Ischaemic reperfusion injury and HF Flashcards
After infarction, dead muscle is replaced by what kind of tissue?
Fibrous tissue
After infarction, the remaining functional part of the heart undergoes ____ to compensate for muscle death.
Hypertrophy
The size of the damage zone from original and ischaemic reperfusion injury (IRI) is determined by what factor?
The site of vessel occlusion
List the four consequences of IRI
- Myocardial stunning
- Reperfusion arrhythmias
- Endothelial dysfunction
- Irreversible cell death
What is meant by ‘myocardial stunning’?
Failure to recover contractile function
Describe the result of endothelial dysfunction after IRI
Impaired endothelial-mediated vasodilatory mechanisms and hyper-responsiveness to vasoconstriction results in the NO flow phenomenon
List some of the ways IRI leads to irreversible cell death
- Maintained hypoxia
- Inflammatory responses
- ROS
- Ca toxicity
Describe the mechanism of the oxygen paradox
- ROS generated from endothelial cells and the inflammatory response upon reperfusion leads to cell death
- Ischaemic endothelial cells upregulate xanthine oxidase after reperfusion which generates super-oxide radicals (hydrogen peroxide, super-oxide anion, hydroxyl radical)
- Oxygen radials damage lipid membranes and proteins, leading to permeable ‘leaky’ membranes. This causes cellular oedema and massive Ca influx (calcium paradox), causing cell lysis
- ROS reacts with and destroys NO (nitric oxide); NO is a vasodilator and is cardio-protective (inhibits neutrophils). This leads to the NO flow effect
Describe the mechanism of the calcium paradox
Abrupt increase in Ca++ released from dying cells causes overwhelming cytoplasmic and mitochondrial Ca++ overload. This causes hyper-contraction of myocardial cells (which are already swelling due to odema and ion influx), resulting in cell death.
Describe the mechanism of the pH paradox
- Absence of O2 during ischaemia increases anaerobic metabolism, causing lactate build-up which decreases pH
- Rapid restoration of normal physiological pH by reperfusion triggers cell death by removing the protective mechanism (driven by acidosis) that was helping to prevent hyper-contraction
List some potential therapies to combat oxygen paradox
- Allopurinol (inhibits xanthine oxidase activity)
- Anti-inflammatory drugs (ineffective so far)
- Anti-oxidants (e.g. vitamin E)
Name a potential therapy to combat calcium paradox
Calcium channel blockers
What can be done to combat pH paradox?
Experimentally reperfusing ischaemic tissues with acidic buffers has had a significant cardio-protective effect
Name the four mechanisms of HF
- Myocardial remodelling
- Venous congestion
- Worsening renal function
- Endothelial dysfunction
Pathogenesis of HF after MI is closely linked with development of what?
Post-infarct remodelling
True or false: structural and functional alterations involve both infarcted and non-infarcted myocardial tissue.
Cardiac remodelling can result in what two kinds of long term effects?
Dilative and fibrotic effects
Cardiac remodelling with dilative effects causes what kind of dysfunction?
Systolic dysfunction
Cardiac remodelling with fibrotic effects causes what kind of dysfunction?
Diastolic
What factors may influence development of dilative or fibrotic effects after cardiac remodelling?
Genetics and comorbidities
Describe the progression of cardiac remodelling
- Myofibroblasts are recruited to damaged area and secrete large amounts of extracellular matrix to preserve structural integrity of the region
- In the myocardium, preservation of geometry and function are dependent on balance between matrix degrading and replacement
- Overactive matrix degradation triggered by excessive prolonged inflammation leads to ventricle dilation and systolic dysfunction
What function of the inflammatory response is crucial to prevent excessive damage and remodelling?
Timely regression
What is acute decompensated heart failure?
Sudden worsening of pre-existing CHF
Describe the development/effect of LHF
- Too much blood in the L) ventricle; fluid backs up into the lungs, causing:
- Pulmonary oedema (crackles)
- Dyspnoea
- Orthopnoea (worsens when supine)
- Narrow pulse pressure (difference between systolic and diastolic BP)
Describe the development/effect of RHF
Blood backs up into venous circulation, causing peripheral oedema and JVD
On which side does hypertrophy primarily occur, the failing side or the adequate side?
Primarily the failing side
What is the role of the sinoatrial (SA) node?
Impulse (heartbeat) generation
What is the role of the atrioventricular (AV) node?
To delay the impulse as it passes from atria to ventricles
The AV node and Bundle of His together form what pathway?
The pathway from atria to ventricles
Describe the process of excitation in the heart
- SA node generates impulse
- Atrial excitation begins
- Impulse is delayed at AV node
- Impulse passes to heart apex along bundle branches
- Ventricular excitation begins
- Impulse travels along Purkinje fibres; ventricular excitation is complete
List the sympathetic effects on the heart via the cardiac nerve
- Increased HR
- Increased force of contraction
- Increased blood flow to the heart
List the parasympathetic effects on the heart via the vagus nerve
- Slows HR
- Decreases force of contraction
Which region of the brain controls cardiac function?
The medulla oblongata (in the brainstem)
List some effects of the sympathetic division of the autonomic nervous system
- “Fight or flight”
- Pulmonary
- Brochodilation
- Increased pulmonary blood flow
- Cardiac
- HR increases
- Increased strength of cardiac contraction
- Coronary vessel dilation
- Ocular
- Dilates pupils
- Relaxes ciliary muscles (improves distance vision)
- Cardiovascular
- Increased blood flow to skeletal muscles ∴ increased O2 and glucose, enabling muscles to work harder
- Constricts vessels in skin and GIT
- Gastrointestinal
- Inhibits peristalsis
- Constricts all intestinal sphincters and the urinary sphincter
- Glycogenolysis (glycogen to glucose)
- Adrenaline secretion
List some effects of the parasympathetic division of the autonomic nervous system
- ‘Rest and digest’
- Calming
- Facilitates GIT function
What is the effect of atropine?
Derived from atropa belladonna, AKA deadly nightshade; blocks the parasympathetic nervous system
