Cardioprotection Flashcards

1
Q

What does STEMI stand for?

A

ST Elevated Myocardial Infarction

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2
Q

What happens in nSTEMI?

A
  • Plaque ruptures and partially blocks an epicardial artery
  • Patients at high risk of recurrence of ischaemia because of occlusion and an active pro-thrombotic surface at the site of plaque rupture
  • Elevated cardiac biomarkers which indicate cell death
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3
Q

Aim of treatment for nSTEMI

A

To prevent additional thrombus formation at the site of plaque rupture (try to balance with risk of bleeds)

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4
Q

What happens in STEMI?

A
  • Complete blockage of an epicardial artery
  • Elevated cardiac biomarkers which indicate cell death
  • Will progress to transmural infarction unless flow is restored
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5
Q

Aim of treatment for STEMI

A

Fast restoration of blood flow

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6
Q

What happens when blood is restored to blood vessels after MI?

A
  • Restores O2, but causes reperfusion injury
  • Anaerobic glucose breakdown → lactate buildup, reduced pH, Ca release
  • Cytochrome C activated by ROS generation and cell stress
  • Contributes to apoptosis
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7
Q

Ischaemic preconditioning

A

Brief episodes of ischaemia and reperfusion BEFORE ISCHAEMIA

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8
Q

When can ischaemic preconditioning only be used?

A

Can only be applied in surgeries with predictable ischaemia and/or reperfusion i.e. coronary bypass

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9
Q

ischaemic postconditioning

A

Brief episodes of ischaemia and reperfusion at the beginning of reperfusion

  • Overcomes most of the problems seen with clinical ischaemic preconditioning
  • Easy to do: inflate, deflate, inflate balloon to create short periods of ischaemia and reperfusion
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10
Q

What did Zhao et al. (2002) demonstrate in dogs?

A

That three cycles of 30-s reperfusion and 30-s left anterior descending (LAD) coronary artery re-occlusion preceding the 3 h of reperfusion minimised the damage caused by MI

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11
Q

What did Staat et al. (2005) showcase in their study?

A

Reduced creatinine kinase in post conditioned patients

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12
Q

What is the name of a trial that involved a larger cohort of post conditioned patients but did not show long-term benefits?

A

Danami-3 Trial

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13
Q

When is preconditioning performed?

A

When the heart is ischaemic

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14
Q

How is remote ischaemic conditioning performed?

A

Performed by inducing short bursts of ischemia-reperfusion in a remote location (i.e. not the heart)

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15
Q

Is remote conditioning clinically relevant?

A

Yes - can be performed in an ambulance on way to hospital (MI)
Has been shown to significantly increase myocardial salvage

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16
Q

Is preconditioning clinically relevant?

A

NO - don’t know when someone is going to have a heart attack

17
Q

When can remote conditioning be used?

A

In primary percutaneous intervention

18
Q

Which anaesthetic has been implicated in removing effects of remote ischaemic conditioning?

A

Propofol

by either reducing beneficial effects or providing beneficial effects itself so changes due to RIPC not seen

19
Q

Examples of larger clinical trials involving RIPC

A
  1. Randomised RIC-STEMI trial
    - Reduced rates of cardiac death & hospitalisation for HF after additional RIC (Gaspar et al., 2018)
  2. LIPSIA conditioning trial
    - Long-term results indicate prevention of post-infarction HF after RIC in combination with post-conditioning
  3. Large RCT CONDI-2/ERIC-PPCI trial
    - Failed to show any beneficial effect of RIC in STEMI patients treated with primary PCI on clinical outcomes (cardiac death, HF re-hospitalisation) (Hausenloy et al., 2019)
20
Q

General problems with translating lab experiments

A
  • Poor experimental designs
  • Low reproducibility
  • Small population sizes
  • Publication bias
21
Q

What will “All-comer” trials lead to?

A

The recruitment of far more patients with small infarcts and little additional myocardial salvage, which may dilute the positive effect elicited by any novel protective strategy

22
Q

Emricasan works via a different pathway and does reduce infarct size more than background drugs alone. What does this suggest?

A

That Emricasan activates a further cardioprotective pathway that background drugs and RIPC is not capable of

23
Q

What are examples of comorbidities that affect IPC?

A

Age, hyperglycemia, hypertension, diabetes