The term ‘coronary’ was first conceived to describe a crown-like arrangement of the arterial blood vessels supplying the heart muscle. If the heart is considered as an upside-down cone with the flat base placed at the level of the atrioventricular groove, then the coronary arteries may be visualized as a ring at the base of the cone with branches which pass towards the tip (Fig. 5.1). This network of coronary arteries arises from two main origins in adjacent aortic sinuses. The anterosuperior sinus gives rise to the right coronary artery (RCA). This passes down the anterior atrioventricular (AV) groove. It gives rise to marginal branches which supply the anterior free wall of the right ventricle (RV). At the junction between the anterior and inferior aspects of the RV it gives off a significant branch—the acute marginal artery. It then passes inferiorly and in 70% of subjects terminates in a right posterior descending branch which supplies the inferior aspects of the RV, left ventricle (LV) and interventricular septum.

Fig. 5.1 Major coronary arterial blood vessels.

The posterior aortic sinus gives rise to the left coronary artery stem which quickly branches into the left circumflex artery. This mirrors the right coronary artery in the posterior AV groove and likewise gives off marginal branches. The other branch is the left anterior descending (LAD) artery which passes down the anterior interventricular groove to the apex and turns on to the posterior surface where it passes in the posterior interventricular groove for a variable distance. During this course the LAD gives off diagonal and septal perforating branches which supply the anteroseptal, anterolateral and apical portions of the left ventricle and the anterior papillary muscle.

The left circumflex artery gives off marginal branches, the obtuse marginal artery being a dominant feature. It passes inferiorly and usually terminates. In some individuals it turns to form a left posterior descending artery which follows the interventricular groove to a watershed with the distal portion of the LAD.

The precise arrangement of branches is variable. In about 70% of individuals the right coronary is dominant and its posterolateral and right posterior descending branches supply the inferior interventricular septum, left ventricular free wall and posterior papillary muscle. In 20% of individuals the left circumflex artery is dominant and gives rise to a left posterior descending artery and supplies the inferior portion of the heart. In 10% neither is dominant and the supply is shared.

The sinoatrial node is supplied by a branch of the RCA in 60% of cases and from the circumflex artery in 40%. The AV node is supplied by the RCA in 90% of cases. Damage to vessels supplying portions of the conducting system may lead to specific defects. In the case of damage to the sinus nodal artery it may lead to ‘sick sinus syndrome’ in which the frequency of generation of cardiac action potentials becomes randomly variable and inappropriate (tachy-brady syndrome). Damage to the supply to the AV node or bundle of His may lead to complete heart block (see Chapter 3) and is particularly associated with inferior myocardial infarction.

Though the arteries cross the surface of the heart, because they pass in the atrioventricular and interventricular grooves they clearly delineate the main chambers of the heart. The majority of the venous drainage is via a system of veins which run against the arterial system back to vessels which drain round the atrioventricular groove. Passing posteriorly is the great cardiac vein and passing anteriorly is the small cardiac vein, both of which drain into the coronary sinus. The coronary sinus passes under the floor of the left atrium and into the right atrium. The anterior cardiac veins drain directly to the right ventricle and atrium. The remainder of the venous drainage is in the tiny Thebesian veins which also connect mainly to the right atrium and right ventricle.

An imbalance between the oxygen demands of the heart and amount that can be supplied by the coronary blood supply leads to the development of an hypoxic pain originating in the heart which is called angina (see p. 55). An outline of a clinical case history is shown in Case 5.1:1.

Case 5.1 Blood supply to the heart: 1

Development of chest pain with exercise

Colin Davies is a 50-year-old smoker. Over the last 3 months he has noticed that he has became more short of breath than usual when walking to the local shops. He has a sensation of pressure and tightness in his chest. More recently he found that when he walks up the stairs in his house he gets a dull, aching pain which feels to come from the left side of his chest and extends down his left arm.

Colin saw his GP who suspected angina pectoris and arranged for him to have an exercise test at the local hospital. After 4 minutes on the treadmill Colin was feeling short of breath and had developed pain in his chest. The ECG showed ST segment depression in the lateral chest leads (V₄–V₆). The test was terminated at 4½ minutes when Colin felt he could not go on. His pain disappeared after 1 minute of rest and this was accompanied by the resolution of the ST segment changes on his ECG.

Colin’s blood pressure was normal and his GP checked his fasting blood lipids and glucose which were also normal. The GP strongly recommended that he stop smoking. In view of Colin’s symptoms and exercise test results his GP commenced him on oral glyceryl trinitrate (GTN) spray. He explained that this was to be used whenever Colin had chest pain symptoms.

This case history raises the following questions:

1. Why does angina pain occur and why does it get worse with exercise?

2. What is meant by ST segment depression and what does this change in the ECG suggest?

3. Why did the GP check Colin’s blood pressure and fasting plasma lipids and glucose?

4. How do nitrate drugs such as GTN help to relieve angina?

Aspects of the answers to these questions are to be found in the text of this chapter. ECG changes are discussed in Chapter 7.

Interesting facts

Under resting conditions, the heart muscle extracts about 75% of all the oxygen which arrives in the coronary arteries. A substantial increase in oxygen delivery can only be provided by an increase in coronary blood flow not by further extraction of oxygen from haemoglobin. The corollary of this is that disease-related limitation of coronary blood flow impairs cardiac performance and leads to cardiac pain (angina).

Regulation of coronary blood flow

At rest the myocardium receives about 5% of cardiac output. In the normal ‘textbook’ person there is a potential for cardiac output to increase about fivefold during exercise (see Chapter 13). This is roughly paralleled by changes in coronary blood flow and the necessity for this is largely dictated by the high oxygen extraction rate of cardiac muscle.

In skeletal muscle, under resting conditions, only of the order of 25–30% of the oxygen carried in arterial blood is extracted for use in the muscle (Fig. 5.2). The saturation of haemoglobin with oxygen in skeletal muscle therefore decreases from about 97–98% (arterial blood) to about 70% (venous blood). Even under resting conditions the venous drainage from cardiac muscle is only 25% saturated, meaning that of the order of 75% of the oxygen in arterial blood has been extracted and used metabolically. During exercise, increased oxygen delivery to contracting skeletal muscle can be provided by a combination of increased blood flow (see Chapter 13) but also by increased (up to 80–90%) extraction of oxygen from haemoglobin. In the heart as oxygen extraction at rest is already about 75% there is limited scope for increasing oxygen delivery by this route. Studies with ¹¹C-acetate positron emission tomography (PET) scanning suggest that, in the heart, oxygen extraction from arterial blood can rise to 90% during exercise but even this is a limited way of increasing oxygen delivery. The bottom line is that if the heart needs increased oxygen supply it must be mainly provided by increased coronary blood flow. The corollary of this is that pathological mechanisms which impair coronary blood flow must limit cardiac performance.

Fig. 5.2 Oxygen–haemoglobin dissociation curve. Extraction of oxygen from arterial blood in skeletal muscle is typically 25–30%. Oxygen extraction by cardiac muscle even under resting conditions is 75%.

Coronary blood flow, particularly to the left ventricle, is particularly affected by the contraction of the myocardium which crushes coronary vessels (Fig. 5.3). This mainly affects blood vessels in the subendocardial layers of the heart muscle and the blood vessels on or close to the surface of the heart are relatively unaffected. The subendocardial layers are therefore more prone to ischaemic damage. In the left ventricle, because of the high pressures developed in the contracting ventricle, coronary blood flow is much higher during diastole than during systole. In the right side of the heart intraventricular pressures are lower and so the effect of ventricular systole on coronary blood flow is less marked. When heart rate increases during exercise the duration of diastole is shortened more markedly than the duration of systole. This imposes a limitation on increases in coronary blood flow and is probably the limiting factor on maximum exercise ability in normal individuals.

Fig. 5.3 Right and left coronary blood flow correlated with ventricular pressure.

Coronary blood flow is autoregulated (Fig. 5.4). This means that over a range of mean arterial pressures, probably in humans from about 50 to 120 mm Hg, coronary blood flow is relatively independent of arterial pressure. This is thought to result especially from responses of arterioles which are less than 150 μm diameter. Thus, as the arterial pressure increases through the autoregulatory range the smooth muscle in the wall of these arterioles contracts to maintain flow constant.

Fig. 5.4 Autoregulation of coronary blood flow.

‘Myogenic’ effects on vascular smooth muscle mean that stretch of smooth muscle results in contraction. It is a mechanism that was first described by Bayliss in 1902 and is probably the dominant mechanism providing autoregulation of coronary flow. There are complex interactions between various blood vessel microdomains and possibly also with non-myogenic components which provide the overall autoregulatory response.

The major regulatory factor determining coronary blood flow is myocardial oxygen demand coupled to the production of vasodilator metabolites. These metabolites particularly affect blood vessels in the 150–170 μm size range. The vascular smooth muscle is thought to be particularly sensitive to changes in [adenosine], [K⁺], [H⁺] and to local changes leading to an increase in interstitial osmolarity (see Chapter 9). A major part of this vasodilator action is mediated by the opening of ATP-sensitive K⁺ channels. This leads to hyperpolarization and consequently to relaxation of the smooth muscle.

The source of the vasodilator adenosine has been a subject of conjecture. Berne (1980) proposed that it was produced under hypoxic conditions by the complete dephosphorylation of ATP. An alternative pathway was put forward by Deussen (1989), in which adenosine was formed from ATP via the intermediate formation of S-adenosyl methionine and S-adenosyl homocysteine. Both pathways are thought to contribute to interstitial [adenosine]. The following points seem to be relevant to understanding these events. ATP, ADP and AMP are all polar molecules as a result of ionization of their phosphate groups and will not easily cross cell membranes. Adenosine is non-polar and can leave the myocardial cell once it has been formed. Adenosine in the interstitium has a very short half-life (of the order of 10 s) and so must be continuously generated. [ATP] inside cells is about 5 mmol/L but interstitial [adenosine] is about 10 nmol/L, a 500 000-fold difference in concentration. Therefore, only a very small proportion of the intracellular ATP would need to be metabolized to provide relatively big changes in interstitial [adenosine] (Fig. 5.5).

Fig. 5.5 Regulation of coronary vascular smooth muscle contraction by the metabolite adenosine and by the endothelial cell-derived mediator nitric oxide (NO).

Endothelial influences on blood vessel diameter are described elsewhere (see Chapter 9). Increased shear stress on the endothelium leads to production of nitric oxide and thence to vasodilatation. This occurs particularly in large coronary arteries but it does not appear to contribute to the mechanism of autoregulation. Endothelial dysfunction leading to impaired nitric oxide release is a characteristic of a number of pathological conditions which will affect the coronary blood vessels including hypercholesterolaemia, atherosclerosis and hypertension. Assessment, prevention and treatment of endothelial dysfunction is emerging as an important area of clinical medicine, especially in relation to the coronary circulation.

Modulation of coronary blood flow via the sympathetic nervous system primarily acts through α₁-adrenoceptors on relatively large vessels. Vessels less than 100 μm diameter predominantly have α₂-adrenoceptors but α₁-receptors are also present. Activation of either of these populations of α-receptors leads to vasoconstriction and this is the dominant sympathetically mediated response. In the past there has sometimes been confusion about the role of β-receptor-mediated vasodilatation. Although such receptors do exist in limited numbers on coronary vessels, the vasodilator response which follows β-agonist infusion is mainly a result of increased metabolite (e.g. adenosine) generation following an increased force of ventricular muscle contraction (i.e. an inotropic response). Coronary vasodilatation directly as a result of β-adrenoceptor activation is a very minor component of coronary vascular control.

The role played by cardiac sympathetic nerves in relation to coronary blood flow is still controversial. During exercise the effects of sympathetic vasoconstrictor nerves are overwhelmed by the effects of vasodilator metabolites. However, α-receptor-mediated coronary vasoconstriction may, in some circumstances, contribute to the genesis of the ischaemic pain angina.