Nitroglycerin reperfusion reduces ischemia-reperfusion injury in non-heart-beating donor lungs.

BACKGROUND: Lung transplantation is severely limited by an inadequate supply of lungs from brain-dead donors. A potential solution is use of lungs from non-heart-beating donors (NHBDs) with retrieval at intervals after circulatory arrest and death. A warm ischemic period with concomitant reperfusion injury is a major limiting factor in the transplantation of lungs retrieved from NHBDs. We hypothesized that the administration of the nitric oxide-donor nitroglycerin to lungs from NHBDs would reduce ischemia-reperfusion injury by activation of guanylate cyclase to form guanosine 3',5'-cyclic monophosphate (cGMP). METHODS: An in situ isolated perfused rat lung model was used. Lungs were retrieved from rats at varying intervals after circulatory arrest and death. Lungs were either ventilated with O(2) in situ or not ventilated. Lungs were reperfused at intervals after death with Earle's solution with or without nitroglycerin (0.1 mg/ml). Lung ischemia-reperfusion injury was assessed by capillary filtration coefficient, wet-to-dry lung weight ratio, and pulmonary hemodynamics. Tissue levels of adenine nucleotides and cGMP concentrations were measured by high-performance liquid chromatography and enzyme immunoassay, respectively. RESULTS: Reperfusion with nitroglycerin decreased capillary filtration coefficient compared with reperfusion without nitroglycerin at all post-mortem ischemic times, irrespective of pre-harvest ventilation. cGMP levels increased significantly with nitroglycerin-reperfusion and attenuated decreases in high-energy adenine nucleotides. CONCLUSIONS: Reperfusion of lungs with nitroglycerin may facilitate safe lung transplantation from NHBDs by reducing capillary leak after reperfusion.

Isoproterenol reduces ischemia-reperfusion lung injury despite beta-blockade.

BACKGROUND: If lungs could be retrieved from non-heart-beating donors (NHBDs), the shortage of lungs for transplantation could be alleviated. The use of lungs from NHBDs is associated with a mandatory warm ischemic interval, which results in ischemia-reperfusion injury upon reperfusion. In an earlier study, rat lungs retrieved 2-h postmortem from NHBDs had reduced capillary leak measured by filtration coefficient (Kfc) when reperfused with isoproterenol (iso), associated with an increase in lung tissue levels of cyclic AMP (cAMP). The objective was to determine if this decrease in Kfc was because of beta-stimulation, or would persist despite beta-blockade. MATERIALS AND METHODS: Donor rats were treated intraperitoneally with beta-blockade (propranolol or pindolol) or carrier, sacrificed, and lungs were retrieved immediately or 2 h postmortem. The lungs were reperfused with or without iso and the beta-blockers in the reperfusate. Outcome measures were Kfc, wet:dry weight ratio (W/D), lung levels of adenine nucleotides and cAMP. RESULTS: Lungs retrieved immediately after death had normal Kfc and W/D. After 2 h of ischemia, Kfc and W/D were markedly elevated in controls (no drug) and lungs reperfused with beta-blockers alone. Isoproterenol-reperfusion decreased Kfc and W/D significantly (P < 0.01) even in the presence of beta-blockade. Lung cAMP levels were increased only with iso in the absence of beta-blockade. CONCLUSIONS: The attenuation of ischemia-reperfusion injury because of iso occurs even in the presence of beta-blockade, and may not be a result of beta-stimulated increased cAMP.

Intrapleural tissue plasminogen activator for complicated pleural effusions.

BACKGROUND: This study is aimed at evaluating the safety and efficacy of intrapleural tissue plasminogen activator (TPA) for complicated pleural effusions, including posttraumatic hemothorax. METHODS: Data were retrospectively collected from hospitalized patients over a 4-year period (1999-2003) who were treated with intrapleural TPA after failing drainage by tube thoracostomy. Pre- and post-TPA imaging studies were reviewed and scored by a blinded radiologist. RESULTS: Forty-one consecutive patients with 42 effusions were identified with the following indications: 6 traumatic hemothoraces (14%), 22 loculated pleural effusions (52%), 2 line-associated hemothoraces (5%), and 12 empyemas (29%). Nine patients (22%) required operative drainage including two with posttraumatic hemothoraces. All patients managed nonoperatively demonstrated radiographic improvement after TPA administration. One patient (2.4%) developed hematuria, requiring transfusion. No trauma patient required TPA-related blood transfusion and no deaths were attributable to TPA therapy. CONCLUSION: Intrapleural TPA administration appears safe for use in complicated pleural effusions and may decrease the need for operative intervention.