Cardiovascular 2: The Heart

1. Cardiovascular 2: The Heart Dr Gareth Noble

2. Objectives To cover in CVS 2 (): Overview of and heart Alterations in cardiac function Disorders of cardiac conduction and rhythm Heart failure Pharmacological management (Cardiotonic, Antiarrhythmic & antianginal agents)

3. Superficial Anatomy of the Heart

4. Internal Anatomy

5. Cardiac Muscle Cells

6. Contraction of the Heart Electrical activity is needed for contraction, which causes ejection of blood -- action potential across cell membranes The heart is autorhythmic -- contracts due to self generated APs 2 types of cardiac muscle cells contractile cells - 99%, do mechanical pumping, normally do not self generate autorhythmic cells - do not contract but generate and conduct the electrical activity

7. Contraction... Nerve and muscle have constant resting membrane potentials unless stimulated -- autorhythmic cells do not, they have PACEMAKER ACTIVITY (ie. Their membrane slowly depolarises between Aps until threshold is reached (see overhead)

8. Contraction... Cardiac cells capable of autorhythmicity are: Sinoartial node (SA); right atrial wall near opening of superior vena cava atrioventricular node (AV); base of right atrium near septum atrioventricular bundle; a tract of cells that orginate at AV Purkinje fibres; small terminal fibres that extend from the bundle of His, tree-like branches

9. Contraction... SA determines heart rate, what would happen if it �stopped�? AV takes over; latent pacemaker potential If the AV, stops but the SA and purkinje fibres do not? Complete heart block What happens if the purkinje fibres become more excitable than the SA node? Ectopic focus; premature AP thus normal can not be generated -- premature beat

10. Contraction... Spread of cardiac excitation must be co-ordinated for efficient pumping Has to satisfy 3 conditions Atrial excitation and contraction should be complete before the onset of ventricualr contraction Excitation of cariac-muscle fibres should be co-ordinated to assure that each heart chamber contracts as a unit to accomplish efficient pumping The pair of atria and pair of ventricles should be functionally co-ordinated so that both members of the pair contract simultaneously

11. Action Potentials in Skeletal and Cardiac Muscle

12. Resting Potential Of a ventricular cell: about �90 mV Of an atrial cell: about �80 mV

13. 3 Steps of Cardiac Action Potential Rapid depolarization: voltage-regulated sodium channels (fast channels) open As sodium channels close: voltage-regulated calcium channels (slow channels) open balance Na+ ions pumped out hold membrane at 0 mV plateau Repolarization: plateau continues slow calcium channels close slow potassium channels open rapid repolarization restores resting potential

14. The Conducting System

16. The Electrocardiogram

17. Features of an ECG P wave: atria depolarize QRS complex: ventricles depolarize T wave: ventricles repolarize

18. Time Intervals P�R interval: From start of atrial depolarization to start of QRS complex It is usually 0.12 to 0.20 seconds. A prolonged PR indicates a first degree heart block Q�T interval: From ventricular depolarization to ventricular repolarization A normal QT interval is usually about 0.40 seconds

19. Abnormal ECGs

20. The ECG has a wide array of uses: Determine whether the heart is performing normally or suffering from abnormalities (eg. extra or skipped heartbeats - cardiac arrhythmia). May indicate acute or previous damage to heart muscle (heart attacks) or ischaemia of heart muscle (angina). Can be used for detecting potassium, calcium, magnesium and other electrolyte disturbances. Allows the detection of conduction abnormalities (heart blocks and in bundle branch blocks). As a screening tool for ischaemic heart disease during an exercise tolerance test. Can provide information on the physical condition of the heart (eg: left ventricular hypertrophy, mitral stenosis). Can suggest non-cardiac disease (e.g. pulmonary embolism, hypothermia)

21. The Cardiac Cycle

22. Cardiac Cycle the period from the end of one contraction of the heart to the end of the next contraction each cycle is generated by the spontaneous generation of an Action Potential by the Sino-Atrial Node

23. Cardiac Cycle... the action potential spreads rapidly through both Atria bringing about contraction of the atrial muscle and stimulation of the Atrio-Ventricular Node At the AV node a delay of 0.1s allows Ventricular filling

25. Autonomic Innervation

26. Parasympathetic Stimulation SA Node Decreases the rate of depolarisation AV Node Increases the nodal delay (K+ permeability) Muscle Fibres Shortens the action potential, therefore weakening atrial contraction

27. Sympathetic Stimulation SA Node Adrenaline (Norepinephrine) decreases K+ permeability. Therefore increases HR AV Node Reduces the nodal delay Muscle Fibres Increases Ca++ , intensifies the contraction

28. CARDIAC DISORDERS

29. Cardiac Disorders Arrthymias: Most common cause of sudden adult death Deviation from normal sinus rhythm Angina: When heart blood demand exceeds supply Congestive Cardiac Failure: Inadequate contractions Myocardial Infarction (heart attack): Death of a segment of heart tissue

30. Arrhythias Atrial Ectopic Beats (extrasystoles) Atrial Flutter Sustained Atrial Fibrillation Paroxysmal Atrial Fibrillation Chaotic And Multifocal Atrial Tachycardia Regular Narrow QRS Tachycardias Broad QRS Complex Arrhythmias Ventricular Fibrillation His Bundle Arrhythmias Atrioventricular Block Bundle Branch Block Hemiblock Nonspecific Intraventricular Conduction Defects Sick Sinus Syndrome

31. Common Arrhythmias

32. Cardiac muscle has nerve and muscle properties MI common cause Build up of K+, cAMP, thromboxane A2 and free radicals believed to initiate Some are caused by abnormal number of electrical impulses: Enhanced: disease causing AV inherent pacemaker activity greater than SA Abnormal impulse conduction (heart block) causing ventricular premature beats due to damage to AV node (infarction) First, second or third degree (Slow � Complete)

33. Antiarrhythmic Drugs Classed according to effects on AP of cardiac cells plus MoA. 4 basic classifications (and several sub-classes) Class I: membrane stabilizing or anesthetic effect Class II: Beta-blockers Class III: Potassium channel blockers Class IV: Calcium channel blockers

34. Class I MoA: block the voltage-dependent sodium channels (dose-dependant) Class Ia (Quinidine, procainamide): MoA: block open or refractory state Na+ gates to slow down depolarisation, increase refraction period to prolong AP Route: Oral, IV Use on pts with ventricular arrhythmias Contra: Heart block, node dysfunction, cardiogenic shock, uncompensated heart failure Adverse Effects: Arrhythmias, N + V, hypersensitivity, thrombocytopenia and agranulocytosis.

35. Class Ib (lidocaine, mexiletine, phenytoin) MoA: Block voltage-dependent Na+ channels Decreasing AP duration Increasing refractory period Route: Lidocaine (IV); others oral or IV Use on pts with ventricular arrhythmias following MI Contra: Pts with SA node disorders, AV block and prophyria Adverse Effects: Hypotension, bradycardia, drowsiness, confusion, convulsions, paraesthesia.

36. Class Ic (Flecainide): MoA: blocks Na+ channels but without preference for refractory channels leading to a general reduction in excitability Route: Oral or IV Use on pts with ventricular tachyarrhymias Contra: heart failure, Hx of MI Adverse Effects: Dizziness, visual disturbances

37. Class II (Beta Blockers): Propranolol, Atenolol, bisprolol & metroprolol Act via an antagonist action of Beta-adrenoceptors found in the heart. MoA: blocking, to cause a decrease in heart rate, in cardiac contractile activity, and in mycocardial O2 demand Route: Oral or IV Use on pts with Angina, post-MI, arrhythmias, hypertension and anxiety Contra: asthmatic pts (beta1), bradycardia, hypotension, AV block, Congestive Cardiac Failure Adverse Effects: Bronchospasm, fatigue, insomnia, dizziness, cold extremities, brandycardia, hypotension, decrease gluscose tolerance in diabetic pts.

38. Class III (Bretylium, Aminodarone, Sotalol, Ibutilide): MoA: K+ channel antagonists to prolong the AP duration and refractory period Aminodarone � Na+ and Ca++ ch blockers; Sotalol � beta-blocker Route: IV or oral (depending on drug) Effective for ventricular arrhythmias Contra: AV block, bradycardia, thyroid dysfunction Adverse Effects: hypotension, N+V, thyorid dysfunction, liver damage, pulmonary disorders, photosensitivity, and neuropathy

39. Class IV � Verapamil (Calan), Amlopidine (Norvasc), Nicardipine (Cardene): MoA: Ca++ ch antagonists; need for contractions; affects coronary arteries (vasodilation); decreases AP duration Effective in Pain Mx of angina attack in variant and stable Angina Verapamil (Calan) used for arrhythmias due to its influence on the AP

40. Antiarrhythmia + Pt Management Perform pre-admin assessments: BP, pulse, respiratory rates and general health Include cardiac monitoring before and throughout Rx to determine reaction to the drug Order lab tests: Renal and hepatic function Complete blood count Serum enzyme and electrolytes levels Any significant changes (red flags) need to be referred

41. Angina A clinical syndrome due to myocardial ischemia characterized by precordial discomfort or pressure, typically precipitated by exertion and relieved by rest or sublingual nitroglycerin.

42. Stable (classical) Angina: Due to fixed stenosis of the coronary arteries Brought on by exercise and stress Unstable Angina: Can occur suddenly at rest Becomes progressively worse (an increase in number and severity of attacks) Coronary atherosclerosis; coronary artery spasm, transient platelet aggregation and coronary thrombosis, endothelial injury, coronary vasoconstriction can all causative pathologies Variant Angina: Occurs at rest at the same time of day, due to coronary artery spasm Characterised by an elevated ST segment on ECG

43. Pharmacological Agents Stable Angina: Long acting Nitrates, antiplatelets, Beta-blockers, Ca++ Channel Blockers, or K+ agonists Unstable Angina: Antiplatelets, Heparin, Standard antianginal agents

44. Nitrates Isosorbide (Isordil) � used for protection and long-term Rx Nitroglycerin (Nitrostat) � sublinginal; pain relief from attack IV nitrates can be used for hypertension Rx�s

45. MoA: Are prodrugs; form Nitric Oxide that increases levels of cGMP, ? activation of Protein Kinase G ?contractile proteins (muscle) are phosphorylated ? dilation of systemic veins ? decrease O2 demand Additional dilation of coronary arteries to increase O2 supply to myocardium

46. Route: Sublingual, Oral, transdermal patches, some IV Contra: hypersensitivity, hypotension Adverse Effects: postural hypotension, tachycardia, headache, flushing, dizziness Rx: avoid nitrate tolerance, 8 hr break needed

47. Nitrates + Pt management Monitor for frequency and severity of attacks Should decrease or disappear with Rx Any chest pain that does not get relief from 3 doses of nitroglycerin given every 5 mins should be highlighted Be aware of tolerance.

48. Calcium Channel Blockers MoA: discussed previously, Class IV antiarrhythmias Route: Oral Used for angina, hypertension, arrhythmias and Raynaud�s syndrome Contra: Cardiogenic shock, arotic stenosis, severe heart failure, pts on beta-blockers (risk of AV block), severe bradycardia. Adverse Effects: not serious; dizziness, N+Dia, constipation, bradycardia, skin irritation, and nervousness

49. Ca+ Ch Antagonists + Pt Management Monitor for signs of heart failure: Dyspnea, Wt gain, peripheral oedema, abnormal lung sounds (crackles) and vein distention May be taken without food; if GI disturbance happens then take with food

50. Potassium-channel agonists Nicorandil � only licensed MoA: Activations K+ ch to cause an outflux of K+ leading to hyperpolarisation ? inhibiting the influx of Ca++ = relaxation! Route: Oral Use for prophylaxis of angina Contra: Cardiogenic shock, left ventricular failure, hypotension Adverse Effect: Headache, cutaneous vasodilation, N+V

51. Cardiac Failure Results from cardiac and metabolic disorders Causes a number of neurohormonal responses: Increased secretion of catecholamines (epinephrine + norepi) by sympathetic NS ? increase HR and vasoconstriction Activation of Renin-Angiotensin-Aldosterone system because of decreased BF to kidneys ? increased BP Remodeling of cardiac cells ? hypertrophy ? increase demand for O2 Described in terms of area of initial ventricular dysfunction: Left VD: most common; decrease cardiac output due to decreased ejection Right VD: decrease output to the lungs for gaseous exchange

52. Pharmacological Agents Agents of choice: Cardiotonic and diuretics Recently, ACE-inhibitors and beta-blockers are becoming the weapon of choice.

53. Cardiotonic (inotrophic) Agents 2 main ways: Increase cardiac output by increasing the contraction of the myocardium Decrease the conduction speed of cAP by influencing the SA and AV nodes. Main agents are Cardiac Glycosides and Phosphodiesterase Antagonists

54. Cardiac Glycosides Digoxin (Lanoxin) most common MoA: Inhibit Na+/K+ ATPase membrane pump ? increased intracellular Na+ levels ? decreasing Ca++ pumped out ? intercellular Ca++ raises ? increased availability for contraction ? increase contraction Alter electrical activity; slow AV node conduction Can cause vasoconstriction to increase BP

55. Route: Oral Contra: Heart block, ventricular arrhythmias Adverse Effects: Arrhythmias, anorexia, N+V+Dia, visual disturbances, abdominal pain NB: Absorption rates are slowed down when taken with food but does not affect amount of agent available for distribution

56. Phosphodiesterase Inhibitors Developed to counteract the adverse effects of Cardiac Glycosides Causes degradation of cAMP; therefore if we inhibit this enyzme it raises cAMP levels that assists in myocardial contractions Route: IV Use on severe acute heart failure that are resistant to other agents Adverse Effects: Arrhythmias, N+V, liver damage, abdominal pain.

57. MI Ischemic myocardial necrosis usually resulting from abrupt reduction in coronary blood flow to a segment of myocardium. MI is predominantly a disease of the LV MI is an acute medical emergency, and outcome is significantly influenced by rapid diagnosis and treatment. Treatment is designed to relieve distress, reverse ischemia, limit infarct size, reduce cardiac work, and prevent and treat complications

58. Pharmacological Agents Optimal early management vital as 50% of deaths occur in 3-4hrs of onset Need to alleviation of pain, stabilization of heart rhythm and BP, administration of a thrombolytic drug if possible Aspirin 160 to 325 mg (if not contraindicated) should be given at presentation and daily indefinitely thereafter. Morphine 2 to 4 mg IV, is highly effective for the pain of MI, but be aware of its depression of respiration

59. Thrombolytic Rx: Streptokinase, anistreplase, alteplase, and reteplase (see last weeks lecture notes) Concomitant antithrombotic therapy: Addition of heparin to prevent thrombosis complications Drugs to reduce cardiac work: Beta-blockers; ACE-inhibitors; Vasodilators

60. Textbook References Karch AM (2006) Focus on Nursing Pharmacology, 3rd Edition. Lippincott Williams & Wilkins Rang et al (2003) Pharmacology, 5th Edition. Churchill Livingstone. Lilley et al (2005) Pharmacology and the Nursing Process, 4th Edition. Mosby Page et al (2002) Integrated Pharmacology, 2nd Edition. Mosby. Martini (2005) Principles of Anatomy and Physiology, Pearson Education Publishers