Custodiol Cardioplegia: A Single-Dose Hyperpolarizing Solution.

Good morning, ladies and gentlemen. Mr. Chairman, it is my great pleasure, but mainly it is an honor for me to be invited for lecturing this audience. I hope I can inform you about some new aspects concerning myocardial protection. The title of my lecture is “Custodiol Cardioplegia: A Single-Dose Hyperpolarizing Solution.” The impact of a low-sodium solution on electrophysiology, physiology, solution’s composition and experimental results, mode of administration, clinical results, and last but not least, the take-home message is demonstrated step by step. The first aspect is related to electrophysiology, which is included in the title— hyperpolarization.What does it mean? We have calculated the membrane potential, especially for this congress (Figure 1). How does the membrane potential change, if you administerHistidine-Tryptophan-Ketoglutarate solution? I always call it HTK solution, since Custodiol is the item being given by the manufacturer. Since HTK solution can be used at cold as well as tepid temperatures, the membrane potential changes. We have a membrane potential of around −50 mV at 8°C. And if you administer the solution at 35°C, the membrane potential increases. For calculation of the membrane potential, we used the following data: intracellular sodium concentration of 15 mMol, 120 mMol potassium, and 135 mMol chloride. So that is the solution’s influence on the electrophysiology. But, to be honest, it plays no role in clinical use. This is only of scientific interest. Let’s move to physiology. Firstly, low-sodium solutions, how do they work? Primarily, it is an action potential of a muscular fiber, and it starts with a fast depolarization (Figure 2). If you significantly reduce sodium, the fast inward current is inhibited and the heart is arrested. Secondly, in our Department of Physiology in Göttingen in the late 1960s, Dr. Bonhoeffer could demonstrate that if you perfuse a heart at 35°C with different solutions, lowsodium solution effects the lowest energy turnover (1). He compared the low-sodium solution being equivalent to the first Bretschneider solution with high-potassium solutions or acetylcholine containing ones. Secondly, it is interesting that the range was the lowest, administering low-sodium solution. To conclude, low-sodium effects lowest energy turnover. Thirdly, there is a problem with any low-sodium solution. Most of you well remember the calcium paradox phenomenon being induced by calcium-free solutions. Therefore, I must explain why this low-sodium solution will never lead to a calcium paradox, because of a natural law, which seems to be a little bit difficult, but I will try to explain the equation very slowly (Figure 3). You see this special law of nature. The sodium intracellular square divided by sodium extracellular square is the same if you divide the intracellular calcium concentration by extracellular calcium concentration. What parameters do we know? We know calcium extracellular and sodium extracellular. And I have chosen a calcium concentration at 1.5 mMol to solve this equation and the sodium concentration at 150 mMol, to make it very simple. What happens now with the appropriate calcium concentration if we reduce the sodium content to 1/10? We know the sodium concentration and the result of this equation, and we have only to look for the calcium concentration. And the calcium concentration is .015 mMol. That means, if you reduce the sodium content to 1/10, you have to reduce the calcium concentration to 1/100. If you use the low-sodium solution, the sodium chloride leads to an osmolarity of 30 mOsmol/L in comparison to a high-sodium solution at 115 mMol (Figure 4). In this case the NaCl osmolarity is 230 mOsmol/L. However, the upper limit of osmolarity in a cardioplegic solution should be within the physiological range, being 300 mOsm/L. So now you can realize that with low-sodium solution an osmotic space is available to add numerous highly concentrated substances, which cannot be added to a highsodium solution, since the osmotic space is restricted. And among these substances, there is a buffer. That means only low-sodium solutions offer the potential to add a highly concentrated buffer. Address correspondence to: Claus J. Preusse,MD,PhD, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany. E-mail: [email protected]