Failing heart muscle

Question 1

What is excitation-contraction coupling?

Answer 1

The process whereby action potentials trigger myocyte contraction

Question 2

What mediates calcium in the cytoplasm?

Answer 2

Ryanodine receptors
L-type channels
SERCA
Na/Ca exchangers

Question 3

What is heart failure?

Answer 3

Inability of the heart to supply adequate blood flow (and oxygen delivery) to organs and tissues

Question 4

What is the consequence of decreased perfusion of organs?

Answer 4

Reduced exercise capacity
Fatigue
Shortness of breath

Question 5

What is the incidence of heart failure?

Answer 5

15 million new cases worldwide each year

Question 6

What are the symptoms of heart failure?

Answer 6

Enlarged heart
Weakened heart muscle
Blood pumped at reduced volume
Shortness of breath
Weakness and fatigue
Swollen feet, ankles, abdomen or veins in the neck

Question 7

What are risk factors in heart failure?

Answer 7

Hypertension
Coronary artery disease
Valvular disease
Obesity
Diabetes
Kidney disease

Question 8

What is the cardiac pathophysiology of heart failure?

Answer 8

Decreased stroke volume and cardiac output
Increased end-diastolic pressure
Ventricular dilation or hypertrophy
Impaired filling 
Reduced ejection

Question 9

What is the vascular pathophysiology of heart failure?

Answer 9

Increased systemic vascular resistance 
Decreased arterial pressure
Impaired arterial pressure
Impaired organ perfusion
Decreased venous compliance
Increased venous pressure
Increased blood volume

Question 10

What are the cardiac compensatory mechanisms?

Answer 10

Frank-Starling mechanism
Ventricular dilation or hypertrophy
Tachycardia

Question 11

What are the autonomic nerves compensatory mechanisms?

Answer 11

Reduced blood pressure initiates baroreceptor reflex
Increases sympathetic adrenergic activity
Reduced vagal activity

Question 12

What are the hormonal compensatory mechanisms?

Answer 12

Renin-angiotensin-aldosterone system
Vasopressin
Circulating catecholamines
Natriuretic peptides

Question 13

What changes occur in myocytes in cardiac failure?

Answer 13

Altered contractile proteins
Altered calcium homeostasis
Altered signal transduction pathways

Question 14

How are contractile proteins altered in the failing heart?

Answer 14

Expression of myosin heavy chains isoforms is unchanged
ATPase activity unchanged
Cross-bridge cycling rate is slower
Phosphorylation of troponin I is reduced

Question 15

How is calcium homeostasis altered in the failing heart?

Answer 15

Decline in intracellular calcium homeostasis
Prolonged duration of the action potential
Systolic Ca concentrations stay the same
Threshold for Ca released from SR increases
Increase in diastolic Ca concentrations
Decreased uptake of Ca into SR

Question 16

What happens to signal transduction in the failing heart?

Answer 16

Decrease in Badrenoreceptor number

Alteration in cAMP signalling pathway

Question 17

What is the cause of decreased contractile force?

Answer 17

SR calcium stores are significantly reduced

Question 18

What happens to the Na/Ca exchanger?

Answer 18

Upregulated
Promotes removal of vital calcium from the cell
Development of delayed depolarisation and triggers arrhythmias

Question 19

What happens to RyRs in failing cardiac muscle?

Answer 19

Hyperphosphorylation to overcome Ca deficiency

Question 20

How is heart failure treated isotropically?

Answer 20

Positive ionotropic drugs

• phosphodiesterase inhibitors
• catecholamine-mediated inotropy

Question 21

How do inotropic agents treat cardiac failure?

Answer 21

Increase force of the B adrenoreceptor system

Question 22

What is the effect of nitric oxide?

Answer 22

Vasodilation

Question 23

What is the role of phophodiesterase inhibitors?

Answer 23

Increase heart contractility
Vasodilates vessels
Alleviates increased pressure