Lecture 43: Ischemic Dirsorders of the Myocardium

Question 1

What are the two types of ischemia?

Answer 1

1. non-lethal
2. lethal
   Ischemia = inadequate blood flow that leads to inadequate O2 and inadequate removal of waste
   Reperfusion can alter these events

Question 2

What does lethal ischemia lead to?

Answer 2

Coagulative necrosis

Question 3

What is ischemia caused by?

Answer 3

1. reduced blood flow

2. increased myocardial demand

Question 4

What is the most important cause of ischemic heart disease?

Answer 4

Atherosclerosis

Clinically important atherosclerosis affects epicardial coronary arteries

Question 5

What is the layer most susceptible to ischemic injury?

Answer 5

Subendocardium because flow is from epicardial to endocardial, and is subjected to most resistance due to shear forces

Question 6

Whats the collateral circulation like in the coronaries?

Answer 6

They are minimal but can form when there is a coronary occlusion

Question 7

What are the earliest changes to myocardium in ischemia?

Answer 7

1. switch from aerobic to anaerobic metabolism
2. cessation of contraction
3. altered electrical activity
4. relaxation of myofibrils, allowing stretch of myocytes by still contracting adjacent myocardium
   Changes are reversible for up to 20-40 minutes

Question 8

How long can myocardial tissue live without perfusion?

Answer 8

20 minutes

Question 9

What happens if myocardium ischemic for >40 minutes?

Answer 9

First coagulative necrosis starting with most susceptible layer (subendocardium)
Necrosis followed by phagocytosis (polys then macrophages)
Healing by replacement with granulation tissue progressing to a scar

Question 10

When you reperfuse myocardium, what modifications may the myocardium undergo?

Answer 10

1. stunning
2. precondition
3. hibernation
4. contraction band necrosis
5. Reperfusion injury

Question 11

When there is an occluded artery, what is the first part of myocardium to necrose?

Answer 11

The subendocarium

Question 12

What are the clinical consequences of MI?

Answer 12

1. silent angina
2. stable angina pectoris (when pain is felt with increased workload/activity and is relieved with rest)
3. Prinzmetal’s (variant) angina
   
   • Cardiac pain occurring during sleep
   • caused by vasospasm
4. acute coronary syndromes (unstable angina)

Question 13

What does stenosis of >75% lead to? >90%?

Answer 13

Angina during exercise

Angina during rest

Question 14

What are the types of acute coronary syndromes?

Answer 14

1. unstable (crescendo) angina
2. acute MI
3. sudden cardiac death

Question 15

What are the susceptible plaques?

Answer 15

30-60% narrowing
Thin fibrous caps
Morell ipid
Less SMC
More inflammation
Disruption leads to superimposed thrombus

Question 16

What does incomplete obstruction by thrombus lead to?

Answer 16

Unstable angina
Subendocardial MI
Sudden death

Question 17

What does complete obstruction lead to?

Answer 17

Transmural MI

Sudden death

Question 18

What can happen to non-lethal thrombi?

Answer 18

1. becomes organized and incorporated into the plaque

2. lysed either spontaneously or with medical intervention

Question 19

What is the difference in consequence between total occlusion and less than total occlusion?

Answer 19

Total occlusion = transmural MI
Not total occlusion = subendocardial infarction
Shock can cause subendothelial infarction

Question 20

Why is there ST depression in subendocardial MI but ST elevation in trasmural MI?

Answer 20

Because movement of current in systole is from normal  ischemic tissue
Movement of currrent in diastole is from ischemic  normal
In systole for the transmural MI, current is going towards the lesion from BOTH SIDES so it is traveling towards the lead right above the lesion (it’s as if the current was traveling to same portion of the heart)
When it is just subendocardium however, the current will go from epidcardium to endocardium (so even though the current is converging, it will ultimately go in direction AWAYfrom the lead placed on the skin)
The green arrows = flow of current during DIASTOL, which makes sense because in diastole, flow moves from ischemic to normal
PT segment is also elevated/depressed during non-transmural/transmural injury respectively during diastole

Question 21

What are the initial microscopic changes in acute MI?

Answer 21

Thin wavy (stretched) myocytes
Occurs in minutes
IMMEDIATELY after infarct
Non-contractile myocardium

Question 22

What is the second microscopic change after acute MI?

Answer 22

6-24 hours
Coagulative necrosis
hypereosinophilia

Question 23

What is the third stage of change

After acute MI?

Answer 23

Poly infiltration
6hr-3 days
Top left

Question 24

What is the 4th stage of change

After acute MI?

Answer 24

Infiltration of macrophages
7 days (top right)

Question 25

What is the 5th stage of change?

Answer 25

Granulation tissue (sprouting of new vessels) Bottom left 2-4 weeks

Question 26

What is the 6th stage of MI change?

Answer 26

Collagen scar | 8-10 weeks (bottom right)

Question 27

What is granulation tissue?

Answer 27

Combination of new vessels and fibroblasts

Question 28

How do the acute changes of MI progress?

Answer 28

From the periphery towards the center Therefore the most advanced changes (furthest stage) is observed at the periphery Necrotic (coagulatively necrotic, first stage) may persist in center for weeks or indefinitely

Question 29

What are the key characteristics of the microscopic changes for acute MI?

Answer 29

Starts at periphery and is dependent on blood supply Changed most advanced then on periphery Edges may not be well defined Necrotic muscle maypersist in center of necrosis indefinitely

Question 30

What are gross features of the gross MI?

Answer 30

1. no gross changes in first 12 hours 2. dark mottling (trapped deox blood) 12-24 hours 3. tan-yellow pallor 1-3 days due to necrosis 4. hyperemic border with softened yellow, depressed pale necrotic center = 3-10 days 5. gray-red depressed periphery (advancing granulation tissue) 10-14 days 6. grey-white scar progressing from periphery to center

Question 31

What GROSS changes of the heart post-MI do we observe from 12-24 hours?

Answer 31

``` Dark mottling Trapped deoxygenated blood (thrombus) Red = normal (because has TTZ) White = infarcted (because no TTZ Since it has no LDH) ```

Question 32

What is triphenyl tetrazolium chlorid (TTZ)? what changes in the MI heart can we see grossly with TTZ stain?

Answer 32

Stains for lactic dehydrogenase (LDH) Red stain = myocardial cells intact because still retain LDH NON-red stain = myocardial cells died prior to death and released all of its LDH

Question 33

What GROSS changes of the heart do we observe 1-3 days post MI?

Answer 33

tan-yellow pallor 1-3 days due to necrosis

Question 34

What GROSS changes of the heart do we observe 3-10 days post-MI?

Answer 34

Hyperemic border with softened yellow, depressed pale necrotic center = 3-10 days

Question 35

What GROSS changes of the heart do we observe 10-14 days post-MI?

Answer 35

gray-red depressed periphery (advancing granulation tissue) 10-14 days

Question 36

What GROSS changes of the heart do we observe weeks to months post-MI?

Answer 36

grey-white scar progressing from periphery to center

Question 37

What does reperfusion after ischmic injury accomplish?

Answer 37

1. rescues non-lethally injured myocytes 2. alters pattern of necrosis of dying cells and leads to CONTRACTION BAND necrosis 3. can cause additional injury (reperfusion injury)

Question 38

How can reperfusion can injury?

Answer 38

``` Caused by oxygen free radicals Oxygen-derived free radicals can injure Endothelium of microvessels, resulting In hemorrhage converting ischemic Infarct (white) to hemorrhagic (red) infarct ```

Question 39

What is preconditioning?

Answer 39

When you reperfuse myocardial tissue and tissue becomes less susceptible to subsequent lethal ischemia

Question 40

How can evaluating impaired contractility overestimate irreversibly injured myocardium?

Answer 40

Because hibernating and stunned myocardium can recover with reperfusion They just cant contract at that time

Question 41

What are the characteristics of contraction band necrosis?

Answer 41

Scrunched up sarcomeres together Caused by reperfusion of already lethally impaired myocytes prior to coagulative necrosis Injured myocytes have leaky membranes that allow calcium ion influx and hypercontraction of myofibrils (which is why you see all these abnormal bands) Notice that picture below has NO nuclei but scrunched up bands These myocytes are non-functional

Question 42

What are the complications of MI?

Answer 42

1. mural thrombus +/- embolization at regions of infarction 2. dysrhythmias 3. contractile dysfunction i. diastolic failure ii. systolic failure 4. MV dysfunction i. mitral valve ring dilation ii. papillary muscle dysfunction iii. changed configuration of valveapparatus 5. pericarditis (transmural MI only) 6. Ventricular rupture of free wall, IV septum or papillary muscle 7. aneurysm 8. remodeling i. infarct expansion ii. distortion by scar iii. hypertrophy of remaining myocardium iv. chamber dilation v. interference with mitral valve apparatus 9. possible role of TGF-beta and ACEi and ARBs

Question 43

What causes acute fibrinous pericarditis?

Answer 43

Acute pericarditis is caused by pericardial effusion and Dressler’s syndrome (development of antibodies to antigens in the heart that will then lead to autoimmune pericarditis Seen as bread and butter (fibrinous) gross appearance

Question 44

When do you get perforation of the free wall of left ventricle?

Answer 44

3-6 days after MI Occurs where the polys are going to be At the edge of the dead tissue because it starts from the periphery

Question 45

What causes aneurysm formation?

Answer 45

A complication of transmural myocardial infarction | Due to progressive outward bulging and thinning of infarcted area

Question 46

What are the histological features of myocardial aneurysm?

Answer 46

Stained different color than myocardium because wall is fibrous