Myocardial Protection and Cardiopulmonary Bypass

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MYOCARDIAL PROTECTION

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

2. Myocardial Ischemic Injury
A. Acute ischemic dysfunction
· Global myocardial ischemia
· Reversible contractile failure, mostly from change in perfusion pressure
· Immediate recovery as oxygen supply is restored

B. Stunning
· Reversible systolic and diastolic dysfunction, no myocardial necrosis
· Begins in subendothelium and progresses outward
· May be accompanied by endothelial dysfunction
· Results from ischemia-reperfusion insult, mediated by increased intracellular calcium accumulation
· Recovery occurs within hours to weeks

C. Hibernation
· Reversible chronic contractile depression
· Related to poor myocardial blood flow
· Recovery occurs within weeks to months

D. Necrosis
· Irreversible ischemic injury with myocardial necrosis
· Hypercontracture occurs first in the subendothelium and is more rapid in the hypertrophied heart
· Typically results in contraction band necrosis, rarely "stone heart"
· Osmotic and ionic dysregulation produce membrane injury and myocyte lysis

3. Cardioplegia
· 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
· The goals of cardioplegia are to protect against ischemic injury, provide a motionless and bloodless field, and allow for effective post-ischemic myocardial resuscitation
· Cardioplegic techniques vary according to perfusate (blood vs. crystalloid), duration (continuous vs. intermittent), route (antegrade vs. retrograde), temperature (warm vs. cold), and additives
· Special consideration is required for the acutely ischemic heart and the neonate

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

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

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

CARDIOPULMONARY BYPASS

1. The Circulatory Environment
· Cardiopulmonary bypass is an abnormal circulatory state
· Non-pulsatile flow, hemolysis, hemodilution, foreign surface exposure, general stress response, and the inflammatory response all contribute

A. Mechanial components
· Roller pumps are slightly non-occlusive, resistance-independent, and may cause less blood trauma
· Centrifugal pumps are dependent on inflow or outflow resistance; will cease flow at very low inflow resistance and very high outflow resistance
· Venous drainage can be active or siphoned
· Active drainage requires vacuum through the venous reservoir or negative pressure from the pump

B. Heat exchanger
· The cooling or warming gradient is usually within 10-14 degrees of the patient's temperature
· This minimizes the tendency for gas to come out of solution and risk of air embolism
· Mixed blood temperature should be less than or equal to 38.5C
· The water bath should stay between 15 and 42C to prevent organ damage (too cold) and hemolysis (too warm)

C. Oxygenator
· Largest foreign surface contact area
· Membrane oxygenators can be microporous, hollow fiber, or silastic (true membrane)
· Gas flow is titrated to maintain PaO2 between 85 and 250mmHg to avoid O2 toxicity
· PCO2 is regulated by gas and blood flow through the membrane
· pH is controlled by adjusting the PaCO2
· alpha stat adjusts the pH to 37C, with the goal of providing optimal enzymatic function during hypothermia
· 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
· The foreign surfaces of the bypass circuit (boundary layer of oxygenator, heat exchanger, filters, tubing) interact with the blood
· Shear stresses include the pump, cardiotomy suction, and cannulae
· 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
· Factor XII (Hageman factor), the alternative complement cascade (C3a), kallekrein, and plasminogen are activated in various degrees
· Other factors interrelate and amplify the inflammatory reaction, including the arachidonic acid cascade, interleukins, TNF, and PAF

C. Cellular
· 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
· Monocytes and mast cells also participate, although their role is unclear
· Lymphocytes have a minor role, if any
· Platelets are activated and elaborate GPIB, IIB, and IIIA
· Absolute number of platelets is reduced by 40% by the end of bypass, and the number of receptors is also decreased
· Endothelial cells are affected by abnormal flow, humoral factors, and local ischemia
· A wide variety of substances are expressed by the endothelium, including prostaglandins, thromboxanes, leukotrienes, and interleukins

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

Last revised 06/29/98

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