Critical hematocrit and oxygen partial pressure in the beating heart of pigs.

In cardiac surgery the substitution of lost blood volume by plasma substitutes is a common therapeutical approach. None of the currently available blood substitutes has a sufficient oxygen transport capacity. This can limit the functional integrity of the myocardium known as highly oxygen consumptive. The study was aimed to get information about the minimal hematocrit, also known as critical hematocrit (cHct), which guarantees a stable and adequate oxygen partial pressure in the myocardium (pO2). In adult female pigs (n=7) the hematocrit was reduced by isovolemic blood dilution with an intravenous infusion of isotonic 4% gelatine polysuccinate solution, The substituted blood volume ranged between 3000ml and 7780ml (mean: 5254±1672ml). In all animals the pO2 of the myocardium of the beating heart and of the resting skeletal muscle increased until blood dilution resulted in a Hct decrease down to 15%. Further blood dilution resulted in a decrease of the pO2. Only after the Hct was <10% the pO2 was lower than before blood dilution and accompanied by a lethal ischemia of the myocardium. These data indicate a cHct of about 10% in the pig animal model.

Anti-proliferative properties of the phosphodiesterase-4 inhibitor rolipram can supplement immunosuppressive effects of cyclosporine for treatment of obliterative bronchiolitis in heterotopic rat allografts.

BACKGROUND: Potent prevention and therapy of obliterative bronchiolitis may enhance long-term survival after lung transplantation. Phosphodiesterase-4 inhibitors have been established for anti-inflammatory treatment, particularly of pulmonary diseases. Using a heterotopic rat model, the effect of rolipram was investigated and compared with cyclosporine for epithelium disturbance and leukocyte infiltration and proliferation, which are key events in the development of obliterative bronchiolitis. METHODS: Tracheae were transplanted into the omentum of allo- and syngeneic animals. Four allogeneic groups were investigated: treatment with rolipram; treatment with cyclosporine; treatment with a combination of rolipram and cyclosporine; and untreated (60-day time course). Using histo- and immunohistochemical stainings, epithelium disturbance, leukocyte subsets, proliferating cells and luminal occlusion were quantified by digital morphometry. RESULTS: In rolipram-treated animals, the epithelium was completely disturbed until Day 14. It was temporarily preserved in rats that received cyclosporine until Day 60. In the acute phase (Day 5), infiltration of monocytes/macrophages was significantly inhibited by rolipram, but less effective than in cyclosporine-treated rats. At later timepoints (Days 28 and 60), rolipram significantly inhibited proliferation, in contrast to enhanced proliferation of fibroblast-like cells after cyclosporine treatment. The combination of rolipram and cyclosporine led to temporary epithelial preservation and effective inhibition of leukocyte infiltration (Day 5) and proliferation (Days 28 and 60). Luminal occlusion was significantly reduced in the combination group compared with the cyclosporine-only group. CONCLUSIONS: Although cyclosporine temporary protects epithelial integrity by the inhibition of acute rejection, rolipram showed greater potency for long-term inhibition of mesenchymal-cell proliferation. The combination of both drugs may be useful for limiting chronic obliterative changes after lung transplantation.