Myocardial Preservation - Cooper University Hospital: School of Perfusion 2014 - Michael F. Hancock, CCP

Myocardial Protection Surgical Goal- Preserve and Protect the heart during any cardiac procedure Surgical preference in many cases is to operate on a bloodless, motionless heart Several different ways to achieve this Careful attention must be paid to preserve it’s function and protect it from injury during this time

Bloodless, Motionless Heart Achieved by: Elective Asystole Induced ischemic periods Elective Ventricular Fibrillation Continuous coronary perfusion Intermittent Aortic Occlusion Intermittent ischemic periods Each method will come with it’s own degree of ischemia and negative sequelae

Myocardial Muscle Contraction Basic structural unit of muscle tissue is the Sarcomere 2 main components involved in contraction are the thick myosin filaments and thin actin filaments An action potential is spread via the transverse tubule Stored intracellular Ca++ is released and the actin filament slides onto the myosin head, know as the Power Stroke ATP then powers the release of Ca++ from the Actin which causes muscle relaxation

Ischemia “Inadequate tissue perfusion to sustain steady-state oxidative metabolism at a given level of cardiac performance”- Gravlee Lack of blood flow to tissues Decreased O2 delivery Decreased Waste removal (Metabolites accumulate) Anaerobic Metabolism takes place during ischemic periods Only 2 moles of ATP produced Compared to 36 moles of ATP during Aerobic Metabolism Makes it very difficult to keep up with the demands of cardiac muscle We must take action to lower O2 requirements during this time

Cardiac Muscle Requirements The cardiac muscle uses ~70% of O2 delivered to it (O2 Extraction) Most organs use only ~30% O2 Consumption- Normal- 8.0cc O2/100g/min at 37° Empty Beating Heart- 5.6cc O2/100g/min Arrested- 1.1cc O2/100g/min Arrested and Cooled- 0.3cc O2/100g/min

Ischemic Injury Injury can occur when oxygen supply does not meet demand Inadequate O2 delivery Inadequate Waste removal Metablites need to be washed out CO2, Lactate, H+ ions Buildup can cause injury, injury can be spread to other areas following reperfusion Warm Unprotected Ischemia Ischemia < 30 minutes = Myocardial Stunning Reversible Ischemia > 30 minutes = Necrosis Irreversible

Ischemic Injury Lack of O2 prevents energy production necessary for membrane stabilization of blood vessels Increased vascular permeability Myocardial edema Intracellular calcium buildup Calcium is the most important ion in reperfusion injury Leads to hypercontracture and death of myocytes and cardiac dysrhythmias Generation of oxgyen free radicals Release of proteolytic enzymes and leukocyte activation that destroy endothelium

Myocardial Protection Goal of myocardial protection is to reduce ischemic injury and reperfusion injury Both surgical technique and pharmacologic interventions are employed to achieve this goal Allow the surgeon to operate on a motionless heart while still protecting and preserving it’s function

Myocardial Protection Strategies Elective Asystole Produced by cardioplegia solution delivery Elective Ventricular Fibrillation Allows continuous coronary perfusion with minimal heart motion Intermittent Aortic Cross-Clamping Intermittent clamping of the aorta during each anastamosis Off-Pump Surgery

Elective Asystole Delivering a cardioplegic solution to provide electromechanical arrest to the heart Cardiac metabolic demands are reduced by 80-90% Places heart in a state of flaccid depolarization Aorta is cross-clamped to isolate the coronary arteries from the systemic circulation Maintenance doses of cardioplegic solution are given throughout the case to keep the heart arrested and protected

Elective Ventricular Fibrillation Ventricular fibrillation is induced to provide a virtually motionless heart Hypothermia induces fibrillation and patient is kept under that temperature Fibrillation can be induced electrically No cross-clamp is applied Continuous coronary artery perfusion is maintained Need local tourniquets on vessels being worked on to allow visualization of grafts Tourniquet sites are potential sites for future injury Used for calcified aorta cases where cross-clamping isn’t possible or dangerous “Porcelain Aorta”- rock hard aorta

Intermittent Aortic Occlusion Aorta is cross-clamped only when surgeon is doing a distal anastamosis Partial sidebiter clamp is applied on the aorta during proximal anastamosis No cardioplegia delivery Forces surgeons to work fast Multiple clamping sites on aorta can be sites for future blockages, thrombus formation or injury

Off-Pump Surgery Beating heart surgery allows the normal physiologic flow of blood to be maintained throughout the case, under ideal conditions Thorough attention must be paid to blood pressure, ECG, and blood gas analysis to ensure adequate perfusion of the heart is taking place Must be able to tolerate manipulation of the heart during distal anastomis

Cardioplegic Arrest Cardioplegic solution is delivered immediately following cross-clamp application to provide rapid electromechanical arrest Prevents depletion of energy rich phosphates that would be caused by ischemia Left ventricular venting must be employed before the cross-clamp application to prevent blood traveling through the heart and being ejected against the clamp Also prevents blood that is in the heart from reaching the coronary arteries during the cross-clamp period Can lead to electrical activity due to coronary perfusion Reduces myocardial O2 demands by 80-90%

Cardioplegic Solution Hyperkalemic (↑ Potassium) Solution- Potassium depolarizes the myocyte membrane by flooding the extracellular matrix of the cell Increased extracellular K+ will prevent myocyte exciteability causing electromechanical arrest Prevents K+ from moving out of the cell, which prevents contraction Heart in a state of flaccid depolarization, or prolonged diastole Cardioplegic solution is washed out by non-coronary collaterals which requires maintenance doses of cardioplegia every 20-30 minutes Concentration of Potassium is usually 12-30 mEq/L under hypothermic conditions Concentrations don’t usually exceed 40-50 mEq/L due to vascular endothelial damage to coronary arteries Higher concentrations may be required for normothermic delivery

Cardioplegia Additives Calcium- Important ion needed for contraction Extracellular hypocalcemia is dangerous because it sets the table for calcium loading during reperfusion Normal levels of Ca++ should be maintained to prevent Ca++ loading during reperfusion Ca++ Loading- Rapid influx of Ca++ ions into the cell which causes hypercontracture, leading to depletion of ATP sources and eventually cell stunning or death

Calcium Low extracellular Ca++ can produce arrest by not having Ca++ available for muscle contraction Excessive Ca++ levels cause “Stone Heart” due to Calcium Loading Paradox causing hypercontracture and cell stunning or death Heart uses all the available ATP to contract rapidly then runs out of energy

Cardioplegia Additives Magnesium- Competitive inhibitor of Ca++ Prevents Ca++ loading in cells Provides membrane stabilization Decreases potential for cardiac arrhythmias Increases myocardial contractility We give 2g of Magnesium in the prime and 2g when the cross-clamp is removed Time of reperfusion is the most critical point for the potential for Ca++ loading

Cardioplegia Additives Sodium- Ion responsible for membrane stability and regulation of fluid shifting Want to keep normal concentrations of Na+ Chloride- Ion responsible for electrical neutrality inside the cell Want to keep normal concentrations of Cl- Bicarbonate/THAM- Buffers used to maintain an alkalotic solution to counteract the acidosis produced by ischemia THAM is a better buffer than bicarbonate in plegic solutions

Cardioplegia Additives Osmotic Regulators A hypertonic solution is ideal to prevent myocardial edema Hypertonic solutions will pull in fluid from myocardial tissue preventing fluid passage into tissue Albumin- plasma protein that provides hypertonicity Mannitol- sugar that provides hypertonicity Oxygen-free radical scavenger Glucose- sugar that provides hypertonicity

Cardioplegia Additives Lidocaine- Ventricular antiarrhythmic Membrane stabilizer Glutamate/Aspartate- Increases myocardial O2 uptake Best given in induction dose and a “hot shot” before x-clamp removal Prevents generation of Oxygen-free Radicals Adenosine- Cardioprotective autocoid produced by the endothelium Acts as a vasodilator during autoregulation of coronary bloodflow KATP Channel opener Prevents Ca++ influx Prevents dysrhythmias

Hypothermic Cardioplegia Hypothermia reduces metabolic oxygen demand 7% for every 1° decrease in temperature Cardioplegia delivered at a profound hypothermic temperature (~4° in our case) will reduce myocardial O2 demand by ~97% Provides great myocardial protection by limiting O2 requirements during the ischemic period Combination of both hyperkalemia and hypothermia will both provide electromechanical arrest and reduce myocardial O2 demands

Warm Cardioplegia Warm continuous cardioplegia Used to prevent myocardial injury due to extreme hypothermia of tissue Advocates claim electromechanical arrest provides enough protection due to hyperkalemia Say hypothermia is an added benefit, but not needed or desired in their case Provides constant washout of metabolites Must delivery plegia at a lower K+ concentration due to it being delivered constantly Also an option for cold agglutinins patients where cold cardioplegia is contraindicated

Cardioplegia Types Straight Crystalloid Solution Pre-made solution with electrolytes and buffers St. Thomas Solution or Plegisol Additional Potassium can be added if desired Can be delivered as straight crystalloid, no blood Blood Cardioplegia (Most common)- Use crystalloid solution mixed in a ratio with blood from the pump We use it mixed 4 parts blood: 1 part crystalloid Some places like Lourdes, use an all blood model, no crystalloid solution in the spike bags “Plegia bag” is whole blood with potassium and other additives injected in Can give in a mixed ratio with pump blood

Straight Crystalloid Plegia No blood buffering, oxygenation, or waste removal More hemodilution due to excessive crystalloid delivery

Blood Cardioplegia Most places use blood cardioplegia mixed in a 4:1 ratio Takes advantage of the buffering capabilities of blood and also it’s delivery of oxgyen, nutrients, and waste removal Can mix blood with a pre-made solution or inject your own drugs into the blood Cold Blood Cardioplegia offers O2 delivery but due to severe hypothermia of blood, the O2 released to the tissues is low due to the oxygen-hemoglobin dissociation curve Do we need a lot ?

Induction Dose and Maintenance Doses Induction doses are typically given at a volume of 10-15 mL/kg (usually ~1L) Higher concentration of K+ is ideal for the induction dose Maintenance doses are given at a lower concentration and lower volume amounts

Cardioplegia Delivery Types Antegrade- follows the normal pathway of the blood Delivered via the aortic root Retrograde- travels backwards into a vein and out of an artery Delivered via the Coronary Sinus Ostial- directly into the coronary ostia Delivered via handheld cannulas Vein Graft- directly into the proximal end of a vein graft providing flow distal to the blockage Delivered via a small vein cannula hooked up to plegia Y line at the field

Antegrade Cardioplegia Root cannula placed between the X-clamp and the aortic valve Often a Vent is Y’d into this line to vent the heart when plegia isn’t running Plegia is delivered at a rate to close the aortic valve and flow into coronary ostia May have to flow hard to close the valve then back down to perfuse with acceptable pressure Antegrade Flows- ~300cc/min Antegrade Pressure- 150-220 mm Hg Read as plegia line pressure at pump

Antegrade Cardioplegia Antegrade with Aortic Root Vent Y’d in

Antegrade Delivery Issues Patient’s with Aortic Insufficiency Plegia will flow into the LV because the valve is incompetant and will not fully close May have to flow higher to pressurize in the root May have to abandon antegrade and go retrograde If a Aortic Root Vent is in place, it must be OFF, or your delivered plegia will be sucked back into your pump before reaching the coronaries Can be detected by not being able to pressurize in the root or extra root vent return

Retrograde Cardioplegia Retrograde given into the Coronary Sinus A balloon cathetar is wedged into the sinus and will auto inflate upon delivery of cardioplegia Balloon is deflated when plegia is off Coronary Sinus pressure is read at the cathetar tip

Retrograde Cardioplegia Retrograde plegia will offer protection distal to coronary blockages that are unable to be perfused by antegrade plegia Coronary sinus is the main venous drainage system of the Left Heart so the Right Heart is slightly under-protected during retrograde delivery

Retrograde Delivery Blood travels into coronary sinus and comes out of the coronary ostia in aortic root Collected by aortic root vent Used for valve surgery when aorta is opened and antegrade isn’t possible Used for CABG patients with critical stenosis Retrograde Flows- 150-200cc/min Retrograde Pressures- 25-40 mm Hg Read from coronary sinus cathetar tip, transduced to anesthesia or back to us at pump using 3rd pressure line Retrograde Line Pressure- maintain line pressure of plegia delivery system at ~100-150 mm Hg

Retrograde Delivery Issues Surgeon can have difficulty inserting it Noticed by unable to pressurize the coronary sinus Balloon rupture, balloon will be unable to inflate, so delivery will go into the coronary sinus and directly into the right atrium, not allowing adequate protection Coronary Sinus cathetar in too far, seen by high sinus pressure and high line pressures Persistent Left Superior Vena Cava- SVC drains into the Coronary Sinus, which prevents us from using retrograde plegia Seen by TEE Coronary Sinus Ostia is huge

Coronary Ostial Plegia Plegia delivered directly into the coronary ostia using small handheld cannulas Used when antegrade delivery is impossible due to AI Used when delivery of retrograde plegia is ineffective Separate cannulas used for Left Coronary Ostia and Right Coronary Ostia Left Main Coronary Ostial Flow- ~150-200 cc/min Pressure read on line pressure- ~150-200 mm Hg Right Main Coronary Ostial Flow- ~100 cc/min Smaller vessel Pressure read on line pressure- ~150-200 cc/min

Vein Graft Cardioplegia Plegia is given directly into a vein graft via a small vessel cannula Used when retrograde is exclusively used, vein graft plegia is often run down the RCA graft to provide protection to the right heart Used to flow down all coronary grafts to both offer protection distal to a blockage, and to check the patency of their graft and to see the flows they will get down it Vein Graft Flow- ~80-120 cc/min depending on vein size Vein Graft Pressure- read on line pressure- 150-200 mm Hg

Issues Arresting the Heart Plegia System? Patient? Solution? Give some examples…

Issues Arresting the Heart Plegia System- Temperature of solution (hypothermia=fast arrest) Inadequate flows/pressures (come up on flow) Occlusions set correctly Solution- K+ levels not high enough K+ bags are clamped out

Issues Arresting the Heart Patient- Delivery impeded Coronary Sinus Cathetar issue Not in correctly Balloon deflated Delivery cannula dislodged Plegia being vented back to us Anatomy Patient has AI (inadequate antegrade delivery) Prior CABG operation, LIMA graft washing out cardioplegia Must clamp the LIMA graft before giving plegia PLSVC- no retrograde delivery

Parameters Monitored ECG- Time Intervals- Look for asystole during cardioplegia induction Monitor ECG activity in between plegia doses If activity presents, alert surgeon and prepare to give a dose of plegia Time Intervals- Time between doses is ischemic time Alert surgeon every 15-20 minutes Potassium Levels- hyperkalemia will ensue due to plegia administration Excessive K+ levels can be treated by us

Hyperkalemia Can produce arrhythmias Can produce a prolonged state of diastole Seen by tall peaked T Waves on ECG ↑ K+ causes Ca++ loading in the cells

Hyperkalemia Interventions- Insulin and Dextrose Administration- Most effective way to combat hyperkalemia on CPB 10 units regular insulin and 25g dextrose for K+ ~6-7 Adjust dose depending on K+ level Insulin acts as a transport mechanism to bring K+ and sugar into the cells Must replace glucose levels to avoid hypoglycemia ZBUF- Zero Balance Ultrafiltration Using hemoconcentrator to pull of K+ and replacing the fluid with normal saline to restore Na and Cl Bicarbonate Administration- Drives K+ into the cells Minimal effect seen

Venting the Heart Constant venting of the heart during cross-clamp period is essential for maintaning arrest Blood returning from the bronchial circulation or blood not drained by the venous cannula can travel through the aortic valve into the coronary ostia and perfuse the coronaries This can lead to premature beats and ECG activity when the surgeon is working Monitor the ECG for P waves or other activity and alert the surgeon