The Physiology of Cardioplegia 
To rapidly arrest the myocardium in diastole and maintain it in a depolarised state, it is necessary to understand the underlying electrophysiology behind hyperkalaemia, which is a fundamental constituent of most cardioplegic solutions. Hyperkalaemia induces diastolic arrest by establishing a new resting membrane potential (RMP) that is more depolarised (i.e. more positive) than normal(11). It is worth noting that the RMP is maintained by the ATP-driven Na+/K+ pump, which creates an electrochemical gradient across the sarcolemmal membrane (Fig.2 ).
In physiological states, AP generation occurs due to activation of voltage-gated channels which allow influx of cations. Following sinoatrial node stimulation, voltage-gated Na+ channels (VGNCs) open, provided the -65mV threshold is reached which enables a rapid influx of Na+ ions, depolarising cardiomyocytes to +20mV (Fig.2 ). This potentiates the opening of L-type Ca2+ channels (LTCCs) leading to a further influx of cations whilst the VGNCs become inactivated. Calcium-induced calcium release from the sarcoplasmic reticulum via ryanodine receptors allows electromechanical coupling, forming the characteristic prolonged plateau of AP in cardiomyocytes (Fig.2 ). As the membrane potential reaches more negative values, LTCCs close and delayed K channels return the RMP back to -85mV.
In the hyperkalemic states of cardioplegia, the constant influx of K+ increase the RMP to -55mV which is beyond the VGNCs threshold thus they remain inactivated. Consequently, both adequate repolarisation and conduction of another AP are prevented – rapid cardiac arrest is induced. Additionally, the myocardial oxygen consumption and significant cellular ATP depletion, both of which are characteristic of I-R injury, are reduced as per Hearse’s principles of cardioplegia(12).
Mitochondrial ATP-sensitive K+ channels allow coupling of membrane potential to the cellular metabolism and therefore play a significant role in myocardial protection(13). This is established by reducing post-ischaemic infarct size and apoptosis, possibly via altering mitochondrial Ca2+ and modulating reactive oxygen species formation(14).
Solutions for Myocardial Protection
Cardioplegic solutions can either be intracellular or extracellular(15). Extracellular solutions contain high concentrations of potassium, magnesium and sodium ions and work by preventing repolarisation of myocytes(15). Intracellular solutions contain low electrolyte concentrations and work by decreasing the sodium-potassium concentration gradients and stopping potassium efflux, thus preventing action potential generation(15). There are several types of these solutions used in clinical practice, some of which are listed below.
Histidine-tryptophan-ketoglutarate (HTK)/Custodiol/Bretschneider’s
The main advantage of HTK is the buffering capacity of histidine which enhances the efficiency of anaerobic glycolysis, providing better myocardial preservation(15,16). The ketoglutarate component is an intermediary in the Krebs cycle and acts as a high energy ATP provider during reperfusion(15,16). The tryptophan component stabilises cell membranes(15). Mannitol, an osmotic diuretic is also added(15). It decreases cellular oedema and has free radical scavenging properties, thus reducing ischaemic injury(15).
HTK induces cardiac arrest by lowering the sodium and calcium concentrations and preventing action potential depolarisation(15). This means that longer time is required to initiate cardiac arrest, which causes greater ischaemic and reperfusion damage(16).  However, only a single dose is required which simplifies the procedure(16).
St Thomas’s solution (STH)   STH is an extracellular cardioplegic solution(15). The original St Thomas’s solution (STH1) was formed by Hearse and colleagues in the early 1970s(17). This STH1 solution was then refined to form Plegisol or St Thomas’s Hospital solution No. 2 (STH2) which is now the most widely used crystalloid cardioplegic solution in the world(17). Many studies show STH2 to have better myocardial protective and antiarrhythmic effects than STH1.
Due to the high potassium and magnesium concentration in STH, it induces rapid cardiac arrest(15). It is effective in providing myocardial protection in patients undergoing procedures like coronary artery bypass graft (CABG)(16). However, it is less protective in patients requiring longer cross-clamp times. STH also increases cellular oedema and damages endothelial function. It thus needs repeated perfusion during ischaemia and must be administered every 20-40 minutes(16).
Del Nido solution   In the early 1990s, Pedro del Nido and colleagues developed a cardioplegic solution that satisfied the requirements of the paediatric heart during surgery(18). It has mainly been used in paediatrics and not very commonly for adults. Due to this there is scarce data available to support the safety and efficacy of its use in adult heart surgery(18).
Del Nido solution is very dilute and consists of lidocaine and magnesium and has lower concentrations of calcium(18). It induces cardiac arrest during surgery and decreases intracellular calcium, slows down rate of energy consumption and scavenges free radicals(18). It also reduces myocardial oedema, preserves high-energy phosphates and also promotes anaerobic glycolysis(18).
It allows uninterrupted surgery due to single cardioplegia dosing, thus reduced overall surgical times(18). However, concerns regarding its use in adults exist due to lack of prospective randomised trials and evidence for safe use(18). The properties of the different cardioplegic solutions are summarised in Table 1.