Lecture 10

• 1. Calcium binds to ryanodine receptor on SR
  2. causes release of Ca from SR into cytosol
  3. cytosolic calcium increases

  
• 1. calcium binds to troponin
  2. changes the shape of tropomyosin
  3. exposes binding sites for actin

  
• 1. myosin heads bind actin - requires ATP
  2. myosin exerts, pulling action on actin
  3. initiates muscle contraction

  
• Hydraulic function:

  1. generation of force allow ejection of blood
  2. longitudinal filament shortening so horizontal and circumferential muscle thickening
  3. recuces LV chamber diameter and causes further ejection

  
• Cardiac reserve = maximal cardiac output - cardiac output at rest
• sarcomere function:

  1. small changes in cardiac sarcomere length result in large variations in tension
  2. physiological stretch, ventricular sarcomere length on ascending limb
  3. stretching LV aid contraction
  4. LV end-diastolic vol determines how stretched LV wall is
  5. increased preload = increased cardiac performance
• 1. muscle stretches diameter of myofibrils reduce
  2. thick and thin filaments closer together
  3. more myosin heads interact w/ actin
  4. more contraction occur
• frank-starling curve dynamic:

  1. left shift = exercise, pharmacological stimulation
  2. right shift = pharmacological depression, myocardical loss
• 1. noradrenaline and adrenaline stimulate cAMP
  2. more calcium enter cell = greater cross-bridge linking in sarcomeres
  3. frank-starling shifts left
• ejection fraction = stroke vol / end-diastolic vol

  1. physiological EF 55-75%
  2. exercose, EF reach 90%
  3. failing heart shows reduced EF
• Myocardium diseased = less contractions

  1. ischaemia -> scarred myocardium
  2. viral infection/alcohol -> wall thinning
  3. increased afterload -> chronic high output
• when heart fails compensated by:

  1. SNS overactivates
  2. RAAS kicks in
• Compensation for heart failure:

  1. measures raise preload but overtime heart stretches
  2. LV stetch exceeds physiological levels so move to descending limb of sarcomere tension curve

  
• Most initial treatment for heart failure:

  1. lungs full of fluid from failing LV so giving oxygen
  2. diuretics due to the fluid in chest, reduce preload to shift normal frank-starling curve