Unit 4 Lec PDF

Unit 4: Cardiac Electropathophysiology Cardiac Anatomy, Cardiac Action Potential GANONG CH. 29 Learning Objectives Describe cardiac anatomy from individual cardiac myocyte to whole organ system anatomy; link with function of heart Define blood flow process through the heart, beginning in the right...

Unit 4: Cardiac Electropathophysiology Cardiac Anatomy, Cardiac Action Potential GANONG CH. 29 Learning Objectives Describe cardiac anatomy from individual cardiac myocyte to whole organ system anatomy; link with function of heart Define blood flow process through the heart, beginning in the right atria Evaluate electrical conduction in the heart, beginning in the SA node Loading… Describe how SA node regulation may occur by changing external factors (ex: autonomic innervation, osmolarity, etc.) Compare/Contrast electrical conduction in cardiac myocyte with cardiac nodal cell vs. skeletal muscle Evaluate role of refractory period in proper cardiac function Compare/Contrast electrical conduction in nodal tissue vs myocytes Link cardiac conduction process with cardiac contraction during a single heart beat  um blood returning S Blood Flow from uppen 18 ↑ Ta 3a O 5 Through The Heart Shaped like an inverted pyramid superior In ba Base = superior body · T Apex = inferior · blood pumped back from lower 4 Points to thoracic circulatory system 1 body 2 semi closed tricuspid lumnar cavity value value 3 everything from periphery goes through * always atria to ventricles. Topa bottom 8 mitral Suc value 5 send out blood Y arterys vains return deoxygenated ?  Cardiomyoctye s Specialized anatomy to fulfill specialized function– to pump blood throughout body to maintain shape : Intercalated disks: attach myocytes together Desmosomes: strengthening connections Gap junctions: electrical connections myo-muscle (layey) Loading… ⑰ surrounds 2 sack so it doesn't get stuck encloses a w contraction relaxing endo- inside Clayen) makes it smooth, Slipperly  Conduction have to depolarize the system of the tissue = contract in specific orde heart don't want$ to depol. @ same time ventricular myocytes Coordinated contraction of heart muscle Atria contract from heart’s base toward apex; Ventricles contract from apex toward base Electrical conduction begins with depolarization of the SA node Automaticity: SA, AV nodes, bundle of His, Purkinje fibers ventricularKEEPER - Atriae or GATE 5 depolarize whole atria maker base of a pace Image from Dr. Perry Carter, http://classes.midlandstech.edu/carterp/Courses/bio211/chap18/chap18.html How can the heart conduct electrical Nat Nat 10 potentials? Ion Channels Nat or Cast lopen! Characterized by ◦ Probability of opening ◦ Length of time remains open Population of ion channels & refractory V period 11 & S S time Imsec) Inactivation gate  Ap cell Ap myocyte SA nodal cell overshoot 2-plated apoi3-repolar at Comparison of Action Potentials = myocyte Plateau phase  Correlation Between Cardiomyocyte Action Potential and Ion Currents Cat by FY) modulated ↑ ) when Na can iNa = cross membrane L-type Cast - channels ca" moving inside cell sustaining depol. repolarization Ion flux during action potential Ventricular Myocyte Cardiac nodal A Z cell Nodal cell 8 3 depol by Cat flux * slope. - by depol] If "Funny current" & uS O Nat in myocyte = Z KT, 3 O Image from Vander, Sherman, and Luciano’s Human Physiology, 9th ed. SA and AV Node Action Potentials A cat. It eflux z repol Loading… depolar. funny current > allows - nodal cells to act indep. AUTOMATICITY : reach thessh/depolarize w out external influence = Cardiac AP and Cardiac Refractory Period Purple- Absolute refractory period; Green- Relative refractory period in $ tetanus = can't get ARP Cardiomyocyte AP: Putting it together Cardiac Conduction System  1. SA Node “Pacemaker” Both sympathetic and parasympathetic nerve endings present to regulate SA node depolarization Sets pace/rhythem Tissue Conduction Rate (m/s) SA node 0.05 Atrial muscle 0.5 b HR AV node 0.05 *HR,efferentSTAV ne Bundle of His 2 Q efferents (Ca based contract) Q regulate speed Purkinje 4 z Fibers Image from Google Images Ventricular 0.5 muscle  Regulation of the SA Node SNS -Increases rate of spontaneous depolarization PSNS SNS PSNS =Decreases rate of spontaneous depolarization NE Ach tachycardia = Fasten H + +1 Normal rate Pf funny currentslope steeper (Ds) ↳ depolarize quicken - bradycardia So = 00 funny current slope Flattens (As) = slows contractility ↳ Inhibit PSNS Ach ASCAMP *PKA *depl  How can we alter SA firing normal A W SNS rate? reach theshold PSNS Left panel, line b: Slope of Phase 4 + depolarize (Autonomic intervention) quicken Left panel, line c: Magnitude of the minimum potential (RMP changes) If Right panel, line b: Level of Threshold potential (TP) FYl What factors could change SA node AP? Positive Chronotropy Fasten AR Negative Chronotropy Slowey AR Sympathetic Stimulation, Parasympathetic Stimulation or Epinephrine, catecholamines in Muscarinic Receptor Agonists blood Beta-adrenergic Receptor Beta-Blockers adrenergic receptor antagonist Agonists => act like Nor-Epi ↳ block Nor-epi effect Acidosis ↳ ph Na+ or Ca++ channel blockers Hypokalemia * RMP = I twitchy Hyperkalemia XRMP (i+ in blood longer to reach teshold  Tissue Conduction Rate (m/s) SA node 0.05 Atrial muscle 0.5 AV node 0.05 essential - Bundle of His 2 normal 2. AV node for funct Purkinje Fibers 4 cardiac Ventricular 0.5 “gatekeeper” muscle AV nodal tissue has slowest depolarization to contract together > - Few gap junctions and slow Phase 0 (reaching threshold potential) Phase 0 of action potentials at flatlining the AV node is not dependent on fast sodium channels as in non-nodal tissue, but instead is ocele RMPAs) is generated by the entry of (NO calcium look on Two functions: * presentation  Tissue Conduction Rate (m/s) SA node 0.05 Atrial muscle 0.5 AV node 0.05 Bundle of His 2 Purkinje Fibers 4 2. AV node Ventricular muscle 0.5 “gatekeeper” AV nodal tissue has slowest depolarization Few gap junctions and slow Phase 0 (reaching threshold potential) Phase 0 of action potentials at the AV node is not dependent on fast sodium channels as in non-nodal tissue, but instead is generated by the entry of calcium Two functions: ◦ Delay impulse: allow atria to contract and complete ventricle filling ◦ Receive impulse and conduct to ventricles Vulnerable to injury from disease ◦ Loss of conduction (heart block) ◦ Delay impulse: allow atria to 3. Bundle of His and Purkinje fibers myocyte NODES Neuronal like Ap : i tre I · N funny Tissue Conduction Rate (m/s) z SA node 0.05 Atrial muscle 0.5 ↳ AV node 0.05 Bundle of His 2 Purkinje Fibers 4 Ventricular 0.5 muscle  Sinus rhythm be consistent should > more - depol depol. atrial AV says"Wait cells allventricular & depolar. arepolarization lead 1 1 In memb , polariz , Status Cardiac electrical conduction mapped to ECG  same The - Original What is the ECG (EKG)? Electrocardiogram (developed in Germany 1893 by ↑ deflection on ECG William Einthoven; electrokardiogram) - deflection on ECG ECG = sum of ALL electrical activity measured in the heart at a given time (sum of membrane potentials at a given time)  “Sinus” ECG, Lead I: what part of the heart is conducting? overal ↓ deflection. top R -left atria * atrial depol -S. atria & A - Lead ! (t) lead 1 (-) S Single Myocyte Depolarization: Building the ECG. sa depol Only see a peak when there is a - - If you swich difference in potential across the t - Polarity leads Ade heading + towards electrode L - R - max depol measurement. What effect would switching the polarity of the leads have on the ECG? bl fewer goes down cells  Changes in Membrane potential: Depolarization (-) (t) Interior of cardiomyocyte is negative relative to the outside when at rest; Depolarization ‘flips’ membrane to a positive potential intr QRS don't see atrial repolarization ever bic during Ventrical depol (much bigger).  Atrial Depolarization and contraction Depolarization wave begins spontaneously in the SA node and travels to the AV node towards AV node is slow conducting tissue. What is vector side left the consequence? PR interval/flatline Why is the ECG at baseline during contraction? - SA node ↑ ad + Y no As in depolanz of cell - Ventricular septal depolarization: Q Wave Depolarization wave moves from Left to Right side of septum - > thin separates tissue RIL ventricles jusirgentricular Why does the peak have a negative deflection? v Short bic. small amount of tissue - ventral depolarization : = 3 moves more to the RIt (ECG - deflection ( "Q" R Wave Direction is aligned with Heart axis Maximum deflection > + - Depolarization occurs from endocardium toward - lots of cells epicardium 6 - Inside -> outside of 97 large bl many cells  S Wave: Ventricle depolarization finishes Last part of ventricle to depolarize is postero-basal region of left ventricle Left ventricle is thicker, so it takes more time for wave to spread across it depol depol Loading… atria ventricle A QRS - P Sing. nothing Zint - T all ventricles depol all atria repol. node Ventricular contraction - -  Ventricles Contract T Wave Ventricles Repolarize “Wringing” motion: ventricles contract toward base (superior) to expel be volume heads Wave repol. - electrode towards Does the ventricle ever close tightly enough to expel all the blood it Octo is contains? endo epi depolarize In- out out - in repolarize epi ende repolar -. 1 3 The Cycle is Complete: Ready to Start Over!!! What event happens next? Canvas Assessment: Cardiac Anatomy Quiz Put your knowledge of cardiac anatomy to the test! Quiz closes at 11:59 pm Sunday, June 19th Unit 4: Cardiac Electropathophysiology Electrocardiogram and Arrythmias MARTINI, CH. 18 Learning Objectives * Evaluate the component parts of an ECG recording on a single lead Map the deflection measured for a specific ECG lead onto a hexaxial diagram; calculate the approximate MEA Define how changes in the MEA would reflect cardiac pathology Evaluate arrythmia generation by alterations in impulse formation or conduction Compare/Contrast arrythmias by a) ECG changes; b) conduction pattern changes; c) location/ generation of abnormal pulse; d) pathological consequences Cardiac electrical conduction mapped to ECG Depolarization wave has direction and magnitude: It is a Vector Depending on lead using, depolarizing wave may look different! Compare/Contrast: Lead I vs II Lead I vs III Lead II vs III rector Hexaxial diagram and 6-lead ECG Hexaxial Leads: I, II, III, aVR, aVL, aVF Additional leads (12-lead ECG): V1-V6-- “view” the heart in the horizontal plane auf  The EKG Leads: MEA : mean electrical axis given on exam What would be recorded on lead I? What lead would record the largest -- ↓ - = t voltage (called deflection)? parallel leads : leadl + avR ------- What lead would record the ↑ Imdeflection smallest voltage (deflection) + deflection Perpendicular : all ↑  & “Building” a complete ECG 3rd I 2nd dist - y (4 ALead I read magn. /Parallel-larger perp smallen 7). (-deft) Vector Magnitude and Direction 18. Any vector originating at center and ending at blue line has a.5 0 magnitude of 1.0 mV Any vector originating at center and ending at green line has a magnitude of 0.5 mV  - Vo b O ECG: Which lead will record the largest deflection during a normal beat? lead 11 Vectors can be Averaged NORMAL Intuitive example h lead Q R S overall - I - 0. 3 1 00. 0 7 mV. G auf ~ 1- o 0 7. -0 2. 0 5 mV. & average between is vector lie ? (closest to Where does MEA (t) alavf() b)aVL (t)c)aURE allead  Parallel vs Perpendicular deflection Parallel leads: highest magnitude deflection Perpendicular leads (90degrees): no deflection; “disappear” *If a vector pointing directly towardlead +60, on what lead(s) would it have no magnitude? avL [I (t) (perpendie) & MEA Atrial Depolarization: P-Waves Atria on top of the ventricles Lead II small. not many atrial cells - SANODE ↳ Lead aVL  The QRS Complex It lead > - repolarize outside ↓ Inside (reverse/reset) + I lead Mean Electrical Axis of Heart (normal sinus) Why does the MEA lie along Lead II? Overall wave of depolariz mumt.  Mean Electrical Axis (MEA) example * Lead Q R S Sum (magnitude) R aVL - 0 1. 1 5. -0 1. 1 3 my. - y ⑳ I waa aVR 0 5-1 70-1 2 mv. - > - MEA slope.. a's S? & R Mean Electrical Axis Abnormalities heart not depolariz direction In right  - What Does a Change in the MEA mean? aVL Y left axis deviation normal normal - A leadI lead aureflection taking longer to depolarize Example 1: MEA shifted toward aVF (right deflection) R ventricle gets. Example 2: MEA shifted toward I (left deflection) biggen works , left ventricle takes harden longer left ventricular hypertrophy = R ventricle. aorta? hypertrophy, hand to pump blood out Heart Failure What If Ventricular depolarization started in the LV? A ↑ A &1 & ectopicfores jop cells (the was &  T-waves on ECG Why does repolarization have positive deflection? M1 What about cardiac Arrhythmias? Quentin Groves died of a heart attack October 15, 2016, at the age of 32. He played in the NFL for several teams. While undergoing medical tests at the NFL Combine, Groves was discovered to have Wolff-Parkinson-White syndrome. Groves told the media, "It's an extra circuit in the heart, and it speeds up your heartbeat, it's nothing too critical, but you have to take care of it.“ Groves elected to have a surgical procedure called ablation. After the procedure, he said. "doctors said I was 100% healed, and I'm good."  Rate/Firing Arrythmias Rate Arrhythmias Caused by Altered Impulse Formation or Conduction still follow sinus rhythm AV node speed & Abnormal Cardiac Conduction - What can go wrong? Back-ups  AV node conduction abnormally slow or blocked damaged S Abnormal pathways for conduction  Accessory pathways wparkin. White Shifts M How would that look? (lead I only) block Sinus it if b dropped QR  NORM Sinus rhythm AV Block (Lead I only) fiti PR interval < 200 mis and P degree infin a block normal PR interval 100 "I beat" skipped a dropped are ↳ may not even know block QRs not usual shape degree a b + - reveals ectopie e - pacemaker ventricle in EXTREME axis deviation = depolarize in wrong dir. Wolf Parkinson White (WPW) Syndrome Anatomical re-entry (lead I) DWaveSee (sp) O accessory pathway it ↓ alt. conduction pathway o  Sinus arrhythmias Normal PQRST on ECG, but abnormal frequency; Normal components, slower or faster rate Sinus bradycardia V Slow. Sinus tachycardia V fast. What has happened to the ability to generate an AP? How might these changes have occurred? Images from Medical Physiology, 2nd ed.  “Sick sinus syndrome” Alternating episodes of fast and slow rhythms (rare) mu Patients may have few or no symptoms and/or symptoms may come and go Symptoms: Bradycardia Fainting (syncope) Weakness What is happening at the SA node Shortness of breath (dyspnea) to cause these symptoms? if Chest pain (angina) ↳ SNS causes tachycardia : ↑ slope Phase 4 & SA node Palpitations (heart racing/pounding/fluttering) Supra-ventricular vs Ventricular Arrhythmias Supraventricular- originates above ventricles and AV node Base ◦ Sinus bradycardia/tachycardia / sick sinus ◦ Premature atrial contractions S◦ Atrial flutter & ◦ Atrial fibrillation ◦ Paroxysmal supraventricular tachycardia (PSVT) ~◦ Wolff–Parkinson–White syndrome · av block ? Junctional- AV node firing rate exceeds SA node Ventricular- ◦ Premature ventricular contractions ◦ Ventricular tachycardia Apex ◦ Ventricular fibrillation ◦ Torsades de Pointes  Premature Atrial Depolarization (PAD) Also called PAC (premature atrial contraction) sporadic 2 be depolarizing !! QRS no break shoulda b PT + bi - 1 Norm o feels like double & beat a What cell(s) in the heart might be responsible for PAD? SA node Why did the QRS wave not change? Av node "gatekeeper" ventricle - depol. is same  - Atrial flutter node QRS SA X o TPP Sa contract consistently too times , many Characteristics: Elevated heart rate Interval between T wave and next P wave is diminished AV node is only activated after 2-3 P waves (2:1 or 3:1 heart block) QRS complex (ventricles) - ok, , normal  Atrial fibrillation (A.Fib) No P-waves; Irregular R-R intervals Irregular contraction of both atria Reduced ventricular filling # R R - " saw to oth interval #- Irreg. Irregular rate of ventricular contraction t , butshapeo & rate May be episodic (brief) or chronic Symptoms may include irregular heartbeat, lightheadedness, fainting, chest pain, etc. QRS Still normal ! PAD may precede A. fib What would this do to ability of heart to pump blood to the body? a) out of atria z Ventricle? b ability c What happens to blood moving ? Lois if not b) ventriclesa body ? I volume, + inconsistent. Edizzy lightheaded , blockage  direction m wrong MEA tricle L ven E in. pacemaker taking longer g O - Y QRS. R vent.. normal Irregul Y ventricle depolar. still in direct. MEA happens in wrong direct - right bundle aka zpurkinje Premature ventricular contraction (PVC) depolarization  wide , Irregular QRS Ventricular tachycardia - When contraction/relaxation cycles occur too quickly, heart doesn’t have O enough time to fill with blood between cycles. Cardiac output reduced. How/Why might a ventricular pacemaker originate? ( ↳ gra Av block ectopic faci/pacemaken degree causes ventricular depol outside usual anatom. Pathway - AV node control superceeding  Ventricular Fib badly... V ventricles so working ) fibrillation "Quivering vents". not passing blood Irregular alterations in ECG without apparent · QRS complex Ventricular contraction is irregular and body shutting down inefficient A Loss of body-wide blood circulation – loss of consciousness and death (within min) Multiple foci ↑ - How do you know it is not Atrial fibrillation? & ↑ NO QRS complex anywhere How to prevent patient dying from V.fib? T cardioversion snock - / & "twisting of the points - Torsades de large small large Pointes Specialized type of V. tachycardia Name (French): “twisting of the points” - QRS complexes vary in shape and amplitude - ECG seems to wrap around baseline like a “ribbon” V Fib -. ↳ cardioversion diff Foci. Long QT Syndrome: Predisposition to Ventricular Arrhythmias How does the QT interval correlate with the cardiac action potential? Irregular repolarization can lead to ventricular arrhythmia Causes: Drugs, Electrolyte abnormalities, ischemia, genetic Genetic variants: Mainly mutations in K+ channels begin ventric ventriculaa depol. L Prolonged  ventricular + Supra us.... Unit 4: Cardiac Electropathophysiology Myocardial Infarction STEMI AND NSTEMI 1/ Muscle cells 1 of not behaving normally Learning Objectives * Define myocardial infarction, transmural, subendocardial, ischemia, necrosis Discuss the change in EKG expected with myocardial infarction Assess cellular consequences of ischemic in coronary tissue Loading… Evaluate the signs and symptoms expected in acute coronary syndrome (ACS) Discuss the relevance of biomarker assessment in differential diagnosis of ACS Compare/Contrast EKG and biomarker differences between STEMI and NSTEMI Discuss potential treatment options for STEMI and NSTEMI (acute and post-MI management) Recall: Cardiac conduction and the EKG EKG Readings may indicate pathology all ventricular cells depol Should be flat not NORMAL. - - & - Loading… & - - b repol -. * Y = & (latey on / - -------- ventric not depol. , should in way they depolarize : endo zepi epitendo repolarize : norm htt T-waves on ECG a myocyte -- abnormal repolar. ~ - 6) endocardial repol 1st v * repolarize (t)/ Inverted T wave epizende A giveaway for stressed damaged dying , cells Why does repolarization have positive deflection? M1 What is Myocardial Infarction (MI)? MI: one or more areas of the heart muscle don't get enough oxygen [demand suppli] Ischemia: imbalance in myocardial oxygen supply and demand Ex legs : hurt when b/c they running O2 getting enough aren't  Chest Pain: Common Complaint at ED munum Z GI Stress or & A pain acute AMI-Acute Myocardial Infarction, UA- Unstable Angina  Fr ↓ Oz supply Acut - -02 energy term long chronic depolarized Cellular repolariz Consequences of. More diff b/ grad +. Ischemia/Hypoxia messed up ↑ & - S - / I How would changing electrolyte concentrations alter Resting Membrane Potential? What does this mean for the action potential? Acute Coronary Syndromes (ACS) less severe comes goes  ACS Serum Biomarkers Presence of biomarkers indicates more severe pathology (cells damaged & release biomarkers) Cardiac troponin (cTn) > - I cells dying & Creatinine kinase (CK) SHOULD BE INSIDE CEL Cause of ACS: Coronary Thrombus Thrombus/Thrombi: blood clot within coronary vessel Loading… Vessel occlusion– prevents proper blood flow; decrease O2 delivery to cardiac tissues Depending on size of thrombus– will see different changes in EKG readings! over decades cholesterol builds up Mapping EKG changes to different ACS ECG alterations of any origin Unst. Ang. NSTEMI STEMI f - Other signs (objective) and symptoms (subjective) autonomic responds Types of MI: Extent of Ischemic Area Endocardium is more vulnerable to ischemia ◦ Coronary arteries perfuse from epi- to endocardium (outer to inner) - ◦ Endocardium least well perfused ~ ◦ Pressure from blood (wall stress) greatest on endocardial side Subendocardial vs. transmural infarcts B Irreversible cardiac necrosis (cell death) depends on length of -7 · pressure Ist to become Ischemic time tissue is ischemic => Is those in endo. Which is more severe: sub-endocardial or transmural infarction? transmural both endo/epi - -Oz = bATP = > YWalk - ATPase function ↑ Nat intracell depol. & rest Why are the EKG changes different with extent of infarct? ↓ downward baseline & upward Shift b/c heads towards (+) lead bk towards (-) lead Transmural- ST elevation (STEMI) Subendocardial- ST depression (non-STEMI) ◦ True baseline (red) is when ventricles completely ◦ True baseline is when ventricles completely depolarized depolarized ◦ Damaged area partially depolarized ◦ Damaged area partially depolarized ◦ Seen as positive charge moving away from electrode ◦ Seen as positive charge moving toward electrode ◦ ECG trace begins a negative deflection ◦ ECG trace begins at positive deflection ◦ ST segment total depolarization ventricles ◦ ST segment total depolarization ventricles ◦ is at true baseline- looks elevated ◦ Is at true baseline- looks depressed Images adapted from Google Images  Case, part 1 Art V., a 51-year-old architect, was working out at the gym with a new trainer. At the end of an hour, he felt exhausted, couldn’t catch his breath, and laid down on the floor. The trainer brought him an orange juice, but after 5 minutes of rest he still couldn’t get up on his own. The trainer called 911, and an ambulance arrived 6 min later. Art’s face was pale, and sweaty. He had a crushing substernal pain radiating down his left arm. He was given oxygen, started on an IV, hooked up to a heart monitor and taken to the nearby hospital. 1. Why did Art feel chest pain? 2. When the EMT saw that Art was pale and sweaty, why did this make him think of heart attack? 3. Why was Art given oxygen? 4. Why was Art started on an IV by the EMTs? Is Art having a heart attack/MI? “General” patient signs/symptoms of MI Diaphoresis-heavy sweating 17  MI progression and damage Need to have timely intervention to prevent cell acute & damage and death if he survives ↓ Phys As. to damaged cells & Fundam Sed.  Biomarker elevation is marker of MI severity Higher cTn levels = higher risk of death !! cTn = Cardiac troponin direct correlation 19 How are cTn released in MI? cell lysis X 5 surgery  Case, part 2 Art is taken to the cardiac care unit of a nearby hospital. The hospital suspects he has had a myocardial infarction and begins to confirm the diagnosis. A nurse takes his vital signs: pulse and respiratory rates, blood pressure and temperature. A blood sample tested positive for CK-MB and troponin I. 1. What would elevated levels of CK-MB and troponin I in blood indicate? 2. Why are these tests specific for damage to heart and not other muscle? Differential diagnosis for ACS NORMAL > - GO HOME ST depression - - * Stelevation ↑ NSTEMI EKG changes can resolve over time What does T wave inversion mean? STEMI EKG changes over time Q wave depression R wave depression T wave inversion R peak O · o Smore (t  Case, part 3 O The ECG indicates Art did have a MI, with a likely location in the Left O Anterior Descending (LAD) coronary artery (common location for occlusion; “widow-maker”). This artery supplies the anterior wall of the left ventricle with blood. He is taken immediately to the cardiac catheter lab. Art is given light anesthesia: he is still conscious, able to talk and watched the E location catheterization on the monitor during the procedure. The cardiologist inserts a catheter into his right femoral artery. The catheter is guided into his heart via the aorta, and into the left coronary artery. The doctor gives a squirt of radiocontrast dye to visualize the blood flow through the coronary artery. A 95% blockage of the LAD is seen. Which lead(s) of the EKG would you expect to see the GREATEST LEAD aVF change? 11 , Recovery from MI Damaged/Necrotic tissue will be replaced by fibrous/scar tissue ◦ How would this affect conductivity? - b gap junct Fibrous/Scar tissue is less flexible ◦ How would this affect ventricle function? doesn't as well, b compliance squeeze ◦ Scar tissue is more likely to rupture– what could this cause? , T ↳ another MI clot - another Decreased contractility and compliance > - cardiac rehabilitat is essential  Management of MI (either STEMI/NSTEMI) 1. Decrease further ischemia/necrosis recovery 2. Decrease work “strain” on the damaged heart 3. If needed– reperfusion/catheterize Case, part 3: what are the treatment options? Art gets percutaneous coronary intervention (PCI) using a stent Left: coronary artery with 95% blockage (visualized with radiocontrast dye) Middle: treatment options– PCI/stent vs. coronary artery bypass graft Right: after PCI/stent procedure, blood flow restored through artery I narrows * Post-PCI treatment and management of MI Pharmacotherapy: Bblocker ◦ Anti-platelet, anticoagulant agents – prevent blood clotting "Badrenergic antagonist" ◦ Clopidogrel, fondaparinux, heparin, warfarin (?) ↳ prevent SNS ? ◦ Fibrinolytics- help dissolve fibrin clots AAR. b contract , Loading… ◦ Tissue plasminogen activator (tPA) (reteplase, tenecteplase (TNK)) to prevent ruptwel ◦ Drug-eluting stents- coated with anti-proliferative and anti-coagulant agents S clots ◦ Prevents growth of tissue over stent ◦ Prevents blood clots from forming on stent Stents– help the vessel remain open & maintain perfusion  Case, part 4 At his six-week follow-up Art’s ECG had virtually returned to normal, and he had successfully completed his rehabilitation exercise routine. The doctor returned him to normal activities. He was maintained on anticoagulants for a year. 1. Why do you think Art was able to recover so quickly? 2. Why does Art complain of easy bruising? 3. Why might Art’s recent interest in fitness have helped his condition?  Overall, review: PCI – percutaneous coronary intervention CABG – coronary artery bypass graft Unit 4: Cardiac Electropathophysiology Post-Myocardial Infarction RE-ENTRANT LOOPS AND ARRYTHMIA GENERATION Learning Objectives Evaluate potential complications/pathologies following a myocardial infarction Discuss changes in cellular function (K+, H+, RMP, etc.) following an ischemic event and how this may change conductivity and responsiveness Evaluate pathophysiological changes in structure and function following MI and fibrosis/scar tissue development Loading… Define uni-directional block and how this may cause development of a re-entrant circuit Compare/Contrast electrical conduction along fast and slow-conducting branches and development of retrograde conduction Evaluate arrythmia pathogenesis following development of a re-entrant circuit Compare/Contrast supra-ventricular and ventricular arrhythmias arising from re-entrant circuits and ectopic pacemakers Following MI, potential consequences: DOt = formation value 6 GBP ↳ tissue coronary ~ bk dead tissue + other tissue => Scar Arrhythmia generation following MI myocytes A Ischemic damage B - much slower -= Loading… C D z How might normal conduction pathway be altered? What does this mean to coordinated contraction of cardiac myocytes? ↓ - - contractility slower depol How might the heart compensate to overcome?. , SNS vasoconstriction Image from Medical Physiology, 2nd  Effect of Ischemia on [A ] acid + J acidity As Cardiac RMP Pacidity Decreased ATP production Na/K-ATPase decreased activity Change in RMP (K+ gradient) · RMP baseline (mir Induced depolarization/Inactive Na+ Hypercalemia channels Y & K+ conc · outside cell Ischemia inactivate Na+ channels cell is closer to threshold => don't work as but channels well - depol.  How does ischemia affect cardiac AP? & baseline sooner -wait longe - risk of ectopic foci (vulnerable( contraction filling/relax Pink = normal ↑ kt outside cell = ARMP Blue = Ischemia How does this affect the conduction rate of damaged tissue? Nat channels = inactivates Conduction through branched pathway (bifurcation) M refract Arnode Adamage yel NEED 1) branched · one fast cond · One slow conduct 2) critically timed wave of depol loop ARP ending Ma never BM back up = WRONG critically timed depol Re-Entry Causes Arrhythmia (new pacemaker) Abnormal pathways can also be caused by a ‘re-entry’ mechanism Damaged tissue may conduct impulses abnormally slow Causing the normal impulse to split into two pathways Self-perpetuating cycles of depolarization in abnormal direction Will manifest itself differently on the ECG depending on location What happens to SA node control? Loading… Re-Entry Video AV re-entry: Premature Atrial Contraction (PAC) ⑮ Sup. inferior- num ↑ re-set to baseline , after ARP ↳ deflection - Vent depol.  as I same above PAC – supraventricular num tachycardia Supraventricular Tachycardia in Re- Entry: Atrial flutter Re-entrant loop includes dysfunctional AV node multiple p-waves Re-entry cycle includes entire right atria (large) EKG alteration: excess P waves (“saw tooth”) Atrial rate increased (300 bpm) Ventricular rate: determined by AV conduction O  Supraventricular saw tooth p-wave Tachycardia in Re-Entry: PSVT Paroxysmal supra-ventricular tachycardia Treat by changing automaticity of heart ↳ 6 HR B-blocker (propanolol) S = slower conduction + & loop cancel re-entry  + biomarkers A Re-Entry in mu ventricles Susceptible tissue: ventricular myocytes have slower conduction than Purkinje fibers ! A) normal conduction; two paths collide and extinguish B) following occlusion/ischemia– slowed conduction branch ↳Create a reentrant loop , what look ? like will EKG · QRS effected is it ? a) unstable Angina - less Severe BINSTEMI not all cells impact. C) STEMI -  Sub-endocardial ischemia; ventricular re- entry circuits * rent not C) Damaged tissue can conduct. retrograde (bottom->top) or normal depol together “fast” conducting pathway can cause retrograde stimulation D) occasional premature beats = wide QRS because uncoordinated stimulation; sustained tachycardia = inc. O2 demand loop Stable CT: conducting tissue ERP: effective refractory period AV node Re-entry: Ventricular fibrillation  Re-entry after Of MI Central fibrosis: no conduction Border zone: some tissue damaged, some normal Criteria to create re-entrant circuit: Multiple parallel paths Uni-directional blockade CT > ERP dead cell,carti a , Post-MI Re-entrant circuit: Ventricular ectopic pacemaker done Possible DM Tware QRS deviation -Extreme axis ectopic foci 2 ↳ Sinus Y ext-axis deviation  D Ventricular Ectopic Foci may have in depth altered/acquired ↓ go automaticity don LAD occlusion Nat chan innact. Hypokalemia; RMP. changed Faster rate; ventricle conduction before normal rate Tachyarrythmia Treatment of Re- Entrant Circuit  Treatment of Re-Entry Anti-arrhythmics Rate Control – change heart rate (beta blockers, calcium channel blockers) Rhythm Control – change cell depolarization (Na+, K+ channel blockers) Meta analysis: favors rate-control Figure from Kotecha, et al. (2017) BMJ Open  Implications of Rate Control If rate set by fastest event– slow everything down! Give damaged area a chance to become refractory and prevent retrograde transmission Image from Basic and Clinical Pharmacology, 12th ed. Other treatment options: Pacemakers lead -> Electrode battery -  Other treatment options: Implanted cardioverter & defibrillator Functions as pacemaker (heart rate maintenance) and defibrillator (detects ectopic-generated tachycardia) Cardioverter: restores all cells to baseline at the same time; allows normal SA-node induced automaticity Treatment option: Ablation of ectopic foci kill Xcells -> leads to scar tissue = possible re-entry loop Mostly supraventricular (atrial) arrhythmias Acquired arrhythmia post-MI; automaticity OR re-entrant loop around pulmonary veins Single foci (PAC); Multiple foci (Atrial fibrillation) Atrial Ablation Catheter- no need for open heart surgery Anticoagulation to prevent stroke Anesthesia Mapping to locate abnormal tissue Radiofrequency pulse or cryoablation to destroy abnormal tissue May need to repeat Anti-coagulant therapy indicated – WHY? Unit 4: Cardiac Electropathophysiology Hemostasis GANONG CH. 31 Learning Objectives Define hemostasis, thrombus, embolus Evaluate Vichow’s triad for coagulation risk Compare/Contrast normal blood flow with impaired flow following vessel damage Loading… Discuss the four steps of platelet activation and aggregation to form a clot Evaluate role of thrombin (Factor IIa) to promote platelet activation and fibrin formation Describe the coagulation cascade, differentiate between intrinsic, extrinsic, and common pathways Discuss role of Vitamin K in producing prothrombin (Factor II) Evaluate potential pathological consequences of untreated atrial fibrillation Suggest potential therapeutic mechanisms to prevent stroke, pulmonary embolism, or venous thromboembolism Hemostasis Definition: “Heme”— blood “Stasis”-- not moving. Stopped Physiological relevance for hemostasis: so you don't bleed out if you cut yourself) don't lose total blood volume balance between mumt (perfusion) VS stasis (prevent hemorrage)  Injury S triggen hypercoaguility = Sticky = Stasis Virchow’s triad of coagulation To have blood clotting, need: & 1) stasis 2) endothelial injury Loading… 3) hyper-coagulability ‘Normal’ Blood Flow branching anteriole ARTERY “Shear” stresses experienced by cells S Flow pattern changes depending on the geometry of blood vessel. In “straight” regions of vasculature, endothelial cells experience ordered laminar shear stress, while at or near branch points and vascular bifurcations, E - endothelial cells experience low or oscillatory shear stress. 3 ran into by RBCs * endothelium Injury “Shear stress” = stress resulting from forces applied parallel to the surface of the object Loss or alteration of shear stresses may trigger platelets to activate Image from Pan, S. (2009) Antiox Redox Signal 11:1669- 1682.  => harder to force flow or blood Restricted Blood Flow even-stasis 1 V - deformation A Why do platelets form a clot when not moving? 1) Stasis– mechanism unknowns 2) Activating factors– cause coagulation cascade  Platelet activating factors exposed - collagen-Tissue Fact = Von Willebrand (UWF) once activated: stick to eachother t clot promote clot form. b Thrombosis regulation i Tendoth · cell damage  What happens when blood platelets D vessel is ↳ · O damaged? 1. Damage & vasoconstriction Formnes a 2. Platelet activation and aggregation 3. Fibrin mesh production, clot Loading… RBC get stuck Soft stabilization StayWhereitI = want 4. Fibrinolysis and clot dissoluation - ↳ recycled  What are platelets? Formed in bone marrow from megakaryocytes (differentiated stem cells) Large, multi-nuclear colonies  Platelet Activation, overview Activation – ◦ attach to fibrin, ◦ put out filopodia, (sticky ◦ begin to flatten (lamellipodia), ◦ then spread after healled ↓ dissolved  Factors involved in platelet aggregation Endogenous Inhibitors: NO, prostacyclin (PGI2), adenosine, thrombomodulin, antithrombin Pro-aggregants: oInitiators- vWF, collagen, fibronectin oConspirators- GPIIb/IIIa, PAR1/PAR4, P2Y12, ADP, fibrinogen, TxA2 Figure from Bhatt, D.L. and Topol. E.J. (2003) Nature Reviews Drug Discovery  Platelet activation 1. Normal function, can lead to 2. then damage Platelet adhesion formation of and activation thrombi and (vWF, collagen exposed) emboli 3. Platelet Platelet aggregation triggers intrinsic pathway of coagulation cascade aggregation cascade (various factors, thrombin, Thrombi = blood clots etc.) Emboli = blood clots & other factors 4. Coagulation cascade triggered; thrombi and/or emboli produced  X dontneedor BABY ASPRIN = COX-1 Inhibitor > - prevents platelet activation - ↓ clot form. Platelet activation Cyclo-oxygenase 1 - secreted mechanisms Within vessel… 1. damaged endothelium - 2. collagen/vWF exposed endothelial cells X 3. platelet activated by GPIa/IIa and GPIb 4. activated COX-1 DAMAGE 5. thrombin (IIa) acts at PAR1/PAR4 6. produce TxA2 7. activate more platelets 8. cross-linking with fibrinogen and GPIIb/IIIa  Thrombin’s involvement (Factor IIa) jo contains its own activator Both platelet activation (PAR1/PAR4) R & fibrin production Thrombin is protease– cleaves N terminus of PAR1 receptor Reveals auto-ligand for activation  Fibrin fibrinogen writes ?cleave Pret * acta mesh 2A Precursor (precursor) & Pro-thrembin Cactivated) : thrombin = - O Creation of fibrin “mesh” to anchor clot DNM Coagulation cascade: intrinsic, extrinsic, dange get thrombin tissue and common pathways 2 pathways together I to come (common CAUSES: outside Hissuedamage * Istasis time Clot disintegration following vessel healing tPA = can be used in stroke/MI to break up clot and restore blood flow Inactive precursor * activated: FY) cuts mess oution of clot Goaled  body prepared to clot if when needed Pre-prothrombin (11) Vitamin K in the coagulation cascade + REDOX cycle proper blood circulation NEEPE Stable CO2 C mum-co2 * ↳ Vitamin K ↳ Prothrombin available "VKOR"  ↑ Pre-prothrombin Prothrombin Warfarin prevents Vit K deficiency Vit. K recycling (vegtables) I & through b VKORC1 coagulation abnormalities by enzyme prothrombin available not AN Outcomes for warfarin treatment? T COAG ↳ a prothromain · product don't clot ↳ thrombin (21 activation) A platelet activation - no M1 or stroke Expected ADR for warfarin? prevents reduction not able to form clot Y rapidly easy bruising · RECALL: Blood flow during A. Fib? MOST COMMON ERRHYTHMIA Uncoordinated atrial contraction (“quiver”) Blood remains in atria, not expelled STASIS ⑧ S Predispose to clot formation ↓ (L. Atria ( Left side clot > out - aorta , could go to coronary go tobrain Stroke = M1 Right side clot go to periphery = Ven Throm =ulmonary embolism Pulm. , art embolism Slung Images from CDC; http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_atrial_fibrillation.htm  SAME As BY Multiple mechanisms increase coagulability in A. Fib A fib most common arrhythmia Consequence of clot formation? How to prevent formation and/or dissolve clots?  A. Fib Complications Stroke  In vein , around valve = prevent back flow. majer clot) thrombus = Secretes smaller clots (emboli ↳ VIR D Venous thromboembolism. TRIAD imobility b/c : Stasis , hypencoagulability , endothelial in;