Isotopic study of L-Arginine kinetics in the lung during pseudomonas sepsis in an ovine model.

UNLABELLED: The objective of the study is to investigate how L-Arginine pulmonary metabolism is altered in response Pseudomonas aeruginosa (P. aeruginosa) induced septic conditions using an ovine model. METHODS: Seven female sheep were infused with a primed-constant infusion of L-[(15)N2-guanidino, 5, 5, (2)H2] L-Arginine for 28 hs. After the initial 4 hs of the L-Arginine infusion, a continuous infusion of live Pseudomonas aeruginosa bacteria started for 24 hs. A NO synthase (NOS) inhibitor, N(G)-Methyl-L-arginine (L-NMA), infusion was added during the last 4 hs of the bacterial infusion. Blood samples were taken at specific time points for isotopic enrichment during control, septic and NOS blocking phases of the study. RESULTS: We observed that the level of total delivery of L-Arginine to the lungs was significantly decreased in septic phase after 24 hours of pseudomonas infusion. In contrast, the fractional uptake and metabolism of L-Arginine by the lungs was doubled during septic phase relative to the control phase (MARG-basal = 100% vs. MARG-septic = 220 ± 56%, P < 0.05). NO production in the lungs was also significantly increased. Infusion of L-NMA markedly blunted this elevated NO production and attenuated the total arginine metabolized in the septic lungs (MARG-septic = 220 ± 56% vs. MARG-NO blocking = -25 ± 20%; P < 0.05). We demonstrated sepsis induced by P. aeruginosa infusion caused an increase in the fractional uptake and metabolic rate of arginine in the lungs. Furthermore, our data suggests that arginine was mainly consumed via arginine - NO pathway, which might be responsible for this enhanced arginine metabolic activity in the septic lungs.

Isotopic study of L-Arginine kinetics in the lung during pseudomonas sepsis in an ovine model.

UNLABELLED: The objective of the study is to investigate how L-Arginine pulmonary metabolism is altered in response Pseudomonas aeruginosa (P. aeruginosa) induced septic conditions using an ovine model. METHODS: Seven female sheep were infused with a primed-constant infusion of L-[(15)N2-guanidino, 5, 5, (2)H2] L-Arginine for 28 hs. After the initial 4 hs of the L-Arginine infusion, a continuous infusion of live Pseudomonas aeruginosa bacteria started for 24 hs. A NO synthase (NOS) inhibitor, N(G)-Methyl-L-arginine (L-NMA), infusion was added during the last 4 hs of the bacterial infusion. Blood samples were taken at specific time points for isotopic enrichment during control, septic and NOS blocking phases of the study. RESULTS: We observed that the level of total delivery of L-Arginine to the lungs was significantly decreased in septic phase after 24 hours of pseudomonas infusion. In contrast, the fractional uptake and metabolism of L-Arginine by the lungs was doubled during septic phase relative to the control phase (MARG-basal = 100% vs. MARG-septic = 220 ± 56%, P < 0.05). NO production in the lungs was also significantly increased. Infusion of L-NMA markedly blunted this elevated NO production and attenuated the total arginine metabolized in the septic lungs (Mnitrate-septic = 43.6 ± 5.7 vs. Mnitrate-septic + L-NMA = 13.4 ± 5.1 umol/kg/min; p < 0.05). We demonstrated sepsis induced by P. aeruginosa infusion caused an increase in the fractional uptake and metabolic rate of arginine in the lungs. Furthermore, our data suggests that arginine was mainly consumed via arginine - NO pathway, which might be responsible for this enhanced arginine metabolic activity in the septic lungs.

Comparison of transfusion with DCLHb or pRBCs for treatment of intraoperative anemia in sheep.

Isoflurane-anesthetized sheep were transfused with packed red blood cells (pRBCs) or diaspirin cross-linked hemoglobin (DCLHb) for treatment of intraoperative hemorrhage. A rapid 15-min hemorrhage with lactated Ringer (LR) infusion maintained filling pressure at baseline and reduced blood hemoglobin (Hb) to ~5 g/dl. Sheep received 2 g/kg Hb, DCLHb (n = 6), or pRBCs (n = 7); control group received LR alone (n = 6). After 2 h, anesthesia was discontinued; sheep were monitored in the animal intensive care unit for 48 h. DCLHb expanded blood volume more, but increased total blood Hb less, than pRBCs. Lower Hb and increased methemoglobin resulted in lower arterial oxygen content compared with the pRBCs. DCLHb caused pulmonary hypertension (from 13 to 30 mmHg) and elevated filling pressure (from 6 to 15 mmHg). Cardiac outputs (CO) were similar for all groups during anesthesia; however, during recovery CO increased only in the LR and packed pRBCs groups. DCLHb may limit the reflex ability to increase CO after volume expansion. Hemodynamic effects of DCLHb may be exaggerated when infused after large-volume LR.