The Heart is a muscle and any muscle requires a blood supply to function. The heart is supplied by 2 main blood vessels. The left coronary artery and the right coronary artery. The left further divides into 2 large branches: The left anterior descending artery (LAD) and the left circumflex artery. Each of these vessels supply a part of the heart and in combination, these 3 vessels supply the whole of the heart. 

When any of these vessels is occluded, the territory supplied by that vessel no longer receives the oxygen it needs and the cells within that territory suffocate and if the occlusion persists, eventually die. When the cells die, they are no longer able to contribute to the pumping ability of the heart and the heart function declines. 

It is therefore logical to say that the single most important factor in terms of prognosis from a heart attack is the size of the affected territory. The larger the territory that dies, the weaker the heart gets. The consequences of death of a large territory include death as a consequence of the heart attack or If the patient is lucky enough to survive the heart attack, a severely weakened heart  and a lugubrious overall prognosis.

If areas within the heart were to receive blood from multiple arteries and therefore not dependent on a single blood artery then even if one vessel blocked off, the amount of damage would be minimised because cells within that territory would continue to receive blood from the other artery.

 Reassuringly, we now know that the coronary arteries are not isolated end vessels. They give off multiple smaller branches which in turn give off very tiny branches which connect to very tiny branches of the other coronary arteries so it is possible for the blood to get to areas of the heart supplied by an occluded vessel through the branches of another non occluded vessel. 

This is known as the coronary collateral circulation.

Let me give you an analogy.

I live in a place called Hull and work in a place called York. Hull and York are connected by a road called the A1079. It is the most direct way for me to get to work. However if this road were to block off one day, it would still be possible for me to get to work. I would go down a little side road and then go through a network of many tiny country streets which are likely to be narrow and slow but I would still eventually get to work. I would get late but I would still get there. These tiny side roads and that network of tiny roads which ultimately get me to my destination are analogous to the Coronary collateral circulation.

So it figures that the magnitude of damage induced by a blocked main coronary artery would be significantly reduced if there was a pre-existing well developed collateral circulation.

Today I wanted to talk to you about what we know about cardiac collateralization and how to enhance it.

Although we know that collateral vessels exist in the undiseased heart, these vessels are very small and do not allow much blood through them. However if there is a progressive narrowing of the main blood vessels over a period of time then that encourages blood to use these collateral vessels and when this happens the collateral vessels start growing in size and the diameter of the collateral vessels can increase as much as by 5-10 fold. 

In one experiment, the researchers found that the diameter of these collateral vessels can range from 10-200 micrometers if the normal coronary arteries are normal but can be as big as 100-800 micrometers in patients with significant coronary artery disease. In addition, it is also believed that when a major blood vessel progressively narrows, the chronic lack of oxygen actually stimulates the production of new collateral vessels as well – so the existing collateral get bigger and you also create more collateral vessels. 

The crucial point is that it takes time to develop these collaterals. If you have unobstructed coronaries and then suddenly one blocks off, then you won’t have had enough time to develop collaterals and therefore the amount of damage is much more likely to be substantial. However if you have progressive narrowings which are getting worse over a course of years then the chances of having a well developed collateral circulation are likely to be much greater. This is why it is not uncommon for us to see patients who have blocked coronary vessels but no visible reduction in the pumping ability of the heart because the blockage has developed over time and therefore the blood is still able to get through via a well developed collateral circulation and hence the cells continue to survive.

A lot of research has therefore focussed on methods by which we could improve our coronary collateral circulation. I will discuss the research that has been done so far.

The first study is called EXCITE.

In this study researchers took 60 patients with significant coronary artery disease and divided them into 3 groups. 20 patients were asked to do high intensity exercise, 20 to moderate intensity and 20 to a control group and they found that patients who engaged in exercise had better collateral flow indices compared to patients who did not exercise. 

We know that coronary blood flow tends to be maximal when the heart is relaxing i.e., in diastole. So if one could prolong diastole by using a pharmacological agent to slow the heart down then the increased blood flow in the coronaries could increase collateral vessel formation. A scientist called Gloekler compared 6 months of therapy with a heart rate slowing agent called Ivabradine and compared it to placebo and found that Ivabradine was associated with improvement of collateral flow indices whereas placebo resulted in worsening of coronary flow indices.

Another scientist called Patel showed that a significantly larger proportion of patients with significant coronary disease with a heart rate of <=50 beats per minute had collateralisation compared to patients with a heart rate of >60/min.

Scientists have also been interested in knowing whether we can stimulate collateralisation by using stem cells, cytokines and physical means.

Stem cell research remains in its infancy. 

VEGF and FGF are 2 growth factors that have been studied and have failed to show improvement in collateralization.

There has also been a study using Granulocyte macrophage colony stimulating factor which looked promising  initially but due to adverse effects, has not been convincing enough.

One very interesting strategy has been the use of a technique called enhanced external counter pulsation (EECP). Here, pressure cuffs are applied to the lower limbs and triggered to inflate to 300mmHG of mercury pressure when the heart is relaxing. This means that blood is pushed into the coronary arteries during diastole. After repeated sessions totalling 30 hours, it does appear that these patients develop a significantly better collateral circulation.

So this was a quick summary of collateralization. Many patients with heart disease are terrified of exercising but as long as your doctor gives you the go-ahead, in general exercise is good for you and a great way to enhance the collateral circulation.

I hope you found this useful and look forward to your comments.