How does the Heart Work?

Question 1

At the _level of the myocyte and myofibri_l what are the 2 key determinants of contractile performance?

Answer 1

1. Calcium handling
2. Calcium sensitivity

Question 2

Name at least 3 factors that influence the calcium sensitivity (EC50) of cardiac muscle

Answer 2

1. pH
2. Temperature
3. Caffeine
4. Sarcomere Length
5. Contractile Protein Phosphorylation

*Changes in these factors typically result in decreased contractile strength/velocity*

Question 3

What is length-tension relationship as it relates to cardiac muscle?

Answer 3

Further a muscle fiber is stretched increases the strength with which it contracts.

• Think of a rubber band

e.g. - When diastolic volume increases the heart shortens more (yeilding a larger ejection fraction/stroke volume)

Question 4

Frank-Starling Effects

1. What is the effect of increasing preload force on contraction?

Answer 4

Greater the volume of blood entering the heart during diastole (end-diastolic volume) ->

Greater the volume of blood ejected during systolic contraction (stroke volume) and vice versa.

*Due to length-tension relationship – increase the fiber length -> force of contraction for a given stimulus is increased*

Question 5

What is the role of Troponin I?

Answer 5

• It the inhibitory troponin (hence the “I”)
  
  • Prevents the troponin complex from allowing tropomysin (on the actin) to bind the ATP head of the myosin

Question 6

1. What is an inotrope?
2. What is a positive inotrope?
3. What is a negative inotrope?

Answer 6

1. An inotrope is an agent that alters the force or energy of muscular contractions.
2. Positive: increase the strength of muscular contraction
3. Negative: weaken the force of muscular contractions

Question 7

List the 6 major responses of the heart muscle to beta adrenergic stimulation

Answer 7

1. Phosphorylation of Ca channels in the SA node cells
2. Phosphorylation of Ca channels in ventricular cells
3. Phosphyrylation of Na pump
4. Phosphorylation of Phospholamban
5. Phosphorylation of FKB
6. Phosphorylation of Troponin I

Question 8

What is the effects of phosphorylating the calcium channels of the SA node cells?

Answer 8

Increased Heart Rate (HR) -> improved cardiac output (co)

• CO = HR x SV (stroke volume)

Question 9

What is the effect of phosphorylation of calcium channels in ventricular cells?

Answer 9

• Increased calcium entry into the cell
• Increased force contraction
  
  • Leads to imprved ejection fraction (EF)
    
    • Otherwise known as (+) inotropy

Question 10

What are the effects of phosphorylating the Na pump in cardiac cells?

Answer 10

• Increases Ca efflux (via Na-Ca exchange)
  
  • Leads to Enhanced relaxation and diastolic filling

Question 11

What are the effects of phosphorylating phospholamban?

Answer 11

• Disinhibition of SR calcium pump (SERCA2)
• Increased SR calcium load
  
  • Leads to improved diastolic filling

Question 12

What is the effect of phosphorylating FKB?

Answer 12

• Enhances Ryr receptor mediated calcium release
  
  • Leads to enhanced contractility

Question 13

What is the effect of phosphorylating of Troponin I?

Answer 13

• Decreases CA affinity for Troponon C (C for calcium)
  
  • Leads to enhanced relaxation

Question 14

What accomodations does our heart make when we wake up/get out of bed?

Answer 14

Postural accomodation

• Venous pump via skeletal musculature
  
  • Increased venous return
    
    • Increased EDV (end diastolic volume aka pre-load)
      
      • Increased SV (stroke volume)

Question 15

What physiologic changes occur during isotonic execises as it relates to the heart?

(Isotonic excercise - jogging, non resistance excercise)

Answer 15

Decreased peripheral vascular resistance

• Increased vnous return (Frank-Starling relationships)
  
  • Increase heart rate
    
    • Increase inotropy

Question 16

What is the physiologic response to isometric execise as it relates to the heart?

Isometric = weight training

Answer 16

Increased peripheral vascular resistance (to maintain blood flow to execrising muscle group)

• Increased HR
  
  • No increase in CO