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 degrees 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 F1 alpha (PGF1 alpha) 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 less than 0.01) and gray matter edema (specific gravity, 1.0408 +/- 0.0009 vs. 1.0365 +/- 0.0008, P less than 0.01) by 2 hours of reperfusion. Production of PGF1 alpha 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 less than 0.05). This difference between the two groups in LTB4 levels was no longer detectable at 2 hours of reperfusion time.(ABSTRACT TRUNCATED AT 250 WORDS)

General versus Specific Actions of Mild-Moderate Hypothermia in Attenuating Cerebral Ischemic Damage

“…Intraischemic hypothermia also preserves the base-excision repair pathway, which repairs oxidative damage (Luo et al, 2007). In addition to those cascades directly associated with neuronal injury, hypothermia further blocks astrocyte activity and inhibits white matter injury (Colbourne et al, 1997;Dempsey et al, 1987;Kimura et al, 2002). Similarly, postischemic hypothermia blocks free radical generation (Horiguchi et al, 2003), attenuates inflammation (Horstmann et al, 2003;Ohta et al, 2007), prevents BBB permeability (Preston and Webster, 2004), and suppresses caspase activities (Van Hemelrijck et al, 2005).…”

Mild Hypothermia Preserves Contractile Function and Inhibits Prostaglandin E2 Release from Metabolically Stressed Skeletal Muscle

“…3538 Moderate hypothermia (30-31°C) reduces leukotriene production at 10 minutes reperfusion, accompanied by reduced post-ischemic edema at 2 hours reperfusion. 39 The fact that a significant part of the change occurs during the reperfusion period is of interest. More importantly, it implies that there may be a window following the ischemic insult during which protective therapy may be instituted.…”

Prehospital Therapeutic Hypothermia for Cardiac Arrest

“…Some animal experiments suggest that neuroexcitotoxicity can be blocked or reversed only if the treatment is initiated in the very early stages of the neuroexcitatory cascade. [28][29][30][31][32][33][34] Acute inflammation early after ROSC plays a harmful role in postcardiac arrest, including cytokines, macrophages, neutrophils, and complement activation, leading to free radical formation. Multiple animal experiments and few clinical studies have shown that hypothermia suppresses all these ischemia-induced inflammatory reactions, leading to a significant reduction in free radical formation.…”