Myocardial Protection

In its broadest, truest sense, myocardial protection refers to all interventions undertaken in the preoperative, intraoperative, and postoperative periods that optimize myocardial oxygen supply and demand. As such, this definition incorporates all medical and interventional cardiology strategies and all manipulations of the determinants of oxygen supply and demand undertaken by the cardiac anesthesiologist. However, the more common and yet much narrower use of the term "myocardial protection" in cardiac surgery refers only to interventions undertaken during CPB and specifically during the period of aortic cross-clamping. Although cardiac procedures are now commonly performed without CPB and aortic cross-clamping, most procedures still use these latter techniques. Moreover, the broader concept of myocardial protection

1977

The earliest cardiac surgical procedures used venous inflow occlusion techniques. However, time limitations precluded performing anything but the simplest procedures. With the development of CPB, hypothermia became the primary technique of tissue protection in general and myocardial protection in particular. However, the limitations of this approach became evident quickly, and further advances in myocardial protection techniques (and as a corollary, the complexity of the cardiac surgical procedure undertaken) awaited the introduction of cardioplegia by the St. Thomas group in 1975.^{[215] [216]} Ironically, the use of high potassium solutions to induce diastolic arrest was introduced 2 decades earlier (about the time that CPB was first described),^[217] but it was not pursued clinically because of the finding of focal myocardial necrosis probably resulting from very high potassium concentrations. Blood cardioplegia was first described only as recently as 1978.^[218]

The overall objective of myocardial protection techniques is to minimize oxygen consumption and the consequences of oxygen deprivation during aortic cross-clamping. Systemic hypothermia (with its influence on collateral flow to the heart), topical hypothermia, and above all, some combination of the available cardioplegic techniques are used to that end. Importantly, however, it is now also well recognized that the consequences of aortic cross-clamping result not only from ischemia during this period but also from reperfusion injury at the end of aortic cross-clamping. A detailed description of the metabolic, signaling, and cellular consequences of ischemia-reperfusion injury is beyond the scope of this chapter. However, it is important to remember that ischemia causes rapid depletion of ATP, increased anaerobic glycolysis, accumulation of lactic acid, eventual inability to maintain cellular ionic gradients, intracellular accumulation of osmotically active ions (including calcium), cell swelling, and, in the continued absence of oxygen, eventual cell death. Reperfusion of ischemic myocytes (if they are still viable) causes additional cellular injury. Production of ROS in particular, leukocyte activation, perturbations in eicosanoid metabolism, and further accumulations in intracellular calcium concentrations are now recognized to be mechanistically important contributors to this component of cellular injury.

Clinically, reperfusion injury can be manifested as dysrhythmia or a stunned myocardium. Mechanistically, stunning is thought to be caused by oxyradical-induced myofibrillar damage (with resultant impaired responses to calcium), as well as intracellular calcium overload.^[219] Ongoing attempts to improve the efficacy of cardioplegia are motivated by our understanding of the mechanisms underlying ischemia-reperfusion injury and the desire to successfully interrogate these mechanisms. For example, manipulating tonicity to attenuate cellular swelling, altering buffering capacity to decrease acidosis, optimizing calcium levels to limit intracellular calcium overload yet maintain contractile function, and adding free radical scavengers to decrease oxyradical injury represent efforts to attenuate ischemia-reperfusion injury. Although these

TABLE 50-14 -- Myocardial oxygen consumption (at 37°C) for different work and electrical conditions

	Myocardial Oxygen Consumption (mL/100 g/min)
Beating (full, perfused)	10.0
Beating (empty, perfused)	5.5
Fibrillating (empty, perfused)	6.5
K+ cardioplegia (empty, cross-clamp)	1.0
Data from Sarnoff SJ, Gilmore JP, McDonald RH Jr, et al: Relationship between myocardial K+ balance, O2 consumption, and contractility. Am J Physiol 211:361–375, 1966; and Sarnoff SJ, Gilmore JP, Daggett WM, et al: Myocardial dynamics, contractility, O2 consumption, and K+ balance during paired stimulation. Am J Physiol 211:376–386, 1966.

are important and ongoing areas of study, the original rationale for using cardioplegic solutions was based on the profound influence of (1) diastolic arrest (versus a beating heart), (2) temperature, and (3) a full versus empty heart on myocardial oxygen requirements ( Table 50-14 and Table 50-15 , Fig. 50-36 ). ^{[220] [221]}

The literature on cardioplegic solutions can be confusing. Consider that in addition to blood cardioplegia, there are several variations in crystalloid cardioplegia. Moreover, cardioplegia can be delivered antegradely or retrogradely, or in combination, and through saphenous vein grafts after the completion of distal anastomoses. Retrograde cardioplegia is technically more difficult, should be delivered with pressures less than 40 mm Hg, does not necessarily deliver cardioplegia to the same capillary bed as antegrade cardioplegia does, and may be the victim of variable venous anatomy, for example, the left superior vena cava draining into the coronary sinus or the tip of the cardioplegia cannulas proximal to the great cardiac vein. Nevertheless, it may be the preferred technique in the presence of aortic incompetence or severe coronary obstruction. The duration, quantity, and frequency of cardioplegia administration vary from surgeon to surgeon and study

TABLE 50-15 -- Influence of temperature on myocardial oxygen consumption for different work and electrical conditions

	Myocardial Oxygen Consumption (mL/100 g/min)
	37°C	32°C	28°C	22°C
Beating (empty)	5.5	5.0	4.0	2.9
Fibrillating (empty)	6.5	3.8	3.0	2.0
K+ cardioplegia	1.0	0.8	0.6	0.3
Data from Sarnoff SJ, Gilmore JP, McDonald RH Jr, et al: Relationship between myocardial K+ balance, O2 consumption, and contractility. Am J Physiol 211:361–375, 1966; and Sarnoff SJ, Gilmore JP, Daggett WM, et al: Myocardial dynamics, contractility, O2 consumption, and K+ balance during paired stimulation. Am J Physiol 211:376–386, 1966.

1978

Figure 50-36 Myocardial oxygen uptake in different states of temperature and workload. (Redrawn from Buckberg GD, Brazier JR, Nelson RL, et al: Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. I. The adequately perfuse beating, fibrillating, and arrested heart. J Thorac Cardiovasc Surg 73:87–94, 1977.)

Finally, the patient's underlying disease may modulate delivery of cardioplegia (e.g., stenosed coronary vessels) or its efficacy (hypertrophied myocardium). However, overall, the most recent data indicate that blood cardioplegia is used in 80% to 85% of cardiac surgery procedures in the United States and that the retrograde approach is used either alone or in combination in 45% of cases.^{[222] [223]} Although cardioplegic solutions are administered with the objective of producing uniform myocardial temperatures of 12°C to 15°C, some evidence suggests that warm induction and reperfusion improves clinically relevant outcome parameters.^{[224] [225]}

Many studies have compared blood and crystalloid cardioplegia and have been reviewed.^[226] Several recent studies have demonstrated either the superiority of blood cardioplegia over crystalloid cardioplegia or have failed to show a difference between the two. Intuitively, we would predict that in patients with well-preserved myocardial function who are subjected to less protracted and complex procedures, the type and route of cardioplegia delivery probably make little difference. The converse may also be true. Indeed, two relatively recent studies illustrate just that. In patients with well-preserved myocardial function, the type of cardioplegia made no difference as assessed by the magnitude of enzyme leak.^[227] In contrast, in patients with ejection fractions less than 40%, blood cardioplegia was superior to crystalloid cardioplegia as determined by enzyme leak, function parameters, and rhythm and conduction abnormalities. ^[228]