Hypoxemic Versus Normoxemic Reperfusion in a Large Animal Model of Severe Ischemia-Reperfusion Injury

Abstract

Prior studies have suggested a significant benefit of using deliberate hypoxemia to reperfuse ischemic tissue beds, primarily by reducing free radical injury. We sought to examine the effects of a hypoxemic reperfusion strategy in a large animal model of severe truncal ischemia. Adult swine were subjected to 30 min of supraceliac aortic occlusion and randomized to two groups: normoxemia group (n = 9), with resuscitation at a pO2 >100 mmHg or hypoxemia group (n = 10), with initial resuscitation at a pO2 of 30-50. The two groups were compared using physiologic parameters, fluid and pressor requirements, inflammatory and oxidative markers, and histologic analysis of end-organ injury. All animals developed significant hemodynamic instability immediately upon reperfusion. Average mean arterial pressure at baseline rose significantly after 30 min of cross-clamp (76.8 versus 166.3 mmHg, P < 0.001). Upon reperfusion, all animals required epinephrine and fluids to maintain mean arterial pressure (MAP) greater than 60 mmHg. After stabilization, the two groups were similar in terms of central and pulmonary hemodynamics. The hypoxemic group required more mean total epinephrine (18.35 mg versus 5.28 mg, P < 0.01) with no significant difference in total fluid volume (hypoxemic 9111 ml versus 8420 mL, P = 0.730). The hypoxemic group demonstrated a more severe metabolic acidosis at all time intervals after reperfusion (pH 7.02 versus 7.16 and lactate 17 versus 13, both P < 0.01). There was no difference in malondialdehyde concentration between the two groups, but the hypoxemic group had a higher antioxidant reductive capacity at all intervals after 30 min of reperfusion (0.23 versus 0.27 uM, P = 0.03). While there was significant end-organ damage on pathologic examination of all liver and kidney specimens (mean severity of injury 1.59 and 1.76, respectively, on a scale of 1-3), there was no significant difference between the two groups. A hypoxemic reperfusion strategy in this large animal model failed to demonstrate any significant clinical benefit. Although there was chemical evidence of improved antioxidant capacity with hypoxemia, it was associated with more instability, metabolic and physiologic derangements, and no evidence of end-organ protection.