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OBJECTIVE Cardiopulmonary bypass (CPB) produces an inflammatory response associated with pulmonary dysfunction. P38 mitogen-activated protein kinase (P38MAPK) have been shown to mediate pulmonary inflammatory response after CPB, we examined the effect of SB203580, a specific p38 MAPK inhibitor, on CPB-induced pulmonary inflammatory response. METHODS Sprague-Dawley rats (n=54) were randomized into three groups (each n=18): (1) S group, rats underwent sham CPB; (2) CPB group, rats underwent CPB; (3) SB group, rats underwent CPB plus pretreatment with SB203580 (10 mg/kg, i.v., 30 min before CPB). The lung samples were collected after 10 min, 60 min, and 150 min lung reperfusion (each n=6) in CPB group and SB group, and after 70 min, 120 min, and 210 min observation in S group as the control. RESULTS The level of lung phospho-IkappaBalpha, nuclear factor (NF)-kappaB activity and activating protein (AP)-1 activity in CPB group was increased than S group. CPB resulted in increased pulmonary tissue tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta expression and production, increased pulmonary inflammatory response. The in vivo administration of SB203580 prevented up-regulation of lung-phosphorylated p38 MAP kinase, decreased pulmonary tissue level of proinflammatory cytokines expression and production, and reduced lung inflammation. CONCLUSIONS These findings suggested that (1) p38 MAP kinase activation is one of the important aspects of the signaling event that mediate the release of TNF-alpha and IL-1beta and contributes to CPB-induced pulmonary inflammatory response, (2) SB203580 selectively inhibiting p38 MAP kinase activation efficaciously reduces pulmonary inflammatory response after CPB, and (3) p38 MAP kinase influence the activation of NF-kappaB in the lung during and after CPB.

Advanced pulmonary arterial hypertension is characterized by extensive vascular remodeling that is usually resistant to vasodilator therapy. As the major component of the vascular media, decreased apoptosis of pulmonary arterial smooth muscle cell (PASMC) plays key roles during pulmonary vascular remodeling. Recent studies showed that enhancement of apoptosis of PASMC can reverse pulmonary vascular remodeling and severe pulmonary arterial hypertension. Enhancement of apoptosis of PASMC is becoming a novel strategy to reverse severe pulmonary arterial hypertension. This review analyzes some potential strategies to reverse pulmonary vascular remodeling.

Macrolides antibiotics may affect neutrophil functions that correlate with the inflammation induced by cardiopulmonary bypass. Our study observed the protective effect of clarithromycin on inflammatory lung injury after cardiopulmonary bypass.Twelve adult sheep were randomly divided into two groups. After cardiopulmonary bypass was established, the lung was perfused through the pulmonary artery with either dextran solution (30 mL/kg) in the control group (n = 6) or dextran solution added to clarithromycin (10 mg/kg) in the experimental group (n = 6). Bypass was withdrawn after 90 minutes. Pulmonary function was determined and inflammatory factors were analyzed. Apoptotic neutrophils in the lung were assayed and lung biopsies were also performed.Pulmonary vascular resistance (102.2 +/- 14.0 dyne.s.cm(-5)) was lower in the experimental group compared with the control group (202.6 +/- 47.3 dyne.s.cm(-5), p0.01) whereas the oxygen index was higher in the experimental group (p0.05). Plasma myeloperoxidase in the experimental group (0.015 +/- 0.006 U/L) was lower than that in the control group (0.029 +/- 0.007 U/L, p0.01). Plasma interlukin-8 (0.18 +/- 0.04 ug/L) and tumor necrosis factor (1.00 +/- 0.13 ug/L) in the experimental group were lower than in the control group (0.39 +/- 0.09 ug/L, 1.55 +/- 0.35 ug/L, p0.01). Histologic analyses showed intra-alveolar hemorrhage and neutrophil accumulation in the control group, whereas there were no significant changes in the experimental group. The apoptosis rate of accumulated neutrophils was significantly lower in the control group (p0.01).Lung perfusion with hypothermic protective solution containing clarithromycin distinctly inhibits inflammatory responses caused by cardiopulmonary bypass and ameliorates lung function.