Canine lung transplantation after more than twenty-four hours of normothermic preservation

BACKGROUND: Consistent clinical results have not been achieved when lung preservation times exceed 6 hours. The aim of this study was to use an alternative normothermic autoperfusion technique for lung preservation and transplantation. METHODS: In six paired dogs, donor lungs were removed, along with the heart, liver, pancreas, duodenum, and both kidneys, and were preserved for 24 to 33 hours in a normothermic autoperfused multiple organ block. Orthotopic left lung transplantation was performed at the end of the preservation period. RESULTS: Lung function was good during the preservation period. With a gas mixture of 50% O2 + 3% CO2 + 47% N2 delivered to the multiorgan block, arterial oxygen tension ranged from 331 +/- 19 to 383 +/- 8 mm Hg; carbon dioxide tension ranged from 18 +/- 5 to 32 +/- 5 mm Hg; and pH ranged from 7.36 +/- 0.02 to 7.45 +/- 0.08. After transplantation, the dogs were kept anesthetized and ventilated for 24 hours with the same gas mixture. The opposite pulmonary artery was occluded 0 to 6 hours after transplantation. Arterial blood pressures were stable after surgery. Arterial oxygen tension was maintained between 205 +/- 39 and 320 +/- 57 mm Hg, and arterial carbon dioxide tension was maintained between 23 +/- 2 and 34 +/- 2 mm Hg. Lung tissue wet/dry weight ratio was 4.94 +/- 0.17 after preservation; this ratio did not differ from that found in normal controls (4.91 +/- 0.10). CONCLUSIONS: This study shows that the lungs were well preserved for more than 24 hours of preservation when the normothermic multiorgan block preparation was used. The transplanted left lung was able to support the anesthetized dog after the opposite pulmonary artery was occluded.     

Restoration of endothelial cell function by chronic cicletanine treatment in Dahl salt-sensitive rats with salt-induced hypertension

Various modes of high-frequency ventilation (HFV) have been developed to avoid the disadvantages of conventional mechanical ventilation. In the present study, we examined the hypothesis that high-frequency oscillation (HFO) is superior to high-frequency positive pressure ventilation (HPPV) and combined high-frequency ventilation (CHFV) in surfactant-deficient rabbits. The aim of the ventilator strategy was to adjust the mean airway pressure to 2 cm above critical opening pressure of the inflation limb of the respiratory system pressure volume (P/V) curve, achieve a normal tidal volume (VT) (5 ml/kg body weight) and apply repeated sustained inflations. We studied the effect of these HFV modes on oxygenation, lung mechanics and lung histology in 15 New Zealand White rabbits during a 6-hour experiment. Statistically, the HFO group demonstrated significantly better oxygenation (P < 0.05), lung mechanics (lung stability index: P < 0.05), and better lung tissue histology compared to the HPPV and CHFV groups. In contrast to the HPPV and CHFV groups, the P/V curves of the HFO group showed significant recovery over the 6-hour period after lavage. The lungs of the HFO-treated group had a more uniform distribution of alveoli and less overdistention than the HPPV group (P < 0.002), and less atelectasis than the CHFV group (P < 0.05). The HFO group had less lung injury than the CHFV groups (P < 0.01) and its lungs contained significantly less water than both other groups (P < 0.05). We conclude that the relationship between mean and end-expiratory pressures impacts strongly on both oxygenation and the progression of injury during HFV at the same mean airway pressures. The HFO group showed less acute lung injury than the other ventilatory groups.     

Abnormal prenatal lung development resulting from maternal zinc deficiency in rats

The effect of maternal zinc deficiency during gestation on fetal lung development was studied. Sprague-Dawley rats were fed from the day of mating (day zero) a zinc deficient diet (0.4 +/- 0.1 ppm zinc) ad libitum, or a zinc supplemented control diet (100 ppm zinc) either ad libitum or with restricted intake. Fetuses were removed by cesarean section on days 17 to 21 of gestation. Fetuses of zinc deficient dams had smaller lungs both in absolute weight and relative to body weight on all days than did either ad libitum-fed or restricted-intake controls. On days 20 and 21 of gestation, concentration of fetal lung lecithin and phosphatidylethanolamine was lower in zinc deficient fetuses than in control groups, indicating a reduced production of pulmonary surfactant. The lecithin to sphingomyelin ratio of amniotic fluid was lower in zinc deficient rats than in controls on days 19, 20, and 21 of gestation. On days 18 through 21 of gestation, fetal lung DNA concentration in zinc deficient fetuses was lower than in controls, but there were no differences in fetal lung zinc concentration. Histological examination of lungs from zinc deficient fetuses at term showed air spaces that were slightly collapsed with smaller lumina of the alveolar ducts than in controls.     

Chronic K-supplementation decreases myocardial [Na,K-ATPase] and net K-uptake capacity in rodents

The effects of high K intake on plasma K, myocardial K content and Na,K-ATPase concentration and on myocardial K uptake during KCl infusion were evaluated in rodents. Myocardial Na,K-ATPase was quantified in crude homogenates by K-dependent pNPPase activity in rats, and in intact samples by3H-ouabain binding in guinea pigs. Na, K-ATPase alpha isoform distribution was assessed by immunoblotting. Plasma K was monitored in anesthetized rats during intravenous infusion of 0.75 mmol KCl/100 g body weight/h. A significant increase in plasma K was observed after 2 days of K supplementation, 4.9+/-0.2 (mean+/-s.e.m.)v 3.0+/-0.2 mmol/l in weight matched controls ( P<0.01,n=5) and this difference remained stable. After 1 day, a significant myocardial K content increase was obtained, 86. 2+/-3.0v 76.7+/-1.9 micromol/g wet weight (P<0.05, n=5); after 4 days myocardial K stabilized 4.9+/-1.2 micromol/g wet weight above control level (P<0.05,n=5). From the 4th day, a significant decrease in myocardial K-dependent pNPPase activity was observed, 1.18+/-0.04v 1. 31+/-0.01 micromol/min/g wet weight in weight matched controls (P<0. 05,n=5); after 2 weeks the decrease was 29% (P<0.05,n=5), with a reduction in alpha1-isoform abundance by 24% (P<0.05,n=5), and a tendency to a decrease in alpha2 of 10% (n.s.,n=5). The measurements were validated by 3H-ouabain binding to myocardial samples from guinea pigs K-supplemented for 2 weeks, showing a decrease of 21% (P<0.05,n=5). During KCl infusion, the myocardial K content increase rate was reduced by 52% (P<0.05) in the K-supplemented rats. The observed effects of K-supplementation on plasma K, myocardial K content and myocardial K-dependent pNPPase activity were abolished within 2 days after reallocation to chow with normal K content. In conclusion, high K-intake is associated with significantly and reversible increased plasma and myocardial K content, and decreased myocardial Na,K-ATPase concentration and net myocardial K uptake capacity. Thus, the heart is protected from major increases in intracellular K concentrations during chronically-high K-intake.     

Effects of partial liquid ventilation with perfluorocarbons on pressure-flow relationships, vascular compliance, and filtration coefficients of isolated blood-perfused rabbit lungs

OBJECTIVES: The density of perfluorocarbons is almost twice that of blood. Therefore, we hypothesized that partial liquid ventilation with these fluids markedly affects pulmonary hemodynamics and filtration coefficients. To test these hypotheses we studied pressure-flow relationships, vascular compliances, capillary pressures, and filtration coefficients in normal and perfluorocarbon-ventilated rabbit lungs. DESIGN: Controlled animal study with an ex-vivo isolated lung preparation. SETTING: Research laboratory for experimental anesthesiology at the Heinrich-Heine-University of Düsseldorf. SUBJECTS: Fourteen New Zealand White rabbits. INTERVENTIONS: The lungs were perfused under zone 3 flow conditions with autologous blood at various flow rates (50 to 250 mL/min, closed circuit, roller pump, 37 degrees C) and ventilated with 5% CO2 in air (positive end-expiratory pressure: 2 cm H2O, tidal volume: 10 mL/kg, respiratory rate: 30 breaths/min) without (control group, n=7) and with (n=7) perfluorocarbon administered intratracheally (15 mL/kg). MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial, left atrial, and airway pressures, as well as blood reservoir volume (reflecting changes in pulmonary blood volume) and lung weight, were measured continuously. Inconsistent with our hypothesis, we found no significant differences between both groups in the slopes and intercepts of the pressure-flow relationships. There were no significant differences in capillary pressures determined by double occlusion (6.7+/-1.2 vs. 6.3+/-1.3 cm H2O for control group, p=.53), vascular compliances (0.51+/-0.10 vs. 0.47+/-0.09 mL/cm H2O for control group, p=.38), and filtration coefficients (0.33+/-0.06 vs. 0.37+/-0.07 mL/min/mm Hg/100 g wet weight for control group, p=.80, Mann-Whitney). CONCLUSIONS: Partial liquid ventilation with perfluorocarbons has no relevant effects on pulmonary filtration coefficients and global hemodynamic variables of isolated zone 3 lungs. These findings suggest that right ventricular afterload is not changed with partial liquid ventilation. It is likely, however, that intrapulmonary blood flow is redistributed toward less-dependent regions, although relevant global hemodynamic changes are absent during partial liquid ventilation.     

Isolated lung perfusion: single-pass system versus recirculating blood perfusion in pigs

BACKGROUND: Cytostatic isolated lung perfusion has been advocated for treating pulmonary metastasis of soft tissue sarcoma. Different techniques of isolated lung perfusion have been developed. METHODS: Isolated lung perfusion with and without doxorubicin was performed on white pigs during 15 minutes either by a single-pass system (n = 7) or by a recirculating-blood perfusion system (n = 7). Three animals with endovenous drug application served as controls. Leakage was assessed using isotopic tracers. Perfusion-induced lung tissue injury was determined by postperfusion chest radiographs, by angiotensin-converting enzyme-to-protein ratio in the plasma and in the bronchioalveolar lavage fluid, and by wet-to-dry weight ratio and histologic examination of lung biopsy specimens at 20 and 50 minutes. Doxorubicin concentration in lung tissue and plasma was compared between the three study groups. RESULTS: All isolated lung perfusion studies were successfully performed without significant systemic leakage (< 0.6%). Wet-to-dry weight ratio was significantly lower after single-pass as compared with recirculating-blood perfusion and endovenous drug application at both time points (5.0 +/- 1.1 and 5.3 +/- 0.8 for single-pass versus 6.6 +/- 1.1 and 6.9 +/- 0.5 for recirculating-blood versus 6.6 +/- 0.2 and 5.9 +/- 0.7 for the control group, respectively; p < 0.05). Angiotensin-converting enzyme-to-protein plasma ratio in the single-pass group was significantly lower only at 20 minutes (6.3 +/- 2.4 versus 9.3 +/- 1.0 versus 9.7 +/- 1.9, respectively; p < 0.05) but not at 50 minutes. Angiotensin-converting enzyme-to-protein ratio in bronchoalveolar lavage fluid, histology of lung biopsy specimens, and chest radiographs did not differ significantly between the three groups. Doxorubicin lung tissue concentration was not significantly different after single-pass (17.5 micrograms/g) and recirculating-blood perfusion (21.9 micrograms/g), but was significantly higher than after endovenous drug application (3.0 micrograms/g; p < 0.01). CONCLUSIONS: Both isolated lung perfusion techniques resulted in a sixfold to sevenfold higher doxorubicin lung tissue concentration than after endovenous application. Isolated lung perfusion-induced lung injury was similar for both techniques, but recirculating-blood perfusion appeared to result in more acute lung injury and was technically more demanding than single-pass perfusion.     

In vivo cyclin E expression as a marker for early cervical neoplasia

BACKGROUND: Heat shock has been associated with the acquisition of tolerance to a wide variety of stressful conditions, including ischemia. This is partly mediated by the production of various heat shock proteins (HSP), including HSP70. One novel approach to the reduction of ischemia-reperfusion injury after lung transplantation is the induction of HSP70 by heat pretreatment of the donor. The purpose of this study was to investigate the feasibility of this approach in an animal model of lung transplantation. METHODS: Animals were divided into six main groups, with groups I to III representing transplanted animals: In groups I and II, donor animals were anesthetized and then underwent heat stress 6 and 12 hours before organ harvest, respectively. Control animals underwent general anesthesia but no heat stress. After harvest, left lungs from groups I to III were preserved for 18 hours at 40 degrees C and then implanted into isogeneic recipients, which were killed 24 hours after reperfusion to assess graft function. Group IV and V animals underwent heat stress followed by a recovery period of 6 and 12 hours, respectively. Lungs were collected both at the time of harvest (right lungs) and after 18 hours of cold preservation (left lungs). Group VI served as nontransplanted controls. Groups IV to VI did not undergo lung transplantation. RESULTS: At the time of harvest but before implantation, HSP70 was significantly increased in heat-shocked nontransplanted donor lungs (groups IV and V) compared with group VI controls. After 18 hours of cold preservation, HSP70 levels were higher in group IV compared with group V and group VI controls. At 24 hours after reperfusion, mean arterial oxygenation was significantly higher in group I compared with group II and group III controls (290.25+/-24.5 vs 154.5+/-23.9 and 119.6+/-11.3 mm Hg, respectively; P < .001). Myeloperoxidase activity was improved in group I compared with group III controls (0.048+/-0.018 vs 0.137+/-0.036 deltaOD/mg/min, respectively; P < .05). The wet/dry weight ratio was also improved in group I compared with group III controls (6.2+/-0.3 vs. 7.8+/-0.4, respectively; P < .05). CONCLUSIONS: Heat pretreatment of the donor 6 hours before harvest results in increased synthesis of HSP70, which offers a dramatic protective effect against subsequent ischemia-reperfusion injury in the lung isograft.     

Respiratory mechanics in normal hamsters

Lung volumes and quasi-static deflation volume-pressure relationships were measured in male golden hamsters anesthetized with pentobarbital. Volume was measured with a pressure plethysmograph, and pleural pressure was estimated by the use of a water-filled esophageal catheter. Mean body weight +/- SE was 122.3 +/-3.0 g, mean lung weight was 0.74 +/- 0.2 g or about 0.6% of body weight. Mean lung volume at 25 cmH2O transpulmonary pressure (TLC25) was 7.2 +/- 0.14 ml, 9.78 +/- 0.17 ml/g lung weight or 5.92 +/- 0.06 ml/100 g body weight. Mean functional residual capacity was 2.4 +/- 0.06 ml or 33.3% of TLC25. Mean vital capacity was 5.2 +/- 0.13 ml. Mean quasi-static compliance of lung was 0.63 +/- 0.03 ml/cmH2O. Chord compliance of chest wall between lung volumes of 1 and 4 ml above RV was 3.39 +/- 0.53 ml/cmH2O. At FRC, the chest wall recoiled inward, so that pleural pressure was positive (1.4 +/- 0.13 cmH2O) and the lung was resisting further collapse. The slope of the lung's deflation volume-pressure curve changed at FRC, ERV was small (0.36 +/- 0.03 ml), and RV was determined by complete airway closure. Thus the mechanisms determining FRC are unusual and include an influence of airway closure.     

Resection hip arthroplasty for malignant pelvic tumor. Outcome in 5 patients followed more than 2 years

BACKGROUND: Vasoactive intestinal peptide (VIP) has been reported to have some properties that provide protection from lung injury. Furthermore, its protective effect in cold storage of donor lungs has been confirmed. We examined its effect and the timing of administration in an in vivo rat lung transplantation model. METHODS: All lungs were flushed with low-potassium dextran-1% glucose solution, and orthotopic left lung transplantations were performed. Rats were divided into four groups (n = 6). Group I received no preservation or storage. Groups II, III, and IV grafts were stored for 18 hours at 4 degrees C. Group II received no VIP. Group III received VIP (0.1 g/ml) via the flush solution. Group IV recipients received VIP (3 microg/kg) intravenously just after reperfusion. Twenty-four hours after transplantation, the right main pulmonary artery and right main bronchus were ligated, and the rats were ventilated with 100% O2 for 5 minutes. Mean pulmonary arterial pressure, peak airway pressure, blood gas analysis, serum lipid peroxide level, tissue myeloperoxidase activity, and wet-dry weight ratio were measured. RESULTS: The partial O2 tension values of groups III and IV were better than group II (groups II, III, and IV: 147.4 +/- 71.4, 402.1 +/- 64.8, 373.4 +/- 81.0 mm Hg; p < 0.05). Peak airway pressure was lower in groups III and IV than in group II (groups II, III, and IV: 19.7 +/- 0.8, 16.7 +/- 0.9. and 16.3 +/- 1.0 mm Hg; p < 0.05). Mean pulmonary arterial pressure in group III was lower than group II (groups II and III: 36.3 +/- 3.0 and 22.1 +/- 2.2 mm Hg; p < 0.01). Wet-dry weight ratio in group III was lower than in groups II and IV (group II, III, and IV: 5.2 +/- 0.2, 4.4 +/- 0.2, and 5.2 +/- 0.3; II vs III; p < 0.05, III vs IV; p < 0.01). Serum lipid peroxide levels in groups III and IV were significantly lower (groups II, III, and IV: 2.643 +/- 0.913, 0.455 +/- 0.147, and 0.325 +/- 0.124 nmol/ml; p < 0.01). CONCLUSION: VIP ameliorates reperfusion injury in an in vivo rat lung transplantation model. Either administration of VIP via the flush solution or systemically just after reperfusion was associated with improved pulmonary function.     

Temporal pattern of accelerated lung growth after tracheal occlusion in the fetal rabbit

Tracheal occlusion in utero is a potent stimulus of fetal lung growth. We describe the early growth mechanics of fetal lungs and type II pneumocytes after tracheal ligation (TL). Fetal rabbits underwent TL at 24 days gestational age (DGA; late pseudoglandular stage; term = 31 to 33 days) and were sacrificed at time intervals ranging from 1 to 5 days after TL. Lung growth was measured by stereological volumetry and bromodeoxyuridine (BrdU) pulse labeling. Pneumocyte II population kinetics were analyzed using a combination of anti-surfactant protein A and BrdU immunohistochemistry and computer-assisted morphometry. Nonoperated littermates served as controls. TL resulted in dramatically enhanced lung growth (lung weight/body weight was 5.00 +/- 0.81% in TL versus 2.52 +/- 0.13% in controls at 29 DGA; P < 0.001, unpaired Student's t-test). Post-TL lung growth was characterized by a 3-day lag-phase typified by relative stagnation of growth, followed by distension of airspaces, increased cell proliferation, and accelerated architectural and cellular maturation by postligation days 4 and 5. During the proliferation phase, the replicative activity of type II cells was markedly increased (type II cell BrdU labeling index was 10.0 +/- 4.1% in TL versus 1.1 +/- 0.3% for controls at 29 DGA; P < 0.02), but their numerical density decreased (3.0 +/- 0.5 x 10(-3)/microm2 in TL versus 4.5 +/- 0.3 x 10(-3)/microm2 in controls at 29 DGA; P < 0.02), suggesting accelerated terminal differentiation to type I cells. In conclusion, post-TL lung development is characterized by a well defined temporal pattern of lung growth and maturation. The rabbit model lends itself well to study the regulatory mechanisms underlying accelerated fetal lung growth after TL.     

Extended preservation of ischemic pulmonary graft by postmortem alveolar expansion

BACKGROUND: If lungs could be retrieved for transplantation from non-heart-beating cadavers, the shortage of donors might be significantly alleviated. METHODS: Peak airway pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and wet to dry weight ratio were measured during delayed hypothermic crystalloid flush in rabbit lungs (n = 6) at successive intervals after death comparing cadavers with lungs left deflated (group 1), inflated with room air (group 2) or 100% oxygen (group 4), or ventilated with room air (group 3), or 100% nitrogen (group 5), or 100% oxygen (group 6). RESULTS: There was a gradual increase in mean pulmonary artery pressure and pulmonary vascular resistance with longer postmortem intervals in all study groups (p = not significant, group 1 versus group 2 versus group 3). There was also a gradual increase in peak airway pressure and wet-to-dry weight ratio over time in all groups, which reflected edema formation during flush (airway pressure, from 14.5 +/- 1.0 cm H2O to 53.7 +/- 12.2 cm H2O, and wet-to-dry weight ratio, from 3.6 +/- 0.1 to 11.5 +/- 1.2, in group 1 at 0 and 6 hours postmortem, respectively; p < 0.05). Compared with group 1, however, the increase in groups 2 and 3 was much slower (airway pressure, 20.9 +/- 0.5 cm H2O and 18.8 +/- 1.2 cm H2O, and wet-to-dry weight ratio, 5.2 +/- 0.3 and 4.6 +/- 0.4 at 6 hours postmortem, respectively; p < 0.05 versus group 1 and p = not significant, group 2 versus group 3). Airway pressure and wet-to-dry weight ratio did not differ between groups 2 and 4 or between groups 3, 5, and 6. CONCLUSIONS: These data suggest that (1) pulmonary edema will develop in atelectatic lungs if hypothermic flush is delayed for 2 hours after death, (2) postmortem inflation is as good as ventilation in prolonging warm ischemic tolerance, (3) inflation with oxygen or ventilation with nitrogen or oxygen is no different from that with room air, and (4) therefore, prevention of alveolar collapse appears to be the critical factor in protecting the lung from warm ischemic damage independent of continued oxygen delivery.     

Effects of ethanol intake on retinol concentration in the milk of lactating rats

The effect of the consumption of ethanol (5%) on retinol concentration in milk was studied in the rat on day 12 after delivery, together with the evolution of dam body weight and pup growth rate. Female Wistar rats receiving alcohol (5%) in drinking water during lactation (N = 7) were compared to normal controls fed ad libitum (N = 6). The mean maternal alcohol intake was 3.96 +/- 0.23 g/kg body weight per day. To determine retinol levels in milk we used the Bessey and Lowry method, modified by Araújo and Flores ((1978) Clinical Chemistry, 24:386-392). The pups were separated from dams for a 2-4-h period, after which the dams were injected intraperitoneally with anesthetic and oxytocin. The concentration of retinol in milk was 162.88 +/- 10.60 micrograms/dl in the control group and 60.02 +/- 8.22 micrograms/dl in the ethanol group (P < 0.05). The ethanol group consumed less food than the controls and lost a significant amount of weight during lactation. On days 8, 10 and 12, the body weight of the pups from rats given ethanol (13.46 +/- 0.43, 16.12 +/- 0.48 and 18.60 +/- 0.91 g, respectively) were significantly lower (P < 0.05) than the weight of pups from controls (15.2 +/- 0.44, 18.36 +/- 0.54, 20.77 +/- 0.81 g). These data show that ethanol intake during the suckling period, even at low concentrations, decreases the amount of retinol in milk and, therefore, the amount available to the pups.     

Chlorine gas induced acute lung injury in isolated rabbit lung

This study was designed to investigate the pathogenesis of chlorine gas (Cl2) induced acute lung injury and oedema. Isolated blood-perfused rabbit lungs were ventilated either with air (n=7) or air plus 500 parts per million (ppm) of Cl2 (n=7) for 10 min. Capillary pressure, measured by analysing the pressure/time transients of pulmonary arterial, venous and double (both arterial and venous) occlusions, was unchanged in both groups. In Cl2-exposed lungs, the fluid filtration rate increased from -0.228+/-0.25 to 1.823+/-1.23 mL min(-1) x 100 g(-1) (p<0.001) and the filtration coefficient increased from 0.091+/-0.01 to 0.259+/-0.07 mL x min(-1) x cmH2O(-1) x 100 g(-1) (p<0.001). No changes were observed in the control lungs. The extravascular lung water/blood-free dry weight ratio was 8.6+/-1.6 in the Cl2 group and 4.0+/-0.5 in the control group (p<0.001), confirming that the increase in lung weight was related to accumulation of extravascular fluid. Although the alveolar flooding by oedema is explained, in part, by the Cl2-induced epithelial injury, our results suggest that Cl2 exposure induces acute lung injury and oedema due to an increased microvascular permeability.     

Transthoracic resistance in human defibrillation. Influence of body weight, chest size, serial shocks, paddle size and paddle contact pressure

Successful defibrillation depends on delivery of adequate electrical current to the heart; one of the major determinants of current flow is transthoracic resistance (TTR). To study the factors influencing TTR, we prospectively collected data from 44 patients undergoing emergency defibrillation. Shocks of 94-450 J delivered energy were administered from specially calibrated Datascope defibrillators that displayed peak current flow, thereby permitting determination of TTR. Shocks were applied from standard (8.5-cm diameter) or large (13 cm) paddles placed anteriorly and laterally. First-shock TTR ranged from 15-143 omega. There was a weak correlation between TTR and body weight (r = 0.45, p less than 0.05) and a stronger correlation between TTR and chest width (r = 0.80, p less than 0.01). Twenty-three patients who were defibrillated using standard 8.5-cm paddles had a mean TTR of 67 +/- 36 omega (+/- SD), whereas 21 patients who received shocks using paddle pairs with at least one large (13 cm) paddle had a 21% lower TTR of 53 +/- 24 omega (p = 0.05, unpaired t test). Ten patients received first and second shocks at the same energy level; TTR declined only 8%, from 52 +/- 19 to 48 +/- 16 omega (p less than 0.01, paired t test). In closed chest dogs, shocks were administered using a spring apparatus that regulated paddle contact pressure against the thorax. Firmer contact pressure caused TTR to decrease 25%, from 48 +/- 22 to 36 +/- 17 omega (p less than 0.01, paired t test). Thus, human TTR varies widely and is related most closely to chest size. TTR declines only slightly with a second shock at the same energy level. More substantial reductions in TTR and declines only slightly with a second shock at the same energy level. More substantial reductions in TTR and increases in current flow can be achieved by using large paddles and applying firm paddle contact pressure.     

Same-day pediatric surgery

HL surfactant was used for vital indications in 12 newborns with respiratory distress syndrome born at 28-36 weeks weighing 1000-2500 g at birth and postgestation age of up to 48 h, without apparent congenital diseases and evident signs of intrauterine infection and with intraventricular hemorrhages no more severe than of the second degree. Control group consisted of 12 babies with similar condition treated similarly but without surfactant. Surfactant HL was administered endotracheally in a dose of 50 mg/kg twice at 12-h interval. Good effect was attained in 4 newborns, stable deterioration in 2, and no effect in 6 children. The majority of artificial ventilation values were virtually the same in both groups, but 2 days after surfactant, FiO2 was significantly lower in the controls than in experimental group (0.37 +/- 0.05 vs. 0.64 +/- 0.4, p < 0.01), and VEI was higher in the controls (0.33 +/- 0.05 vs. 0.18 +/- 0.03, p < 0.05). VR, MAP, FiO2, and oxygenation index decreased slower in the test group than in the controls. The mean duration of treatment with hypoxic gaseous mixtures and artificial ventilation of the lungs in the test vs. control group were 143 +/- 60 and 288 +/- 45 h vs. 45.5 +/- 8.3 and 200.8 +/- 28.5 h, respectively. The incidence of air leakage syndrome was 83% (10 cases) in the test group and 17% (2 cases) in the control group, chronic pulmonary diseases developed in 3 (25%) babies in the test and in 1 (8.3%) in the control group. Seven (67%) children in the test group developed obstructive changes in the lungs vs. 1 child in the control group. One child (test group) died from causes other than pulmonary. Hospital stay was longer in the test group than in control (14.8 +/- 1.7 vs. 8.3 +/- 1.3 days, p < 0.01).     

Gender differences in body fat content are present well before puberty

To determine whether gender differences in body fat could be detected in prepubertal children using dual energy X-ray absorptiometry (DEXA), body composition was measured in 20 healthy boys aged 3-8 y matched for age, height and weight with 20 healthy girls. Although boys and girls did not differ in age, height, weight, body mass index (BMI) or bone mineral content, the boys had a lower percentage of body fat (13.5 +/- 5.1 vs 20.4 +/- 6.1%, P < 0.01), a lower fat mass (3.2 +/- 2.0 vs 4.9 +/- 3.1 kg, P < 0.01), and a higher bone-free lean tissue mass (18.6 +/- 4.3 vs 17.0 +/- 3.5 kg, P < 0.01) than the girls. Girls had approximately 50% more body fat than the boys. This is the first DEXA study to show that boys aged 3-8 y have less body fat than girls of similar age, height and weight. Thus, this technology demonstrates that significant gender differences in body composition are evident, well before the onset of puberty.     

Effects of cardiomyoplasty on cardiac growth in rats

BACKGROUND AND AIM OF THE STUDY: Cardiomyoplasty (CMP) has been proposed as a treatment for pediatric patients, but restriction of cardiac growth by the muscle wrap is a potential source of concern. This possibility was investigated in an immature animal model. METHODS: Six-week-old rats (body weight 203.8 +/- 5.4 g, mean +/- SEM) underwent either left thoracotomy with CMP (group I, n = 7), or thoracotomy without CMP (group II, n = 8). A third group (group III, n = 7) served as untreated controls. Final measurements were made 20 weeks later after body weights had reached a plateau. RESULTS: Preoperative body weights were not significantly different between the groups. At elective sacrifice, the body weights of animals that underwent surgery did not differ significantly (group I, 558.0 +/- 21.5 g and group II, 617.3 +/- 20.3 g), but were significantly less than those of control animals (727.6 +/- 13.3 g, p < 0.001 and p < 0.01, respectively). Cardiac ventricular weights in the CMP group were significantly less than those of control animals (group I, 1.21 +/- 0.06 g; group III 1.45 +/- 0.04 g; p < 0.01), but were not statistically different from those of the sham thoracotomy group (group II, 1.36 +/- 0.05 g). Mean left ventricular end-diastolic volumes were similar in all groups (group I, 0.67 +/- 0.07 mL; group II, 0.66 +/- 0.07 mL; and group III, 0.69 +/- 0.10 mL; p = ns). CONCLUSIONS: A major surgical procedure impairs growth in juvenile rats. no evidence emerged from this study for additional restriction of cardiac development due to cardiac wrapping. However, studies that include stimulated muscle wraps are needed before CMP should be considered for the pediatric age group.     

Placebo-controlled comparison between a single dose and a multidose of betamethasone in accelerating lung maturation of mice offspring

OBJECTIVE: Our purpose was to determine, in a placebo-controlled manner with a mouse model, whether a multidose of betamethasone is more beneficial than a single dose in accelerating fetal lung maturation. STUDY DESIGN: Ninety gravid CD-1 mice were randomly assigned to 1 of 3 groups (n = 30) to receive either a placebo (0.25 mL subcutaneously) or betamethasone (0.1 mg subcutaneously) as a single dose on gestational day 14 or as a multidose twice daily on gestational day 14 and 15. Ten pregnancies in each group were terminated at gestational day 16.5 to observe the neonatal breathing pattern (scale 0 to 5; 5 is unlabored breathing) and the lung histologic findings (scale 0 to 5; 5 is alveolar budding). The lungs of the offspring belonging to the remaining 20 pregnancies in each group were removed and weighed at postnatal day 1, 3, 5, or 120. RESULTS: Fetuses exposed to a multidose of betamethasone displayed a higher breathing score at gestational day 16.5 than either to a single dose or to the placebo (mean score 4.6 vs 3.8 or 1.3; P <. 001). Alveolar development was greater after exposure to a multidose of betamethasone than after a single dose or after a placebo (mean score 4.4 vs 3.5 or 1.6; P <.001). The lung weights at gestational day 16.5 were less after a multidose of betamethasone than after a single dose of either betamethasone or a placebo (18.3 +/- 1.0 g vs 21.4 +/- 1.3 g or 23.3 +/- 1.3 g; P <.02). The lung/body weight ratio was similarly affected. This reduced weight of the lungs persisted postnatally into adulthood. CONCLUSIONS: With a CD-1 mouse model, a multidose of antenatal betamethasone accelerated fetal lung maturation more than after a single dose but was accompanied with a decrease in lung weight that persisted into adulthood.     

Repeated intracerebroventricular administration of glucagon-like peptide-1-(7-36) amide or exendin-(9-39) alters body weight in the rat

Central nervous system glucagon-like peptide-1-(7-36) amide (GLP-1) administration has been reported to acutely reduce food intake in the rat. We here report that repeated intracerebroventricular (i.c.v.) injection of GLP-1 or the GLP-1 receptor antagonist, exendin-(9-39), affects food intake and body weight. Daily i.c.v. injection of 3 nmol GLP-1 to schedule-fed rats for 6 days caused a reduction in food intake and a decrease in body weight of 16 +/- 5 g (P < 0.02 compared with saline-injected controls). Daily i.c.v. administration of 30 nmol exendin-(9-39) to schedule-fed rats for 3 days caused an increase in food intake and increased body weight by 7 +/- 2 g (P < 0.02 compared with saline-injected controls). Twice daily i.c.v. injections of 30 nmol exendin-(9-39) with 2.4 nmol neuropeptide Y to ad libitum-fed rats for 8 days increased food intake and increased body weight by 28 +/- 4 g compared with 14 +/- 3 g in neuropeptide Y-injected controls (P < 0.02). There was no evidence of tachyphylaxis in response to i.c.v. GLP-1 or exendin-(9-39). GLP-1 may thus be involved in the regulation of body weight in the rat.     

Effects of hyperbaric oxygen on rat embryos

The aim of the study was to investigate the toxic effects of hyperbaric oxygen (HBO) on rat embryos. Two groups of Fischer pregnant rats were exposed to oxygen at pressures of 324 and 426 kPa for 90 min per day for 5 consecutive days (8-12 days of gestation). The third group was exposed to normobaric oxygen for 12 h on the eighth day of gestation. Two control groups were used; the first was comprised of intact and the second of sham-treated animals. The HBO treatment did not significantly affect maternal weight gain or reduce litter size, nor did it induce any embryonic abnormalities. However, the fetal body weight was reduced and the placental weight increased in the groups exposed to HBO at pressures of 324 and 426 kPa. When female fetuses which had been exposed to oxygen at 324 or 426 kPa were compared to the intact control group, a reduction in wet weights of 9.2 (p < 0.05) and 12.1% (p < 0.01), respectively, was noted. Male fetuses exposed to oxygen at 324 and 426 kPa displayed a reduced body weight of 11.7 (p < 0.01) and 16.6% (p < 0.01), respectively. Placental weight was increased by 18.9 (p < 0.01) and 23.6% (p < 0.01) in the groups exposed to oxygen at 324 and 426 kPa, respectively. These data suggest that HBO, either at 324 or 426 kPa, is not potent at inducing malformations and that the largest embryotoxic effects are upon fetal body weight and placental weight.(ABSTRACT TRUNCATED AT 250 WORDS)