Influence of lung mechanical properties and alveolar architecture on the pathogenesis of ischemia-reperfusion injury.

We tested the hypothesis that lung preservation techniques disarrange lung architecture, increase pulmonary impedance and lead to ischemia-reperfusion injury, which can be prevented by re-establishment of optimal lung geometry. In the first phase, fresh, cold ischemic, preserved lungs insufflated to total lung capacity (TLC) and preserved lungs ventilated with tidal volume prior to reperfusion were submitted to a 60-min ex-vivo reperfusion to evaluate the gas exchange, pulmonary hemodynamic and lung mechanics' properties. In the second phase, we evaluated the mechanical properties of lungs submitted to the same conditions of the first phase.

Alveolar recruitment prevents rapid-reperfusion-induced injury of lung transplants.

Background: Physical factors play an important role in ischemia-reperfusion-induced injury of lung transplants. For example, rapid restoration of reperfusion resulted in severe pulmonary edema and deterioration of pulmonary function of lung explants in an ex vivo reperfusion system. This type of injury can be prevented by a stepwise increase in the perfusion flow rate, or by adding prostaglandin E1 (PGE1) to the blood perfusate during the first 10 minutes.

Prevention of rapid reperfusion-induced lung injury with prostaglandin E1 during the initial period of reperfusion.

We have found that the instantaneous restoration of blood flow causes acute dysfunction and massive edema in rat lungs after 4 hours of room temperature ischemia. This is associated with an early increase in pulmonary artery pressure (Ppa) and can be prevented by a stepwise increase in flow rate during the first 10 minutes of reperfusion. The objectives of this study were to determine whether rapid reperfusion causes lung injury after hypothermic preservation, and whether this injury can be attenuated by a short-course of prostaglandin E1 (PGE1).

Rapid reperfusion causes stress failure in ischemic rat lungs.

Objective: Rapid reperfusion may be injurious to the ischemic lung. Our aim was to confirm that slow reperfusion improves postischemic pulmonary function and to elucidate the ultrastructural changes associated with slow versus rapid reperfusion. METHODS.

Optimal inflation volume for hypothermic preservation of rat lungs.

Background: Recent studies have suggested that preservation of donor lungs with inflation provides better pulmonary function after transplantation, but hyperinflation of pulmonary grafts during storage increases reperfusion pulmonary edema. To elucidate the optimal inflation volume during the preservation period, and the possible role of barotrauma in lung injury after atelectatic storage, we examined the effects of inflation volume and reinflation protocols in hypothermically preserved rat lungs.

Methods: Adult rat lung blocks were preserved at 4 degrees C for 18 hours at various levels of inflation.

Major histocompatibility complex expression and lung ischemia-reperfusion in rats.

Background: Clinical studies in kidney and liver transplantation have suggested that poor early function is associated with increased graft loss due to rejection. Ischemia-reperfusion injury may contribute to rejection by enhancing graft immunogenicity.

Methods: A rat model of unilateral in situ pulmonary ischemia-reperfusion was used to examine class II major histocompatibility complex (MHC) antigen expression.

Use of a hypoxic lung as a deoxygenator to provide extended assessment of pulmonary function in rats.

Isolated perfused lung systems are commonly used to assess lung function in experimental studies. Assessment of hemodynamics and gas-exchange function in these systems is limited by the availability of venous blood. This study describes and validates a rat lung perfusion circuit in which a double-lung block ventilated with a hypoxic gas mixture [inspired O2 fraction (FIO2) 0.

Effect of hypotension preceding death on the function of lungs from donors with nonbeating hearts.

Background: A shortage of suitable brain-dead donors continues to severely limit lung transplantation. Use of donors with nonbeating hearts has been suggested as a solution. Lungs are unique, in that aerobic metabolism can continue in the absence of blood circulation because oxygen is present in airways and alveoli.

Effect of the combination of human thioredoxin and L-cysteine on ischemia-reperfusion injury in isolated rat lungs.

We studied the role of human thioredoxin and L-cysteine in ischemia-reperfusion lung injury. Thirty adult Wistar rats were allocated to five groups, according to the drug added to the pulmonary artery flush solution before ischemia (groups 1 and 2: none; group 3: human thioredoxin; group 4: L-cysteine, and group 5: human thioredoxin and L-cysteine) and according to the ex vivo ischemic interval at 37 degrees C (group 1: no ischemia; groups 2-5: 90 min). After ischemia, the lungs were reperfused for 60 min with Krebs-Henseleit solution containing 4% bovine serum albumin.

Lung oxidant injury in a model of lung storage and extended reperfusion.

Donor lungs for transplantation are susceptible to "preservation" injury during both storage and postimplantation reperfusion. We investigated whether lung dysfunction seen after storage and reperfusion was associated with any biochemical hallmarks of direct cellular oxidant injury to lipid, protein, or DNA. Heart/lung blocks were extracted from adult rats following pulmonary vascular flush.

In situ ischemia and hypoxia enhance alveolar macrophage tissue factor expression.

Alveolar and interstitial fibrin deposition is a prominent pathologic feature in many acute lung injury syndromes. Previous studies have suggested that ischemic lung preservation has a stimulatory effect on donor alveolar macrophages (Mphis) during transplantation. An animal model of lung preservation was developed to examine the hypothesis that ischemia enhances Mphi procoagulant activity (PCA) as a potential mechanism contributing to lung reperfusion injury.

A short course of FK506 can induce limited donor-specific graft acceptance.

To examine the hypothesis that a short course of FK506 would induce permanent graft acceptance after lung transplantation, left lung allotransplantation was performed in 14 mongrel dogs. In group 1 (control; n = 3), no immunosuppressive agent was given. In group 2 (n = 7), FK506 (1.

Effect of methylprednisolone on angiogenesis in syngeneic rat tracheal grafts.

Airway anastomotic complications remain a cause of morbidity after clinical lung transplantation. The use of corticosteroid therapy to control pulmonary rejection has raised concern over delayed airway healing. We therefore investigated the hypothesis that the effects of methylprednisolone (MP) impair the revascularization and epithelial regeneration of heterotopic syngeneic tracheal isografts.

Functional and biochemical assessment of postpreservation lung viability in a rat model.

We examined the relationship between DNA synthesis and postpreservation lung hemodynamics and gas exchange. Adult male Wistar rats (n = 168) were randomly allocated into seven groups (n = 24) according to the pulmonary vascular flush used [EuroCollins (EC), saline, or no flush] and to the temperature of flush and storage (4, 21, or 37 degrees C). In each group, lungs were stored for four different time periods (0-24 h).

Assessment of postpreservation rat lung function using a new model for extended venous reperfusion.

Understanding the physiological significance of biochemical events after lung preservation in rats has been hampered by the lack of a suitable model for physiological assessment. We have developed an ex vivo paracorporeal rat lung perfusion model that permits hemodynamic and gas exchange evaluation of lung function. After anesthesia and heparinization, the heart-lung block was removed and the left lung was reperfused for 1 h at a constant flow of 4 ml/min with homologous venous blood drained from the inferior vena cava of the paracorporeal (host) rat.