Lecture 11 - Ischemic heart disease Flashcards
Describe the coronary circulation
The coronary circulation consists of two major coronary arteries, the left and right coronary arteries.
They run from the base of the aorta to their respective sides, before giving branches that run down the surface of the heart towards the apex.
RCA has no branches we really need to know
LCA gives rise to the left anterior descending, and to the circumflex which wraps around the back of the heart.
What parts of the heart does the RCA supply?
- The right ventricle
- Right atrium
- Parts of the septum
- The posterior wall of the left ventricle
What parts of the heart does the LCA supply?
Circumflex - left atrium, side and back of the left ventricle.
Left Anterior Descending artery (LAD) - supplies the front and bottom of the left ventricle and the front of the septum.
Where does the venous drainage of the coronary circulation drain into?
The coronary sinus.
Blood from the coronary sinus drains directly into the right atrium.
A little bit of venous blood drains into all chambers of the heart through thebesian veins (hence why it’s 95% O2 saturation).
What factors are responsible for the fluctuations in coronary flow rate?
The rhythmic pulsations in aortic pressure are responsible for these phasic fluctuations.
The other main contributor is the changing intramural myocardial pressure.
What happens to the coronary blood vessels during systoe?
The intramural myocardial pressure rises, and this compresses coronary blood vessels (compression is mainly in sub-endocardium).
There is complete interruption of blood flow into the left ventricle during early systole due to high pressure development
When does blood flow in the left ventricle coronary arteries occur?
Primarily in diastole
Describe changes in blood flow in the right coronary artery during the cardiac cycle
In the right ventricle intramural pressure is lower.
- RCA blood flow can occur during systole
- RCA blood flow follows the fluctuations in aortic pressure
When does maximum blood flow in the coronary sinus occur?
During systole there is max. flow rate through the coronary sinus. This is due to the compression of the musclar wall of the heart.
Then during diastole coronary venous flow subsides.
Describe the blood supply to the ventricular muscle.
And why is the subendocardial area the most vulnerable during systole?
Nutrient blood flow needs to penetrate through the heart wall to the subendocardial regions from the epicardium.
The way that vessels need to penetrate the myocardium to reach the subendocardial layer makes the vessels vulnerable to compression.
The subendocardial arteries are the most vulnerable since they are compressed the most during systole.
What makes the endocardial and sub-endocardial regions of the left ventricle more vulnerable than other locations?
There is a thick wall here, so epicardial arteries need to penetrate fruther to reach the subendocardium.
And because in this region they lie at the ‘end of the line’ of coronary artery blood flow.
Because the coronary arteries traverse the ventricular wall, delivery of blood to the endocardial regions of the left ventricle is influenced by intramyocardial pressure.
During exercise, how does the heart get more O2 if it’s already reached its maximum O2 extraction
The increased O2 requirement must be met by increasing blood flow.
- Increasing coronary blood flow is achieved by
- Dilation of the coronary blood vessels, causing a reduction in resistance to increase flow
- This is done by either myogenic, or metabolic, or neurogenic/hormal - there are 3 ways we can control the tone. In the heart its primarily metabolic means
What is the most important mechanism in the control of coronary blood flow?
Local metabolic control.
- One of the strongest stimuli to dilate the coronary arteries is O2 deficiency
- Even a 5% drop in coronary artery blood O2 content will lead to coronary vasodilation
- We match increased O2 consumption with increased O2 delivery.
What metabolite is the key regulator of coronary blood flow?
Adenosine - causes vasodilation increase O2 delivery. Using more O2 increases adenosine production, causing more vasodilation, resulting in more O2 delivery.
It’s a breakdown product of ATP from myocardial cells during:
- During heavy exercise
- Hypoxia
- Ischaemia
Adenosine then leaves the cell to reach the extracellular space and then acts on the arterial wall as a vasodialtor.
Other than adenosine, what is another key metabolite (smaller role than adenosine)
Nitric oxide - NO is sensitive to flow, they aren’t sure how it works
- NO is a vasodilator which is synthesised in endothelial cells.
- NO diffuses to nearby vascular smooth muscle cells where it does the following
- Increases concentration of cGMP
- Reduces intracellular conc. of Ca2+
- Relaxation of vascular smooth muscle
- Dilation of coronary artery
At what point does a coronary stenosis begin to show symptoms?
- Reductions in diameter of coronary lumen of up to 70% show no major sympoms
- But more than 70% you get a dramatic increases vascular resistance and fall in blood flow - this is why people can live without symptoms for a long time, then get severe symtpoms all of a sudden since a small change in radius can have a huge impact of resistance
- since flow is proportional to 1/r4
When coronary blood flow is reduced due to complete coronary occlusion, why does the sub-endocardial zone suffer more than the epicardial tissue?
The sub-endocardial zone of the ventricle has a lower O2 tension than the epicardial area because higher mechanical stresses - higher rate of metabolism - lower blood flow
During cardiac ischaemia when CP and ATP levels get used up and decrease, what happens ?
- the high energy phosphate levels fall
- ATP sensitive K+ channels open and K+ ions leave the cell and increase the extracellular K+ for surrounding cardiac muscle cells (causing increased extracellular K+ concentration to keep the RMP negative)
How does elevated K+ reduce contractility of the heart?
- The RMP for surrounding cells become less negative (towards 0)
- The Phase 0 also becomes less steep
- And the amplitude of the ATP is reduced
- this happens because some fast Na channels remain inactive in high extracellular K+ conditions
What effect does raised extracellular K+ have on the fast Na+ channels in cardiomyocytes?
- During depolarisation there are fewer Na+ channels open
- which means the inward Na+ current is not as strong
- The upstroke of the AP is smaller and less perpindicular ie. slower
How is the action potential altered by extracellular K+?
- Phase 0 less steep
- The amplitude of the AP is reduced
- due to Na+ channels remaning inactive
- Plateau phase is shortened
- Late repolarisation occurs earlier than normal
- due to ATP sensitive K+ channels being closed (in normal cells repolarisation is due to K+ (ik) through K+ channels
- Ca2+ entry into the cell is reduced and the force of contraction is weaker
Why does ischaemia cause ST elevation during mid-systole?
- Normal tissue is more positive than the ischaemic areas
- A current of injury flows from the normal to the ischaemic tissue, towards the detecing electrode
- Causes ECG changes since some of the tissue is at one potential, with the ischaemic tissue being at another potential.
- The major ECG change is elevation of the S-T segment.
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