Myocardium derives its energy production, adenosine triphosphate (ATP), from various sources that include free fatty acids, glucose, glycogen, lactate, pyruvate, ketones, and amino acids. In the adult heart under aerobic conditions, 95% of energy production is from oxidation of long-chain fatty acids (7). In contrast, glucose is the main substrate for the neonatal heart, and is supplemented by oxidation of fatty acids, lactate, ketones, and amino acids (8). The timing of the shift in substrate preference from glucose to fatty acids varies
between species and is thought to be due to upregulation of 5′-adenosine monophosphate-activated protein kinase (9). During this period of development, the neonatal myocardium shows a progressive decline in glucose uptake which can be stimulated by insulin, that is, insulin resistance and a much greater capacity to store glycogen (10). The greater ability of the immature myocardium to utilize anaerobic glycolysis may partially account for the greater tolerance to ischemia. Laboratory and clinical studies in adults have found that enhanced glucose uptake and oxidation is associated with enhanced functional myocardial recovery, despite normalization of fatty acid oxidation (6).

Immature myocardium is significantly more sensitive to and dependent on extracellular calcium than adult myocardium (Fig. 29.1). The sarcoplasmic reticulum in immature myocardium is less well developed and the sarcoplasmic reticular Ca²⁺-ATPase activity is also reduced. The result is a reduced storage capacity for calcium, reduced calcium uptake into the sarcoplasmic reticulum, and decreased calcium release following ryanodine receptor activation. Therefore, there is greater dependence on movement of calcium from the extracellular to the intracellular space (11,12,13,14). The decreased capacity for calcium sequestration may explain why the immature myocardium is susceptible to postischemic calcium overload. Several studies have found adverse effects with cardioplegia solutions containing normal or high concentrations of calcium (15,16). Most cardioplegia solutions in use currently contain very low levels of calcium (17,18,19,20,21).

Two enzyme systems seem to be important for myocardial protection during periods of ischemia: the antioxidant system and 5′ nucleotidase. The antioxidant system includes superoxide dismutase, catalase, and glutathione reductase and is responsible for scavenging the oxygen-derived free radicals generated during reperfusion. Reactive oxygen species (ROS), which comprise superoxide, hydrogen peroxide, hydroxyl radical, and lipid peroxides, cause peroxidation of phospholipids in cell membranes leading to loss of cellular integrity and function. In addition to enzyme depletion during long periods of ischemia, the activity of this enzyme system is reduced in immature myocardium (22). Another study, however, found significantly increased baseline catalase activity and reduced xanthine oxidase activity in newborn rat heart (23). Neonates with tetralogy of Fallot have a significant reduction in the activity of antioxidant enzymes (24), and may be at even greater risk.

The enzyme 5′ nucleotidase catalyzes the conversion of adenosine monophosphate (AMP) to adenosine. While AMP is unable to pass through the cell membrane, adenosine passes easily and is rapidly lost to the extracellular space, thereby depleting the adenine nucleotide pool (AMP, ADP, and ATP). The size of this adenine nucleotide pool is important for, though not predictive of, postischemic recovery of the myocardium (25,26,27). The 5′ nucleotidase system is reduced in immature myocardium and may be an additional explanation as to why immature myocardium is more tolerant to ischemia (28). If the pool is depleted more than 50%, immediate full recovery of contractile function is not possible (27,29,30).

The sensitivity to catecholamines is decreased in immature hearts. An in vitro study found evidence to suggest that this is due to functionally incomplete coupling of myocardial β-adrenergic receptors to adenylate cyclase at birth (31). In contrast, the kinetics of cyclic AMP hydrolysis and the inhibitory potential of phosphodiesterase inhibitors were not affected by age. Whether this decreased catecholamine sensitivity plays a role in tolerance to ischemia is uncertain.

Ischemic preconditioning can be defined as the adaptive mechanism induced by a brief period of reversible ischemia increasing the heart’s resistance to a subsequent longer period of ischemia (32). Although protective for older age groups, ischemic preconditioning was not found to be effective in the newborn rat heart (33). Conversely, chronic hypoxia is associated with reduced tolerance to myocardial ischemia.

There is a general feeling among pediatric cardiac surgeons that immature myocardium is significantly more vulnerable to stretch injury. Stretch injury typically occurs with overdistension of the left heart and excessive retraction on myocardial tissues, causing ventricular injury and contractile dysfunction. It can also lead to distension of the left atrium and pulmonary veins, resulting in elevated pulmonary transcapillary pressure and development of significant pulmonary edema and pulmonary dysfunction. Ventricular distension can occur with aortic valve insufficiency prior to cross-clamping the aorta. Excessive pulmonary venous return in the setting of reduced heart rate and myocardial function, ventricular fibrillation during cooling, or multiple aortopulmonary collaterals can also cause distension of the left ventricle.

The cardiac surgeon needs to be acutely aware of instances when distension of the left heart can occur. Slow cooling with maintenance of ventricular ejection until application of the aortic cross-clamp is important in the setting of aortic insufficiency. Inspection and palpation of the main pulmonary artery and left ventricle, as well as massage of the left ventricle, are important. Left heart venting should be performed either through the right superior pulmonary vein or through an atrial septal defect to keep left atrial and ventricular pressures low. The safest time to insert a left atrial vent is after the aortic cross-clamp is applied in order to prevent entrainment of air into the left ventricle and ejection into the systemic circulation. Depending on the etiology, pulmonary venous return can be reduced by preoperative coil occlusion of collaterals, shunt, or PDA ligation after commencement of CPB, or opening of the pulmonary artery on CPB. An instant measure to reduce left ventricular distension is having the perfusionist quickly drop the flow rate and perfusion pressure until the issue is resolved. Removal of the left heart vent can also result in entrainment of air, and so should only occur when the heart is contracting and the patient is on partial bypass with the left heart filled with blood above atmospheric pressure.

Excessive retraction to improve exposure can injure the myocardium and conduction system. Retraction force of assistants needs to be monitored and adjusted as necessary.

Myocardial edema can result from ischemia and reperfusion injury, delivery pressure of cardioplegia, cardioplegia osmolarity and chemical composition, excessive hemodilution, the inflammatory response to CPB, impaired myocardial lymphatic drainage, and handling of the myocardium (18,51). Myocardial edema causes impaired diastolic function.

A ventriculotomy is a component of some surgical repairs and may cause direct myocardial injury and dysfunction. Typical operations include repair of tetralogy of Fallot, some ventricular septal defects, and placement of a right ventricle-to-pulmonary artery conduit.

Injury to the coronary arteries may occur during reimplantation (arterial switch operation, aortic root/ascending aorta surgery), incisions in the anterior wall of the right ventricle (some cases of tetralogy of Fallot), or mitral valve surgery. Reoperations also pose a risk of coronary artery injury.