Authors: Christopher Busack MD, Chinwe Unegbu MD, and Daniela Perez-Velasco DO – Children’s National Hospital
A 4-year-old male patient with an atrial septal defect presents for surgical repair with cardiopulmonary bypass. The surgeon plans on using a clear pump prime with a hyperpolarized cardioplegic arrest. Which cardioplegia solution produces a hyperpolarized cardiac arrest?
The ability to induce cardiac arrest and facilitate open-heart surgery by infusing a high potassium-containing solution into the coronaries was first demonstrated by Melrose et al. in 1955 in a canine experimental model. Different cardioplegia solutions today consist of varying amounts of electrolytes (potassium, sodium, calcium and magnesium), buffers and medications. Cardioplegia is administered after cross clamp of the aorta either in an antegrade fashion via the coronary arteries or retrograde via the coronary sinus. Cardioplegic solutions cause diastolic arrest, decrease cardiac metabolic demand, and improve myocardial tolerance to ischemia.
The most common method for achieving cardiac arrest is by providing a high concentration of potassium (K+ ) ions into the extracellular space. Extracellular cardioplegic solutions often contain high concentrations of sodium (Na+ ), calcium (Ca2+ ), potassium (K+ ), magnesium (Mg2+ ), and bicarbonate and cause cardiac arrest by depolarizing the myocardial membrane. The Buckberg and St. Thomas’ Hospital cardioplegia solutions both contain high K+ content and are delivered with blood. A major drawback with both of these solutions is that they require frequent re-dosing.
A concern with depolarizing arrest is Ca2+ accumulation in the myocytes, thereby preventing myocardial relaxation. To mitigate this effect, contemporary depolarizing cardioplegia solutions contain lidocaine and magnesium. These agents repolarize the cell membrane to some degree and prevent Na+ and Ca2+ accumulation within the cell. Del Nido cardioplegia includes lidocaine and magnesium and is categorized as a modified extracellular depolarizing solution. A 2016 retrospective review by Buel et al. demonstrated a six-fold decrease in the rate of defibrillation post cross-clamp with del Nido cardioplegia compared to the St. Thomas Hospital solution. The del Nido cardioplegia solution was developed for pediatric cardiac surgery due to the specific needs of an immature and developing myocardium. The immature myocardium has a higher sensitivity to intracellular Ca2+ since the sarcoplasmic reticulum is underdeveloped with a reduced capacity to store Ca2+ . Studies in adults have also shown benefit of the del Nido solution and it is used in many adult centers.
Intracellular cardioplegia solutions have low levels of Na+ and Ca2+ mimicking the intracellular electrolyte concentration. These solutions induce a hyperpolarizing arrest of the myocardium which decreases energy consumption and intracellular accumulation of Ca2+ . Histidine–tryptophan–ketoglutarate (HTK) solution (Custodiol HTK®/Bretschneider solution) is an intracellular cardioplegic solution that was introduced in the 1970s. Histidine buffers ischemia-induced acidosis; tryptophan is an effective cell membrane stabilizer; ketoglutarate enhances energy production and recovery following reperfusion; and mannitol minimizes cellular edema by maintaining the osmolality of the cellular environment and functions as a free radical scavenger. HTK solution is particularly useful for long complex repairs as it reliably produces cardiac arrest for up to 120 minutes without redosing.
There is no consensus regarding the “best” cardioplegia solution. Numerous studies have demonstrated that multiple cardioplegia options safely achieve myocardial protection. However, a recent 2018 study by Panigrahi et al suggests that the del Nido solution may offer some additional benefits including quicker resumption of normal cardiac rhythm and decreased inotropic support compared to conventional blood cardioplegia. A 2019 randomized controlled trial by Talwar et al. compared HTK solution and del Nido solution. The del Nido group demonstrated a better cardiac index, less mechanical ventilation days, and shorter ICU stays. Electron microscopy also showed less edema of the myocardium and better myofibrillar architecture with del Nido solution. The higher cellular edema seen with the HTK solution may be related to its very low sodium content. Nonetheless, there is more research to be done in this area.
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