Aortic Surgery by Mike Poullis

Due to advances in surgical techniques, cardiopulmonary bypass and anaesthesia cardiac surgery has become a routine procedure. Of these advances, the developments in myocardial protection techniques have been the most significant in making surgical outcomes successful. The systems used today allow the surgeon to operate on more and more difficult pathological conditions [1, 2].

The aim of myocardial protection is to facilitate the operative repair of cardiac pathology by allowing the surgeon to work in optimal conditions without damage to the myocardium. These conditions vary according to the type of operation and the surgical requirements. For example, difficult, distal coronary anastomoses are best performed in a motionless, dry, bloodless operative field.

The procedure of a cardiac operation is a compromise between ideal operative conditions and preservation of the myocardium.

This technique involves intermittent ischaemia, by application of the aortic cross-clamp, combined with systemic mild hypothermia (30 - 32^oC). It is particularly advantageous in coronary artery bypass grafting, where there is uncertainty concerning the uniform distribution of the cardioplegic solution to all parts of the myocardium due to coronary artery stenoses and an unpredictable degree of non coronary collateral flow. It is thought that graft length and orientation can be judged more precisely with a full and beating heart. The technique also provides the heart with a new, improved blood supply as each graft is completed. However, disadvantages include the risk of aortic damage and atheromatous embolization due to repeated cross clamping.

Optimal conditions for this technique include venting of the heart to prevent ventricular distension and spontaneous or brief induction of fibrillation before application of the cross-clamp.

NB. Venting of the heart is particularly important during cardiac surgery as ventricular distension greatly increases metabolic demands and is important immediately before and after the cross-clamp interval. Passive decompression of the heart may be accomplished by manual massage, stab wound in the pulmonary artery, elevation of the operating table or amputation of the tip of the left atrial appendage. It does not create negative pressure within the heart, and therefore introduction of air into the cardiac chambers is minimal. Active venting involves placing a catheter into the left ventricle, pulmonary artery or suction on the ascending aorta. All of these may introduce air; therefore de-airing manoeuvres must be carried out prior to removal of the cross-clamp [1].

On initiation of cardiopulmonary bypass (C.P.B) the patient is systemically cooled to 30 - 32^oC. The heart is vented either by active or passive venting (placement of the catheter into the pulmonary artery or the left ventricle). Ventricular fibrillation and cross clamp of the aorta is carried out for each distal coronary anastomosis. The heart is then defibrillated and the clamp is removed. The heart is filled at this stage (by limiting the venous return to the reservoir) to assess the length of the graft for the top anastomosis. A side clamp is then placed onto the aorta and each proximal end of the graft is attached to the aorta. Towards the end of the surgical procedure (usually when there is only one top end to attach to the aorta) the left internal mammary artery (L.I.M.A) is usually anastomosed to the left anterior descending artery (L.A.D). The patient is rewarmed back to a nasopharyngeal temperature of 37^oC, the vent is removed and when the surgeon is ready the patient is weaned off bypass.

NB. For almost all of the coronary artery bypass graft (C.A.B.G) operations performed at this unit the surgeon prior to bypass takes down the left internal mammary artery (L.I.M.A).

Cardioplegia is a crystalloid or blood-based solution used during surgical procedures to chemically arrest the heart. It is also one of the most effective ways of reducing metabolism as the heart requires approximately 1/5 of the oxygen that is normally required by the beating heart at 37^oC. Important considerations include the heterogeneity of delivery and the effect of non-coronary collateral flow during the administration of cardioplegia as these influences the degree of protection offered to the heart during the ischaemic period.

1) Heterogeneity of delivery - coronary stenoses and myocardial hypertrophy may result in under/over dosage of some regions of the myocardium.

2) Non coronary collateral flow - when the aorta is cross-clamped blood flow may still return to the coronary vasculature resulting in cardioplegic washout.

If the cardioplegia differs greatly from the blood or the interstitial fluid the heart becomes exposed to wide biochemical fluctuations as the solution is infused washed out, reinfused, washed out. Cardioplegic solutions therefore aim to mimic blood or interstitial fluid.

1) Antegrade - infusion of cardioplegia into the right and left coronary arteries by direct cannulation of the coronary ostia or the aortic root.

2) Retrograde - infusion into the coronary venous system by direct cannulation of the coronary sinus or the right atrium (see appendix (ii) for the advantages and disadvantages of retrograde and antegrade delivery of cardioplegia).

A variety of cardioplegic solutions are available, but it is the hyperkalaemic ones that are most widely used. The following techniques use various types of hyperkalaemic cardioplegic solutions to arrest and protect the heart.

Crystalloid cardioplegia is a solution that aims to resemble as close as possible the ionic composition of the normal extracellular fluid. It is used to induce mechanical and electrical arrest of the heart as quickly as possible, prevent intracellular ion loss, cool the myocardium, provide substrate to meet the reduced metabolic demands, buffer any changes in pH and prevent intracellular and interstitial oedema.

St Thomas' cardioplegia was originally formulated by D.J Hearse and associates from research and experimentation on isolated rat and dog hearts, carried out at St. Thomas' Hospital in London. There are two commercially available formulations of the cardioplegia, no.1 and no.2, as shown by table 1.

This centre uses solution 1 (Plegivex), currently supplied by IVEX Pharmaceutical Ltd. It provides the surgeon with a relaxed heart and a bloodless field of operation whilst protecting the myocardium during arrest (see appendix (iii) for the action and function of each of the constituents in the solution).

Concentration in mmol/l
Constituent	No.1	No.2
Sodium Chloride	144.0	110.0
Potassium Chloride	20.0	16.0
Magnesium Chloride	16.0	16.0
Calcium Chloride	2.4	1.2
Sodium Bicarbonate	-----	10.0
Procaine Hydrochloride	1.0	-----
pH	5.5 - 7.0

St Thomas' cardioplegia is used in conjunction with moderate hypothermia (28^o) and topical cooling (sodium chloride or Hartmanns solution cooled to 4^oC).

NB. Cooling the heart is an important part of myocardial protection as every 10^oC reduction in temperature decreases the metabolic rate by a factor of 2. The myocardium can be cooled by infusion of cold solutions into the coronary arteries (perfusion hypothermia), systemic cooling on C.P.B, local cooling with iced saline solution, cold irrigation or cooling pads placed around the heart. Crystalloid solutions can achieve myocardial temperatures as cold as 4^oC and blood based solutions 15 - 20^oC. Perfusion hypothermia is the most effective way of cooling the myocardium. However, coronary artery disease may cause heterogeneous hypothermia and so result in heterogeneous recovery of myocardial function on rewarming. Perfusion hypothermia is therefore usually combined with local irrigation to achieve more uniform cooling and recovery after the ischaemic interval [1].

Once the aorta is cross-clamped the initial dose of St. Thomas' cardioplegia (cooled to approximately 4^oC) is infused into the coronary ostia/aortic root at a pressure of 100 - 150 mm Hg (usually by the anaesthetist). Subsequent doses are given at 20 minute intervals. For C.A.B.G procedures the cross-clamp is removed once the distal anastomoses are complete and for valve procedures it is removed once the heart has been de-aired and closed. Rewarming of the patient is usually initiated prior to the cross-clamp being removed.

Blood-based cardioplegic solutions have potential advantages, since blood is a physiological medium providing the tissues with natural nutrients, large quantities of oxygen, trace elements, proteins and enzymes. It also has a very effective protein buffering system for the removal of acid and has an oncotic effect that reduces and prevents interstitial oedema.

If a warm cardioplegic arrest is utilised for myocardial protection blood cardioplegia is particularly advantageous as it provides the heart with all the necessary nutrients, oxygen, trace elements and so is preferred over crystalloid cardioplegia. However, when hypothermia is incorporated into the technique blood cardioplegia becomes less advantageous as a reduction in temperature results in a decrease in oxygen release to the tissues (due to a shift of the oxygen dissociation curve to the left resulting in oxygen being tightly bound to haemoglobin). Blood is also more viscous than a crystalloid solution, especially at lower temperatures, and so the rate of flow to the myocardium may be reduced resulting in a 'sludging' effect in the coronary vasculature and an uneven distribution of the cardioplegia. Blood-based solutions also impair precise visualisation of distal coronary anastomoses.

Compared to crystalloid cardioplegia blood-based solutions are particularly advantageous when used to resuscitate the myocardium if it has been exposed to an ischaemic period prior to cardioplegic arrest. Warm, blood cardioplegia used under these circumstances has shown to improve recovery of myocardial function and structure.

Blood based cardioplegia has also been shown to reduce the incidence of fibrillation during reperfusion (when a warm dose is given), reperfusion arrhythmia's and transfusions (reduces haemodilution) [3].

The technique was developed by Buckberg et al in the late 1970's, early 1980's and is based on the concept that because metabolic activity continues in a cold heart and there may be heterogeneity in cooling. A supply of nutrients and oxygen by a blood-based solution will therefore be beneficial to the myocardium and so aims to enhance the cold cardioplegic technique [1].

The technique involves an infusion circuit, which mixes arterial blood from the oxygenator with a crystalline solution. A blood-crystalline mixture is achieved with a haematocrit of approximately 15 - 20 %, potassium concentration of 20 mmol/l, low calcium concentration, alkaline pH and substrate enhancer.

The stock cardioplegic solution used at this centre is supplied by the pharmacy department and table 2 shows its constituents.

Constituent	Concentration in g/l
Glucose Anhydrous	38.19
Sodium Citrate Dihydrate	1.61
Sodium Chloride	1.65
Citric Acid Monohydrate	0.20
Tris(hydroxymethyl)methylamine	6.99
Tris(hydroxymethyl)methylamine Chloride	1.11
Sodium Dihydrogen Orthophosphate Dihydrate	0.15

The infusion circuit is the Gish box system, consisting of a reservoir with an integrated heat exchanger (as shown by diagram 1) and a giving set for either administration or recirculation of the cardioplegia.

The cardioplegia is a mixture of arterial blood (taken from an outlet port on the oxygenator) and stock crystalloid cardioplegic solution at a ratio of 4:1, respectively. For example, 400 ml of blood requires 100 ml of stock solution. The cardioplegia is cooled to 4 - 6^oC by circulating it through the heat exchanger (connected to an iced water supply) and administered antegrade and retrograde (as with the warm, blood, continuous technique). The cardioplegia is used in conjunction with moderate/mild hypothermia (28 - 32^oC) and topical cooling in an attempt to achieve homogeneous cooling of the myocardium. A warm dose is usually given before the removal of the aortic cross-clamp to restore the metabolic state of the heart prior to reperfusion and so help dissipate chemical cardioplegic arrest.

On initiation of C.P.B the first dose of cardioplegia is made up. This consists of 250 ml of the stock cardioplegic solution mixed, in the Gish box, with 1000 ml of arterial blood. Neat potassium chloride is added to the cardioplegia to attain a potassium concentration of 20 mmol/l (one full ampoule of 20 mmol potassium chloride in 10 ml). Once the solution has cooled to 4 - 6^oC and the patient is cooling to the desired temperature, the aorta is cross-clamped and the first dose is delivered antegrade/ retrograde.

After the initial 250 ml of stock cardioplegic solution has been removed, 12 mmol

(6 ml) of potassium chloride is added to the remaining solution in the bag, to achieve a concentration of approximately 10 mmol/l for the subsequent doses.

When the procedure is complete (valve has been replaced and / or distal anastomoses have been complete) the patient is rewarmed and the warm dose of cardioplegia is administered prior to the removal of the cross-clamp. Any proximal anastomoses are then completed in the usual way, using a side clamp on the ascending aorta.

Electrochemical arrest of the heart at normothermia reduces the metabolic rate and hence oxygen consumption by 90 %. Maintaining the heart in a warm condition is thought to preserve its metabolic integrity as the chemical processes necessary for cellular maintenance are in balance. The entire arrest period is thought to represent a period of myocardial resuscitation.

The technique provides protection of the myocardium by mixing oxygenated blood with potassium chloride and pumping it into the coronary circulation. Arterial blood is continuously taken from a branch line on the oxygenator outlet and passed through a fully occluded low flow roller pump. Neat potassium chloride (20 mmols in 10 mls) is added constantly to the blood from a syringe pump to provide a hyperkalaemic blood cardioplegic solution that is then pumped into the patients coronary system (as shown by diagram 2).

The initial concentration of potassium chloride is 20 mmol/l and is reduced gradually to 10 mmol/l once arrest has been achieved. The change in potassium concentration is achieved by altering the flow of potassium (ml/hr) in the syringe pump. This flow, however, depends upon the blood pump flow (ml/min) and the systemic serum potassium concentration of the patient. The following equation is used to calculate the syringe pump flow required to achieve the desired cardioplegic solution concentration.

Rearranging the above equation to the following allows the flow rate of the syringe pump to be calculated.

NB. The concentration of potassium chloride used is 2 mmol / ml therefore [K]_sp is assumed to be 2.

This technique involves no topical or systemic cooling. The patient is therefore maintained at 36 - 36.5^oC throughout the procedure.

When the aorta is cross-clamped administration of the warm cardioplegia is commenced with an initial high dose of potassium (20 mmols/l) which is infused into the aortic root (with a root pressure no greater than 100 mm Hg). Once the heart has arrested the cardioplegia is switched to retrograde and is administered via the coronary sinus (pressures between 20 -50 mm Hg). The flow rate of the potassium in the syringe pump is gradually reduced to a value or rate that will deliver a low potassium dose (10 mmols/l). Once the distal anastomoses/valve replacement is complete the cardioplegia is discontinued and the cross-clamp is removed. Proximal anastomoses of grafts are completed using the side clamp on the ascending aorta.

This technique follows the same principles as warm, blood continuous cardioplegia (W.B.C.C) as the heart is electrochemically arrested by potassium enriched normothermic blood. However, unlike the previous technique administration of the cardioplegia is antegrade only and intermittent. During the aortic cross-clamp period each distal anastomosis is completed during an ischaemic interval (10 -15 minutes) when no cardioplegia is being delivered. Intermittent administration of cardioplegia was introduced as continuous infusion of warm blood cardioplegia appears to disturb the operating field, making temporary interruption of the infusion necessary.

Recent data and research [4,5] suggest that this technique can be safely used without causing obvious myocardial dysfunction. The intermittent doses of cardioplegia aim to restore the metabolic demands of the arrested myocardium and prepare it for the next ischaemic period (normothermic blood has physiologically every component necessary to counteract damage due to ischaemia and reperfusion).

The technique has the same set-up as W.B.C.C. However, the syringe pump contains neat potassium chloride (20 mmol/l in 10 ml) and magnesium sulphate

(20 mmol/l in 10 ml) at a ratio of 4:1, respectively (see appendix iii, for the role of magnesium in cardioplegia).

Initially the Calafiore Protocol was followed; however, a modified version is currently used at this centre, as shown by table 4.

The following equation can be used to calculate the potassium concentration of the cardioplegia in mmol/l (modification of the equation used for W.B.C.C.).

1) Fsp/60 x T x [K]sp = the potassium delivered by the syringe pump (mmols).

NB. For the first dose an initial 2 ml bolus of potassium is delivered into the blood, the equation therefore becomes:

The temperature of the patient is allowed to drift down to 35^oC. When the aorta is cross-clamped the first dose of cardioplegia is initiated (see table 4). Once the heart has arrested the cardioplegia is stopped, even if the full dose has not been given. During the ischaemic periods the aorta is continuously vented on low suction (50 -100 ml/min). This is discontinued when the subsequent doses of cardioplegia are delivered into the root and started again once the cardioplegia is in. When the distal anastomoses are complete the cardioplegia is no longer required and the cross-clamped is removed. Proximal anastomoses of the grafts are completed in the usual way.

The patient is cooled to 30˚C and the blood cardioplegia is given at this temperature.

A final dose of 1000 mls warm blood only is given just before the cross clamp is removed. Two vent lines are used to remove any air venting simultaneously from the aortic root and the left ventricle.

i) The following section briefly describes the history of myocardial protection techniques.

For over 100 years it has been known that pharmacological manipulation of the extracellular fluid can cause derangements in both electrical and mechanical activity of the heart. Ever since Ringer described the importance of maintaining the concentration of electrolytes within precise ranges, ionic control has become a particularly important aspect of cardiac function [6].

Bigelow et al first investigated the concept of hypothermia at the University of Toronto in 1950. The experiments carried out by Bigelow and his colleagues showed that moderate hypothermia (25 - 28^oC) was able to protect the heart from ischaemic injury [7]. Hypothermia became the most important component of myocardial protection during cardiac surgery. Cold cardioplegia combined with systemic hypothermia therefore became a standard technique to preserve the heart.

In 1955 Melrose et al performed the first reported procedure which involved potassium arrest of the heart. Boluses of potassium citrate solution were used to increase the extracellular potassium concentration in patients undergoing repair of congenital heart defects [7]. In 1957 Lam, who is credited with the introduction of the term 'cardioplegia', used a syringe to inject potassium into a cross-clamped aorta and so direct it into the coronary arteries to achieve arrest. Unfortunately, the high concentration of potassium (240 mmol) resulted in severe cardiac injury. This lead to the introduction of cold, crystalloid cardioplegia, an intracellular formulation developed by Kirsch et al and Bretschneider et al in the 1960's. A lower concentration of potassium was used to achieve arrest with minimal energy requirements, enabling the surgeon to selectively arrest the heart. Multidose infusions of cold cardioplegia also prevented an increase in myocardial temperature and replacement of the cardioplegia caused by non-coronary collateral flow. The initial use of intermittent aortic cross clamping was therefore abandoned by many surgeons as it was shown that ventricular fibrillation greatly increased energy requirements of the heart. In the 1970's pharmacological cardioplegia was resurrected by the work of Gay, Ebert and Tyers et al, using potassium as an arresting agent.

The cold cardioplegic techniques were shown to have various disadvantages and detrimental effects on the myocardium and so further research resulted in the introduction of warm cardioplegia.

i) Does not prevent ischaemia during the cross-clamp period and so conversion to anaerobic metabolism occurs, resulting in a build up of lactic acid.

ii) Hypothermia has deleterious effects on membrane stability, myocardial metabolism, myocardial and systemic oedema, impairs enzyme function and A.T.P generation/utilisation, and inhibits calcium sequestration and autoregulation.

Warm cardioplegia is based on the realization that oxygen demand can be reduced as much as with the cold techniques but without the detrimental effects of hypothermia. It is the chemical content of the warm cardioplegia that causes the arrest and not the temperature. However, non-homogenous delivery (via the coronary sinus), systemic hyperkalaemia and visualisation of distal anastomoses were later discovered to be problems associated with warm cardioplegia [1].

Present studies include the use of beta-blockers (Esmolol) to improve myocardial protection [8] and other pharmacological agents to precondition the heart prior to surgery [9].

ii) The following section discusses the advantages and disadvantages associated with retrograde and antegrade delivery of cardioplegia.

Antegrade and retrograde perfusion have been investigated and compared by many researchers (Buckberg, Masula, Menasche, Fabioni, Diehl etc) and in terms of protection of the myocardium during ischaemic arrest and its post-operative recovery retrograde perfusion is now claimed to be more preferable to the antegrade approach.

Retrograde perfusion into the coronary sinus is usually carried out at a perfusion pressure of 40 mm Hg. It can be adequately monitored and the flow easily adjusted by inflation/deflation of the balloon. The position of the catheter can be confirmed by finger palpation of the atrioventricular groove, when the hand is placed behind the heart. Alternatively, retrograde cardioplegia can be given directly into the right atrium. Some studies have suggested that this method is better than sinus perfusion as the cardioplegia also goes into the thebesian veins and so allows better perfusion of the myocardium and hence right ventricular recovery. However, this method can not be used for atrial septal defects and it also requires more volume of cardioplegia than the sinus or antegrade techniques as the right atrium, right ventricle and proximal pulmonary artery need to be filled before the start of reperfusion [10].

The retrograde technique avoids the problems associated with aortic root and ostia cannulation, for example, trauma to the right and left coronary arteries and ostia stenosis. A retrograde flow out of the ostia reduces the risk of coronary artery embolism as it flushes out any atheromatous debris or air and so is particularly beneficial for patients with calcified valves [10]. Antegrade infusions via the aortic root also become a problem when the aortic valve is incompetent, due to disease or retraction of the heart, as cardioplegia is more likely to leak into the left ventricle and so effectively reduces the protective effects of the cardioplegia [11]. This is eliminated with the retrograde technique and also avoids the more cumbersome alternative of direct ostia cannulation. Even so, cannulation of the coronary sinus is a major concern with the retrograde technique as trauma to the right ventricle and sinus system can easily be induced [12].

Retrograde cannulation of the sinus therefore requires a careful and gentle approach, which can be made easier under transoesophageal echocardiographic control. Further injury is reduced by avoiding over distension of the balloon and excessive retraction of the heart (this increases the pressure on the wall of the coronary sinus). When retracting to expose the base of the heart deflating the balloon and maintaining decompression by the use of a left ventricular vent [12] is also important. Using retrograde perfusion also gives the surgeon more flexibility during surgery as the order of the procedure does not really matter, for example, an aortic valve replacement and coronary bypass grafts may be done in any order as the return from the ostia may not be significant enough to impair the technical aspects of the valve replacement.

Perfusion of the myocardium can be easily assured by the retrograde technique as the return of the cardioplegia via the coronary ostia is easily noticeable, especially when warm blood cardioplegia is used as the cardiac veins will have an arterial appearance and the return of blood out of the ostia will be desaturated. Retrograde infusions are also thought to give a more homogenous distribution of the cardioplegia compared to the antegrade delivery as it perfuses those areas distal to any coronary obstruction [11]. A study carried out by L.Noyez et al at the University Hospital Nijmegen, Netherlands [13] compared antegrade and retrograde crystalloid cardioplegia. They concluded that the retrograde technique gave better preservation of cardiac energy reserve during cardioplegic arrest and so improved the post-operative recovery of the myocardium. When the aorta was cross-clamped measuring the lactate produced in the coronary sinus (due to anaerobic ALP synthesis) and its extraction on reperfusion assessed myocardial metabolism. Their results showed that during the cross-clamp period lactate concentrations for both antegrade and retrograde perfusion increased. However, immediately after the cross-clamp was released lactate increased for the antegrade group and decreased for retrograde. The extraction rate of the lactate was also greater when retrograde perfusion was used. This was thought to be due to a faster return of aerobic ALP synthesis back to a normal level on reperfusion which is thought to be due to better tissue perfusion during the ischaemic period and so resulting in improved myocardial recovery.

Whilst the retrograde technique appears to be better at protecting the heart its benefits are counteracted to some extent by its delay in the initial arrest of the heart at the start of the procedure [11]. Unlike the antegrade technique it does not produce a rapid asystole and so increases the likelihood of myocardial damage. The use of both techniques during the same procedure would therefore seem a logical response. An initial antegrade infusion results in rapid asystole of the heart followed by subsequent or a continuous retrograde infusion to maintain cardioplegic arrest and protection of the myocardium [10]. Recent studies have also suggested retrograde balloon inflation in the coronary sinus during antegrade infusions as this is thought to aid homogenous cardioplegic delivery and improve the distribution of the cardioplegia to the jeopardised regions [10]. Therefore, a combination of the two techniques is now being used and incorporated into many cardioplegic techniques as it is thought to give better right and left heart protection than just the antegrade or retrograde techniques alone [14].

iii) The following sections concentrate on each of the constituents, outlining their action and function in the cardioplegic solution.

Potassium is used in St. Thomas' Solution as the main cardioplegic agent to stop the heart. During infusion of the cardioplegia the extracellular potassium concentration is increased so much that changes in the membrane potential of the cell occur. This effects the action potential of the cell and hence the excitability of the myocardium. Under normal physiological conditions the potassium concentration in the extracellular fluid is 3.5 - 5.5 mmol/l, hence the heart is almost certainly to arrest when solutions with potassium concentrations of 16.0 and 20.0 mmol/l respectively, are infused.

The direct effect of a hyperkalaemic solution is to reduce the resting membrane potential by lowering the concentration gradient of potassium ions across the cell

(resulting in a slower diffusion of potassium out of the cell). This will affect the action potential as the reduction in the resting potential occurs over many milliseconds (instead of a fraction of a millisecond as under normal conditions) allowing more time for the inactivation of the voltage-gated sodium channels and hence their closure in the purkinje and work cells of the myocardium. Therefore, if these sodium gates are closed there is no initial development of the action potential and so the myocardium remains unexcited and is said to be in diastolic arrest.

The sodium, calcium and chloride ions are included into the solution to maintain electroneutrality of the solution and hence the integrity of the cell membrane.

During cardioplegic arrest the sodium - calcium pump is partially inhibited and so the movement of calcium ions out and sodium ions into the cell is reduced. The cardioplegic solution must therefore aim to balance this by regulating the extracellular sodium and calcium ion concentrations. For example, if the extracellular sodium concentration is too low calcium will either move into the cell or its movement out of the cell will be inhibited. This causes an increase in intracellular calcium ions, which may then stimulate the contractile processes within the myocardium to produce systolic arrest of the heart and possible cellular damage of the myocardium. To prevent the likelihood of this the calcium ion concentration can be reduced or removed. However, if the calcium concentration is too low flooding of calcium back into the cell (calcium paradox) may result on reperfusion and so result in systolic arrest. Similarly, if the calcium concentration is too high this may cause the heart to effectively overwork on reperfusion and so induce cellular damage.

The concentrations of sodium and calcium (110.0 and 1.2 mmol/l, respectively) in solution 2 were experimentally determined using the creatine kinase assay (creatine kinase is a precursor of ATP production, the energy source required for the contractile processes that occur within the myocytes). When cellular damage of the myocardium occurs creatine kinase is released from the cell into the extracellular fluid. This assay was therefore used to determine the amounts of creatine kinase leakage and hence the level of damage induced during cardioplegic arrest. When the concentrations of sodium and calcium were above or below the values for solution 2 the kinase leakage was greater and so at these levels it is thought that the sodium and calcium ions add to the protection of the heart and help to preserve ATP for reperfusion.

Except for potassium, magnesium is the most abundant intracellular ion in the heart. It complexes with ATP to form the substrate used in the reactions of muscle contraction and relaxation. It is thought to help modulate muscle tension and is a cofactor in all energy transferring reactions of the cell and also in many oxidation, synthetic and transportation processes [15].

Magnesium has a negative inotropic effect on the heart (reduces the force of contraction) and so counteracts the positive inotropic effect of calcium. This protects the heart by allowing calcium to be present in the solution whilst avoiding the risk of the calcium paradox and hence impaired recovery of the heart during reperfusion.

Experiments have shown that solutions, which contain no magnesium and a low concentration of calcium (0.1 and 1.2 mmol/l) during hypothermic cardioplegia, may result in myocardial contraction. This increases coronary vascular resistance and reduces ATP levels and so on reperfusion may impair the functional recovery of the heart. When magnesium is included at a concentration of 16 mmol/l it has been found to improve recovery and so is added to the solution as a protective agent to help stabilise the membrane of the myocardial cells and preserve ATP for post-ischaemic activity.

During ischaemic conditions when the aorta is cross-clamped the heart will start to use energy produced from anaerobic glycolysis, even in hypothermia conditions. Such a process results in a build up of lactic acid and hence hydrogen ions, resulting in intracellular acidosis. This inhibits further anaerobic energy production and activates lysosomal enzymes, which damage the myocardium by breaking down the cell membranes. To avoid this detrimental effect sodium bicarbonate is added to the solution to act as a buffer and mop up the excess hydrogen ions and so prevent the pH from falling too far below the normal value of pH 7.4. St. Thomas' solution 2 contains 10.0 mmol/l of sodium bicarbonate to give a pH of 7.8. This slightly alkaline solution was selected to counteract the reduction in pH, which occurs during cooling, and so maintain cell metabolism. Solution 1 contains no buffer allowing the pH to adjust to that within the tissue. Studies comparing the two solutions have shown no conclusive accounts that buffering aids protection of the heart during cardioplegic arrest. It is now thought that the buffer concentration in solution 2 is too low to inhibit ischaemic acidosis and only stabilises the various constituents before the solution is used.

Procaine is a local anaesthetic agent, which binds to the lipid components of cellular membranes blocking the movement of sodium and calcium ions. It is thought to maintain cellular depolarisation during cardioplegic arrest by blocking sodium ion outflow and protect the heart by inhibiting calcium ion inflow. It also has anti-arrhythmic properties, which are more important for the post-ischaemic reperfusion period.

Experiments with solution 1 have shown reduced creatine kinase leakage when procaine is added at 1.0 mmols/l. If the concentration of procaine is increased above 1.0 mmols/l then it may have a detrimental effect on the heart [16] as it is thought that the cell membrane becomes progressively more unstable and leaky to the movement of calcium into the cell.

	Usual components^*
Solution	Sodium	Potassium	Magnesium	Calcium	Bicarbonate	pH	Osmolarity (mOsm/L)	Other components

Bretschneider's no. 3	12.0	10.0	2.0	�	�	5.5�7.0	320	Procaine; mannitol
Lactated Ringer's	130.0	24.0	�	1.5	�	7.14	�	Lactate; chlorine
Tyer's	138.0	25.0	1.5	0.5	20.0	7.8	275	Acetate; gluconate; chloride
St. Thomas no. 2	110.0	16.0	16.0	1.2	10.0	7.8	324	Lidocaine
Roe's	27.0	20.0	1.5	�	�	7.6	347	Glucose; tris buffer
Gay/Ebert	38.5	40.0	�	�	10.0	7.8	365	Glucose
Birmingham	100.0	30.0	�	0.7	28.0	7.5	300�385	Glucose; chloride; albumin; mannitol
Craver's	154.0	25.0	�	�	11.0	�	391	Dextrose
Lolley's	�	20.0	�	�	4.4	7.78	350	Dextrose; mannitol; insulin

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[4] - Calafiore A.M et al: Intermittent Antegrade Warm Blood Cardioplegia. Ann Thorac Surg 59: 398-402, 1995.

[5] - Tonz M et al: Effect of Intermittent Warm Blood Cardioplegia on Functional Recovery After Prolonged Cardiac Arrest. Ann Thorac Surg 62: 1146-1151, 1996.

of Mechanical Devices in Providing Cardioprotective Strategies. Int Anaesthesiol Clin 34: 61-84, 1996.

[7] - Rao V et al: Preconditioning to Improve Myocardial Protection. Ann-N-Y-Acad-Sci 30: 338-354, 1996.

[8] - Mehlhorn U: Improved Myocardial Protection using Continuous Coronary Perfusion with Normothermic blood and Beta-blockade with Esmolol. Thorac Cardiovasc Surg 45: 224-231, 1997.

[9] - Flameng W.J: Role of Myocardial Protection for Coronary Artery Bypass Grafting on the Beating Heart Ann Thorac Surg 63: 518-522, 1997.

[10] - Buckberg G.D: Antegrade Cardioplegia, Retrograde Cardioplegia, or both. Ann Thorac Surg 45: 589-590, 1988.

[11] - Thomas A. et al: Technique and pitfalls of Retrograde Continuous Warm Blood Cardioplegia. Ann Thorac Surg 11: 359-362, 1996.

[12] - Vibhu R. et al: Coronary Sinus Injury during Retrograde Cardioplegia (a report of three cases). J Thorac Cardiovasc Surg 11: 359-362, 1996.

[13] - Noyez L. et al: Antegrade versus Retrograde crystalloid Cardioplegia (perioperative assessment of cardiac energy metabolism by means of myocardial lactate measurement). J Thorac Cardiovasc Surg 43: 194-199, 1995.

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[15] - Hearse D.J et al: Myocardial Protection during Ischaemic Cardiac Arrest (the importance of magnesium in cardioplegic infustates). J Thorac Cardiovasc Surg 73: 848-855, 1977.

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Dose	Roller Pump (ml/min)	Syringe Pump (ml/min)	Duration (min)	[K⁺] (mmol/l)
First	300	Push 2ml then 150	2	18 - 20
Second	200	120	2	20
Third	200	90	2	15
Fourth	200	60	3	10
Fifth	200	40	4	6.3
Sixth	200	40	5	6.3