Lecture 22 - myocardial ischemia etiology

Question 1

Describe osmotic overload

Answer 1

large increase in number of small molecules in the cytoplasm
this can be due to ATP being broken down, breakdown of phosphocreatine, breakdown of glycogen
When reperfusion occurs, lots of fluid enters cells and causes rupture which leads to apoptosis

Question 2

Describe the immune response

Answer 2

neutrophils release of ROS causes damage to heart

complement system activated by ischemia, activates MAC (membrane attack complex) which kills cells

Question 3

Describe the pH paradox

Answer 3

when acidosis occurs due to increase in lactic acid and no more ATP production, there is negative inotropy. Ion channels are dysfunctional, lower myofilament Ca2+ sensitivity at TnC site II, no ATPase activity (less cross bridge cycling), but rapid reperfusion causes further damage.

large increase in H+ causes inactivation of NKA and activation of NHE. This means that there is lots of Na in the cell, so this flips the direction of NCX. This means that Ca enters the cell, and eventually with enough overload, the mitochondria produce signals leading to apoptosis.

Question 4

Describe the three types of injury currents

Answer 4

1) diastolic injury current - TQ elevation. side that is injured has increase in resting membrane potential, therefore, during diastole, depolarizing current flows from endocardium to epicardium, this is seen as positive current so positive deflection
2) systolic injury current - ST depression - during systole, endocardium can’t depolarize as much, therefore there is current flowing away from electrode therefore negative deflection
3) transmural infarction - ST elevation - endocardium recovers better due to preconditioning, therefore the fringe tissue fully depolarizes, while epicardium cannot, so current flows towards electrode and seen as positive deflection

Question 5

how is injury current determined?

Answer 5

diastolic voltage - J point, tail of vector indicates origin of injury

Question 6

Describe changes in the ECG after MI

Answer 6

heightened t waves, t wave inversion
ST elevation
deep Q waves due to dead tissue

Question 7

Describe serum changes with myocardial infarction

Answer 7

increase in LDH, and creatine kinase and troponin I

troponin I degraded by calpain

Question 8

Describe preconditioning

Answer 8

Reduces damage and infarction size
Mechanism:
increase Katp activity (repolarize back to normal)
release vasodilator molecules (adenosine, CO2)
hypoxia (increases VEGF and HIF to cause blood vessel proliferation)
release NE, bradykinin and opioids to activate G proteins and protein kinases (PKC, MAP, P13-K)

Question 9

Describe postconditioning

Answer 9

restart flow in brief bursts to give less damage, smaller infarction size