Lecture 5: Ischemia and Re-perfusion Injury Flashcards
What is AMI?
Acute Myocardial Infarction refers to the macroscopic death of myocardium due to vascular insufficiency (VI). VI itself refers to myocardial ischaemia, which is the imbalance between the supply flow (perfusion) and demand for oxygenated blood.
Describe the cause and consequences of ischemic heart diseases.
It involves an imbalance between cardiac blood supply and myocardial oxygen demand.
- Caused by:
- Increased demand
- Diminished oxygen-carrying capacity
- Reduced coronary flow due to obstructive atherosclerosis
- Consequences:
- limits tissue oxygenation (thus ATP generation)
- reduces the availability of nutrients and the removal of metabolic wastes
What is the major underlying cause of AMI?
In 95% of the case, the cause is atherosclerosis (disease caused by fibro-fatty plaques in intima of large arteries)
Recall the various pathways in the progression of ischemic heart disease (IHD).
What is Acute Coronary Syndrome? What are its outcomes?
Acute coronary syndrome (ACS) is a set of signs and symptoms due to decreased blood flow in the coronary arteries such that part of the heart muscle is unable to function properly or dies.
The common feature of ACS is downstream MI. The outcomes of ACS are:
- Stable angina
- Unstable angina
- Myocardial Infarction (heart attack)
Recall the factors affecting the outcome of ischaemia.
Recall the time of onset of key events in ischaemic cardiac myocytes.
What is atherosclerosis?
Atherosclerosis is a chronic inflammatory and healing response of the arterial wall to endothelial injury.
Lesion progression occurs through the interaction of modified lipoproteins, macrophages, and T-lymphocytes with the normal cellular constituents of the arterial wall.
Describe the pathogenesis of atherosclerosis.
Recall the structure of an atherosclerotic plaque.
Recall the pathogenesis of AMI caused by atherosclerosis
The possible outcomes if plaque progresses:
- Aneurysm and rupture
- Occlusion by thrombus
- Critical Stenosis
Recall the major components of a well-developed intimal atheromatous plaque.
Recall the progression of myocardial necrosis after coronary artery occlusion.
Necrosis begins in a small zone of myocardium beneath the endocardial surface in the centre of the ischemic zone. The area that depends on the occluded vessel for perfusion is the “at-risk” myocardium.
Describe the pathogenesis of the AMI at the cellular level.
- Cell death by necrosis and apoptosis - occurs rapidly post-ischaemia
- Apoptosis inhibitors reduce infarct size
- Reperfusion - in <20 min myocytes survive infarct event
- No reperfusion - necrosis complete in 6-12 hour
Recall the evolution of the infarct site in a surviving patient.
Recall the role of IL-1ß in acute myocardial infarction.
When there is a normal regulation of IL-1ß, cardiomyopathy is still reversible. However, when there is dysregulation of IL-1ß, there is a progression to the acute phase of AMI due to inflammasome-mediated injury (headed by the IL-1ß).
What are the inflammatory markers of AMI?
The release of myocyte proteins acts as inflammatory markers of AMI. Some of these proteins are:
- troponin I, C, T
- creatine phosphokinase ‘Muscle-Brain’ isoenzyme (CK-MB)
These proteins are used as diagnostic biomarkers.
Mention the clinical features and tests for AMI.
Most laboratories run a troponin assay, either troponin T or I, and may also offer testing for CK-MB and/or myoglobin. Troponin demonstrates improved myocardial specificity and sensitivity over both CK-MB and myoglobin.
What can be done to modify the infarct?
- Restoration of coronary blood flow (reperfusion)
- Thrombolysis
- streptokinase or tissue plasminogen activator
- activates fibrinolytic enzyme systems
- dissolves thrombus
- streptokinase or tissue plasminogen activator
- Balloon angioplasty
- procedure used to increase the flow of blood through a narrowed artery
- Coronary arterial bypass graft (CABG)
How to achieve inhibition of myocardial death?
Explain the effects of reperfusion on myocardial viability and function.
If flow is restored, some necrosis is prevented, the myocardium is salvaged, and some function can return. The earlier reperfusion occurs, the greater the degree of salvage.
However, the process of reperfusion itself may be damaging (reperfusion injury), and return of function of salvaged myocardium may be delayed for hours to days. (postischaemic ventricular dysfunction)
What is the source of reperfusion injury?
Ischaemic myocardiocytes have a buildup of reactive oxygen species/free radicals. When blood flow returns, it spreads these ROS to surrounding tissue-damaging them. Immune cells (such as neutrophils) are also brought into the area, generating more inflammatory responses, releasing a host of inflammatory factors such as interleukins as well as free radicals in response to tissue damage. Cytoplasmic xanthine oxidase is also activated - producing more ROS/FR.
Note: Blood without polymorphs (leukocytes or granulocytes) and usage of inhibitors of xanthine oxidase lead to better outcomes
Mention the complications of AMI.
- contractile dysfunction
- arrhythmias
- rupture-severe effect
- pericarditis
- infarct expansion
