CARDIOVASCULAR PHYSIOLOGY

1. CARDIOVASCULAR PHYSIOLOGY STUDENT MANUAL Dr. Guido E. Santacana

2. CARDIOVASCULAR PHYSIOLOGYLECTURES STUDENT LECTURE NOTEBOOK Guido E. Santacana Ph.D. DEPT. of PHYSIOLOGY

3. INTRODUCTION TO CARDIOVASCULAR PHYSIOLOGY GENERAL ASPECTS OF THE CARDIOVASCULAR SYSTEM

4. MAIN FUNCTIONS OF THE CIRCULATORY SYSTEM • Transport and distribute essential substances to the tissues. • Remove metabolic byproducts. • Adjustment of oxygen and nutrient supply in different physiologic states. • Regulation of body temperature. • Humoral communication.

5. THE MAIN CIRCUIT COLLECTING PUMP TUBULES DISTRIBUTING THIN VESSELS TUBULES

6. ELASTIC TISSUE MUSCLE Pressure Profile of the Circulatory System

7. Distribution of Blood in the Circulatory System

8. Organization in the Circulatory System SERIES AND PARALLEL CIRCUITS

9. CARDIAC ELECTROPHYSIOLOGY LECTURE NOTEBOOK Guido E. Santacana Ph.D.

10. EK = -60 LOG ([Ki]/[Ko]) = -94mv ENa = -60 LOG ([Nai]/[Nao]) = +70mv PK (K+)o + PNa(Na+)o + PCl(Cl-)i Em = RT/F ln PK (K+)I + PNa(Na+)i + PCl(Cl-)o GENESIS OF THE MEMBRANE POTENTIAL AND EQUATIONS TOREMEMBER!!

11. THE RESTING MEMBRANE POTENTIAL OF THE CARDIAC CELL If membrane permeable only to K+ If membrane permeable To both Na+ and K+ If membrane permeable To Na+, K+ plus with A Na+/K+ Pump

12. EXTRACELL. INTRA-CELL. Em 145Mm 15Mm Na+ 70mv Ca++ 10-7 M 132mv 3Mm K+ -100mv 5Mm 145Mm WHY NOT Na+ 0R Ca++ FOR THE CARDIAC CELL MEMBRANE POTENTIAL ?

13. 0 0 mv mv -80mv -80mv 0 mv -80mv ACTION POTENTIALS FROM DIFFERENT AREAS OF THE HEART ATRIUM VENTRICLE SA NODE time

14. ELECTROPHYSIOLOGY OF THE FAST RESPONSE FIBER

15. Na+ Na+ m m m A B h h -65mv -90mv Na+ Na+ m m C D h h 0mv +20mv Na+ m E h +30mv PHASE 0 OF THE FAST FIBER ACTION POTENTIAL Chemical Gradient Electrical Gradient

16. K+ CURRENTS AND REPOLARIZATION • PHASE 1-TRANSIENT OUTWARD CURRENT (TOC) Ito • PHASE 1-3-DELAYED RECTIFIER CURRENT IK • PHASE 1-4-INWARDLY RECTIFIED CURRENT IKl

17. THE PLATEAU PHASE AND CALCIUM IONS OPEN CLINICAL VALUE L Ca++ CHANNELS Ca++ BLOCKERS +10MV T Ca++ CHANNELS -20MV NO (physiological)

18. EFFECTS OF Ca++ CHANNEL BLOCKERS AND THE CARDIAC CELL ACTION POTENTIAL ACTION POTENTIAL CONTROL DILTIAZEM 10 uMol/L 30 uMol/L 10 30 CONTROL 10 FORCE 30 TIME

19. Clinical CorrelationEarly After-Depolarizations Torsades de Pointes 0mV -60mV -90mV Early After-Depolarization

20. OVERVIEW OF SPECIFIC EVENTS IN THE VENTRICULAR CELL ACTION POTENTIAL

21. Overview of Important Channels in Cardiac Electrophysiology

22. More Channels!

23. ELECTROPHYSIOLOGY OF THE SLOW RESPONSE FIBER 0 2 0 mvs -40 3 4 ERP RRP -80 time (msec) RECALL: INWARD Ca++ CURRENT CAUSES DEPOLARIZATION

24. CONDUCTION OF THE ACTION POTENTIAL IN CARDIAC FIBERS LOCAL CURRENTS - - - - - - - - + + + + + + + - - - - - - - - + + + + + + + + FIBER A FIBER B DEPOLARIZED ZONE POLARIZED ZONE

25. CONDUCTION OF THE ACTION POTENTIAL • FAST RESPONSE: Depends on Amplitude,Rate of Change,level of Em. • SLOW RESPONSE: Slower conduction.More apt to conduction blocks. • WHAT ABOUT MYOCARDIAL INFARCTS AND CONDUCTION?

26. EFFECTS OF HIGH K+ ON CONDUCTION AND AP OF FAST FIBERS 0MV AP-AMP Em K+=3mM K+=7mM K+=14mM 0MV K+=16mM K+=3mM WHAT HAS VARIED? LOOK AT: Em,AP SLOPE-AMPLITUDE

27. HIGH K+ AND m/h Na+ GATES LOWER Em HIGH K+ CLOSED h GATES (SOME) LOWER AP AMPLITUDE LOWER Na+ ENTRY

28. EXCITABILITY OF FAST AND SLOW FIBERS FAST m/h GATES COMPLETE RESET AFTER PHASE 3 CONSTANT AND COMPLETE RESPONSE IN PHASE 4 SLOW LONG RELATIVE REFRACTORY PERIOD. POST-REPOLARIZATION REFRACTORINESS

29. AFTER THE EFFECTIVE OR ABSOLUTE REFRACTORY PERIOD (FAST FIBER) 0 MV ARP -80 RRP TIME

30. POST-REPOLARIZATION REFRACTORINESS (SLOW FIBER) 200 MSEC C 0 B MV A -60 POSTREPO TIME

31. RHYTMICITY AUTOMATICITY SA NODE AV NODE ectopic foci IDIOVENTRICULAR- PACEMAKERS

32. THE SA NODE PACEMAKER POTENTIAL

33. CHARACTERISTICS OF THE PACEMAKER POTENTIAL RECALL: PHASE 4-PACEMAKER POTENTIAL(PP) OBSERVED HERE. FREQUENCY DEPENDS ON: THRESHOLD,RESTING POTENTIALS AND SLOPE OF THE PP

34. CAUSES OF THE PACEMAKER POTENTIAL K+ if iCa OUT IN iK Na+ Ca++

35. THE PACEMAKER POTENTIAL CURRENTS AFTER DEPOLARIZATION iCa if iK WHICH CURRENT WILL BE MORE AFFECTED BY ADRENERGIC STIMULATION? WHICH BY CHOLINERGIC STIMULATION?

36. LOOKING AT THE PACEMAKER CURRENTS voltage iK if ionic currents iCa

37. EFFECTS OF Ca++ CHANNEL BLOCKERS ON THE PACEMAKER POTENTIAL NIFEDIPINE CONTROL (5.6 X 10-7 M) 0 MV -60 TIME

38. OVERDRIVE SUPRESSION AND AUTOMATICITY OF PACEMAKER CELLS • Na+/K+ ATPase ENHANCEMENT BY HIGH FREQUENCY. • CONSEQUENT HYPERPOLARIZATION. • SUPRESSION OF AUTOMATICITY. • RECOVERY TIME REQUIRED. • ECTOPIC FOCI/SICK SINUS SYNDROME.

39. THE CONDUCTION SYSTEM OF THE HEART

40. BACHMANS PATH RA LA SAN AN REGION INTERNODAL PATHS AV NODE N REGION NH REGION BH LV RV RIGHT BUNDLE BRANCH LEFT BUNDLE BRANCH ATRIAL AND ATRIOVENTRICULAR CONDUCTION

41. AV NODE NA REGION FAST CONDUCTION LONGER PATH SHORTER PATH N REGION SLOW CONDUCTION NH REGION FAST CONDUCTION REFLECTED IN THE P-QRS INTERVAL OF THE ECG NODAL DELAY REGION OF DELAY

42. UNI AND BIDIRECTIONAL BLOCKCLINICAL IMPLICATIONS B A ANTEGRADE BLOCK NORMAL D C REENTRY UNIDIRECTIONAL BLOCK BI

43. Clinical CorrelationRe-entry TachycardiasParoxysmal Supraventricular Tachycardia Ischemic Tissue Fast Pathway Slow Pathway Fast Pathway Slow Pathway Normal Conduction Re-Entry Circuit

44. AV NODE AND AV BLOCKS FOCUS ON N REGION ECG NORMAL 1ST DEGREE PROLONGUED AV CONDUCTION TIME 2ND DEGREE 1/2 ATRIAL IMPULSES CONDUCTED TO VENTRICLES 3RD DEGREE VAGAL MEDIATION IN N REGION/COMPLETE BLOCK

45. CONDUCTION IN THE VENTRICLES • PURKINJE FIBERS WITH LONG REFRACTORY PERIODS. • PROTECTION AGAINST PREMATURE ATRIAL DEPOLARIZATIONS AT SLOW HEART RATES. • AV NODE PROTECS AT HIGH HEART RATES.

46. QUICK QUIZ Which of the following is not true about the effect of acetylcholine (Ach) in the electrophysiology of the cardiac pacemaker cell: A. Ach lowers the magnitude of the minimum repolarization potential. B. Ach lowers the slope of the pacemaker potential. C. Ach decreases the SA node frequency. D.Ach increases the ik current of the pacemaker cell. E. Ach decreases the iCa++ current of the pacemaker cell. The main reason why the AV node filters out high stimulation frequencies from the SA node is: A. The long pathway that the stimulus must traverse in the AV node. B. Post Repolarization Refractoriness of AV nodal cells. C. The AV nodal cell is always hyperpolarized D. Ca++ is the main ion in Phase 0 of the AV nodal cell. E. I need to review this section very fast.

47. CARDIAC MECHANICS MAIN THEMES THE HEART AS A PUMP THE CARDIAC CYCLE CARDIAC OUTPUT CHAPTER 3 B&L

48. LENGHT/ TENSION AND THE FRANK-STARLING RELATION LEFT VENTRICULAR PRESSURE INITIAL MYOCARDIAL FIBER LENGHT LEFT VENTRICULAR END-DIASTOLIC VOLUME

49. PRELOAD AND AFTERLOAD IN THE HEART • INCREASE IN FILLING PRESSURE=INCREASED PRELOAD • PRELOAD REFERS TO END DIASTOLIC VOLUME. • AFTERLOAD IS THE AORTIC PRESSURE DURING THE EJECTION PERIOD/AORTIC VALVE OPENING. • LAPLACES’S LAW & WALL STRESS, WS = P X R / 2(wall thickness)

50. LEFT VENTRICULAR PRESSURE AND AFTERLOAD AT CONSTANT PRELOADS EFFECT OF INCREASED PRELOAD LEFT VENTRICULAR PRESSURE PEAK ISOMETRIC FORCE AFTERLOAD (aortic pressure) NOTE: WHAT HAPPENS IN THE NORMAL HEART VS ONE IN THE LAST PHASES OF CARDIAC FAILURE?