A primary function of the blood stream is to transport oxygen and glucose to all living cells in the body, including brain cells. These cells require glucose as a fuel, and they use oxygen to metabolize it. Although the human brain comprises only 2% of total body mass, it accounts for about 20% to 25% of total oxygen consumption, and depends on an uninterrupted supply to satisfy its demands. Reserves of oxygen in the brain are extremely limited.
When blood flow cesaes or is inadequate to oxygenate the tissue, it is known as ischemia. Many people have experienced mild, transient cerebral ischemia, for instance when standing up suddenly after resting for a while. As blood pressure falls in the brain, cells receive less oxygen than they need, and the visual field may darken while sounds seem to recede for a couple of seconds. Then the pulse rate increases, blood pressure is restored, brain cells are resupplied with oxygen, and senses return to normal.
Cardiac arrest inflicts sudden and total ischemia, terminating the brain’s supplies of oxygen and glucose completely. Unconsciousness occurs within less than 10 seconds, and a flat EEG is seen after about 20 seconds
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For the next four to six minutes, brain cells continue to burn some remaining reserves of glucose in the absence of oxygen. This can be compared with a flame on a gas stove which burns blue when oxygen is mixed with the gas but turns yellow, creating waste byproducts, if oxygen is insufficient. In brain cells, the transition from aerobic (oxygen-based) metabolism to anaerobic (oxygen free) metabolism creates byproducts including lactic acid. Acidity also increases as carbon dioxide (which is no longer being removed by the blood stream) dissolves in water to form carbonic acid. The increase in acidity alone has harmful consequences, but other processes also begin to disrupt the extremely complex chemistry of brain cells, jeopardizing their survival.
Cells normally use a large part of their energy to maintain a higher concentration of potassium salts and a lower concentration of sodium salts inside their membranes than outside them. When a cell runs out of energy, it cannot sustain these chemical differentials. Potassium leaves the cell and sodium enters, together with water, which causes cells to swell.
The imbalance of sodium and potassium results in the release of glutamate (glutamic acid), which is a neurotransmitter. This in turn triggers receptors which allow calcium ions to enter the cell, provoking a further release of glutamate in a positive-feedback loop. High levels of calcium eventually activate proteolytic enzymes that destroy many cell proteins (especially in cell membranes) and initiate apoptosis, causing cells literally to self-destruct
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We can use three approaches to prevent the cascade of harmful events that normally begins after the blood stops flowing.
1. Cardiopulmonary support
Chest compressions squeeze the heart, restoring some blood flow. The lungs can be ventilated to oxygenate the blood, although this may be contraindicated if warm ischemia has persisted for too long.
2. Medications
A variety of medications can block biochemical processes or may help to mitigate their effects.
3. Rapid cooling
Hypothermia (lowered body temperature) slows the chemical reactions that cause injury. At normal body temperature, successful resuscitation becomes unlikely after more than five minutes without blood flow. If the body temperature is reduced sufficiently (for example, during hypothermic surgery), resuscitation may be possible after as long as one hour without a heartbeat.
We feel we have good reason to expect that nanotechnology will enable cellular repair at some time in the future. Nevertheless, we see three vital reasons for minimizing ischemic injury.