Deep hypothermic circulatory arrest and global reperfusion injury: Avoidance by making a pump prime reperfusate—A new concept

Abstract

A global reperfusion injury after deep hypothermic circulatory arrest was identified and changed. The injury is mediated by oxygen-derived free radicals, resulting in organ and endothelial dysfunction. Modification of global organ and endothelial damage is achieved by modifying the blood prime in the cardiopulmonary bypass circuit to deliver a controlled global reperfusate when reinstituting bypass.

Resuscitation after prolonged cardiac arrest: effects of cardiopulmonary bypass and sodium–hydrogen exchange inhibition on myocardial and neurological recovery☆

“…Temporary CPB successfully salvaged the heart, but severe neurological damage occurred in survivors that did not receive other therapy. HOE-642 therapy augmented cardiac output and reduced the adverse neurological score, but this improvement was quite limited in comparison to the complete recovery observed in our previous study [10,11]. A potential culprit is the adverse effect of this agent on vascular tone, as our preliminary studies showed that profound hemodynamic vasodilation following the conventional 5 mg kg À1 HOE-642 dose allowed complete brain recovery after prolonged ischemia with DHCA [10,11].…”

“…Counteracting intracellular acidosis after ischemia, the sodium-hydrogen ion antiporter (NHE) activation leads to sodium overload of the cell that subsequently promotes intracellular calcium accumulation. In previous experimental studies, we have demonstrated markedly improved myocardial and neurological recovery by controlling post-ischemic intracellular calcium accumulation through NHE inhibition with HOE-642 after prolonged deep hypothermic circulatory arrest (DHCA) [10,11]. The aims of this study were to determine whether use of CPB as a resuscitation tool and NHE inhibition with HOE-642 will limit whole-body-reperfusion injury and improve myocardial and neurological recovery in an experimental model of 15 min no-flow CA.…”

Sudden cardiac death: Directing the scope of resuscitation towards the heart and brain

“…In the future, the duration of cerebral anoxia that is tolerated in humans may be further extended by controlling the whole body reperfusate after cardiopulmonary collapse, as has been shown in our recent animal studies (30).…”

Resuscitation After Prolonged Cardiac Arrest: Role of Cardiopulmonary Bypass and Systemic Hyperkalemia

“…Subsequent alteration of the pump prime and rapid CPB-assisted cooling to moderate whole-body hypothermia (32°to 34°C), which has been shown clinically to improve neurologic recovery and reduce mortality in post-CA patients [28], might be the keys to limiting reperfusion organ damage. Our prior studies showed attenuation of brain and whole-body ischemic injury after deep hypothermic circulatory arrest by "controlling" (modifying) the initial CPB reperfusate [15,16]. Future studies may use this information to avoid brain injury by adjusting the pump prime to make it a controlled reperfusate (whole-body "hot shot") after prolonged CA.…”

“…Neurologic assessment was performed at 4 and 24 hours after CPB using a species-specific behavior scale, and seizure activity was evaluated [15,16]. The neurologic deficit score assesses five neurologic components (cranial nerves, motor and sensory, respiration, consciousness, behavior) with a score of 0 to 100 in each category: 0 ϭ normal, 500 ϭ brain death.…”