PBL 5 - cardiac remodelling following a MI

Question 1

what are the 2nd most common causes of MI?

Answer 1

• rupture of an atherosclerotic plaque in a coronary artery
• formation of intracoronary thrombus
• cause infarction downstream of the occluded blood vessel

Question 2

how does blockage of a coronary artery lead to heart failure?

Answer 2

• blockage of coronary artery
• ischaemia and MI
• necrosis
• inflammation response to remove dead cells
• infarct healing and scar formation
• hypertrophy, dilation, reduced function
• HF

Question 3

what does death in a proportion of the LV wall and the development of scar tissue lead to?

Answer 3

• heart undergoes this adverse remodelling to result in a change in the heart shape (chamber dilation)
• chamber dilation leads to deterioration in cardiac function

Question 4

loss of a significant amount of cardiac muscle ultimately leads to what?

Answer 4

scar formation

Question 5

is myocardium endogenous regernative captacity good or bad?

Answer 5

bad

Question 6

what does cells dying by necrosis cause?

Answer 6

• release of IC contents

- initiates an intense inflammatory response

Question 7

what is used as a diagnostic tool?

Answer 7

release of troponins — not usually found in circulation

Question 8

describe the rise in troponin levels

Answer 8

• levels rise within 4-8 hours of MI

- remain elevated for 4-7 days

Question 9

what is the inflammatory response to an infarct?

Answer 9

1. neutrophils infiltrate infarct
2. secrete MMPs (matrix metalloproteinases) and phagocytose debris
3. pro-inflammatory cytokine levels increase
4. leads to recruitment of other inflammatory cells
5. pro-reparative phase: neutrophils undergo apoptosis — further recruitment of inflammatory cells — initiation of the healing process

Question 10

describe the inflammatory phase where dead cells are starting to be cleared away

Answer 10

1. neutrophils infiltrate the infarct
2. secrete MMPs and phagocytose debris
3. pro-inflammatory cytokine levels increase (IL-1B, IL-6, IL-18, IFN-y, TNFa)
4. leads to recruitment of other inflammatory cells

— further clearing of dead cells by recruited macrophages
— recruitment of other leukocytes — NKC, T and B lymphocytes, dendritic cells
— transition to pro-reparative phase

Question 11

describe the pro-reparative phase (day 3 of infarction)

Answer 11

• neutrophils undergo apoptosis — reduction in pro-inflammatory macrophages in infarct zone
• further recruitment of inflammatory cells
• increased expression of IL-10 and TGF-B — inhibit pro-inflammatory cytokines
• initiation of healing process

Question 12

what is a negative effect of the whole process of clearing away dead cells and debris?

Answer 12

makes the infarct zone very weak and prone to rupture —

cardiac rupture accounts for 10-20% of acute death following an MI, usually 4-7 days post MI

Question 13

what replaces cardiomyocytes in the infarct zone?

Answer 13

a collagen-rich scar

Question 14

what do cardiac fibroblasts turn into?

Answer 14

myofibroblasts

Question 15

what do myofibroblasts do?

Answer 15

secrete new ECM proteins such as collagen

Question 16

what can too much collagen result in?

Answer 16

increase in wall stiffness, leading to cardiac dysfunction

Question 17

what does too little scar deposition result in?

Answer 17

a thin infarct wall — thin ventricular wall at risk of aneurysm or even rupture

Question 18

what happens at the end of the collagen deposition process?

Answer 18

clearance of myofibroblasts by apoptosis

Question 19

what is the ventricle left with after being strengthened by the scar?

Answer 19

a non-contracting region of the LV wall

Question 20

what happens to the remaining healthy part of the myocardium?

Answer 20

LV undergoes hypertrophy to compensate for the lost muscle mass in the infarct area in order to maintain cardiac function

Question 21

what happens in concentric hypertrophy?

Answer 21

• cardiomyocytes are thickened by the addition of more sarcomeres
• over time the heart can’t maintain this increased workload on the remaining healthy bits of the LV
• heart undergoes dilation
• LV chamber expands — heart looses its pump function
• loose the rhythmic contraction and relaxation of the heart wall

WALLS THICKEN BUT CAPACITY IS REDUCED

Question 22

how does ejection fraction correlate its survival post MI?

Answer 22

the lower the ejection fraction (amount of blood pumped from the heart), the higher the death rate post MI

Question 23

what joins adjacent cardiomyocytes?

Answer 23

gap junctions

Question 24

within mins/hours of an MI, how does irreversible cell damage increase risk of ventricular arrhythmias?

Answer 24

• irreversible cell damage —> disruption of gap junctions causing electrical uncoupling of cardiomyocytes
• increased risk of ventricular arrhythmias eg.. ventricular tachycardia

Question 25

what may ventricular tachycardia deteriorate into?

Answer 25

ventricular fibrillation and then cardiac rest

Question 26

describe myocytes at infarct border weeks to months after an MI

Answer 26

myocytes at infarct border interspersed with ECM

Question 27

what does fibrosis and abnormal cell communication lead to?

Answer 27

slow conduction and creates conduction blocks

Question 28

what does this ECG show?

Answer 28

atrial fibrillation, indicative of a patient with mitral valve disease

Question 29

what does this ECG show?

Answer 29

1st degree AV block dye to delay in conduction through the AV node

Question 30

what does this ECG show?

Answer 30

sinus tachycardia

Question 31

what does this ECG show?

Answer 31

ST elevation indicative of an MI (STEMI)

Question 32

a patient with a recent MI would have raised levels of what?

Answer 32

cardiac troponin