Moderate Hypothermia Reduces Postischemic Edema Development and Leukotriene Production

Abstract

Using the bilateral carotid artery occlusion model of cerebral ischemia in the gerbil, we studied the effect of moderate hypothermia (30 to 31°C) on the postischemic production of prostanoids (cyclooxygenase pathway) and leukotrienes (lipoxygenase pathway) and accompanying changes in cerebral edema formation. Hypothermia capable of slowing central evoked potential conduction time was studied over the course of 40 minutes of cerebral ischemia and for up to 2 hours of reperfusion. The successful induction of cerebral ischemia was confirmed by somatosensory evoked potential amplitude changes. Measurements of 6-ketoprostaglandin F_1α (PGF_1α) and leukotriene B₄ (LTB₄) (radioimmunoassay) and cerebral edema (specific gravity) were made at early (10 minutes) and late (2 hours) reperfusion times. Although both white and gray matter showed no early significant difference in edema accumulation between normothermic and hypothermic gerbils at 10 minutes of reperfusion, hypothermic animals demonstrated significantly less white matter edema (specific gravity, 1.0397 ± 0.0010 vs. 1.0341 ± 0.0012, P < 0.01) and gray matter edema (specific gravity, 1.0408 ± 0.0009 vs. 1.0365 ± 0.0008, P < 0.01) by 2 hours of reperfusion. Production of PGF_1α was not significantly different between normothermic and hypothermic animals during the reperfusion period; however, hypothermic gerbils demonstrated significantly lower production of LTB₄ at 10 minutes reperfusion time compared to normothermic animals (1.49 ± 0.79 vs. 5.28 ± 1.49 pg/mg of protein, P < 0.05). This difference between the two groups in LTB₄ levels was no longer detectable at 2 hours of reperfusion time. In this study, moderate hypothermia was shown to exert a protective effect on the development of ischemic edema and to decrease significantly the early postischemic peak of LTB₄, an arachidonate metabolite linked to the development of such edema. These results are consistent with a potentially harmful role of arachidonate metabolites after ischemia (particularly those of the lipoxygenase pathway) and may offer a mechanism explaining the common observation of the protective effect of hypothermia on injured central nervous system tissue.