Phosphodiesterase type 4 inhibitor prevents acute lung injury induced by cardiopulmonary bypass in a rat model.

Abstract

OBJECTIVES:

Cardiopulmonary bypass (CPB) induces systemic inflammatory response with neutrophil activation and subsequent lung dysfunction. Rolipram, a selective phosphodiesterase type 4 inhibitor, blocks the decrease in levels of cyclic adenosine monophosphate associated with neutrophil activation. Here, we tested the protective effect of rolipram on CPB-induced lung injury in the rat.

METHODS:

Rats were divided into three groups: control (C), rolipram (R) and sham (S). In the C and R groups, animals underwent CPB at a flow rate of 60 ml/kg per min for 60 min followed by another 60-min observation, whereas the S group rats were sustained for 120 min only with median sternotomy and the placement of cannulae for CPB. Rolipram (40 microg/kg per min) was administered to the R group rats by continuous intravenous infusion from 10 min before the establishment of CPB to the end of the experiment.

RESULTS:

The R and S groups showed significantly higher mean arterial oxygen pressure and lower mean lung wet-to-dry weight ratio compared with those observed in the C group (R: 489+/-44 or S: 527+/-55 vs. C: 287+/-185, and R: 5.0+/-0.4 or S: 4.7+/-0.3 vs. C: 5.9+/-0.5, respectively; (P < 0.01). Although CD11b expression levels on circulating neutrophils in the C group doubled after CPB, those in the R and S groups remained almost the same (P = 0.0008). Intrapulmonary tumor necrosis factor-alpha concentrations (pg/microg protein) in the C group tended to be higher than those observed in the R and S groups (R: 5.2+/-2.1, S: 5.0+/-2.1 and C: 8.9+/-5.4; R vs. C: P = 0.09 and S vs. C: P = 0.08). Pathological study of lungs revealed that more alveolar hemorrhage and neutrophil accumulation were observed in the C group compared to the R and S groups.

CONCLUSIONS:

These results suggest that rolipram prevents acute lung injury via the inhibition of neutrophil activation during and after CPB in this setting of a rat model.

• Authors: Masaki Hamamoto, Michiharu Suga, Takeshi Nakatani, Yuzo Takahashi, Yukio Sato, Shuji Inamori, Toshikatsu Yagihara, Soichiro Kitamura
• Journal: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery (Eur J Cardiothorac Surg) Vol. 25 Issue 5 Pg. 833-8 (May 2004) ISSN: 1010-7940 [Print] Germany
• PMID: 15082290 (Publication Type: Journal Article)

Chemical References

• CD11b Antigen
• Phosphodiesterase Inhibitors
• Tumor Necrosis Factor-alpha
• L-Selectin
• 3',5'-Cyclic-AMP Phosphodiesterases
• Cyclic Nucleotide Phosphodiesterases, Type 4
• Rolipram

Topics

• 3',5'-Cyclic-AMP Phosphodiesterases (antagonists & inhibitors)
• Animals
• CD11b Antigen (blood)
• Cardiopulmonary Bypass (adverse effects)
• Cyclic Nucleotide Phosphodiesterases, Type 4
• Disease Models, Animal
• L-Selectin (blood)
• Male
• Neutrophil Activation (drug effects)
• Phosphodiesterase Inhibitors (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Respiratory Distress Syndrome (etiology, pathology, prevention & control)
• Rolipram (therapeutic use)
• Tumor Necrosis Factor-alpha (metabolism)