How Therapeutic Hypothermia Works

Chain of Death
Mitochondria in the human heart
Mitochondria in the human heart
© Visuals Unlimited/Corbis

Our organs experience significant injuries not only when oxygen-supplying blood flow is curtailed, but also when it suddenly returns. Mitigating the neurological effects of this ischemia-reperfusion injury (aka post-cardiac arrest syndrome) is one of therapeutic hypothermia's primary applications [source: Delfin].

When blood and oxygen flow to the brain cease, a cascade of biochemical events kicks off, one that can continue to destroy brain cells for hours or days after circulation is restored [source: Delfin]. One of the most pivotal aspects of this process concerns mitochondria, the vital, sausage-shaped organelles that power our cells.

Without oxygen, mitochondria's normal energy processes fail, and cells switch to anaerobic respiration. This causes lactic acid to build up, essential mechanisms to shut down and calcium to accumulate within the cell. The resulting glut of calcium prompts the discharge of the neurotransmitter glutamate, which excites brain cells, sparking a more urgent call for nonexistent oxygen and triggering a whole host of harmful chemicals, including highly reactive free radicals [sources: Deckard and Ebright; Delfin; Merck Manual].

Meanwhile, cell walls lose integrity and let in additional harmful substances, including more calcium, as well as sodium, which causes inflammation (edema). Overcome, the mitochondria die and break down, releasing toxins and other chemicals that can trigger apoptosis. If the cell then kicks the bucket, it releases glutamate and toxins into its surroundings, exciting nearby neurons. The immune system dispatches neutrophils and macrophages to sweep up dead cells, kicking off a chain reaction by producing free radicals that further damage cells, deepening the inflammatory response, aggravating cerebral swelling and causing further neurological injury. Meanwhile, the combination of ischemia, swelling and pressure cause the protective blood-brain barrier to grow more permeable [sources: Deckard and Ebright; Gibson and Andrews].

That's the bad news. The worse news is that when circulation resumes it further damages these already weakened tissues and cells. Leaky cell membranes and a destabilized blood-brain barrier mean further cerebral edema as newly delivered white blood cells gather in the brain and, provoked by damaged tissue, let loose a horde of inflammatory factors and free radicals. Meanwhile, blood coagulation and the formation of microclots can block blood flow, causing localized ischemia. Seizure activity can further influence the course of such complications [source: Delfin].

This is, of course, a vastly simplified overview, but it reveals the harmful mechanisms that therapeutic hypothermia helps to shut down.