Physiology of the Cardio-Vascular System Lecture 1 / The Myocardium Dr. Sherwan R Sulaiman MD / MSc / PhD 2011-2012

1. Physiology of the Cardio-Vascular SystemLecture 1 / The MyocardiumDr. Sherwan R SulaimanMD / MSc / PhD2011-2012

2. Structure of the Heart • Adult human heart = 300-350 g • Built upon a “collagenous skeleton” located at atrioventricular junction (fibrotendinous ring) • The ring isolates the atria electrically from the ventricles, except at the bundle of His

3. Fibrous skeleton of the heart

4. Cardiac and Skeletal MusclesSimilarities • Both- Striated muscle • Both use proteins actin and myosin • Both contract in response to an action potential on the sarcolemmal membrane

5. Cardiac and Skeletal MusclesDifferences Skeletal muscle • Neurogenic (motor neuron-end plate-acetylcholine) • Insulated from each other • Contracts in all or none fashion • Short action potential Cardiac Muscle • Myogenic (action potential originates within the muscle) • Gap-junctions • Action potential is longer

6. Cardiac Muscle Fiberscontractile or conductile • Contractile Action potential leads to vigorous force development and/or mechanical shortening • Conductile initiation or propagation of action potentials

7. Conduction SystemConductile Fibers • Sinoatrial (SA) node 100-110/min • Atrioventricular (AV) node 40-60/min • AV bundle (Bundle of His) 20-40/min • Left and right bundle branch • Purkinje fibers (rapid conduction) 20-40/min Specialised cardiac muscle cells

8. AV node (node of Tawara) irregularly arranged branching fibers Bundle of His unbranched fibers

9. endothelium endocardium Purkinje fibers Ventricular myocardium Purkinje fibers

10. Nodal Cells • Smaller than contractile cells or Purkinje cells • Low propagation velocity(0.05m/sec) • Reduced density of gap junctions • Lack fast Na channels

11. Purkinje Cells • Larger than ordinary cardiac fibers and bundle fibers • Conduct action potentials four times faster than a ventricular myocyte(4m/sec) • May be binucleate • Few myofibrils • Vacuous cytoplasm (filled with glycogen) • Subendocardial location • Linked to cardiac fibers and bundle fibers by gap junctions and desmosomes

12. Excitation and Contraction of Cardiac Myocyte

13. Cardiac Myocyte Myofiber:is a group of myocytes held together by surrounding collagen connective tissue excess collagen, may cause LV diastolic dysfunction (e.g. left ventricular hypertrophy)

14. endothelium endocardium Purkinje fibers Ventricular myocardium Purkinje fibers

16. Cardiac Myocyte • 10-20 mm in diameter • 50-100 mm long • Single central nucleus • The cell is branched, attached to adjacent cells in an end-to-end fashion (intercalated disc) • Desmosomes (proteoglycan glue) • Gap junction (region of close apposition)

17. Gap Junctions • Low resistance connections • Small pores in the center of each gap junction • Allows ions and small peptides to flow from one cell to another • Action potential is propagated to adjacent muscle cells Heart behaves as a single motor unit

18. Theoretically, An ion inside an SA nodal cell could travel throughout the heart via the gap junctions

19. Sarcomere Basic contractile unit within the myocyte • Refers to the unit from one Z band to the next • Resting length:1.8-2.4 mm • Composed of interdigitating filaments • Thick myosin protein • Thin actin protein

20. T: T tubules mit: mitochondria g: glycogen contractile unit: sarcomere Z line: the actin filaments are attached I: band of actin filaments, titin and Z line A: band of actin-myosin overlap H: clear central zone containing only myosin

21. Sarcolemma (sarco = flesh; lemma = thin husk) • Each cell is bounded by a complex cell membrane • Composed of a lipid bilayer • Hydrophilic heads • Hydrophobic tails • Impermeable to charged molecules (barrier for diffusion) • Contains membrane proteins, which include receptors, pumps and channels

22. Sarcolemma contains a number of ion channels and pumps that contribute to overall Ca2+ levels within the myocyte

23. Transverse Tubular System(T-tubules) • The sarcolemma of the myocyte invaginates to form an extensive tubular network • Extends the extracellular space into the interior of the cell • Transmit the electrical stimulus rapidly (well developed in ventricular myocytes but is scanty in atrial and purkinje cells)

24. Mitochondria • Generate the energy in the form of adenosine triphosphate (ATP) • Maintain the heart’s contractile function and the associated ion gradients

25. Sarcoplasmic Reticulum (SR) • A fine network spreading throughout the myocytes • Demarcated by its lipid bilayer • Close apposition to the T tubules • Junctional sr • Longitudinal SR

26. JSR: junctional SR LSR: longitudinal SR

27. Subsarcolemmal Cisternae Junctional SR • the tubules of the SR expand into bulbous swellings • contains a store of Ca2+ ions • release calcium from the calcium release channel (ryanodine receptor) to initiate the contractile cycle

28. Longitudinal or Network SR • consists of ramifying tubules • concerned with the uptake of calcium that initiates relaxation • achieved by the ATP-requiring calcium pump (SERCA= sarcoendoplasmic reticulum Ca2+ -ATPase)

29. Cardiac Cycle • Systole • isovolumic contraction • ejection • Diastole • isovolumic relaxation • rapid inflow- 70-75% • diastasis • atrial systole- 25-30%

31. Onset of Ventricular Contraction • Isovolumic contraction • Tricuspid & Mitral valves close • as ventricular pressure rises above atrial pressure • Pulmonic & Aortic valves open • as ventricular pressure rises above pulmonic & aortic artery pressure

32. Ejection of blood from ventricles • Most of blood ejected in first 1/2 of phase • Ventricular pressure peaks and starts to fall off • Ejection is terminated by closure of the semilunar valves (pulmonic & aortic)

33. Ventricular Relaxation • Isovolumetric (isometric) relaxation-As the ventricular wall relaxes, ventricular pressure (P) falls; the aortic and pulmonic valves close as the ventricular P falls below aortic and pulmonic artery P • Rapid inflow-When ventricular P falls below atrial pressure, the mitral and tricuspid valves will open and ventricles fill

34. Ventricular Relaxation (cont) • Diastasis-inflow to ventricles is reduced. • Atrial systole-atrial contraction actively pumps about 25-30% of the inflow volume and marks the last phase of ventricular relaxation (diastole)

35. Ventricular Volumes • End Diastolic Volume-(EDV) • volume in ventricles at the end of filling • End Systolic Volume- (ESV) • volume in ventricles at the end of ejection • Stroke volume (EDV-ESV) • volume ejected by ventricles • Ejection fraction • % of EDV ejected (SV/EDV X 100%) • normal 50-60%

40. Terms • Preload-stretch on the wall prior to contraction (proportional to the EDV) • Afterload-the changing resistance (impedance) that the heart has to pump against as blood is ejected. i.e. Changing aortic BP during ejection of blood from the left ventricle

41. Atrial Pressure Waves • A wave • associated with atrial contraction • C wave • associated with ventricular contraction • bulging of AV valves and tugging on atrial muscle • V wave • associated with atrial filling

42. Function of Valves • Open with a forward pressure gradient • e.g. when LV pressure > the aortic pressure the aortic valve is open • Close with a backward pressure gradient • e.g. when aortic pressure > LV pressure the aortic valve is closed

43. Heart Valves • AV valves • Mitral & Tricupid • Thin & filmy • Chorda tendineae act as check lines to prevent prolapse • papillary muscles-increase tension on chorda t. • Semilunar valves • Aortic & Pulmonic • stronger construction

44. Valvular dysfunction • Valve not opening fully • stenotic • Valve not closing fully • insufficient/regurgitant/leaky • Creates vibrational noise • aka murmurs

45. Heart Murmur Considerations • Timing • Systolic • aortic & pulmonary stenosis • mitral & tricuspid insufficiency • Diastolic • aortic & pulmonary insufficiency • mitral & tricuspid stenosis • Both • patent ductus arteriosis • combined valvular defect

46. Law of Laplace • Wall tension = (pressure)(radius)/2 • At a given operating pressure as ventricular radius  , developed wall tension . •  tension   force of ventricular contraction • two ventricles operating at the same pressure but with different chamber radii • the larger chamber will have to generate more wall tension, consuming more energy & oxygen • Batista resection • How does this law explain how capillaries can withstand high intravascular pressure?

47. Terminology • Chronotropic (+ increases) (- decreases) • Anything that affects heart rate • Dromotropic • Anything that affects conduction velocity • Inotropic • Anything that affects strength of contraction • eg. Caffeine would be a + chronotropic agent (increases heart rate)

48. Control of Heart Pumping • Intrinsic properties of cardiac muscle cells • Frank-Starling Law of the Heart • Within physiologic limits the heart will pump all the blood that returns to it without allowing excessive damming of blood in veins • heterometric & homeometric autoregulation • direct stretch on the SA node

49. Mechanism of Frank-Starling • Increased venous return causes increased stretch of cardiac muscle fibers. (Intrinsic effects) • increased cross-bridge formation • increased calcium influx • both increases force of contraction • increased stretch on SA node • increases heart rate

50. Heterometric autoregulation • Within limits as cardiac fibers are stretched the force of contraction is increased • More cross bridge formation as actin overlap is removed • More ca++ influx into cell associated with the increased stretch