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Previous studies reported that the degree of hypoxemia following acute pulmonary thromboembolism (APTE) was highly variable and that its mechanism was mainly due to the creation of many high and low ventilation/perfusion (V/Q) units, as a result of the heterogeneous regional blood flow (Q) caused by embolic obstruction. We studied the effect of changing cardiac output (Q t ) on gas exchange after APTE in 5 embolized piglets (23 ± 3 Kg), using Dobutamine intermittently at approximately 20 μg/kg/min for 120 minutes. The distribution of ventilation (V) and perfusion (Q) at various times was mapped using fluorescent microspheres in 941 ± 60 lung regions. After APTE, increase in Q t by Dobutamine improved venous oxygen tension (PvO 2 ) but arterial PaO 2 did not change consistently. On the other hand, cluster analysis showed that the V/Q ratio of most lung regions was lowered due to increases in Q at the same time. We concluded that the effect of changing cardiac output on gas exchange following APTE was affected by the simultaneous and varying balance between the changing V/Q mismatch and the concomitantly changing PvO 2 , which might explain the unpredictability of PaO 2 in the clinical setting.

In the current study, we used a canine model of radiation-induced lung injury to test the effect of a single i.v. infusion of 10×10(6)/kg of marrow fibroblasts on the progression of damage following 15 Gy exposure to the right lung. The fibroblasts, designated DS1 cells, are a cloned population of immortalized cells isolated from a primary culture of marrow stromal cells. DS1 cells were infused at week 5 post-irradiation when lung damage was evident by imaging with high-resolution computed tomography (CT). At 13 weeks post-irradiation we found that 4 out of 5 dogs receiving DS1 cells had significantly improved pulmonary function compared to 0 out of 5 control dogs (p = 0.047, Fisher's Exact). Pulmonary function was measured as the single breath diffusion capacity-hematocrit (DLCO-Hct), the total inspiratory capacity (IC), and the total lung capacity (TLC), which differed significantly between control and DS1-treated dogs; p = 0.002, p = 0.005, and p = 0.004, respectively. The DS1-treated dogs also had less pneumonitis detected by CT imaging and an increased number of TTF-1 (thyroid transcription factor 1, NKX2-1) positive cells in the bronchioli and alveoli compared to control dogs. Endothelial-like progenitor cells (ELC) of host origin, detected by colony assays, were found in peripheral blood after DS1 cell infusion. ELC numbers peaked one day after infusion, and were not detectable by 7 days. These data suggest that infusion of marrow fibroblasts stimulates mobilization of ELC, which is associated with a reduction in otherwise progressive radiation-induced lung injury. We hypothesize that these two observations are related, specifically that circulating ELC contribute to increased angiogenesis, which facilitates endogenous lung repair.