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Biomedical subjects

Marcelo Gama de Abreu

Publications and source records attributed to Marcelo Gama de Abreu.

8 recordsLinked to original sources

Effects of vaporized perfluorohexane and partial liquid ventilation on regional distribution of alveolar damage in experimental lung injury.

OBJECTIVE: To determine whether the patterns of distribution of histological effects of vaporized perfluorohexane (PFH) and partial liquid ventilation (PLV) differ significantly in acute lung injury. DESIGN AND SETTING: Experimental study in an animal research laboratory. SUBJECTS: Eighteen pigs. INTERVENTIONS: After induction of acute lung injury by means of infusion of oleic acid animals were randomly assigned to PFH, PLV, or gas ventilation (GV) groups. Six hours thereafter animals were killed, and lung tissue samples were taken for analysis. MEASUREMENTS AND RESULTS: Histopathological analysis revealed less damage with PFH than with GV or PLV in the nondependent and central regions. PFH and PLV showed less injury in the dependent regions than GV. GV and PFH were associated with less histological damage in the nondependent than the dependent regions, whereas PLV presented the opposite pattern. Morphometric analysis showed increased aeration in nondependent than dependent regions with PFH and GV. PLV led to more aeration in the periphery than in central areas. CONCLUSIONS: PFH was associated with a more homogeneous attenuation of alveolar damage across the lungs, although this therapy had more pronounced effects in nondependent zones. PLV showed the opposite pattern, with more important reduction in alveolar damage in dependent lung regions. Interestingly, reduction in alveolar damage with PFH was as effective as with PLV in dependent zones. Our findings suggest that vaporized perfluorocarbon could be advantageous as adjunctive therapy in the treatment of acute lung injury.

Animals↗

Comparative effects of vaporized perfluorohexane and partial liquid ventilation in oleic acid-induced lung injury.

BACKGROUND: It is currently not known whether vaporized perfluorohexane is superior to partial liquid ventilation (PLV) for therapy of acute lung injury. In this study, the authors compared the effects of both therapies in oleic acid-induced lung injury. METHODS: Lung injury was induced in 30 anesthetized and mechanically ventilated pigs by means of central venous infusion of oleic acid. Animals were assigned to one of the following groups: (1) control or gas ventilation (GV), (2) 2.5% perfluorohexane vapor, (3) 5% perfluorohexane vapor, (4) 10% perfluorohexane vapor, or (5) PLV with perfluorooctane (30 ml/kg). Two hours after randomization, lungs were recruited and positive end-expiratory pressure was adjusted to obtain minimal elastance. Ventilation was continued during 4 additional hours, when animals were killed for lung histologic examination. RESULTS: Gas exchange and elastance were comparable among vaporized perfluorohexane, PLV, and GV before the open lung approach was used and improved in a similar fashion in all groups after positive end-expiratory pressure was adjusted to optimal elastance (P < 0.05). A similar behavior was observed in functional residual capacity (FRC) in animals treated with vaporized perfluorohexane and GV. Lung resistance improved after recruitment (P < 0.05), but values were higher in the 10% perfluorohexane and PLV groups as compared with GV (P < 0.05). Interestingly, positive end-expiratory pressure values required to obtain minimal elastance were lower with 5% perfluorohexane than with PLV and GV (P < 0.05). In addition, diffuse alveolar damage was significantly lower in the 5% and 10% perfluorohexane vapor groups as compared with PLV and GV (P < 0.05). CONCLUSIONS: Although the use of 5% vaporized perfluorohexane permitted the authors to reduce pressures needed to stabilize the lungs and was associated with better histologic findings than were PLV and GV, none of these perfluorocarbon therapies improved gas exchange or lung mechanics as compared with GV.

Administration, Inhalation↗

Vaporized perfluorohexane attenuates ventilator-induced lung injury in isolated, perfused rabbit lungs.

BACKGROUND: The authors tested the hypothesis that administration of vaporized perfluorohexane may attenuate ventilator-induced lung injury. METHODS: In isolated, perfused rabbit lungs, airway pressure-versus-time curves were recorded. At baseline, peak inspiratory pressure and positive end-expiratory pressure of mechanically ventilated lungs were set to obtain straight pressure-versus-time curves in both the lower and upper ranges, which are associated with less collapse and overdistension, respectively. After that, peak inspiratory pressure and positive end-expiratory pressure were set at 30 cm H2O and 0, respectively, and animals were randomly assigned to one of two groups: (1) simultaneous administration of 14% perfluorohexane vapor in room air (n = 7) and (2) control group-ventilation with room air (n = 7). After 20 min of cycling collapse and overdistension, tidal volume and positive end-expiratory pressure were set back to baseline levels, administration of perfluorohexane in the therapy group was stopped, and mechanical ventilation was continued for up to 60 min. Lung weight, mean pulmonary artery pressure, and concentration of thromboxane B2 in the perfusate were measured. In addition, the distribution of pulmonary perfusate flow was assessed by using fluorescent-labeled microspheres. RESULTS: Significantly higher peak inspiratory values developed in control lungs than in lungs treated with perfluorohexane. In addition, upper ranges of pressure-versus-time curves were closer to straight lines in the perfluorohexane group. Lung weight, mean pulmonary arterial pressure, and release of thromboxane B2 were significantly higher in controls than in perfluorohexane-treated lungs. Also, redistribution of pulmonary perfusate flow from caudal to cranial zones was less important in the treatment group. CONCLUSION: The authors conclude that the administration of perfluorohexane vapor attenuates the development of ventilator-induced lung injury in isolated, perfused rabbit lungs.

Animals↗

Perfluorohexane vapor has only minor effects on spatial pulmonary blood flow distribution in isolated rabbit lungs.

We tested the hypothesis that administration of perfluorohexane (PFH) vapor does not significantly affect the relative pulmonary blood flow (Qrel) distribution in isolated rabbit lungs. Fourteen isolated rabbit lungs were perfused with a Krebs-Henseleit buffer solution (flow 150 mL/min). Pulmonary afterload was set to 3 mm Hg. The lungs were ventilated with 4% CO(2) in room air using a small animal ventilator (respiratory rate, 30 breaths/min; tidal volume, 12 mL/kg body weight; positive end-expiratory pressure, 2 cm H(2)O). After a steady-state period, 18 vol. % of PFH vapor was administered to 9 lungs for 30 min. In a second set of experiments five lungs served as controls. Change in (Qrel) distribution was assessed using fluorescent-labeled microspheres. The unpaired Student's t-test was used to compare variables between groups. The paired Student's t-test, the one-sample Student's t-test, the Anderson-Hauck test of equivalence, and Pearson correlation were used to analyze changes within groups. The mean correlation coefficients of (Qrel) were 0.564 +/- 0.182 for the PFH group and 0.502 +/- 0.295 for the control group, respectively. No significant changes in (rel) distribution over time and between groups were found. However, in the PFH group a tendency towards redistribution of (Qrel) to more ventral lung areas was noted. Our results suggest that PFH vapor has no significant effects on redistribution of (Qrel) in isolated rabbit lungs.

Algorithms↗

One-lung ventilation with high tidal volumes and zero positive end-expiratory pressure is injurious in the isolated rabbit lung model.

UNLABELLED: We tested the hypothesis that one-lung ventilation (OLV) with high tidal volumes (VT) and zero positive end-expiratory pressure (PEEP) may lead to ventilator-induced lung injury. In an isolated, perfused rabbit lung model, VT and PEEP were set to avoid lung collapse and overdistension in both lungs, resulting in a straight pressure-time (P-vs-t) curve during constant flow. Animals were randomized to (a) nonprotective OLV (left lung) (n = 6), with VT values as high as before randomization and zero PEEP; (b) protective OLV (left lung) (n = 6), with 50% reduction of VT and maintenance of PEEP as before randomization; and (c) control group (n = 6), with ventilation of two lungs as before randomization. The nonprotective OLV was associated with significantly smaller degrees of collapse and overdistension in the ventilated lung (P < 0.001). Peak inspiratory pressure values were higher in the nonprotective OLV group (P < 0.001) and increased progressively throughout the observation period (P < 0.01). The mean pulmonary artery pressure and lung weight gain values, as well as the concentration of thromboxane B(2), were comparatively higher in the nonprotective OLV group (P < 0.05). A ventilatory strategy with VT values as high as those used in the clinical setting and zero PEEP leads to ventilator-induced lung injury in this model of OLV, but this can be minimized with VT and PEEP values set to avoid lung overdistension and collapse. IMPLICATIONS: One-lung ventilation with high tidal volumes and zero positive end-expiratory pressure (PEEP) is injurious in the isolated rabbit lung model. A ventilatory strategy with tidal volumes and PEEP set to avoid lung overdistension and collapse minimizes lung injury during one-lung ventilation in this model.

Airway Resistance↗

Performance of the partial CO2 rebreathing technique under different hemodynamic and ventilation/perfusion matching conditions.

OBJECTIVE: The partial CO2 rebreathing technique has been demonstrated to accurately measure the effective pulmonary capillary blood flow (PCBF) in different clinical situations. Usually, PCBF is calculated from changes in CO2 elimination (VCO2) and end-tidal partial pressure of CO2 (PetCO2 ), which can be obtained noninvasively. In this study, we investigated the performance of the partial CO2 rebreathing technique under different conditions of ventilation/perfusion matching and hemodynamic states. In addition, we investigated whether the determination of arterial blood gases combined with mathematical modeling of gas exchange can improve the performance of this method. DESIGN: Prospective, controlled animal laboratory study. SETTING: Experimental research facility of a university hospital. SUBJECTS: Sixteen female sheep weighing 45-55 kg. INTERVENTIONS: Cardiac output and ventilation/perfusion matching were manipulated during three phases: phase I, variation in cardiac output to achieve normal, hyperdynamic and hypodynamic states; phase II, increase of alveolar deadspace and variation in cardiac output; phase III, lung injury and increased alveolar deadspace. Partial CO2 rebreathing maneuvers were performed to obtain variations in VCO2 and PetCO2 between a nonrebreathing (NR) and a rebreathing (R) period. MEASUREMENTS AND MAIN RESULTS: PCBF was measured by the rebreathing method as PCBF = -DeltaVCO2/f(Pc'CO2 (R), Pc'CO2(NR), Hb), where f is the CO2 dissociation curve in blood, Pc'CO2 is the end-capillary partial pressure of CO2, Delta is the variation between NR and R periods, and Hb is hemoglobin concentration. Pc'CO2 was estimated from PetCO2 according to two algorithms. In the so-called "noninvasive algorithm," Pc'CO2 = PetCO2, with PetCO2(NR) and PetCO2(R) being determined as the mean PetCO2 value of the last 60 secs preceding rebreathing and within 15-30 secs of rebreathing, respectively. In the "semi-invasive algorithm," Pc'CO2(NR) was estimated as the PaCO2, and Pc'CO2(R) was estimated as follows: First, a monoexponential function was fitted to PetCO2 values during rebreathing and the asymptote represented PetCO2(R). Second, the Pc'CO2(R) to PetCO2(R) difference was calculated by means of a bicompartmental, tidal model of gas exchange, which showed that such differences decrease with the degree of rebreathing. PCBF values obtained with both algorithms were compared with thermodilution cardiac output minus intrapulmonary shunt flow. Bias and precision calculations with the noninvasive algorithm in phases I, II, and III were, respectively, -1.0 +/- 1.9, -2.1 +/- 2.6, and -2.4 +/- 1.2 L/min. The semi-invasive algorithm had an overall better performance in the phases investigated: -1.2 +/- 1.9, -0.6 +/- 2.0, and -0.2 +/- 3.0 L/min, respectively. The noninvasive algorithm showed a slight tendency to overestimate lower reference PCBF values and, importantly, to underestimate higher PCBF values in all three phases (r = -.66, p<.0001; r = -.75, p<.001; r = -.60, p<.0001, respectively). A similar figure was observed with the semi-invasive algorithm in phase I (r = -.47, p<.01) but not in phases II and III (r = -.1, p=.54; r =.62, p<.001, respectively). CONCLUSIONS: Although PCBF is systematically underestimated during hyperdynamic cardiac output states and high alveolar deadspaces, the performance of the partial CO2 rebreathing technique can be improved by means of arterial blood gas sampling and an algorithm that takes in account the effects of nonequilibration of PetCO2 during rebreathing and the variation of Pc'CO2 to PetCO2 differences from the nonrebreathing to the rebreathing period. Such an algorithm may prove useful under moderately increased alveolar deadspace and normal to hypodynamic cardiac output states.

Animals↗

Evaluation of a new device for noninvasive measurement of nonshunted pulmonary capillary blood flow in patients with acute lung injury.

OBJECTIVES: To evaluate the performance of a new device for noninvasive measurement of nonshunted pulmonary capillary blood flow (PCBF) by partial CO2 rebreathing. DESIGN AND SETTING: Prospective clinical trial in an intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Twenty mechanically ventilated patients with acute lung injury. INTERVENTIONS: Variations in PEEP of +/-3 cmH2O. MEASUREMENTS AND RESULTS: Initially PCBF was measured invasively as cardiac output minus venous admixture (Q(VA)/Q(t)) flow, and by partial CO2 rebreathing at baseline PEEP (PEEP(b)). The PEEP was then reduced by 3 cmH2O (to PEEP(b-3)) and measurements were repeated after 30 min. PEEP was then increased by 6 cmH2O (to PEEP(b+3)), and measurements were repeated after 10, 20, and 30 min. The overall correlation coefficient between noninvasive and invasive PCBF measurements at PEEP(b) was high ( r=0.97), with close agreement between methods being observed (0.1+/-0.6 l/min, bias and precision, respectively). Accordingly, both the correlation coefficient and agreement between methods for changes in PCBF from PEEP(b-3) to PEEP(b+3) levels were satisfactory ( r=0.71; 0.2+/-0.5 l/min, bias and precision). The new device was able to detect the correct PCBF trend in 17 of 20 patients investigated and in all patients who showed invasive PCBF changes equal to or greater than 0.3 l/min ( n=12). Noninvasive PCBF changes were stable as early as 10 min after variation in PEEP, as compared to 30 min values. CONCLUSIONS: The new device appears to be clinically useful for the monitoring of PCBF in patients suffering from acute lung injury. Our results suggest that titration of PEEP aimed at improving PCBF can be performed with the new device.

Adolescent↗