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.