Protective effect of plasmin in marginal donor lungs in an ex vivo lung perfusion model

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• 作者：Hideki Motoyama ; MD ; Fengshi Chen ; MD ; PhD ; Akihiro Ohsumi ; MD ; Kyoko Hijiya ; MD ; Kenji Okita ; MD ; Daisuke Nakajima ; MD ; Jin Sakamoto ; MD ; Tetsu Yamada ; MD ; Masaaki Sato ; MD ; PhD ; Akihiro Aoyama ; MD ; PhD ; Toru Bando ; MD ; PhD ; Hiroshi Date ; MD ; PhD ; ^{motoyama@kuhp.kyoto-u.ac.jp}
• 关键词：lung transplantation ; marginal donor ; ex vivo lung perfusion ; fibrinolytic treatment ; plasmin
• 刊名：The Journal of Heart and Lung Transplantation
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：32
• 期：5
• 页码：505-510
• 全文大小：629 K

文摘

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Background

Donor lung thrombi are considered an important etiology for primary graft dysfunction in lung transplantation. We hypothesized that thrombolysis before lung transplantation could alleviate ischemia-reperfusion injury. This study was designed to evaluate the effect of the fibrinolytic agent plasmin on lungs damaged by thrombi in an ex vivo lung perfusion (EVLP) system.

Methods

Rats were divided into control, non-plasmin, and plasmin groups (n = 7 each). In the control and plasmin groups, cardiac arrest was induced by withdrawal of mechanical ventilation without heparinization. Ventilation was restarted 150 minutes after cardiac arrest. The lungs were flushed, and the heart and lungs were excised en bloc. The lungs were perfused in the EVLP system for 60 minutes, and plasmin or placebo was administered upon EVLP initiation.

Results

Fibrin/fibrinogen degradation products in the perfusate were significantly higher in the plasmin group than in the control and non-control groups (p < 0.001 for both). Plasmin administration significantly decreased pulmonary vascular resistance (plasmin vs non-plasmin, p = 0.011) and inhibited the exacerbation of dynamic compliance (plasmin vs non-plasmin, p = 0.003). Lung weight gain was less in the plasmin group than in the non-plasmin group (p = 0.04).

Conclusions

Our results confirmed that plasmin administration in an EVLP model dissolved thrombi in the lungs, resulting in reconditioning of the lungs as assessed by various physiologic parameters.