1. CPB & Effects on the Lung Seoul National University Hospital Department of Thoracic & Cardiovascular Surgery

2. Postpump Syndrome on Lung  Characteristics Increased alveolo-arterial gradient (A-aDO2) and intrapulmonary shunt Decreased pulmonary compliance Increased pulmonary vascular resistance Increased pulmonary vascular perrmeability

3. Effects of CPB on the Lung 1. Clinical features of lung injury 2. Pathogenesis of lung injury 3. Future prevention of lung injury 4.Pulmonary vascular response

4. Lung Injury from Prolonged CPB This may be related to both inflammatory as well as ischemic effects of CPB This can result in substantial accumulation of fluid in the lung during CPB, which leads to decreased pulmonary compliance and increased pulmonary vascular resistance Prevention or diminishment of pulmonary ischemia during CPB may limit the pulmonary injury and protect the lung from excessive fluid accumulation

5. CPB-induced Lung Injury  Etiology 1. Oxygenation / re-oxygenation, hypoxia, ischemia, reperfusion & surfactant dysfunction 2. Systemic inflammatory response during CPB as blood contacts non-physiologic surfaces 3. Hypothermia and non-pulsatile perfusion induce injury by altering the patterns of blood flow.

6. Lung Injury Following CPB  Pathogenesis 1. Preexisting pulmonary endothelial cell dysfunction 2. Postoperative pulmonary endothelial dysfunction 3. Mechanisms of lung injury a. Complement activation b. Neutrophil mediated lung injury c. Oxygen free radical injury d. Injurious effects of lysosomal enzymes e. Endotoxin medicated lung injury 4. Impaired lung function

7. Endothelial Transduction Pathways Endothelial transduction signal pathways for NO (through ACh and BK) and for PGI2

8. Lung Injury following CPB  Clinical features 1. Reduced oxygenation 2. Reduced lung compliance 3. Pulmonary vascular lability 4. Bronchial hypersensitivity

9. Lung Injury following CPB  Morphological features 1. Preexisting lung damage a. Development of pulmonary vascular disease b. Operability in pulmonary hypertension c. Hypoperfused lung 2. Lung morphology following OHS 3. Special problems associated with intracardiac repair in children

10. Edema following CBP  Susceptibility in neonate 1. Capillary permeability is naturally higher in younger 2. Greater exposure to bypass prosthetic surface area relative to neonate’s endothelial surface area 3. Larger prime volume to blood volume than in older 4. Exposure to greater extremes of temperature as well as low-flow or circulatory arrest, thereby increasing the risk of ischemia-reperfusion injury

11. Effects of CPB on Lung Function 1.Lung fluid exchange : excessive pulmonary capillary fluid filtration due to capillary damage induced by complement release and/or activation of coagulation cascade 2.Hemodilution reduce complications of intravascular coagulation & increase pulmonary lymph flow & decrease blood use. 3.Pulmonary capillary hydrostatic pressure : effective LV venting 4.Interacting causes of alveolar collapse 5.Pleural cavity : opening the pleura lower lung volume and increase the amount of alveolar collapse 6.Decrease in lung volume due to chest wall pain & increase in interstitial fluid in the lung

12. Changes of Pulmonary Vasculature  Postoperative response 1. Enhanced pulmonary vascular reactivity Circulating vasoactive mediators Catecholamines Endothelin* Prostacyclin Thromboxane-A 2 * * Endothelium-derived vasoconstrictor 2. Others Obstructive pulmonary vascular disease Parenchymal lung disease

13. Future Prevention of Lung Injury 1.Improving the artificial materials of circuit 2.Drug therapy to reduce neutrophil activation 3. Pulmonary vascular problems 4.Leucocyte depletion 5.Prevention of lung ischemia during CPB (maintain antegrade pulmonary flow)