Myocardial Preservation During Cardiopulmonary Bypass

1. Pathophysiology of Injury During CPB

• Ischemia - Aortic cross-clamping halts coronary blood flow entirely. Anaerobic glycolysis becomes the sole energy source; fatty acid oxidation fails. High-energy phosphate stores (ATP, creatine phosphate) are rapidly consumed and intracellular acidosis accumulates. Intracellular calcium rises due to failure of energy-dependent ion pumps.
• Reperfusion injury - After unclamping, the return of oxygenated blood paradoxically causes additional damage. Mechanisms include:
  • Rapid intracellular calcium overload
  • Oxygen-derived free radical generation (superoxide, hydroxyl radical)
  • Abnormal endothelial-leukocyte interactions
  • Myocardial cellular edema
• Myocardial stunning - Reversible systolic and diastolic dysfunction following ischemia-reperfusion. Responds to inotropic support and resolves with time. Distinct from irreversible necrosis.
• Vulnerable patients - Those with poor preoperative LV function, ventricular hypertrophy, or diffuse severe CAD are at highest risk.

2. Core Pillars of Myocardial Preservation

A. Cardioplegia

B. Hypothermia

• Systemic hypothermia is achieved by cooling through the CPB circuit.
• Topical myocardial cooling is achieved by bathing the arrested heart with cold saline/ice slush, targeting myocardial temperature of 10-15°C.
• Desirable myocardial temperature is 10-15°C (directly monitored with a needle temperature probe).

C. Left Ventricular Decompression (Venting)

3. Cardioplegic Solutions - Composition

4. Cardioplegia Delivery Routes

Antegrade Cardioplegia

• Infused proximal to the aortic cross-clamp, into the aortic root at 60-100 mmHg, or directly into coronary ostia (used when aortic regurgitation is present or when operating on the aortic valve).
• Most physiological approach; mirrors normal coronary perfusion direction.
• Limitation: areas distal to high-grade coronary obstructions (the very areas at greatest risk) may not receive adequate cardioplegia.
• Arrest occurs in 30-60 seconds.

Retrograde Cardioplegia

• A balloon-tipped catheter is placed through the right atrium into the coronary sinus. Solution is delivered at 200-400 mL/min to a venous pressure of 30-50 mmHg.
• Bypasses coronary artery obstructions, reaching ischemic territory reliably.
• Limitation: the right ventricular free wall and posterior one-third of the interventricular septum (RCA territory) are poorly perfused by retrograde delivery. The microvascular areas reached by retrograde cardioplegia are less able to sustain normal energy metabolism.
• Arrest takes 2-4 minutes.

Combined Antegrade + Retrograde

• The most complete protection strategy. Some centers deliver both simultaneously.
• Particularly favored in patients with severe CAD or aortic valve pathology.
• During CABG, individual bypass grafts can be used to deliver cardioplegia after each distal anastomosis is completed, extending coverage.

5. Cardioplegia Dosing Strategies

Multidose (Intermittent) Cold Cardioplegia

• Most widely used strategy.
• Induction dose: 1000-1500 mL of "high-K" solution (20-30 mEq/L).
• Maintenance doses: 200-500 mL of "low-K" solution (~10 mEq/L) every 20-30 minutes to wash out metabolites and re-establish arrest.
• Cold cardioplegia provides 20-30 minutes of safe arrest between doses.

Single-Dose Cardioplegia

• Increasingly used in adult cardiac surgery.
• del Nido solution: 1 part blood + 4 parts crystalloid, with lidocaine, magnesium sulfate, sodium bicarbonate, mannitol, and KCl. Provides safe arrest for up to 45 minutes. Allows single-shot delivery for anticipated short cross-clamp times.
• HTK (Histidine-Tryptophan-Ketoglutarate) solution: Pure crystalloid; provides up to 90 minutes of safe arrest.

Warm/Normothermic (Continuous) Cardioplegia

• Warm blood cardioplegia continuously delivered; maintains metabolic activity at near-normal temperature.
• Associated with better postoperative cardiac indices in some studies.
• Requires continuous delivery - surgeons must operate with some coronary flow present, making this impractical in some settings.
• Cardiac surgery at true normothermia raises concerns about loss of cerebral protection.

6. Blood vs. Crystalloid Cardioplegia

• Crystalloid cardioplegia (e.g., HTK, St. Thomas') is simple and effective for short procedures.
• Blood cardioplegia is now favored in most North American centers. Blood provides oxygen-carrying capacity, and oxygenated blood cardioplegia delivers more oxygen to the arrested myocardium than crystalloid alone. Evidence suggests benefit especially in high-risk patients.
• Common blood:crystalloid ratios: 4:1 or 8:1 (Buckberg, St Thomas formulas); 1:4 (del Nido formula).

7. Management of Reperfusion

• "Hot shot" (warm blood cardioplegia before unclamping): A warm, reduced-potassium blood cardioplegic solution is given just before releasing the cross-clamp. This washes out accumulated acidic metabolites, replenishes energy substrates, and allows controlled reperfusion. Considered a separate technique from warm continuous cardioplegia.
• Avoid hypercalcemia during the immediate reperfusion period - calcium exacerbates cell death.
• Free radical scavengers (mannitol, vitamins C and E): Help mitigate oxygen free radical-mediated reperfusion injury. Mannitol is routinely incorporated into both cardioplegic and CPB priming solutions.
• Leukocyte-depleted blood cardioplegia: Some studies show improved preservation, likely by reducing inflammatory-mediated reperfusion injury.

8. Monitoring Adequacy of Preservation

• ECG quiescence - isoelectric ECG throughout cross-clamp time confirms arrest.
• Time since last cardioplegia dose - empirical guide for redosing.
• Myocardial temperature (needle probe) - target 10-15°C.
• LV filling/venting - TEE monitoring; LV distension triggers urgent venting and re-cardioplegia.
• Post-CPB markers - reduced cardiac output, worsened LV function on TEE, or arrhythmias at the end of bypass indicate inadequate preservation.

9. Complications of Cardioplegia

10. Inflammatory Modulation - Adjuncts

• Corticosteroids before and during CPB - attenuate the complement/cytokine cascade, though routine outcome benefit remains debated.
• Ultrafiltration (hemofiltration) during CPB - removes inflammatory cytokines; clearly beneficial in pediatric cardiac surgery.
• Leukocyte depletion - reduces inflammatory cell-mediated injury; improves myocardial preservation in some studies.
• Antifibrinolytics (tranexamic acid, epsilon-aminocaproic acid) - reduce bleeding rather than directly preserve myocardium, but limit CPB-related coagulopathy.

Summary Table: Key Preservation Strategies