| Title | Nebulized phosphodiesterase III inhibitor during warm ischemia attenuates pulmonary ischemia-reperfusion injury. | | Author(s) | Zhang J, Chen F, Zhao X, Aoyama A, Okamoto T, Fujinaga T, Shoji T, Sakai H, Cui Y, Bando T, Date H | | Institution | Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan. | | Source | J Heart Lung Transplant 2009 Jan; 28(1):79-84. | | MeSH | Aerosols
Animals
Cyclic Nucleotide Phosphodiesterases, Type 3
DNA Nucleotidylexotransferase
In Situ Nick-End Labeling
Lung
Lung Transplantation
Male
Milrinone
Models, Animal
Nebulizers and Vaporizers
Phosphodiesterase Inhibitors
Postoperative Complications
Rats
Reperfusion Injury
Vascular Resistance
| | Abstract | BACKGROUND: The control of warm ischemia-reperfusion injury is crucial in managing donors after cardiac death for lung transplantation. We focused on transalveolar administration as a drug-delivery route for such donors. Milrinone is a phosphodiesterase 3 inhibitor that inhibits the breakdown of cyclic adenosine monophosphate and selectively relaxes smooth muscle. We hypothesized that nebulized milrinone would mitigate warm ischemia-reperfusion injury of lung.
METHODS: This study was conducted with an isolated rat lung perfusion model. Lungs were excised, exposed to 55-minute ischemia at 37 degrees C, and reperfused for 60 minutes. During ischemia, nebulized milrinone (n = 6) or saline (n = 6) was inhaled. Lungs were continuously perfused without ischemia as a sham group (n = 6). Airway resistance, pulmonary vascular resistance, pulmonary compliance, weight gain and blood gas were measured. Adenine nucleotide levels and apoptosis were investigated in the reperfused lungs.
RESULTS: Milrinone nebulization decreased post-ischemic pulmonary vascular resistance (0.98 +/- 0.05 and 1.74 +/- 0.17 cm H(2)O/ml.min at 60 minutes of reperfusion in the milrinone and control groups, respectively [p < 0.01]). It did not alter cyclic adenosine monophosphate levels, but it did elevate adenosine triphosphate levels (9.87 +/- 0.38 and 6.91 +/- 0.45 in the milrinone and control groups, respectively [p < 0.01]) and suppressed apoptosis (3.83 +/- 0.91 and 46.17 +/- 3.39 of mean apoptotic cell numbers in the milrinone and control groups, respectively [p < 0.01]).
CONCLUSIONS: Milrinone nebulization decreased post-ischemic pulmonary vascular resistance, elevated adenosine triphosphate levels, and suppressed apoptosis. Nebulized milrinone has some protective effects against warm ischemia. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19134535 |
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