BPK 305 - Lecture 22

What does cell damage lead to?

- hypocontractility

- increased incidence of arrhythmia

Cause of ischemia injury

1. Osmotic overload

2. pH paradox

Osmotic overload

- large increase in small molecule in the cytoplasm

- breakdown of ATP, phosphocreatine, and glycogen

How much does osmolarity increase?

300mOsm/l to 400mOsm/l

What happens upon repurfusion after ischemia due to osmotic overload?

- water enters cells causing them to swell and rupture

- Intracellular organs swell and rupture

- toxic substances release

pH paradox

Rapid relief of acidosis causes additional injury to myocytes

Why is ischemia associated with acidosis?

- due to increased lactic acid

- and unbalanced ATP production and breakdown

Why does acidosis decrease contractility?

-decreases ion channel function

-affects Ca2+ handling proteins

-decreases myofilament Ca2+ sensitivity (site II TnC) -decreases ATPase activity

pH paradox injury

1. Ischemic event increased Intracellular H

2. NKA becomes impaired and NHE1 activity increased causing intracellular Na to increase

3. Upon reperfusion H decreases outside the cell causing the NHE1 to work even more

4. High Na reverses NCX

5. Ca influx

6. Ca causes activation of proteases and mitochondrial overload

7. Cell death

NHE blockers

Induce acidosis at rest to sort of protect against reperfusion injury

Normal ECG ventricular depolarization and repolarization

Endocardium depolarizes first and depolarizes last

Subendocardial ischemia diastolic injury current

- injured area has elevates RMP

- persistent flow of charge into neighbouring regions

- Elevated T-Q segment

PQ diastolic injury current

Vendo > Vepi causing a raised segment

ST diastolic injury current

Vendo = V epi normal

Systolic injury current

- if ischemia prevents normal depolarization then Vepi > Vendo during AP plateau

- causes ST depression

Transmural infarction

• some endocardial depolarization persists due to ↑ preconditioning in endocardium

• bump in the epicardial AP disappears, contributing to S-T elevation

• deep Q due to dead tissue

Determining the injury current

Diastolic voltage - J

Tail originates at the injury

ECG after MI recovery

- heightened T waves followed by inversion

- ST elevation due to injury current

- deep Q haves from dead myocardium

What are the Q waves?

septal and RV depolarization

ST elevation in leads I, V2-4 and V5

-anterior infarction with some lateral involvement

-anterior infarct = LAD

-lateral involvement = circumflex

ST depression in leads III and aVF

- inferior ischemia

- right coronary

Pathological Q waves in V1 and 2

Anterior infarction

Who may have T wave inversion?

Athletes

Serum changes with MI

- Lactate dehydrogenase

- creatine kinase

- TnI

- cardiac myosin binding protein C

Changes in TnI after MI

- calpain degrades TnI

- blood levels rise

cMyC after MI

-cardiac-specific and more abundant that cTnI

-more rapid increase in levels

-faster discrimination and earlier treatment = less time in care

Preconditioning for MI

• Reduces damage of subsequent more severe infarct

• Reduces infarct size

Preconditioning mechanism

Brief and mild ischemia

- increases Katp

- increases vasodilator metabolites

- release Na, bradykinin, opioids

Postconditioning

• Restarting the flow in brief bursts rather than all at once

• Short bursts of reperfusion produce the least damage