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Ribose in Open Heart Surgery

Ribose in Open Heart Surgery - Basic Concepts

Ribose in High Risk "Off Pump" Bypass Surgery

Ribose in Open Heart Surgery - Basic Concepts

In standard "on pump" open heart surgery, the heart is arrested, and a bubble-pump oxygenator is utilized to temporarily supply oxygenated blood to the rest of the body. Oxygen supply to the heart is thus cut off, so cardiac ATP production will cease. The heart cells would die, except that:
            · The heart is arrested, such that its requirement for oxygen and ATP is lessened
            · The heart is cooled within an ice bath, also decreasing its energy needs
            · The surgeon works expeditiously, to minimize the period of time that the heart is oxygen starved.

Despite these measures, the oxygen deprived heart cells will stop burning fatty acids to generate ATP; they will turn to anaerobic metabolism of glucose, but that will not last long. ATP content will fall. The heart will then burn two ADP molecules to make one ATP and one AMP, but then it will burn off its ADP and AMP to adenosine, which will diffuse out of the cardiac cell, never to return. The heart "on pump" soon becomes a heart with a depleted adenine nucleotide pool - there won't be much AMP left.

So the surgeon finishes his work. Fresh bypass grafts were placed, the heart is restarted, and the bubble pump oxygenator is disconnected. The heart is back on its own, but now with a normal blood supply - no more oxygen deficiency for this heart. Blood flow through its new grafts is intact so the cells can make as much ATP as they want, because they now have all the oxygen that they need - except that they can't make ATP.

They can burn fatty acids and sugar. The mitochondria are intact. They can strip electrons off the carbon atoms in sugar and fat, and they can transport these electrons, such that they should be able to convert this caloric energy into biological energy, to rephosphorylate ADP to ATP. But there's not enough ADP; there's not enough AMP. A significant portion of the adenine nucleotide pool was burned down to adenosine and lost forever. The longer the surgery took, the greater percentage of ATP, ADP, and AMP that was lost, the more difficult it will be to regenerate ATP. The heart will have to regenerate AMP from scratch, a process that takes weeks. In the meantime, the heart will be ATP deficient; the ATP deficient heart will be stiff and hypocontractile (see the CoQ10 in open heart surgery section), and if this is your heart you will be in the ICU on diuretics and inotropic support. The surgery will be a success, but your heart will be struggling; it will struggle until enough time has gone by such that the heart can make AMP from scratch, such that it has something to phosphorylate to make ATP, the source of energy that it needs if it is to function like a normal heart.

What if we provided ribose to patients undergoing on-pump open heart surgery? Ribose administered orally or IV rapidly makes its way into the myocardial cells. With ribose present, the heart can rapidly regenerate AMP from adenosine. The AMP can be further phosphorylated to ADP and ATP, and - voila - the heart can start converting caloric energy into biochemical energy. Systolic and diastolic function should improve. Let's see if this can really happen:

Ribose in "On Pump" Bypass Surgery

% Patients with EF > 15% below baseline

In this study, ejection fraction (the percentage of blood filling the heart that is ejected with each beat; normal is ³ 50%), was measured in 20 patients before and seven days after successful coronary artery bypass surgery and/or aortic valve replacement. As the procedure began, the subjects were begun on a five day infusion containing ribose 70 gm/day or placebo solution. Their care was otherwise the same. While the surgery was technically a success in all, in 80% of the placebo patients the seven day ejection fraction remained at least 15% below baseline. Only 20% of the ribose treated patients still had systolic dysfunction of this degree. This makes sense. One week is not long enough for the heart to generate enough ribose to generate enough AMP to allow you to regenerate ATP, no matter how much oxygen is now available - pump function will remain below what it could be and you and your heart will struggle. However, if we provide you with ribose, you can rapidly regenerate AMP, you can rapidly regenerate ATP, and your pump function will return to normal more rapidly. Our hospitals will not administer ribose to you during open heart surgery, and they will not let you take it on your own, but I will give it to you as soon as you get out of the hospital, and it is my observation that ribose (along with CoQ, carnitine, magnesium, thiamine, and related agents) speeds up your recovery.

Ribose in High Risk "Off Pump" Bypass Surgery

Dr. Perkowski, in Orange Co. California, has observed that pre-treatment with ribose improves outcome in patients requiring urgent bypass surgery following a heart attack. The heart involved in a heart attack will be under severe metabolic strain. Heart muscle was lost; the remaining cells will be called upon to generate an increased quantity of ATP, and their blood supply may be compromised as well. Surgical outcome when bypass surgery is carried out soon after a heart attack is thus much worse than when surgery is carried out after a four week period of convalescence. The heart then has enough time to recover, to generate enough ribose to allow for the regeneration of ATP. Surgeons will thus advise delaying bypass surgery. But what if all three of your arteries are severely narrowed? What if you continue to experience angina, signifying that you are at risk for further damage? In this scenario, the surgeon's hand is literally forced. If bypass surgery is not carried out you will sustain a second heart attack and you will likely not survive it. Urgent, high risk bypass surgery is necessary. OK, your risk is increased, but could we decrease this risk if we could rapidly regenerate your ATP supply by giving your ribose pre-operatively. The study above showed that ribose supplementation lead to a more rapid recovery of pump function in "on pump" bypass surgery. What will happen with urgent, high risk "off pump" bypass surgery?

Dr. Perkowski and his colleagues carried out bypass surgery on forty four adults with coronary insufficiency. One third of these patients had sustained a recent heart attack. Surgery was carried out "off pump". Off pump bypass surgery is a major advance, and is discussed elsewhere in this website. Off pump bypass minimizes oxygen deficiency during the surgical procedure. The off pump approach certainly makes sense in the high risk patient, who doesn't need any more oxygen deficiency, with its attendant depletion of cardiac ATP content, and attendant compromise of the heart's ability to regenerate ATP. Twenty four of Dr. Perkowski's patients received pre-operative ribose, and twenty did not. The groups were matched with respect to baseline pump function, clinical characteristics, and anticipated surgical risk. Early post-bypass, the ribose treated patients demonstrated a 50% greater increase in cardiac functional indices in comparison to the control group. Dr. Perkowski's findings are currently available only in abstract form; when his paper is published I will amend this website entry with charts and more detail.

James C. Roberts MD FACC
1/01/07