CTSN Myocardial Protection and Cardiopulmonary Bypass

**Myocardial Protection and Cardiopulmonary Bypass**
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MYOCARDIAL PROTECTION 1. Multiple studies in non-diseased animal hearts Inconsistent correlation with clinical results Diseased hearts Species differences Influenced by perioperative events that precipitate, extend or enhance damage 2. Cardioplegia - Goals Protect against ischemic injury Provide a motionless, bloodless field Allow effective post-ischemic myocardial resuscitation 3. Conditions of Myocardial Perfusion Normally subendocardial blood flow > subepicardial blood flow Myocardial blood flow altered by CBP Coronary perfusion pressure Wall tension Regulatory / inflammatory factors affecting coronary resistance Microemboli from circuit Endothelial / myocardial edema 4. Subendocardial vulnerability increased by Hypertrophy Coronary disease Fibrillation Poor reflow in acute ischemia 5. Spectrum of Myocardial Ischemic Injury Acute ischemic dysfunction Reversible contractile failure Perfusion pressure O2 supply Immediate recovery Stunning Reversible systolic / diastolic dysfunction May be accompanied by endothelial dysfunction (NO) causing reduced coronary blood flow Result of ischemia - reperfusion insult Mediated by increased intracellular Ca accumulation Recovery in hours to weeks 6. Hibernation Reversible contractile depression (chronic) Related to poor myocardial blood flow Recovery in weeks to months Necrosis Irreversible ischemic injury Hyper contracture - "contraction band necrosis", "stone heart" Osmotic / ionic dysregulation, membrane injury Myocyte lysis 7. Cardioplegia - Options No cardioplegia Cardioplegia Type (blood vs crystalloid, cont. vs intermittent) Route (antegrade vs retrograde) Temperature (warm vs cold) Additives Special considerations Acute infarction Neonate 8. Mechanisms of Cardioplegic Protection Mechanical arrest (K-induced) 80% reduction in O2 consumption Hypothermia 10-15% further reduction in O2 consumption Aerobic metabolism - oxygenated cardioplegia Maintain hypothermic arrest with readministration every 15-20 minutes Retrograde delivery: LV > RV protection 9. Other considerations Protect from rewarming Systemic hypothermia Aortic / ventricular vents Total bypass (caval occlusion) Acute ischemia Warm induction Substrate enhancement (glutamate, aspartate) Controlled reperfusion Warm, hypocalcemic, alkaline cardioplegia Retrograde or low-pressure antegrade perfusion Energy replenishment while arrested Uniform warming 10. Neonates and Children Children similar to adults (older than 2 months) Differences with neonates Withstand hypoxia better Greater glycogen stores More AA utilization Slower ATP breakdown (deficient 5' nucleotidase) Ischemic times 65-85 minutes Multi dose cardioplegia disadvantageous Cyanosis may worsen resistance to ischemia AA substrate enhancement beneficial 11. Cardioplegic Composition Blood vs. Crystalloid O2 carrying capacity (Hematocrit 15-20%) Buffers - histidine Free radical scavengers in RBCs Improved rheologic / oncotic properties Metabolic substrates Buffers THAM, histidine, NaHCO3 Slightly alkaline reperfusion Calcium Small amounts (0.1-0.5 mM/L) Ca chelated in blood with citrate 12. Potassium 10 - 25 mM/L (first dose highest) > 30 mM/L - endothelial dysfunction Free radical scavengers Allopurinol, SOD, Deferoxamine Others Metabolic substrates, adenosine, nucleoside transport inhibitors, K-channel openers CARDIOPULMONARY BYPASS 13. Abnormal Circulatory Environment Non-pulsatile arterial flow Blood trauma - hemolysis Hemodilution Foreign surface exposure General stress response Inflammatory response 14. Mechanics Arterial inputs (pumps) Roller pumps Slightly non-occlusive, less blood trauma Resistance independent Vortex / centrifugal pumps Biomedicus Flow dependent on inflow or outflow resistance +/- 500 mmHg flow ceases Flowmeter necessary 15. Venous drainage Siphonage Active Vacuum through venous reservoir Negative pressure via centrifugal pumps Oxygenators Largest foreign surface contact area Bubble oxygenators - increase microemboli Membrane oxygenators Microporous Hollow fiber Silastic (true membrane) 16. Heat exchanger (coil and bath) Cooling / warming gradient 10-14oC from patient Minimize tendency for gas to come out of solution Mixed blood temperature < or = 38.5o C Water bath < or = 42o C (hemolysis) < or = 15o C - Organ damage Gas flow Maintain PaO2 85-250 mm Hg with gas mixture > 250 mm Hg - O2 toxicity (in theory) PCO2 regulated by gas flow / blood flow through membrane pH controlled with PaCO2 manipulation Alpha stat - pH at 37o C optimal enzymatic function during hypothermia pH stat - pH corrected for temperature relative hypercarbia, increases cerebral blood flow 17. Agents of Damage Foreign surface Boundary layer of oxygenator Heat exchanger Filters Tubing Shear stresses Pump Cardiotomy suckers Cannulas 18. Microemboli Pump oxygenator particles Platelet aggregates Fibrin aggregates Greatest in first 10-15 minutes of CPB 19. The Abnormal Response Humoral Factor XII = Hageman factor Alternative complement cascade (C3a) Kallikrein to bradykinin Plasminogen to plasmin Coagulation cascade (incomplete blockage) Arachidonic acid cascade Interleukins, tumor necrosis factor, platelet activating factor Many factors interrelate to amplify and propagate reaction 20. Cellular Neutrophil major role - Humoral activation Pulmonary sequestration Release cytotoxins, free radicals Vasoreactivity, vascular permeability Monocytes, mast cells Participate, specific role unclear Lymphocytes (T and B cells) Minor (if any) role 21. Platelets Trigger for activation unclear Elaboration of GPIB (VWF), IIB, IIIA (fibrinogen) Receptors decreased by end of CPB Platelet number reduced by 40% Endothelial cells Abnormal flow, humoral factors, local ischemia Elaborate PGs, thromboxanes, leukotrienes, interleukins 22. Other Facts Circulatory arrest / Profound hypothermia (18-20o C) < 45 minutes - few deficits > 60 minutes - increased deficits 45 - 60 minutes - debated Histologic > functional injury Retrograde cerebral perfusion Low flow perfusion Rapid cooling - uneven cerebral cooling (4 - 6o C gradient) Surface brain cooling - debated 23. ACT >400 sec Pulsatile no better than non-pulsatile flow Protamine reaction Classical complement cascade Histamine release in IDDM Direct myocardial depression Aprotinin - antifibrinolytic ACT higher (600-800 sec) Neutralizes kallikrein cascade Protects platelet receptors EXTENDED OUTLINE 1. History a) 1953-Gibbon-First intra-cardiac operation w/heart-lung machine b) 1954-Lillehei-Cross-circulation c) 1955-Kirklin began first successful series 2. The Heart-Lung machine a) Venous cannulae i) Gravity drainage-reservoir 25-30 inches below plane of great veins ii) One (two-stage) or two cannulae iii) Flow is limited if tip is >1/2 the diameter of the vein iv) CVP must be kept <15mmHg, but > 0 (veins collapse) b) Oxygenator i) O₂ and CO₂ exchange ii) Bubble oxygenator a) Oxygen diffused through a diffusion plate (sparger) b) Reservoir and heat exchanger incorporated - unit is upstream to pump c) 36 micron bubbles allow adequate exchange(smaller bubbles favor O₂exchange, larger bubbles CO₂) d) Flow rates 1-7 L/min - 350-400ml O₂, 300-330ml CO₂ iii) Membrane a) Gradient 12-15mm Hg/Liter flow b) Flow rates 1-7 L/min - 470ml O₂, 350ml CO₂ c) Surface area 2m² d) Turbulence and secondary flow improve oxygen diffusion e) Resistance to flow, most are upstream to pump f) Silicone rubber membrane or hollow fiber (microporous polypropylene) g) Less blood trauma iv) Human lung a) Up to 15L/min, pressure difference 2mmHg, 2L O₂, 1.6L CO₂ b) Surface area 90m² c) Heat exchanger i) Safest Tmax for blood = 42°C to avoid injury to proteins ii) Cooling occurs more rapidly than rewarming (0.7-1.5°C/min vs 0.2-0.5) iii) Oxygen, CO₂ and nitrogen more soluble in cold blood iv) Max temp gradient 12-14°C d) Pumps i) Centrifugal a) Flow varies according to line pressure, \ need flow meter b) Disposable c) Cannot pump large gas emboli ii) Roller e) Filters i) Screen fibers of nylon or polyester ii) 25-40 micron f) Arterial cannulae g) Cardiotomy suction i) Major cause of hemolysis due to air-blood interface and turbulence required to suck blood ii) Filter is required h) LV vent i) Decompresses LV ii) R superior PV, LA appendage, LV apex iii) PA cath can vent - no valves in pulmonary venous system iv) Removes blood from field i) Cell saver i) 20Micron filter ii) Centrifuge 3. Conduct of cardiopulmonary bypass (CPB) a) Priming i) ~ 2 liters for adults, at least 800ml for infants ii) Hct maintained 20-25% - hemolution a) Fewer transfusions b) Fewer RBCs traumatized c) Less free hemoglobin produced d) ¯ incidence oliguria and ATN w/hemodilution e) interstitial edema b) Anticoagulation i) Heparin a) Activates antithrombin III (AT-III) 1000-fold b) AT-III - plasma protease inhibitor of Factors IXa, Xa, and thrombin c) Variable anticoagulant effect d) Slightly increases bleeding time e) Major stimulus of complement activation when complexed w/protamine f) Heparin-induced thrombocyytopenia - 2-5% g) ACT - artifactually increased w/aprotinin ii) Thrombin is progressively formed during CPB, despite anticoagulation iii) Protamine a) 50% have hypotension and ¯ CO, due to hep/prot complex activating complement b) Rarely, will cause TxA2 release from platelets à pulmonary vasoconstriction c) May be cleared from circulation faster than heparin à heparin rebound c) Flow rates & pressures i) 2.2l/min/m²is adequate in adult at 37°C ii) MAP 50-70mmHg - <45mmHg associated with neurologic complications d) Temperature i) O2 requirements ¯ 50% for every 10 degrees e) Deep hypothermia = <20 i) At least 30min cooling