Mild Hypothermia Inhibits Systemic and Cerebral Complement Activation in a Swine Model of Cardiac Arrest

Abstract

Complement activation has been implicated in ischemia/reperfusion injury. This study aimed to determine whether mild hypothermia (HT) inhibits systemic and cerebral complement activation after resuscitation from cardiac arrest. Sixteen minipigs resuscitated from 8 minutes of untreated ventricular fibrillation were randomized into two groups: HT group (n=8), treated with HT (33°C) for 12 hours; and normothermia group (n=8), treated similarly as HT group except for cooling. Blood samples were collected at baseline and 0.5, 6, 12, and 24 hours after return of spontaneous circulation (ROSC). The brain cortex was harvested 24 hours after ROSC. Complement and pro-inflammatory markers were detected using enzyme-linked immunosorbent assay. Neurologic deficit scores were evaluated 24 hours after ROSC. C1q, Bb, mannose-binding lectin (MBL), C3b, C3a, C5a, interleukin-6, and tumor necrosis factor-α levels were significantly increased under normothermia within 24 hours after ROSC. However, these increases were significantly reduced by HT. Hypothermia decreased brain C1q, MBL, C3b, and C5a contents 24 hours after ROSC. Hypothermic pigs had a better neurologic outcome than normothermic pigs. In conclusion, complement is activated through classic, alternative, and MBL pathways after ROSC. Hypothermia inhibits systemic and cerebral complement activation, which may provide an additional mechanism of cerebral protection.

The complement lectin pathway after cardiac arrest

“…We expect the classical and the alternative pathway to contribute to the formation of common pathway components in post‐cardiac arrest syndrome; however, the extent is still unknown. A previous animal study has demonstrated that all 3 initiating pathways were activated after cardiac arrest, but from the LP Gong et al only included MBL. Thus, the complement system may play an important role in exacerbating the damage after cardiac arrest, and therefore, studies to target complement system proteins should be of future interest.…”

Impact of age on cardiovascular function, inflammation, and oxidative stress in experimental asphyxial cardiac arrest

“…Endothelial activation is closely coupled to leukocyte activation and the systemic inflammatory response, why the different development in cytokine levels over time and increased levels of elastase in the aged animals is consistent with the increased endothelial activation also observed in these animals. Several studies have shown leukocyte activation and increased cytokine levels in patients after CA, however, without investigating the effect of age . Two clinical studies have established an association between plasma levels of IL‐6 and elastase and poor outcome in post‐CA patients .…”

Therapeutic Hypothermia Improves Hind Limb Motor Outcome and Attenuates Oxidative Stress and Neuronal Damage in the Lumbar Spinal Cord Following Cardiac Arrest

“…It has been proven that hypothermic therapy can effectively protect multiple injuries of the brain and spinal cord [7]. In a swine model of CA, previous studies have shown that mild hypothermia has protective effects against ischemic damage in the brain and demonstrated that reduction of oxidative stress, enhancement of antioxidant enzyme expressions [8], inhibition of brain edema, proinflammatory cytokine [9], and complement activation [10] are underlying mechanisms for cerebral neuroprotection after applying hypothermia.…”