Coronary arteries
Two arteries leaving the aorta just above the aortic valve, each supplying a fixed patch of heart muscle, and filling the left ventricle mainly while the heart is relaxed.
What it normally does
The left main and right coronary arteries arise from the aortic sinuses immediately above the aortic valve cusps, and each supplies a territory that is fairly constant between people. The left main divides into the left anterior descending (anterior wall, interventricular septum, apex) and the circumflex (lateral wall); in a minority there is also a ramus intermedius. The right coronary supplies the right ventricle, and in the roughly 85% of people who are right dominant it also gives the posterior descending artery to the inferior wall; in the remaining left dominant or codominant hearts the inferior wall comes from the circumflex. The AV nodal artery arises from the right coronary in about 80 to 90% of people, and the sinus node artery in around 60%. Because territories are fairly fixed, the ECG lead groups map onto vessels: II, III and aVF inferior (usually right coronary), V1 to V4 septal and anterior (left anterior descending), I, aVL, V5 and V6 lateral (usually circumflex, with V5 to V6 sometimes fed by a long left anterior descending).
an ST elevation pattern names the likely culprit vessel before angiography, and predicts which extra structures (AV node, right ventricle) are in the firing line.
The left ventricle is perfused predominantly in diastole. Contracting muscle compresses the intramural vessels during systole, so wall flow occurs mainly between beats, driven by the coronary perfusion pressure, which is aortic diastolic pressure minus left ventricular end-diastolic pressure. The right ventricle, whose wall tension is far lower, is perfused throughout the cardiac cycle.
anything that shortens diastole (tachycardia) or lowers diastolic pressure (shock, aortic regurgitation) or raises filling pressure (a stiff, failing ventricle) can starve the left ventricle with no blockage at all.
Cardiac muscle extracts about 70% of the oxygen delivered to it even at rest, far more than most tissues, so there is very little extraction reserve. Increasing myocardial oxygen supply therefore depends mainly on increasing flow, which can rise roughly four to five-fold from rest in a healthy adult (coronary flow reserve); the other lever is the oxygen content of the blood, so anaemia or hypoxaemia removes supply that flow alone cannot make up.
demand ischaemia is possible with normal arteries, and correcting anaemia or hypoxaemia is a genuine way to raise supply when flow cannot rise further.
The large epicardial arteries are conduits with little resistance; almost all coronary resistance sits in the downstream arterioles, which autoregulate. As a fixed stenosis grows, those arterioles dilate to keep resting flow normal, so resting flow is typically maintained until the lumen is narrowed by roughly 70% of its diameter, and only falls at rest with very tight (around 90%) lesions. What is lost first is the reserve, not the resting flow.
a patient can have a severely diseased artery, a normal resting ECG and no symptoms at rest, yet become ischaemic the moment demand rises.
The coronaries behave as functional end arteries: anastomoses between territories exist but are usually too small to protect against an abrupt occlusion, though they can enlarge into useful collaterals over months of chronic ischaemia. Within the wall, the subendocardium is furthest from the epicardial vessels and is compressed hardest in systole.
the subendocardium is the first layer to become ischaemic and the last to be rescued, and an abrupt occlusion of an uncollateralised artery infarcts the full wall thickness.
What goes wrong
An atherosclerotic plaque fixes the lumen. Downstream arterioles dilate to preserve resting flow, so the coronary flow reserve is quietly spent while the patient is well. On exertion the myocardium demands several times more flow and there is none left to give, so the subendocardium, already the worst served layer, becomes ischaemic. Demand falls when the patient stops, and the pain settles.
Fixed stenosis, spent flow reserve: symptoms only on exertion, resting ECG usually normal, relieved by rest or nitrate within minutes.
You would find: Central chest tightness on walking uphill, gone within a few minutes of stopping or after a glyceryl trinitrate spray. Nothing to find on examination between attacks, and the resting ECG is usually normal.
- Acute coronary syndrome without ST elevation (unstable angina and NSTEMI)← from “The coronaries behave as functional end arteri…”
The plaque cap tears and platelets aggregate on the exposed subendothelial surface, forming a thrombus that occludes the artery partially or intermittently. Flow now falls below resting need, so ischaemia occurs without any extra demand. The subendocardium goes first, and subendocardial rather than full-thickness ischaemia is what produces ST depression rather than elevation.
Partial thrombotic occlusion, subendocardial ischaemia: ST depression or T inversion, and troponin is the only thing separating unstable angina from NSTEMI.
You would find: Chest pain at rest or on minimal effort, lasting longer and not settling with rest. ST depression or T wave inversion in a lead group. Normal serial troponin means unstable angina; a rise and fall means NSTEMI.
- ST elevation myocardial infarction (STEMI)← from “The coronaries behave as functional end arteri…”
The thrombus occludes the artery completely. Without established collaterals the territory infarcts from the subendocardium outwards until the full wall thickness is involved (transmural infarction), and that is what lifts the ST segment in the leads facing it. Necrosis begins roughly 20 to 30 minutes after complete occlusion and the wavefront is largely complete by about 6 hours, later where collaterals exist, which is why reperfusion is judged in minutes.
Complete occlusion, transmural wavefront from endocardium outwards: ST elevation localises the vessel, and time to reperfusion is the outcome.
You would find: Persistent crushing chest pain with ST elevation in a contiguous lead group, and a substantial troponin rise. The lead group names the likely artery. This calls for reperfusion now: primary angioplasty, or thrombolysis where timely transfer is not possible.
- Inferior infarction with heart block or right ventricular involvement← from “The left main and right coronary arteries aris…”
In a right dominant circulation one proximal right coronary occlusion can take the inferior wall, the right ventricle and the AV nodal artery together. Losing the node's supply gives sinus bradycardia or AV block. A stunned right ventricle cannot push blood through the lungs to fill the left side, so cardiac output becomes almost entirely preload dependent, and a venodilator that empties the veins can collapse the blood pressure.
Inferior ST elevation means think AV node and right ventricle: check V4R, expect preload dependence, and treat hypotension with fluid rather than a nitrate.
You would find: ST elevation in II, III and aVF with a slow pulse, or hypotension in someone whose lungs are clear. Ask for right sided chest leads: ST elevation in V4R indicates right ventricular involvement.
- Ischaemia with unobstructed arteries (demand ischaemia, type 2 myocardial infarction)← from “The left ventricle is perfused predominantly i…”
No plaque rupture is needed. A fast rate eats into diastole, when the left ventricular wall is perfused, while simultaneously raising demand. Anaemia or hypoxaemia lowers the oxygen content of each millilitre delivered, and hypotension lowers perfusion pressure. The subendocardium, perfused last, is starved. Correcting the arrhythmia, the anaemia or the sepsis resolves the ischaemia.
Supply-demand mismatch with open arteries: treat the precipitant, not the plaque, and expect the troponin to settle as the trigger is corrected.
You would find: Chest pain and a troponin rise in someone with fast atrial fibrillation, sepsis, severe anaemia or tight aortic stenosis, and coronary arteries that turn out to be unobstructed.
What we give, and how it works
Open a drug to see what it binds, what that does to the cell, and what you then see in the patient.
- Binds
- not a receptor: the drug is denitrated to nitric oxide inside vascular smooth muscle, and the nitric oxide activates soluble guanylate cyclase in that cell
- Which does
- cyclic GMP rises, protein kinase G lowers intracellular calcium and activates myosin light chain phosphatase, and the smooth muscle cell relaxes
- So you see
- veins dilate, so preload, ventricular wall tension and oxygen demand fall; epicardial arteries and collaterals dilate, redistributing flow toward ischaemic subendocardium. It has relatively little effect on the resistance arterioles, which is why it relieves angina rather than causing coronary steal
- And the same mechanism causes
- throbbing headache and facial flushing, because the same nitric oxide and cyclic GMP pathway dilates meningeal and cutaneous vessels, and hypotension where cardiac output is preload dependent
- Handling
- continuous exposure produces tolerance within about a day, so long-acting nitrates are used with a nitrate-free interval overnight; this changes how a preventive nitrate is scheduled, not whether it is used
Catches people out: Contraindicated within 24 hours of sildenafil or vardenafil and within 48 hours of tadalafil, which is far longer acting: both drugs raise cyclic GMP by different steps in the same pathway and the combination can cause profound hypotension. Also withhold in inferior infarction until right ventricular involvement has been excluded, because that ventricle depends on preload and a nitrate removes it.
- Binds
- beta-1 adrenoceptors on cardiac pacemaker and working myocardial cells (carvedilol additionally blocks alpha-1 receptors on vascular smooth muscle)
- Which does
- competitive blockade lowers Gs-coupled cyclic AMP and protein kinase A activity, reducing funny current and L-type calcium current, so pacemaker firing, AV conduction and contractility all fall
- So you see
- slower heart rate lengthens diastole, which both cuts oxygen demand and lengthens the window in which the left ventricle is perfused; blood pressure and contractility fall, further lowering wall stress
- And the same mechanism causes
- bradycardia, AV block, fatigue and exercise intolerance, and decompensation if started during acute low-output failure, all of them the intended negative chronotropy and inotropy carried too far
Catches people out: Avoid in existing significant bradycardia, in second or third degree heart block, and in acute decompensated heart failure with low output. Beta-1 selectivity is only relative, so avoid in poorly controlled or severe asthma; a cardioselective agent can be used with care in mild to moderate asthma or COPD when the cardiac indication is strong. They should not be stopped abruptly after prolonged use, because receptor upregulation makes rebound tachycardia and angina likely.
- Binds
- aspirin irreversibly acetylates cyclo-oxygenase-1 inside the platelet; the P2Y12 inhibitors block the platelet ADP receptor P2Y12 (clopidogrel and prasugrel irreversibly, as prodrugs requiring hepatic activation; ticagrelor reversibly and without activation)
- Which does
- aspirin abolishes thromboxane A2 production for the life of that platelet, which has no nucleus to make new enzyme, so the effect lasts the platelet lifespan of roughly 7 to 10 days; P2Y12 blockade prevents ADP-driven amplification and glycoprotein IIb/IIIa activation
- So you see
- platelets no longer aggregate effectively on the exposed plaque, so the growing thrombus is limited and reocclusion, including of a freshly stented segment, is much less likely
- And the same mechanism causes
- bleeding is the mechanism working elsewhere, not bad luck, and it is why the second agent is time-limited; aspirin also causes gastric mucosal injury because the same cyclo-oxygenase-1 makes the protective mucosal prostaglandins. Ticagrelor commonly causes breathlessness that is not cardiac, from inhibition of red cell adenosine uptake
- Handling
- clopidogrel needs CYP2C19 activation, so response is variable and reduced in poor metabolisers; prasugrel is avoided after prior stroke or TIA because of intracranial bleeding risk. Both facts change which agent is chosen
Catches people out: Chewed aspirin is absorbed within minutes, which is why it is given that way in suspected acute coronary syndrome. Dual therapy suppresses pathological clot and normal haemostasis to the same degree, so bleeding risk rises predictably; withholding it around surgery or after major bleeding is a balance against stent thrombosis.
- Binds
- HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, in the hepatocyte
- Which does
- hepatic cholesterol synthesis falls, intracellular sterol depletion activates SREBP-2, and the hepatocyte upregulates LDL receptors on its surface
- So you see
- LDL is cleared from the circulation, the lipid core of existing plaques shrinks and the cap stabilises, and inflammation within the plaque falls, so fewer plaques rupture
- And the same mechanism causes
- muscle aches and, uncommonly, true myopathy with a raised creatine kinase, arising from the same mevalonate pathway being blocked in skeletal muscle; a modest transaminase rise reflects the hepatic site of action
- Handling
- drugs that inhibit statin metabolism, such as clarithromycin and some azole antifungals, raise statin exposure and myopathy risk, which changes what is co-prescribed
Catches people out: After an acute coronary syndrome a high-intensity statin is standard regardless of the baseline cholesterol (Heart Foundation and eTG guidance in Australia). It does nothing for today's pain, being entirely about the next event, and muscle symptoms are the usual reason people stop it.
- Binds
- the dihydropyridine binding site on L-type (Cav1.2) calcium channels of arterial smooth muscle, to which these agents bind far more avidly than to the equivalent channels in nodal tissue
- Which does
- calcium entry falls, so less calcium-calmodulin is available to activate myosin light chain kinase, and the smooth muscle relaxes
- So you see
- arteries and arterioles dilate, afterload and blood pressure fall, epicardial coronary tone falls and spasm is relieved; because the vascular selectivity spares the nodes, heart rate is not directly slowed
- And the same mechanism causes
- ankle oedema, because precapillary arteriolar dilation raises capillary hydrostatic pressure while venules stay constricted; this is not fluid overload and does not respond to a diuretic. Flushing and headache follow from the same arterial dilation
- Handling
- these are the calcium channel blockers that can safely be combined with a beta blocker, unlike the rate-limiting group
Catches people out: Short-acting nifedipine is not used for angina, because abrupt vasodilatation causes reflex tachycardia, which shortens diastole and worsens the ischaemia. The non-dihydropyridines, verapamil and diltiazem, act on the AV node as well as the vessel, so combining one with a beta blocker risks profound bradycardia or complete heart block, and verapamil is avoided in significant left ventricular systolic dysfunction.
Read the lead groups as a map of arteries. II, III and aVF look at the inferior wall, usually right coronary. V1 to V4 look at the septum and anterior wall, left anterior descending. I, aVL, V5 and V6 look laterally, usually circumflex. So when you see inferior ST elevation you already know two more things before touching the patient: the AV node is usually fed by the same artery, so watch for bradycardia and heart block, and the right ventricle may be involved, so ask for right sided leads before a nitrate goes anywhere near them. Same drug, same disease, opposite result, decided by which artery. The caveat that keeps you honest is dominance: in the roughly 15% who are not right dominant, the inferior wall belongs to the circumflex.
Now test whether it stuck
Reading this through is not the same as being able to reconstruct it. Every question in the bank is free, with a full debrief on each option.