Hyperoxic reperfusion exacerbates postischemic renal dysfunction.

BACKGROUND: Hyperoxic reperfusion from global ischemia worsens functional outcome because of oxygen radical-mediated injury. This study tested the hypothesis that hyperoxic reperfusion would exacerbate postischemic renal dysfunction. METHODS: Twenty-nine healthy, uninephrectomized, male mongrel rabbits (Oryctolagus cuniculus) in 3 groups were subjected to 30 minutes of complete normothermic renal ischemia followed by reperfusion under hyperoxic or normoxic conditions. The groups were: hyperoxically reperfused (n = 8), normoxically reperfused (n = 8), hyperoxic sham (no ischemia, n = 5), and allopurinol-pretreated (50 mg/kg, intravenously), hyperoxically reperfused animals (n = 8). Plasma concentrations of creatinine, urea nitrogen and electrolytes were measured at 0, 24, 48, and 72 hours after ischemia and served as functional outcome markers. Histopathologic analysis of kidneys for injury was performed by an expert who was blinded to the procedures. RESULTS: Plasma creatinine in hyperoxically reperfused rabbits was significantly elevated above normoxic (P =.02) and sham (P =.003) animals by 48 hours and remained elevated to 72 hours. Plasma urea nitrogen in hyperoxically reperfused rabbits was significantly elevated above the normoxic group (P = .01), the sham group (P = .02), and the allopurinol group (P = .04) by 72 hours. These coincided with a significantly elevated histopathologic injury score in hyperoxically reperfused rabbits compared with sham (P = .019), normoxic (P = .035), and allopurinol-pretreated hyperoxically reperfused animals (P = .037). CONCLUSIONS: Hyperoxic reperfusion exacerbates renal dysfunction after 30 minutes of complete normothermic ischemia. This dysfunction may be mediated by oxygen radical-related injury.

Systemic pressor response during hindlimb ischemia is inversely related to femoral artery pressure and fractional inspired oxygen.

BACKGROUND: Delayed-onset reflex increases in mean arterial pressure (MAP) occur during clamping of the infrarenal aorta. This study investigated the afferent limb of the reflex by independently altering femoral artery blood pressure (FBP) or fractional concentration of inspired oxygen (FIO2) while monitoring systemic arterial blood pressure. METHODS: The infrarenal aorta was divided, and an occlusive roller pump delivered incremental flow to the distal aorta thus controlling FBP. In six dogs the FBP was reduced in random order to 50, 40, 30, 20, and 10 mm Hg and held constant for 30 minutes. In another six dogs the FBP was held at 20 mm Hg, whereas the FIO2 was randomly varied among 0.13, 0.21, and 1.0 for 30-minute intervals. RESULTS: Under these conditions MAP was significantly and inversely correlated with FBP (MAP was 172 +/- 8 mm Hg when FBP was 10 mm Hg, p < 0.0001; MAP was 158 +/- 8 mm Hg when FBP was 20 mm Hg, p = 0.0001; MAP was 138 +/- 7 mm Hg when FBP was 30 mm Hg, p = 0.0048; and MAP was 130 +/- 7 mm Hg when FBP was 40 mm Hg, p = 0.0045). MAP was significantly and inversely related to the FIO2 value when FBP was fixed at 20 mm Hg (MAP of 186 +/- 9 mm Hg at FIO2 of 0.13 and was significantly higher than MAP of 163 +/- 11 mm Hg at FIO2 of 0.21, p = 0.01; and MAP of 157 +/- 10 mm Hg at FIO2 of 1.0, p = 0.0001). CONCLUSIONS: The magnitude of the delayed systemic pressor response is inversely proportional to the FBP. We suggest that this pressor response is also particularly sensitive, in part, to arterial blood oxygen tension when hindlimb perfusion pressure is low.

Hypoxic cardiopulmonary-cerebral resuscitation fails to improve neurological outcome following cardiac arrest in dogs.

Hyperoxic cardiopulmonary resuscitation (CPR) is associated with an increase in neurologic dysfunction upon successful resuscitation with much of the damage attributable to an increase in reperfusion oxidant injury. We hypothesized that by contrast, hypoxic ventilation during resuscitation would improve neurologic outcome by reducing available substrate necessary for oxidant injury. Specifically, this study investigated the effects of 2 levels of hypoxic ventilation during resuscitation: F1O2 = 0.085, PaO2 = 26.6 +/- 3.4 mmHg, (HY8), and F1O2 = 0.12, PaO2 = 33.0 +/- 4.2 mmHg, (HY12), and normoxic resuscitation: F1O2 = 0.21, PaO2 = 60.6 +/- 17.0 mmHg, (N) on survival and neurological outcome following 9 min of normothermic cardiac arrest. Concentrations of malonaldehyde (MDA) and 4-hydroxynonenal (4-OH) in plasma and concentrations of glutathione (GSH) in erythrocyte lysates were measured to quantify possible radical damage. Physiological variables including arterial blood gases were followed for 24 h after resuscitation. Neurologic outcome was assessed using a standardized scoring system. Hypoxically (HY8) resuscitated dogs tended to have a greater neurologic deficit than normoxically resuscitated dogs and had reduced overall survival (16.9 +/- 8.9 h) compared to N dogs (24.0 +/- 0.0 h). Overall survival time correlated negatively (-0.693) and significantly (P = 0.0018) with plasma glucose concentration. Arterial plasma glucose concentrations were higher in the HY8 group compared to the N group immediately (HY8, 312 +/- 86 mg/dL; N, 196 +/- 82 mg/dL; P = 0.17) and 30 min (HY8, 331 +/- 109 mg/dL; N, 187 +/- 74 mg/dL; P = 0.077) following resuscitation. No statistically discernible differences in markers of oxidant injury were apparent among the 3 groups, but pooled data increased significantly with time for MDA and 4-OH. Pooled data for GSH showed a significant drop at 1 h following resuscitation and returned to normal by 6 h. Data from these markers suggested attendant oxidant injury in all groups. Thus, hypoxic ventilation at 2 depths of hypoxia during resuscitation failed to improve neurologic outcome beyond that achieved by ventilation with air, suggesting that normoxia rather than hyperoxia or hypoxia is the ideal target for arterial oxygenation during resuscitation.