Effects of prednisone on mucociliary clearance in a murine model.

All transplant patients are at increased risk of developing pulmonary infections, a significant cause of morbidity and mortality. Immunosuppressants increase the incidence of lung infection by acting not only directly on the inflammatory cells, but also on the native immune system. Experimental studies have shown corticosteroid therapy, which is used in most immunosuppressive protocols after transplantation, to suppress mucus production by inhibiting calceiform. The objective of this study was to evaluate the effects of prednisone on mucociliary clearance. A total of 120 male Wistar rats were distributed into 4 groups. Animals in P1, P2, and P3 groups received daily doses of prednisone (0.625, 1.25, and 2.5 mg/kg/d), and hosts in the Sal group underwent gavage with saline solution (2.5 mL/d). After 7, 15, and 30 days, treatment, animals were killed. We assessed ciliary beating frequency (CBF), mucociliary transport velocity (MCTV), and mucus transportability (MT). There was no significant difference for CBF regarding dose (P = .089) or treatment duration (P = .175). MCTV values of 0.60 ± 0.14 in group P1, 0.59 ± 0.13 in group P2, 0.51 ± 0.19 in group P3, and 0.61 ± 0.08 Group Sal, showed P3 to significantly differ from P1 (P = .048) and Sal (P = .007) groups. Regardless of the prednisone dose, all groups displayed impaired MT compared with the Sal group: P1 (P = .02); P2 (P = .02) P3 (P = .03). There was no interaction between the therapy and the treatment time for CBF (P = .10), MCTV (P = .71), and MT (P = .64). Prednisone reduced the transportability of mucus even when administered at low doses; however, this change was not sufficient to alter the mucociliary clearance. Only high doses of prednisone impaired mucociliary clearance.

Comparing the performance of rat lungs preserved for 6 or 12 hours after perfusion with low-potassium dextran or histidine-tryptophan-ketoglutarate.

INTRODUCTION: In lung transplantation, graft dysfunction is a frequent cause of mortality; the etiopathogenesis is related to ischemia-reperfusion injury. We sought to compare the lung performance of rats after reperfusion after presentation with 3 solutions at 2 ischemia times. METHODS: We randomized 60 male Wistar rats to undergo anterograde perfusion via the pulmonary artery with low-potassium dextran (LPD), histidine-tryptophan ketoglutarate (HTK), or saline. After extraction, the heart-lung blocks were preserved in a solution at hypothermia for 6 or 12 hours before perfusion with homologous blood for 60 minutes using ex vivo system Isolated Perfused Rat or Guinea Pig Lung System (Harvard Apparatus). Respiratory mechanics, pulmonary weight, pulmonary artery pressure (PAP), and relative lung oxygenation capacity (ROC) measurements were obtained every 10 minutes. RESULTS: Comparing tidal volume (TV), compliance, resistance, ROC, PAP, and pulmonary weight the LPD, HTK, and saline group did not differ at 6 and 12 hours. The TV was higher in the lungs with 6-hour ischemia in the LPD, HTK, and saline groups. Compliance was higher in the lungs with 6-hour ischemia in the LPD and saline groups. There were no differences in ROC values comparing lungs with 6- versus 12-hour ischemia in the LPD group. A significant difference was observed between lungs in the HTK and saline groups. Resistance was higher in the lungs with 12-hour ischemia among the LPD, HTK, and saline groups. There was a gradual weight increase in the lungs, particularly those undergoing 12-hour ischemia, despite the absence of a significant difference between groups. CONCLUSION: Rat lungs perfused with LPD and HTK preservation solutions showed similar reperfusion performances in this ex-vivo perfusion model.

Comparison between Perfadex and locally manufactured low-potassium dextran solution for pulmonary preservation in an ex vivo isolated lung perfusion model.

INTRODUCTION: Lung transplantation, a consolidated treatment for end-stage lung disease, utilizes preservation solutions, such as low potassium dextran (LPD), to mitigate ischemia-reperfusion injury. We sought the local development of LPD solutions in an attempt to facilitate access and enhance usage. We also sought to evaluate the effectiveness of a locally manufactured LPD solution in a rat model of ex vivo lung perfusion. METHODS: We randomized the following groups \?\adult of male Wistar rats (n = 25 each): Perfadex (LPD; Vitrolife, Sweden); locally manufactured LPD-glucose (LPDnac) (Farmoterapica, Brazil), and normal saline solution (SAL) with 3 ischemic times (6, 12, and 24 hours). The harvested heart-lung blocks were flushed with solution at 4°C. After storage, the blocks were connected to an IL-2 Isolated Perfused Rat or Guinea Pig Lung System (Harvard Apparatus) and reperfused with homologous blood for 60 minutes. Respiratory mechanics, pulmonary artery pressure, perfusate blood gas analysis, and lung weight were measured at 10-minute intervals. Comparisons between groups and among ischemic times were performed using analysis of variance with a 5% level of significance. RESULTS: Lungs preserved for 24 hours were nonviable and therefore excluded from the analysis. Those preserved for 6 hours showed better ventilatory mechanics when compared with 12 hours. The oxygenation capacity was not different between lungs flushed with LPD or LPDnac, regardless of the ischemic time. SAL lungs showed higher PCO(2) values than the other solutions. Lung weight increased over time during perfusion; however, there were no significant differences among the tested solutions (LPD, P = .23; LPDnac, P = .41; SAL, P = .26). We concluded that the LPDnac solution results in gas exchange were comparable to the original LPD (Perfadex); however ventilatory mechanics and edema formation were better with LPD, particularly among lungs undergoing 6 hours of cold ischemia.

Effects of short-term dietary restriction on survival of mammary ascites tumor-bearing rats.

We studied the effects of short-term dietary restriction on the survival of 3-4-month-old tumor-free and tumor-bearing Fisher rats. The diet-restricted food regimen consisted of alternate day ad libitum feeding followed by alternate day fasting. Diet-unrestricted control rats were fed ad libitum daily. Six tumor-free rats on the diet-restricted regimen compensated for the dietary restriction by an increase in food consumption during the alternate feeding days, and lost an average of only 2-3% of their weight in 13 days. Six tumor-free rats on a daily ad libitum feeding regimen gained an average of 6.8% in 15 days. The above dietary-restricted regimen was initiated 1 week before 24 rats were inoculated intraperitoneally with 15 million Mat 13762 ascites tumor cells. Sixteen of 24 (66.7%) diet-restricted tumor-bearing hosts and 5/24 (20.8%) diet-unrestricted tumor-bearing hosts survived at 9 days after tumor inoculation (p less than 0.005). Twelve of 24 (50%) diet-restricted tumor-bearing hosts, and 3 of 24 (12.5%) diet-unrestricted tumor-bearing hosts, survived at 10 days after tumor inoculation (p less than 0.025). Thus, the survival of tumor-bearing rats was enhanced by short-term relatively mild dietary restrictions. We suggest that relatively mild dietary restrictions should be included in clinical trials designed to inhibit cancer growth and enhance the survival of human cancer patients.