CPR 7.06, 7.09, 7.10 Cardiac Muscle Mechanics and Responses

Question 1

At otherwise constant conditions; Increased Pre-load will have what effect on…

• Magnitude of shortening
• Force of contraction
• Velocity of shortening

Answer 1

• Increased Magnitude of shortening (same minimum)
• Increased Force of contraction
• Increased Velocity of shortening

Question 2

At otherwise constant conditions; Increased Afterload will have what effect on…

• Magnitude of shortening
• Velocity of shortening

Answer 2

• Decreased magnitude of shortening (longer minimum length)

- Decreased velocity of shortening.

Question 3

At otherwise constant conditions; Increased Inotropy will have what effect on…

• Magnitude of shortening
• Rate and Force of contraction
• Velocity of shortening

Answer 3

• Increased magnitude of shortening (decrease end systolic length)
• Increased rate and force of contraction
• Increased velocity of shortening.

Question 4

Describe the body’s response to an Increased Preload in terms of EDV and SV as well as Afterload and ESV

Answer 4

↑ in Preload causes an ↑ SV, attenuated by compensatory ↑ in Afterload which causes an ↑ ESV.

Question 5

Describe the body’s response to an Increased Afterload in terms of ESV and SV as well as Preload and EDV

Answer 5

↑ in Afterload causes a ↓ SV, attenuated by compensatory ↑ in Preload which causes an ↑ EDV.

Question 6

Describe the body’s response to an Increased Inotropy in terms of SV and EF as well as Preload and EDV.

Answer 6

↑ in Inotropy causes an ↑ SV, attenuated by compensatory ↓ EDV (preload). Will also result in ↑ EF.

Question 7

How would reduced after load benefit a pt. in heart failure?

Answer 7

Reduced Afterload leads to a secondary decrease in preload, particularly in the presence of heart failure

Question 8

How would enhanced isotropy benefit a pt. in heart failure?

Answer 8

Enhancing ventricular Inotropy increases SV and decreases Preload, particularly in acute heart failure.

Question 9

Describe the mechanism by which calcium entry into myocytes regulates cardiac contraction.

Answer 9

largely regulated by phosphorylation of L-type calcium channels.

(a) Gs: NE/Epi→ β adrenoreceptor→ Gs Protein coupled receptor activate AC→ ↑ cAMP → Activate Protein Kinase A→ PKA phosphoarylates L type calclium channels and allows increased calclium influx during AP’s→ ↑ Inotropy
(b) Gi: ACh→ M2 receptors→ Gi protein coupled receptor Inhibits AC and thus ↓ cAMP→ ↓ Inotropy.
(1) Adenosine binds to A1 receptors that are also coupled to Gi protein.

Question 10

Describe the mechanism by which calcium release from the SR regulates cardiac contraction.

Answer 10

↑ Calcium release by SR→ ↑ Inotropy.

(a) Gs: ↑ cAMP and PKA phosphorylation of SR leads to ↑ Calcium release→ ↑ Inotropy.
(b) Gq: NE binds α1-adrenoreceptors/ANG-II binds AT1 receptors/Endothelin-1 binds ETA receptors→ Stimulates PL-C to form IP3 → Stimulates Ca++ release by SR→ ↑ Inotropy.

Question 11

Describe the mechanism by which calcium binding to TN-C regulates cardiac contraction.

Answer 11

Greater [Ca++]∝ Greater binding of Ca++ to TN-C→ Greater force between actin and myosin.

(a) Acidosis (as in myocardial hypoxia) decreases TN-C affinity for Ca++.
(b) ↑ Preload increases Ca++ affinity for TN-C.

Question 12

Describe the mechanism by which myosin ATPase activity regulates cardiac contraction.

Answer 12

(a) Phosphorylation of myosin light chains (MLC’s) by myosin light chain kinase (MLCK) causes an increase of Inotropy.
(b) Increased cAMP is associated with increased phosphorylation of these MLC’s.

Question 13

Describe the mechanism by which calcium reuptake by the SR regulates cardiac contraction.
-How does hypoxia affect this process.

Answer 13

(a) PK-A phosphorylation of phospholamban removes its inhibitory effects on SERCA→ ↑ rate of Ca++ transport into SR.
(b) This enhanced sequestering of Ca++ by the SR causes an increase in subsequent release→ ↑ Inotropy.
(c) SERCA requires ATP, so hypoxic conditions that reduce ATP production can diminish pump activity.

Question 14

Describe the mechanism by which regulation of calcium efflux from myocytes regulates cardiac contraction.
Discuss the effect of Dixin and Cardiac glycosides on the Na/K/ATPase.

Answer 14

(a) Sarcolemmal Na+/Ca++ exchange pump and ATP-Ca++ pump transport calcium out of the cell.
(b) Inhibition of this extrusion of Ca++ results in increased intracellular calcium→ More available to be taken up by SR and released→ ↑ Inotropy.
(c) Digoxin and Cardiac glycosides inhibit the Na/K/-ATPase→ ↑ intracellular Na which leads to ↑ intracellular Ca++ via Na+/Ca++ exchange pump-→ ↑ Inotropy.
(1) Hypoxia decreases activity of Na/K atpase and Ca++ ATPase,which does result in increased IC Ca++, but not increased intropy because the lack of ATP decreases myosin ATPase activity.

Question 15

How will a supine body posture affect the resting preload and and thus the reserve rates available during exercise?

Answer 15

Higher resting preload and SV-> Less starling reserve

Lower resting HR-> Greater HR reserve

Question 16

How will an erect body posture affect the resting preload and and thus the reserve rates available during exercise?

Answer 16

Lower resting preload and SV-> Greater starling reserve

Higher resting HR-> Reduced HR reserve

Question 17

How does conditioning effect responses to exercise in terms of EF, ventricular size, perfusion, and HR at given workload?

Answer 17

• Increased EF and Ventricular hypertrophy
• Improved muscle perfusion
• Lower heart rate at same workload

Question 18

How does temperature and humidity affect response to exercise?

Answer 18

Max CO and O2 consumptions are reached at lower work loads. Increased skin blood flow to reduce heat at expense of O2 supply to muscles.

Question 19

Why does MAP fall in heart failure patients during exercise?

Answer 19

The decrease in SVR is relatively greater than the increase in CO