Biomedical subjects

J D Mrozek

Publications and source records attributed to J D Mrozek.

5 recordsLinked to original sources

PubMed1998

High-frequency oscillation versus conventional ventilation following surfactant administration and partial liquid ventilation.

Surfactant followed by partial liquid ventilation (PLV) with perfluorocarbon (PFC; LiquiVent) improves oxygenation, lung compliance, and lung pathology in lung-injured animals receiving conventional ventilation (CV). In this study, we hypothesize that high-frequency oscillation (HFO) and CV will provide equivalent oxygenation in lung-injured animals following surfactant repletion and PLV, once lung volume is optimized. After saline-lavage lung injury during CV, newborn piglets were randomized to either HFO (n = 10) or CV (n = 9). HFO animals were stabilized over 15 min without optimization of lung volume; CV animals continued treatment with time-cycled, pressure-limited, volume-targeted ventilation. All animals then received 100 mg/kg of surfactant (Survanta). Thirty minutes later, all received intratracheal PFC to approximate functional residual capacity. Thirty minutes after PLV began, mean airway pressure (MAP) in both groups was increased to improve oxygenation. MAP was directly adjusted during HFO; PEEP and PIP were adjusted during IMV, maintaining a pressure sufficient to deliver 15 mL/kg tidal volume. Animals were treated for 4 h. The CV group showed improved oxygenation following surfactant administration (OI: 26.79 +/- 1.98 vs. 8.59 +/- 6.29, P < 0.0004), with little further improvement following PFC administration or adjustments in MAP. Oxygenation in HFO-treated animals did not improve following surfactant, but did improve following PFC (0I: 27.78 +/- 6.84 vs. 15.86 +/- 5.53, P < 0.005) and adjustments in MAP (OI: 15.86 +/- 5.53 vs. 8.96 +/- 2.18, P < 0.03). After MAP adjustments, there were no significant intergroup differences in oxygenation. Animals in the CV group required lower MAP than animals in the HFO group to maintain similar oxygenation. We conclude that surfactant repletion followed by PLV improves oxygenation during both CV and HFO. The initial response to administration of surfactant and PFC was different for the conventional and high-frequency oscillation groups, likely reflecting the ventilation strategy used; animals in the CV group responded most to surfactant, whereas animals in the HFO group responded most after PFC instillation. The ultimately similar oxygenation of the two groups once lung volume had been optimized suggests that HFO may be used effectively during administration of, and treatment with, surfactant and perfluorocarbon.

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PubMed1998

Dynamics of spontaneous breathing during patient-triggered partial liquid ventilation.

This study evaluates different ventilator strategies during gas (GV) and partial liquid ventilation (PLV) in spontaneously breathing animals. We hypothesized that during PLV, spontaneously breathing animals would self-regulate respiratory parameters by increasing respiratory rate (RR) and minute ventilation (V'E) when compared to animals mechanically ventilated with gas, and further that full synchronization of each animal's effort to the ventilator cycle would decrease RR at stable tidal volumes (V(T)). We studied 12 newborn piglets (1.54 +/- 0.24 kg) undergoing GV and PLV in 3 different modes: intermittent mandatory ventilation (IMV), synchronized IMV (SIMV), and assist control ventilation (AC). Modes occurred sequentially in random order during GV first, with the same order then repeated during PLV. Animals initially received continuous positive airway pressure (CPAP) and returned to CPAP during PLV at the end of the experiment. Pressure-limited, volume-targeted ventilation was used with a tidal volume goal of 13 cc/kg. Rate was set at 10/min during IMV and SIMV, with a back-up rate of 10/min during AC. RR, V'E, mechanical (V(T)) and spontaneous tidal volumes (sV(T)) were measured breath-to-breath using a computer-assisted lung mechanics analyzer; mean values were determined over 30-min periods. Data analysis used paired t-tests with Bonferroni correction as needed (P < 0.05). Blood gases were stable in all modes during GV and PLV. RR (min(-1)) and V'E (L x min(-1)/kg) increased in all modes from GV to PLV (RR: CPAP 71 vs. 128; IMV 69 vs. 112; SIMV 65 vs. 107; AC 33 vs. 47. V'E: CPAP 0.47 vs. 0.72; IMV 0.46 vs. 0.61; SIMV 0.45 vs. 0.61; AC 0.38 vs. 0.53; P < 0.05). Intermode comparisons during PLV showed a lower RR with AC (P < 0.02), and a higher V'E with CPAP (P < 0.05). V(T) and dynamic respiratory system compliance decreased from GV to PLV (V(T) P < 0.05; C(rs,dyn) P < 0.01); sV(T) remained unchanged. V(T) and sV(T) did not differ in intermode comparisons. We conclude that during PLV, spontaneously breathing piglets with normal lungs maintain physiologic blood gases by increasing V'E through increased RR. AC produced the most efficient respiratory pattern during PLV, with increased V'E achieved by a modest increase in RR.

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PubMed1997

Prolonged partial liquid ventilation using conventional and high-frequency ventilatory techniques: gas exchange and lung pathology in an animal model of respiratory distress syndrome.

OBJECTIVE: To evaluate the effect of prolonged partial liquid ventilation with perflubron (partial liquid ventilation), using conventional and high-frequency ventilatory techniques, on gas exchange, hemodynamics, and lung pathology in an animal model of lung injury. DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory of the Infant Pulmonary Research Center, Children's Health Care-St. Paul. SUBJECTS: Thirty-six newborn piglets. INTERVENTIONS: We studied newborn piglets with lung injury induced by saline lavage. Animals were randomized into one of five treatment groups: a) conventional gas ventilation (n = 8); b) partial liquid ventilation with conventional ventilation (n = 7); c) partial liquid ventilation with high-frequency jet ventilation (n = 7); d) partial liquid ventilation with high-frequency oscillation (n = 7); and e) partial liquid ventilation with high-frequency flow interruption (n = 7). After induction of lung injury, all partial liquid ventilation animals received intratracheal perflubron to approximate functional residual capacity. After 30 mins of stabilization, animals randomized to high-frequency ventilation were changed to their respective high-frequency modes. Hemodynamics and blood gases were measured before and after lung injury, after perflubron administration, and then every 4 hrs for 20 hrs. Histopathologic evaluation was carried out using semiquantitative scoring and computer-assisted morphometric analysis on pulmonary tissue from animals surviving at least 16 hrs. MEASUREMENTS AND MAIN RESULTS: All animals developed acidosis and hypoxemia after lung injury. Oxygenation significantly (p < .001) improved after perflubron administration in all partial liquid ventilation groups. After 4 hrs, oxygenation was similar in all ventilator groups. The partial liquid ventilation-jet ventilation group had the highest pH; intergroup differences were seen at 16 and 20 hrs (p < .05). The partial liquid ventilation-oscillation group required higher mean airway pressure; intergroup differences were significant at 4 and 8 hrs (p < .05). Aortic pressures, central venous pressures, and heart rates were not different at any time point. Survival rate was significantly lower in the partial liquid ventilation-flow interruption group (p < .05). All partial liquid ventilation-treated animals had less lung injury compared with gas-ventilated animals by both histologic and morphometric analysis (p < .05). The lower lobes of all partial liquid ventilation-treated animals demonstrated less damage than the upper lobes, although scores reached significance (p < .05) only in the partial liquid ventilation-conventional ventilation animals. CONCLUSIONS: In this animal model, partial liquid ventilation using conventional or high-frequency ventilation provided rapid and sustained improvements in oxygenation without adverse hemodynamic consequences. Animals treated with partial liquid ventilation-flow interruption had a significantly decreased survival rate vs. animals treated with the other studied techniques. Histopathologic and morphometric analysis showed significantly less injury in the lower lobes of lungs from animals treated with partial liquid ventilation. High-frequency ventilation techniques did not further improve pathologic outcome.

Animals↗

PubMed1997

Exogenous surfactant and partial liquid ventilation: physiologic and pathologic effects.

We compared the effects of surfactant and partial liquid ventilation (PLV), and the impact of administration order, on oxygenation, respiratory system compliance (Crs), hemodynamics, and lung pathology in an animal lung injury model. We studied four groups: surfactant alone (S; n = 8); partial liquid ventilation alone (PLV-only; n = 8); surfactant followed by partial liquid ventilation (S-PLV; n = 8); and partial liquid ventilation-followed by surfactant (PLV-S; n = 8). Following treatments, all animals had improved oxygenation index (OI) and Crs. Animals in PLV groups showed continued improvement over 2 h (% change OI: PLV-S -83% versus S -47%, p < 0.05; % change Crs: S-PLV 73% versus S 13%, p < 0.05). We also saw administration-order effects: surfactant before PLV improved Crs (0.92 ml/cm H2O after surfactant versus 1.13 ml/cm H2O after PLV, p < 0.02) without changing OI, whereas surfactant after PLV did not change Crs and OI increased (5.01 after PLV versus 8.92 after surfactant, p < 0.03). Hemodynamics were not different between groups. Pathologic analysis demonstrated decreased lung injury in dependent lobes of all PLV-treated animals, and in all lobes of S-PLV animals, when compared with the lobes of the S animals (p < 0.05). We conclude that surfactant therapy in combination with PLV improved oxygenation, respiratory system mechanics, and lung pathology to a greater degree than surfactant therapy alone. Administration order affected initial physiologic response and ultimate pathology: surfactant given before PLV produced the greatest improvements in pathologic outcomes.

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PubMed1991

X-chromosome inactivation in the liver of female heterozygous OTC-deficient sparse-furash mice.

X-chromosome inactivation patterns were investigated in livers of nine spfash female heterozygous ornithine transcarbamylase (OTC)-deficient mice. Quantitative morphometric analysis of cellular mosaicism was performed on sections of frozen liver reacted with purified anti-OTC antibody and prepared for immunofluorescent microscopy. Analysis of enzymatic OTC activity was performed on sections of these livers using a radiochromatographic technique. Several areas of cellular mosaicism were seen in each of the histological sections that were studied. The distribution of the volume fraction of the liver tissue cells having cells with normal OTC content among the nine mice ranged from 20 to 70% and it correlated (r = 0.8, P = 0.005) with the enzymatic activities of the respective livers. The extreme variegation of mosaic patches in the liver suggests the high probability that a single needle biopsy will be diagnostic in females heterozygous for an OTC mutation. This study also suggests that at the time of X inactivation, the number of primordial liver embryonic cells is small and the observed variegation of liver mosaicism probably results from complex migration patterns of liver cells during fetal development. This study shows that the spfash mouse is a suitable animal model for quantitative studies of X-chromosome inactivation in liver using immunohistochemical staining of OTC protein.

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