History of Cardioplegia in a Nutshell
Rapid cardiac arrest before cardiac surgery, and therefore the concept of cardioplegia, with a hyperkalaemic solution was introduced by Melrose et al. in 1955, and it enabled better post-ischaemic recovery of myocardial function compared to mere aortic cross clamping(3). However, it also led to [Ca2+]I overload, and Hearse et al. found that myocardial damage was related to ATP depletion along with this [Ca2+]I overload(4). Hence, Hearse proposed three components of myocardial protection by cardioplegia during cardiac surgery: (a) rapid diastolic cardiac arrest to conserve energy by [Na+]I and [Ca2+]I depletion, extracellular K+ and Mg2+ elevation and infusion of local anaesthetic agents or Ca2+ antagonists, (b) hypothermia to slow down cellular metabolic demands, and (c) application of substances (i.e. oxygen, energy substrates etc.) to prevent or reverse IR injury(5). These principles now form the foundation for most cardioplegic solutions.
Bretschneider et al. developed Custodiol, an intracellular crystalloid cardioplegic solution which is Ca2+-free with a low Na+ concentration to reduce the Na+ gradient causing the loss of action potential (AP) and consequently inducing cardiac arrest(6). In comparison, Hearse introduced an optimal extracellular crystalloid cardioplegic solution, called the St. Thomas’ Hospital solution, which mainly relies on depolarised hyperkalemic (16mM) arrest. In addition, Lolley et al. developed glucose cardioplegic solutions containing insulin and K+ to enhance ATP production during I-R, which was later found to reduce myocardial injuries in animal models of I-R(7).
Cold blood cardioplegia was proposed by Buckberg et al. to arrest, perfuse then reperfuse the myocardium with different compositions of hyperkalaemic crystalloid cardioplegic solution mixed with blood in a 1:4 ratio(8). Calafiore et al. later introduced warm blood cardioplegia containing K+/Mg2+ which provides myocardial protection when applied continuously(9).
Cardioplegic delivery can be anterograde, retrograde or combined. Anterograde delivery involves running the cardioplegia solution down the coronary arteries and supplying the myocardium in the same fashion that blood normally does. In retrograde cardioplegia however, the flow of solution is administered in a retrograde manner, and it is indicated in cases such as critical coronary stenosis or when anterograde delivery does not provide sufficient cardioplegic solution to the myocardium distal to the occlusion(10). Despite the extensive study of cardioplegia solutions over the last decades (Fig.1 ), the ideal myocardial protection method during cardiac surgery is still uncertain.