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Myocardial Protection

Myocardial Protection and Cardiopulmonary Bypass

1. Myocardial Perfusion

A. Normally, subendocardial flow exceeds subepicardial flow
B. Myocardial perfusion, however, is altered by cardiopulmonary bypass
C. Narrow pulse pressure and variable mean pressure affects coronary perfusion pressure
D. Wall tension is increased in the empty, smaller heart
E. Ventricular fibrillation also increases wall tension
F. Regulatory and inflammatory factors are released which affect coronary resistance
G. Microemboli from the circuit and hemodilution impair oxygen delivery
H. Endothelial and myocardial edema further affect perfusion
I. Subendothelial vulnerability is increased by hypertrophy, coronary disease, fibrillation, cyanosis, shock, and chronic heart failure
J. The acutely ischemic heart may have poor reflow to the injured area

2. Myocardial Ischemic Injury

A. Acute ischemic dysfunction
1) Global myocardial ischemia
2) Reversible contractile failure, mostly from change in perfusion pressure
3) Immediate recovery as oxygen supply is restored
B. Stunning
1) Reversible systolic and diastolic dysfunction, no myocardial necrosis
2) Begins in subendothelium and progresses outward
3) May be accompanied by endothelial dysfunction
4) Results from ischemia-reperfusion insult, mediated by increased intracellular calcium accumulation
5) Recovery occurs within hours to weeks
C. Hibernation
1) Reversible chronic contractile depression
2) Related to poor myocardial blood flow
3) Recovery occurs within weeks to months
D. Necrosis
1) Irreversible ischemic injury with myocardial necrosis
2) Hypercontracture occurs first in the subendothelium and is more rapid in the hypertrophied heart
3) Typically results in contraction band necrosis, rarely "stone heart"
4) Osmotic and ionic dysregulation produce membrane injury and myocyte lysis

3. Cardioplegia

A. Studies in animals have inconsistent correlation with clinical results due to species differences, extent of disease, and perioperative events that precipitate, extend, or enhance myocardial damage
B. The goals of cardioplegia are to protect against ischemic injury, provide a motionless and bloodless field, and allow for effective post-ischemic myocardial resuscitation
C. Cardioplegic techniques vary according to perfusate (blood vs. crystalloid), duration (continuous vs. intermittent), route (antegrade vs. retrograde), temperature (warm vs. cold), and additives
D. Special consideration is required for the acutely ischemic heart and the neonate

4. Mechanisms of Cardioplegic Protection

A. Mechanical arrest (potassium-induced) will reduce oxygen consumption by 80%
B. Hypothermia will reduce consumption by another 10-15%
C. Aerobic metabolism can be maintainted with oxygenated cardioplegia
D. Hypothermic arrest is sustained with readministration every 15-30 minutes
E. Retrograde delivery protects the left ventricle more completely than the right ventricle
F. Prevent myocardial rewarming with systemic hypothermia, aortic and ventricular vents, and caval occlusion
G. In acute ischemia, use warm induction with substrate enhancement (glutamate, aspartate)
H. Reperfusion should be controlled, using warm, hypocalcemic alkaline cardioplegia
I. This approach combats intracellular acidosis and rapid calcium infusion injury
J. Retrograde or low-pressure antegrade perfusion is preferred for reperfusion
K. Ensure uniform warming

5. Neonates and Children

A. Children older than 2 months have similar myocardial physiology to adults
B. The neonatal myocardium, however, is different in several ways
C. Hypoxia is more easily tolerated
D. There are greater glycogen stores and more amino acid utilization
E. ATP breakdown is slower due to deficiency in 5' nucleotidase
F. Multidose cardioplegia is disadvantageous
G. Cyanosis may worsen resistance to ischemia
H. Amino acid substrate enhancement is beneficial

6. Cardioplegia Composition

A. Blood has the advantage of oxygen carrying capacity, histidine and hemoglobin buffers, free radical scavengers in RBCs, and metabolic substrates
B. Blood also has improved rheologic and oncotic properties, which may lessen myocardia edema
C. Buffers such as THAM, histidine, and NaHCO3 form a slightly alkaline solution for reperfusion that can counteract intracellular acidosis
D. Small amounts of calcium (0.1-0.5 mM/L) restores calcium that has been chelated by citrate
E. Potassium concentrations range from 10-25 mM/L, with the first dose being the highest
F. Other substrates are being evaluated, including allopurinal, SOD, deferoxamine, adenosine, nucleoside transport inhibitors, and potassium-channel openers


1. The Circulatory Environment

A. Cardiopulmonary bypass is an abnormal circulatory state
B. Non-pulsatile flow, hemolysis, hemodilution, foreign surface exposure, general stress response, and the inflammatory response all contribute
C. Mechanial components
1) Roller pumps are slightly non-occlusive, resistance-independent, and may cause less blood trauma
2) Centrifugal pumps are dependent on inflow or outflow resistance; will cease flow at very low inflow resistance and very high outflow resistance
3) Venous drainage can be active or siphoned
4) Active drainage requires vacuum through the venous reservoir or negative pressure from the pump
B. Heat exchanger
1) The cooling or warming gradient is usually within 10-14 degrees of the patient's temperature
2) This minimizes the tendency for gas to come out of solution and risk of air embolism
3) Mixed blood temperature should be less than or equal to 38.5C
4) The water bath should stay between 15 and 42C to prevent organ damage (too cold) and hemolysis (too warm)
C. Oxygenator
1) Largest foreign surface contact area
2) Membrane oxygenators can be microporous, hollow fiber, or silastic (true membrane)
3) Gas flow is titrated to maintain PaO2 between 85 and 250mmHg to avoid O2 toxicity
4) PCO2 is regulated by gas and blood flow through the membrane
5) pH is controlled by adjusting the PaCO2
6) alpha stat adjusts the pH to 37C, with the goal of providing optimal enzymatic function during hypothermia
7) pH stat corrects the pH to the temperature of the patient's blood, with the goal of relative hypercarbia to increase cerebral blood flow

2. Mechanisms of Injury

A. Mechanical
1) The foreign surfaces of the bypass circuit (boundary layer of oxygenator, heat exchanger, filters, tubing) interact with the blood
2) Shear stresses include the pump, cardiotomy suction, and cannulae
3) Microemboli can form as particles from the oxygenator, platelet aggregate, or fibrin aggregates, and are greatest within the first 15 minutes of bypass
B. Humoral
1) Factor XII (Hageman factor), the alternative complement cascade (C3a), kallekrein, and plasminogen are activated in various degrees
2) Other factors interrelate and amplify the inflammatory reaction, including the arachidonic acid cascade, interleukins, TNF, and PAF
C. Cellular
1) Neutrophils play a major role in humoral activation and are sequestered in the lung, releasing cytotoxin and free radicals which increase vasoreactivity and vascular permeability
2) Monocytes and mast cells also participate, although their role is unclear
3) Lymphocytes have a minor role, if any
4) Platelets are activated and elaborate GPIB, IIB, and IIIA
5) Absolute number of platelets is reduced by 40% by the end of bypass, and the number of receptors is also decreased
6) Endothelial cells are affected by abnormal flow, humoral factors, and local ischemia
7) A wide variety of substances are expressed by the endothelium, including prostaglandins, thromboxanes, leukotrienes, and interleukins

3. Miscellaneous

A. Circulatory arrest with profound hypothermia (18-20C) is generally safe up to 45 minutes
B. Over 60 minutes is associated with increased incidence of neurologic deficit
C. The period between 45 and 60 minutes is unclear, as histologic injury seems to be greater than functional injury
D. Maintain a gradient of 4-6C, as rapid cooling produces uneven cerebral cooling
E. Retrograde and low flow cerebral perfusion are currently being evaluated
F. Pulsatile flow has not been shown to be superior to non-pulsatile flow
G. Lower ACT of 300-350 seconds is not associated with greater complications compared to standard ACT of 450
H. Aprotinin will elevate the ACT (600-800), neutralizes the kallikrein cascade, and protects platelet receptors
I. Protamine reactions occur through the classical component pathway and cause direct myocardial depression