Guerra-Mora JR, Perales-Caldera E, Aguilar-León D, Nava-Sanchez C, Díaz-Cruz A, Díaz-Martínez NE, Santillán-Doherty P, Torres-Villalobos G, Bravo-Reyna CC. Effects of Sildenafil and Tadalafil on Edema and Reactive Oxygen Species Production in an Experimental Model of Lung Ischemia-Reperfusion Injury.
Transplant Proc 2018;
49:1461-1466. [PMID:
28736024 DOI:
10.1016/j.transproceed.2017.03.089]
[Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2016] [Revised: 03/14/2017] [Accepted: 03/30/2017] [Indexed: 12/23/2022]
Abstract
BACKGROUND
Lung ischemia-reperfusion injury is characterized by formation of reactive oxygen species and cellular swelling leading to pulmonary edema and primary graft dysfunction. Phosphodiesterase 5 inhibitors could ameliorate lung ischemia-reperfusion injury by interfering in many molecular pathways. The aim of this work was to evaluate and compare the effects of sildenafil and tadalafil on edema and reactive oxygen species formation in an ex vivo nonhuman animal model of lung ischemia-reperfusion injury.
METHODS
Thirty-two Wistar rats were distributed, treated, perfused and the cardiopulmonary blocks were managed as follows: control group: immediate excision and reperfusion without pretreatment; ischemia reperfusion group: treatment with dimethylsulfoxide 0.9% and excision 1 hour later; sildenafil group: treatment with sildenafil (0.7 mg/kg) and excision 1 hour later; and tadalafil group: treatment with tadalafil (0.15 mg/kg) and excision 2 hours later. All cardiopulmonary blocks except control group were preserved for 8 hours and then reperfused. Pulmonary arterial pressure, pulmonary venous pressure, and capillary filtration coefficient were measured. Reactive oxygen species were measured.
RESULTS
Edema was similar between control and sildenafil groups, but significantly greater in the ischemia-reperfusion (P ≤ .04) and tadalafil (P ≤ .003) groups compared with the sildenafil group. The malondialdehyde levels were significantly lower in the sildenafil (P ≤ .001) and tadalafil (P ≤ .001) groups than the ischemia-reperfusion group.
CONCLUSIONS
Administration of sildenafil, but not tadalafil, decreased edema in lung ischemia-reperfusion injury. Both drugs decreased reactive oxygen species formation in a lung ischemia-reperfusion injury model.
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