stress, and is consumed in the process. Previous studies have indicated that cells can be protected against oxidative stress by extracellular GSH through its degradation catalyzed by the exoenzyme gamma-glutamyl transpeptidase (gamma GT) and its de novo synthesis within the cytosol. We hypothesized that gamma GT would be increased as part of the adaptation of cells to oxidative stress. We examined whether oxidative stress could increase gamma GT activity, protein, and mRNA in a lung epithelial cell line (L2). Cultures were subjected to H2O2-mediated toxicity by 15 min of exposure to the redox cycling quinone, menadione. Menadione (50 microM) caused an initial decrease (27 +/- 9% of baseline after 15 min) in intracellular GSH, followed by resynthesis to levels significantly higher than baseline (335 +/- 40% after 24 h, P < 0.001). This elevation was prevented by acivicin, a gamma GT inhibitor. Menadione also caused a dose-dependent increase in gamma GT enzymatic activity (715 +/- 125% of control at 24 h after 15 min of exposure to 100 microM menadione, P < 0.001) that was prevented by actinomycin D. Western blot analysis indicated increased levels of gamma GT protein with increasing menadione. A concentration-dependent increase in gamma GT-mRNA was also observed. Previous investigation has demonstrated that an increase in gamma GT activity enhances the capacity of cells to utilize extracellular GSH. The findings presented here are consistent with a role for gamma GT in cellular adaptation to oxidative stress.

Animals↗

PubMedDate not supplied

Reduction of respiratory system resistance of rabbits with surfactant deficiency using a novel ultra thin walled endotracheal tube.

The ultra thin walled, two-stage endotracheal tube (UTW-TS-ETT) is very flexible, nonkinking, and has a widened extralaryngeal portion. The UTW-TS-ETT has a greater ID/OD (internal diameter/outer diameter) ratio than a comparable standard endotracheal tube (ST-ETT) because of its thinner wall: 0.2-0.25 mm in UTW-TS-ETT, compared to 0.55-0.8 mm in ST-ETT. The authors hypothesized that in an animal model of lung disease, significant reductions in respiratory system resistance (Rrs) of 30-40% would be achieved using the UTW-TS-ETT, compared to Rrs achieved with the comparable ST-ETT. This study compared the pulmonary mechanics of rabbits (N = 17, body weight 3.4-4.7 kg) before and after induction of surfactant deficiency, using either ST-ETT (OD 4.9 mm, ID 3.5 mm) or UTW-TS-ETT (OD 5.0 mm, ID 4.6 mm). Animals were sedated, paralyzed, and ventilated by an ETT placed through a tracheotomy incision. Surfactant deficiency was induced by lavaging the lungs with normal saline (10 ml/kg). Pulmonary mechanics were measured on identical ventilator settings for each ETT used at baseline and at 45 min after lavage. Compared to ST-ETT, UTW-TS-ETT reduced Rrs by 50.6 +/- 8.7% in normal lungs (significantly more than 40%; p < 0.01), and by 41.47 +/- 16.2% in surfactant deficient lungs (significantly more than 30%; p < 0.05). Tidal volume increased with UTW-TS-ETT in all animals but did not achieve statistical significance. The UTW-TS-ETT did not induce significant changes in respiratory system compliance, PaO2, PaCO2, or pH. It is concluded that UTW-TS-ETT significantly reduces Rrs in rabbits with either normal lungs or with surfactant deficient lungs. This novel ETT may be beneficial for ventilated patients with increased Rrs, by effecting a decrease in Rrs and thus reducing the work of breathing and improving ventilation efficiency.

Animals↗

PubMedDate not supplied

Pulmonary cyst caused by septic emboli in the preterm infant.

A pulmonary cyst appeared in a growing preterm infant. The presumptive diagnosis was septic pulmonary embolism associated with the central venous catheter. The infant was successfully treated with antibiotic therapy and removal of the central venous catheter.

Catheterization, Central Venous↗