Myocardial Protection


Myocardial Protection

Optimizing clinical outcomes in cardiac surgery depends upon the performance of a technically proficient operation without incurring myocardial damage during the procedure. Adherence to this principle is imperative, whether a minimally invasive, robotic, off‐pump, or conventional surgical approach through a median sternotomy is performed. With the widespread application of percutaneous coronary interventions, patients requiring surgical revascularization tend to have severe coronary disease and more impaired ventricular function, requiring optimal myocardial preservation. The same holds true for patients undergoing surgery for complex valve problems that may not be amenable to percutaneous approaches. In most of these cases, the surgeon must conscientiously apply the well‐developed principles of cardioplegic arrest to minimize ischemia/reperfusion injury, which contributes to postischemic myocardial dysfunction. Excellent myocardial protection is essential to optimize the short‐ and long‐term results of surgery. In some situations, modifications of traditional approaches to myocardial protection with cardioplegia may prove beneficial.

I. Techniques to Minimize Myocardial Injury During Cardiac Surgical Procedures (Table 6.1)

Table 6.1 Options for Myocardial Protection

  1. Off‐pump surgery

    1. Intraluminal shunting
    2. Aortocoronary shunting
    3. Perfusion‐assisted shunting
    4. Ischemic preconditioning

  2. On‐pump surgery

    1. Cardioplegic arrest (antegrade/retrograde)
    2. On‐pump beating heart
    3. Hypothermic fibrillatory arrest
    4. Intermittent ischemic arrest
    5. Redo AVR with patent ITA – cold retrograde blood or blood cardioplegia

AVR, aortic valve replacement; ITA, internal thoracic artery

  1. The problem of ischemic arrest. Aortic cross‐clamping interrupts the coronary circulation and will result in conversion to anaerobic metabolism with lactate accumulation, myocardial acidosis, depletion of myocardial energy stores, and cellular swelling. There is an accelerated accumulation of intracellular calcium during ischemia as the ATP‐dependent active transport mechanism to extract sodium and calcium is impaired. Upon reperfusion, the high intracellular calcium levels cause severe myocardial dysfunction. Thus, without a reduction in myocardial metabolism, either by hypothermia or chemical cardiac arrest, aortic occlusion producing ischemic arrest for more than 15–20 minutes results in severe myocardial dysfunction.
  2. Cardioplegic arrest with aortic cross‐clamping is used during most types of cardiac surgery to allow the surgeon to operate upon an arrested heart with a relatively bloodless field. This produces diastolic arrest, preserves energy stores, and minimizes calcium entry into myocardial cells. With appropriate replenishment, this allows the surgeon to arrest the heart for several hours without experiencing ischemic myocardial damage.13
  3. Off‐pump coronary artery bypass surgery (OPCAB) is performed without cardiopulmonary bypass (CPB) and thus on a beating heart. The need to provide myocardial protection is limited, because only the region subtended by the artery which is transiently occluded while being bypassed should be in ischemic jeopardy. Careful positioning of the heart for anastomoses to the inferior and lateral walls is essential to minimize systemic hypotension, which can also induce ischemia. If ischemia develops during vessel occlusion, as evidenced by ECG changes or ventricular dysfunction, intracoronary shunting or aortocoronary shunting can be used to provide distal flow until the anastomosis is completed.4,5 Additional support using miniaturized CPB systems or right ventricular (RV) assist can be used in high‐risk off‐pump cases.68 Despite fairly comparable morbidity and mortality to standard on‐pump/cardioplegic arrest techniques, off‐pump surgery may have some advantages in patients with severe left ventricular (LV) dysfunction.9
  4. On‐pump beating‐heart surgery for coronary bypass grafting can be performed without aortic cross‐clamping, using stabilizing OPCAB platforms to allow for the construction of distal anastomoses on a beating heart while the pump provides systemic flow. Despite the lower oxygen demand of the empty beating heart, ischemia in the distribution of severely diseased nonbypassed arteries is often noted due to the lower perfusion pressures on pump. Although ischemia should be better tolerated than during a standard OPCAB, shunting techniques can still be used to optimize protection. Applications of this technique include:

    1. When safe aortic clamping cannot be performed (usually with a calcified or severely atherosclerotic aorta), when off‐pump surgery is not technically feasible, or when the risk of arresting the heart is considered very high due to a recent myocardial infarction, ongoing ischemia, marked LV hypertrophy, or severe ventricular dysfunction.10 In these high‐risk cases, studies have shown equivalent if not better results with this technique than with OPCABs and conventional CABGs.1113
    2. Intracardiac operations, such as resection of a LV aneurysm or surgical ventricular restoration, allowing the surgeon to palpate the border zone between viable muscle and scar tissue better than if the heart were arrested.
    3. Minimally invasive mitral valve surgery when access to the aorta for clamping may be difficult (although a balloon “endoclamp” can be used). This is tolerated as long as there is no aortic valve regurgitation, either at baseline or with retraction of the left atrial wall during valve exposure.1418 The latter problem can be avoided using a transseptal approach.
    4. Reoperative aortic valve surgery with a patent internal thoracic artery (ITA) graft that cannot be dissected free and controlled during cardioplegic arrest. Use of continuous retrograde cold blood or blood cardioplegia with at least moderate systemic hypothermia can be used for myocardial protection.1921 Performing reoperative aortic valve surgery using normothermic noncardioplegic retrograde blood perfusion has been used successfully as well.14,15

  5. Hypothermic fibrillatory arrest is a variant of the “empty beating heart” approach. It can be used for coronary surgery, with the aorta remaining unclamped and the distal anastomoses performed on a cold vented fibrillating heart with high perfusion pressures. Stabilizing platforms can be used if necessary to optimize exposure. This technique provides less than ideal protection, especially in the hypertrophied heart. Although it confirmed the concept that coronary surgery could be performed safely without aortic cross‐clamping, this technique is rarely used anymore.22
  6. Intermittent ischemic arrest involves multiple short periods of cross‐clamping during mild systemic hypothermia to perform each distal anastomosis. Conceptually, this is a violation of the principle of preserving the heart by inducing diastolic arrest during the period of aortic cross‐clamping. However, the heart is able to tolerate these brief periods of ischemia without adverse sequelae.23,24
  7. Ischemic preconditioning refers to a phenomenon in which a transient reduction in blood flow to myocardial tissue enables it to tolerate a subsequent longer period of ischemia. The ideal application of this concept is in off‐pump surgery, because, in the absence of collateral flow, there is obligatory transient ischemia with occlusion of a target vessel that might be lessened by ischemic preconditioning. Although some studies suggest that this technique reduces troponin leakage, myocardial dysfunction, and arrhythmias compared with surgery using cardioplegic arrest, others have not.2528
  8. Ischemic postconditioning involves the administration of medications at the time of initial reperfusion when the aortic cross‐clamp is removed to modify ischemia/reperfusion damage. Use of adenosine 1.5 mg/kg has been shown to reduce troponin leakage.29

II. Principles of Cardioplegia13 (Table 6.2)

Table 6.2 Principles and Composition of Modified Buckberg Cardioplegia

Principle Composition

  1. Prompt diastolic arrest
KCl 20–25 mEq/L

  1. Buffering
THAM, bicarbonate

  1. Reduction of calcium levels
Citrate‐phosphate‐dextrose (CPD) or double‐dextrose (CP2D)

  1. Adequate delivery
Antegrade ± retrograde administration

  1. Temperature
Cold vs. tepid vs. warm

  1. Substrate additives to optimize myocardial metabolism or prevent cell damage
Na+/H+ exchange inhibitors
Calcium‐channel blockers

THAM, tromethamine; CPD, citrate‐phosphate‐dextrose; CP2D, double‐dextrose

  1. Prompt diastolic arrest of the heart is achieved using a delivery solution containing about 20–25 mEq/L of potassium chloride (KCl). The potassium may be added to a crystalloid solution which is administered undiluted (“crystalloid cardioplegia”), or it may be concentrated in a smaller bag of crystalloid solution and administered in a mixture with blood in varying ratios (most commonly 4:1 or 8:1 blood:cardioplegia solution) (“blood cardioplegia”). Systems are available that add the potassium directly to blood to minimize hemodilution (so‐called miniplegia or microplegia). In these systems, the lack of hemodilution provides superior oxygen‐carrying capacity to diluted blood cardioplegia along with natural osmotic properties. They have been shown to reduce postoperative myocardial edema, increase buffering, and permit more rapid recovery of LV function compared with 8:1 blood cardioplegia.3032

    1. Crystalloid cardioplegia (CCP) provides little substrate and no oxygen to the heart during the period of ischemic arrest. It functions primarily by arresting the heart at cold temperatures. It can be oxygenated by bubbling oxygen through the solution, but this is not a common practice.

      1. St. Thomas and Plegisol are extracellular solutions with high potassium levels that produce arrest by depolarization. They require replenishment every 20 minutes or so to optimize protection. St. Thomas solution also contains procaine, and high doses can trigger postoperative seizures. A comparison of these two solutions showed less ventricular fibrillation after unclamping with use of St. Thomas solution.33
      2. Bretschneider solution (Custodiol) is an intracellular hyperpolarizing solution with low sodium and potassium that contains histidine–tryptophan–ketoglutarate.34 The histidine provides a buffer and is a free‐radical scavenger, and this reduces the risk of ischemia‐reperfusion injury. This solution can provide myocardial protection for up to 2–3 hours with just one dose.3537 Studies comparing cold antegrade blood cardioplegia with Custodiol showed similar or better protection with Custodiol for mitral valve surgery and equivalent results in aortic valve surgery, although better results were noted with blood cardioplegia in patients with reduced ejection fractions.3638

    2. Blood cardioplegia (BCP) solutions provide oxygen, natural buffering agents, antioxidants, and free‐radical scavengers. Standard supplemental additives to these solutions include other buffers to achieve an alkaline pH (THAM), citrate‐phosphate‐dextrose (CPD) or double‐dextrose (CP2D) to lower the level of calcium, and occasionally drugs to maintain slight hyperosmolarity (mannitol).

      1. Buckberg solution and its modifications contain the ingredients listed above in a variety of different concentrations. It produces potassium‐induced cellular depolarization and requires replenishment every 20–30 minutes. The cardioplegia mixture passes through a separate heater/cooler system in the extracorporeal circuit with a 4:1 or 8:1 mixture of blood:cardioplegia stock solution. The infusion rate, temperature, and pressure are controlled by the perfusionist. Various additives can be used to optimize protection in various clinical situations by replenishing ATP stores (see sections II.D and E).
      2. del Nido (DN) cardioplegia is a hyperkalemic, low calcium solution that contains lidocaine and magnesium (polarizing agents), bicarbonate (to maintain an intracellular pH), and mannitol (a free‐radical scavenger that also reduces myocardial edema). Myocardial protection is optimized by low diastolic intracellular calcium levels attributable to lidocaine blockade of Na+ channels and the presence of magnesium. The solution is given in a ratio of 1:4 blood to cardioplegia stock solution.39,40 Although it has been administered primarily antegrade in most studies, there is no specific reason why it could not be given retrograde as well.

        1. DN cardioplegia was initially developed for congenital heart surgery and has now seen more widespread application in adult cardiac surgery. Earlier studies evaluated its benefits in valvular surgery, with subsequent studies reporting its use in adult congenital cases, complex valve and combined operations, reoperations, and coronary surgery.4147 When used with mild hypothermic CPB, it provides equivalent protection in patients with and without LVH and with cross‐clamp times of up to about 90 minutes.48
        2. A dose of 20 mL/kg to a maximum of one liter is given antegrade, with half that dose given if the anticipated cross‐clamp time will be less than 30 minutes (except a full dose should be given if LVH is present).39 One dose usually suffices for cross‐clamp times less than 90 minutes, and not having to re‐administer cardioplegia generally shortens the cross‐clamp and bypass times. The heart usually does not fibrillate after unclamping of the aorta.
        3. If a longer cross‐clamp time is anticipated or has occurred, redosing with about 10 mL/kg after 45–90 minutes is suggested.42,43 However, the heart is often sluggish for a short period of time after unclamping the aorta, especially after redosing or when an additional dose is given close to unclamping.49,50 Furthermore, very few reports include patients requiring very prolonged cross‐clamp times (>2 hours). Thus, it is still not clear when redosing should take place in such patients.
        4. Clinical results are comparable to those with Buckberg‐type solutions and probably better than with St. Thomas solution.40,41,4347,51,52

    3. The oxygen demand of the heart is reduced nearly 90% by simply arresting the heart at normothermia, so maintenance of arrest during the cross‐clamp period is essential (Figure 6.1). For Buckberg‐type solutions, this is accomplished by re‐administering the solution every 15–20 minutes to deliver potassium and wash out metabolic byproducts. A low‐potassium solution (12–15 mEq/L) is used to maintain the arrest to avoid an excess potassium load. The high‐potassium solution should be re‐administered if the heart resumes any activity. For DN cardioplegia, re‐administration may be given empirically every 45–90 minutes or when the heart resumes activity. Cold blood alone can be given retrograde into the coronary sinus as an alternative to subsequent doses of cardioplegia to optimize tissue oxygenation and metabolism while minimizing the potassium load. This is adequate as long as the heart remains arrested. It is especially beneficial in patients with renal dysfunction, who are predisposed to the development of hyperkalemia.
    4. Clinical studies generally suggest that both cold and warm BCP provide superior myocardial protection to cold CCP, with less troponin release and better hemodynamic performance post‐pump. However, the rate of myocardial infarction and operative mortality has not been shown to differ.5357 The advantage of BCP is probably most evident in patients with acute ischemia and more advanced LV dysfunction, especially when given both antegrade and retrograde. However, myocardial protection remains suboptimal even with BCP in hypertrophied hearts.58

  2. Temperature. Before the development of cardioplegia solutions, myocardial protection was provided entirely by systemic and topical hypothermia. It was found that myocardial oxygen consumption did decrease about 50% for every 10 °C decrease in myocardial temperature. It only seemed logical that administering cardioplegia at a cold temperature would be a significant factor in decreasing myocardial metabolism. However, the reduction in myocardial metabolism attributable to hypothermia is actually quite insignificant compared with that achieved by diastolic arrest (Figure 6.1). Nonetheless, systemic hypothermia and topical cold (not iced) saline are routinely used in patients receiving cold cardioplegia, with occasional use of a topical cooling insulation device to surround the LV and protect the phrenic nerve from cold injury.

    1. Some surgeons monitor myocardial temperatures with the presumption that adequate hypothermia (<15 °C) of the myocardium is providing satisfactory myocardial protection. However, in clinical practice, only one site is usually selected for monitoring (usually the LV apex or septum), and there is commonly a significant discrepancy between the temperatures of different areas of the LV, and especially between the left and right ventricles. It should be understood that temperature monitoring provides only a relative assessment of the degree of myocardial protection. A more scientific means of doing so can be accomplished using a pH probe. The development of significant acidosis caused by a derangement in myocardial metabolism is indicative of poor protection.59 Studies have shown little correlation between pH and temperature, suggesting that temperature is actually not a good indicator of the state of myocardial metabolism.60
    2. Use of intermittent “tepid” BCP (whether at 32 °C or 20 °C) allows the heart to utilize more oxygen and glucose than a colder heart.61 It may provide better metabolic and functional recovery than cold cardioplegia, with improved long‐term results.62 Optimizing its benefits may require administration through both antegrade and retrograde routes, especially in hypertrophied hearts.63,64

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Nov 6, 2022 | Posted by in CARDIAC SURGERY | Comments Off on Myocardial Protection

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