Cardioprotection Flashcards
What does STEMI stand for?
ST Elevated Myocardial Infarction
What happens in nSTEMI?
- 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
Aim of treatment for nSTEMI
To prevent additional thrombus formation at the site of plaque rupture (try to balance with risk of bleeds)
What happens in STEMI?
- Complete blockage of an epicardial artery
- Elevated cardiac biomarkers which indicate cell death
- Will progress to transmural infarction unless flow is restored
Aim of treatment for STEMI
Fast restoration of blood flow
What happens when blood is restored to blood vessels after MI?
- 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
Ischaemic preconditioning
Brief episodes of ischaemia and reperfusion BEFORE ISCHAEMIA
When can ischaemic preconditioning only be used?
Can only be applied in surgeries with predictable ischaemia and/or reperfusion i.e. coronary bypass
ischaemic postconditioning
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
What did Zhao et al. (2002) demonstrate in dogs?
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
What did Staat et al. (2005) showcase in their study?
Reduced creatinine kinase in post conditioned patients
What is the name of a trial that involved a larger cohort of post conditioned patients but did not show long-term benefits?
Danami-3 Trial
When is preconditioning performed?
When the heart is ischaemic
How is remote ischaemic conditioning performed?
Performed by inducing short bursts of ischemia-reperfusion in a remote location (i.e. not the heart)
Is remote conditioning clinically relevant?
Yes - can be performed in an ambulance on way to hospital (MI)
Has been shown to significantly increase myocardial salvage
Is preconditioning clinically relevant?
NO - don’t know when someone is going to have a heart attack
When can remote conditioning be used?
In primary percutaneous intervention
Which anaesthetic has been implicated in removing effects of remote ischaemic conditioning?
Propofol
by either reducing beneficial effects or providing beneficial effects itself so changes due to RIPC not seen
Examples of larger clinical trials involving RIPC
- Randomised RIC-STEMI trial
- Reduced rates of cardiac death & hospitalisation for HF after additional RIC (Gaspar et al., 2018) - LIPSIA conditioning trial
- Long-term results indicate prevention of post-infarction HF after RIC in combination with post-conditioning - 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)
General problems with translating lab experiments
- Poor experimental designs
- Low reproducibility
- Small population sizes
- Publication bias
What will “All-comer” trials lead to?
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
Emricasan works via a different pathway and does reduce infarct size more than background drugs alone. What does this suggest?
That Emricasan activates a further cardioprotective pathway that background drugs and RIPC is not capable of
What are examples of comorbidities that affect IPC?
Age, hyperglycemia, hypertension, diabetes
