What is Ischemic Preconditioning?

Ischemia is a condition of inadequate supply of blood and oxygen to the cells. Since cells need oxygen for maintenance and function, lack of oxygen can lead to cell death. The heart and the brain consume more oxygen compared to other organs. Because of this, they are very prone to damage if there is a sudden decrease in their blood supply, which happens during a heart attack or a stroke. The leading causes of death worldwide.

Ischemic preconditioning (IPC) is a method to improve the survival of not only the heart and the brain but also the other organs.

Murry and his group in 1986 noted that those people who have prodromal episodes of chest pains before a heart attack have fewer complications and have higher survival than those who had a heart attack without having any prior chest pains.

Ischemic Preconditioning Studies

To confirm if their observation is reproducible, research was done on dogs. They reproduced the mechanism of ischemia by occluding a coronary artery for 5 minutes, followed by 5 minutes of reperfusion. They did this repeatedly for a total of 4 occlusions.

Next, they clamped the same artery for 40 minutes to cause a heart attack. The investigators found out that the animals who had their coronaries clamped before the “heart attack” had a smaller infarct size than the control group. A smaller infarct size means fewer complications and improved survival. They called the phenomenon ischemic preconditioning. The control group of animals just had the 40-minute heart-attack-inducing occlusion alone

Blausen_0260_CoronaryVessels_Anterior

Remote Ischemic Preconditioning

Since the phenomenon of IPC was so intriguing, more studies were done. The research that followed involved clamping a coronary artery for a few minutes several times, but this time, a different coronary artery was clamped. The results were the same. The heart muscle or myocardium fared better even if the occluded vessel is not precisely the same one that supplied that area. They called this remote ischemic preconditioning.

Remote Limb Ischemic Preconditioning

The next question is, what if the conditioning is done on an artery much farther away from the heart? What if it is done on the arm or the thighs? Would it do the same thing for the heart? The research was done on pigs and involved using a standard blood pressure cuff inflated for 5 minutes and released for 10 minutes consecutively for four times. The answer is yes. Remote limb IPC provided the same protection to the heart without splitting open the animal’s chest.

The same studies were done on humans, but this time, a blood pressure cuff was applied on the upper arm or the thighs to simulate the restricted blood flow. Then they checked the heart and the blood vessels by imaging either by 2-D ECHO, near-infrared spectrometry, and serum cardiac enzymes to assess the damage to the heart. The results showed that the heart did better.

The benefits of ischemic preconditioning went beyond the heart but to other organs that need a lot of oxygen, too, like the brain, liver, kidneys, skin, and the intestines. This is called interorgan ischemic preconditioning.

The Science behind Ischemic Preconditioning

There are many mechanisms and pathways on how ischemic preconditioning works. It turns out that an organ adjusts to the restricted blood flow by producing substances locally that are circulated by the blood and nervous system all over the body. These substances, and signals increase the capacity of the organs to withstand ischemia and reperfusion injury.

Reperfusion injury happens after blood flow resumes to previously ischemic cells. The resumption of blood flow and oxygen produces free radicals that cause further damage to the cells and increases the amount of damaged tissue or infarct size.

Remote Ischemic Perconditioning

The problem with ischemic preconditioning in real life is that no one can predict when they will have a heart attack or stroke. Ischemic perconditioning is done when someone is actively having a heart attack or ischemic stroke. The results have shown the same cardioprotection as ischemic preconditioning.

Ischemic Postconditioning

Ischemic postconditioning happens immediately after a heart or a stroke. When an occluded blood vessel is reopened, the ischemic tissue is prone to reperfusion injury. To me, the practicality of the postconditioning lies in situations where pre or perconditioning is not applied. It is another opportunity for cardioprotection.

At the moment, IPC is not part of any stroke or cardiac guidelines in spite of the favorable literature attesting to its benefits.

Other Uses of Ischemic Preconditioning

IPC is being used now by some hospitals, surgeons, and anesthesiologists, to improve the outcome of cardiac surgery, primarily pediatric congenital heart surgery. IPC also preserves renal, intestinal, and brain function postoperatively.

IPC is also being used in rehabilitation medicine, physical therapy, and sports medicine.

In future articles, I will describe the use of ischemic preconditioning in exercise to increase muscle size, and it’s relevance in High-intensity interval exercises, resistance exercises, and IPC’s potential applications for the elderly.

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