Effects of anemia and hypotension on porcine optic nerve blood flow and oxygen delivery.

BACKGROUND: Perioperative ischemic optic neuropathy occurs after major surgical procedures, which are often associated with hypotension, anemia, or venous congestion. However, the effects of these conditions on optic nerve (ON) blood flow are unknown and cannot be studied adequately in humans. METHODS: Farm-raised pigs were anesthetized with isoflurane, kept normocapnic and normothermic, and subjected to conditions of euvolemic or hypovolemic hypotension (mean arterial pressure 50-55 mm Hg), anemia (hematocrit 17%), venous congestion, and combinations thereof. Control animals were kept euvolemic and normotensive for the entire experiment. Fluorescent microspheres were used to measure cerebral blood flow (CBF) and ON blood flow at baseline and after experimental conditions, and to calculate oxygen delivery (DO2). RESULTS: No significant changes in CBF or ON blood flow or DO2 occurred with euvolemic hypotension (n = 5), compared with controls (n = 12). Hypovolemic hypotension (n = 4) resulted in stable CBF and cerebral DO2, but significant reductions in ON DO2 (P = 0.032). The significant increase in CBF associated with anemia (n = 6) resulted in stable cerebral DO2. In contrast, ON blood flow did not significantly change with anemia, with (n = 5) or without (n = 6) euvolemic hypotension, resulting in significant reductions in ON DO2 (P < 0.01). CONCLUSION: Compensatory mechanisms for porcine CBF maintain stable DO2 under specified conditions of hypotension or anemia, whereas ON compensatory mechanisms were unable to maintain blood flow and to preserve DO2. The authors conclude that the porcine ON is more susceptible to physiologic perturbations than the brain.

Red blood cells prevent inhibition of hypoxic pulmonary vasoconstriction by nitrite in isolated, perfused rat lungs.

Nitrite reduction to nitric oxide (NO) may be potentiated by a nitrite reductase activity of deoxyHb and contribute to systemic hypoxic vasodilation. The effect of nitrite on the pulmonary circulation has not been well characterized. We explored the effect of nitrite on hypoxic pulmonary vasoconstriction (HPV) and the role of the red blood cell (RBC) in nitrite reduction and nitrite-mediated vasodilation. As to method, isolated rat lungs were perfused with buffer, or buffer with RBCs, and subjected to repeated hypoxic challenges, with or without nitrite. As a result, in buffer-perfused lungs, HPV was reduced at nitrite concentrations of 7 muM and above. Nitrite inhibition of HPV was prevented by excess free Hb and RBCs, suggesting that vasodilation was mediated by free NO. Nitrite-inhibition of HPV was not potentiated by mild acidosis (pH = 7.2) or xanthine oxidase activity. RBCs at 15% but not 1% hematocrit prevented inhibition of HPV by nitrite (maximum nitrite concentration of approximately 35 muM) independent of perfusate Po(2). Degradation of nitrite was accelerated by hypoxia in the presence of RBCs but not during buffer perfusion. In conclusion, low micromolar concentrations of nitrite inhibit HPV in buffer-perfused lungs and when RBC concentration is subphysiological. This effect is lost when RBC concentration approaches physiological levels, despite enhanced nitrite degradation in the presence of RBCs. These data suggest that, although deoxyHb may generate NO from nitrite, insufficient NO escapes the RBC to cause vasodilation in the pulmonary circulation under the dynamic conditions of blood flow through the lungs and that RBCs are net scavengers of NO.

Pulmonary vascular effects of red blood cells containing S-nitrosated hemoglobin.

The role of S-nitrosated hemoglobin (SNO-Hb) in the regulation of blood flow is a central and controversial question in cardiopulmonary physiology. In the present study, we investigate whether intact human red blood cells (RBCs) synthesized to contain high SNO-Hb levels are able to export nitric oxide bioactivity and vasodilate the pulmonary circulation, and whether SNO-Hb dependent vasodilation occurs secondary to an intrinsic oxygen-linked, allosteric function of Hb. RBCs containing supraphysiological concentrations (100-1,000x normal) of SNO-Hb (SNO-RBCs) were synthesized and added to isolated, perfused rat lungs during anoxic or normoxic ventilation, and during normoxic ventilation with pulmonary hypertension induced by the thromboxane mimetic U-46619. SNO-RBCs produced dose-dependent pulmonary vasodilation compared with control RBCs during conditions of both normoxic (U-46619) and hypoxic pulmonary vasoconstriction. These effects were associated with a simultaneous, rapid, and temperature-dependent loss of SNO from Hb. Both vasodilatory effects and the rate of SNO-Hb degradation were independent of oxygen tension and Hb oxygen saturation. Furthermore, these effects were not affected by inhibition of the RBC membrane band 3 protein (anion exchanger-1), a putative membrane facilitator of NO export from RBCs. Whereas these data support observations by multiple groups that synthesized SNO-Hb can vasodilate, this effect is not under intrinsic oxygen-dependent allosteric control, nor likely to be relevant in the pulmonary circulation at normal physiological concentrations.