Proinflammatory and prothrombotic status in emphysematous rats exposed to intermittent hypoxia

To develop an "overlap syndrome (OS)" rat model by intermittent hypoxia (IH) exposure on the base of pre-existing emphysema, and to explore whether "OS" exposure results in more severe systemic inflammation, and whether the inflammation changes levels of coagulant/anticoagulant factors and oxidative stress status.

Sixty Wistar rats were put into 4 groups: Control group; IH group, IH exposure; Emphysema group, smoke exposure; Overlap group, smoke exposure and IH exposure. We obtained peripheral blood for apoptosis of CD3(+)CD4(+), CD3(+)CD8(+) T lymphocytes and neutrophils, and for endothelial progenitor cell (EPC) counts. Tumor necrosis factor (TNF)-α, interleukin (IL)-6 and coagulant/anticoagulant factors [antithrombin (AT), fibrinogen (FIB), Factor VIII (FVIII) and von Willebrand factor (vWF)] were evaluated. We also obtained tissue blocks of lung, liver, pancreas, and right carotid artery for pathologic scoring and measurements of liver oxidative stress [superoxide dismutase (SOD) activity, catalase (CAT) activity and malondialdehyde (MDA) concentration].

The levels of TNF-α and IL-6, CD3(+)CD4(+) T lymphocyte apoptosis, EPC counts, coagulant factors and MDA are the highest in Overlap group, the lowest in Control group, when the levels of neutrophil apoptosis, CD3(+)CD8(+) T lymphocyte apoptosis, AT, SOD and CAT are the lowest in Overlap group, the highest in Control group (all P values < 0.05).

In model animals, when IH is combined with emphysema, there will be a more severe or an "overlapped" systemic/multiple organic inflammation, oxidative stress and hyper-coagulability. And the pro-inflammatory and pro-thrombotic status resulted from "OS" exposure may elicit a robust EPC mobilization, which needs further investigation.