This is also relevant to the contractile function of the heart. Laplace stated that the pressure within a sphere is proportional to wall stress (in the heart this is equivalent to after-load) and inversely proportional to its radius. Thus, as the heart enlarges beyond the point at which Starling’s law conferred an advantage, the wall stress increases and cardiac output falls. The conduction system of the heart Each natural heart beat begins in the heart’s pacemakerthe sinoatrial (SA) node. This is a crescent-shaped structure that is located around the medial and anterior aspect of the junction between the superior vena cava and the right atrium (Fig. 11.4). Progressive loss of the diastolic resting membrane potential is followed, when the threshold potential has been reached, by a more rapid depolarization of the sinus node tissue. This depolarization triggers depolarization of the atrial myocardium. The atrial tissue is activated like a ‘forest fire’, but the activation peters out when the insulating layer between the atrium and the ventricle-the annulus fibrosus-is reached.
The depolarization continues to conduct slowly through the atrioventricular (AV) node. This is a small, bean-shaped structure that lies beneath the right atrial endocardium within the lower interatrial septum. The AV node continues as the His bundle, which penetrates the annulus fibrosus and conducts the cardiac impulse rapidly towards the ventricle. The His bundle reaches the crest of the interventricular septum and divides into the right bundle branch and the main left bundle branch. The right bundle branch continues down the right side of the interventricular septum to the apex, from where it radiates and divides to form the Purkinje network, which spreads throughout the subendocardial surface of the right ventricle.
The main left bundle branch is a short structure which fans out into many strands on the left side of the interventricular septum. These strands can be grouped into an anterior superior division (the anterior hemibundle) and a posterior inferior division (the posterior hemibundle). The anterior hemibundle supplies the subendocardial Purkinje network of the anterior and superior surfaces of the left ventricle, and the inferior hemibundle supplies the inferior and posterior surfaces. Impulse conduction through the AV node is slow and depends on action potentials largely produced by slow transmembrane calcium flux. In the atria, ventricles and His-Purkinje system conduction is rapid and is due to action potentials generated by rapid transmembrane sodium diffusion.
Nerve supply of the cardiovascular system
Adrenergic nerves supply atrial and ventricular muscle fibres as well as the conduction system. f31 Receptors predominate in the heart with both adrenaline and noradrenaline having positive inotropic and chronotropic effects. f32 Receptors predominate in the vascular smooth muscle . Cholinergic nerves from the vagus supply mainly the SA and AV nodes via M2 muscarinic receptors. The ventricular myocardium is sparsely innervated by the vagus. Under basal conditions vagal inhibitory effects predominate over the sympathetic excitatory effects resulting in a slow heart rate.
The coronary circulation
The coronary arterial system consists of the right and left coronary arteries. The right coronary artery arises from the right coronary sinus and courses through the right side of the atrioventricular groove, giving off vessels that supply the right atrium and the right ventricle. The vessel usually continues as the posterior descending coronary artery, which runs in the posterior interventricular groove and supplies the posterior part of the interventricular septum and the posterior left ventricular wall.
The left coronary artery arises from the left coronary sinus. The first part is known as the left main coronary artery, and is usually not more than 2.5 ern long. It then divides into the left anterior descending and the left circumflex arteries. The left anterior descending artery runs in the anterior interventricular groove and supplies the anterior septum and the anterior left ventricular wall. The left circumflex artery travels along the left atrioventricular groove and gives off branches to the left atrium and the left ventricle (marginal branches).
The sinus node and the AV node are supplied by the right coronary artery in 60% and 90% of people, respectively. Therefore, disease in this artery may cause sinus bradycardia and AV nodal block. The majority of the left ventricle is supplied by the left coronary artery, so that stenosis in the left main artery is extremely dangerous; total obstruction of this vessel is rarely compatible with life.
Functions of the vascular endothelium
The vascular endothelium is a cardiovascular endocrine organ which occupies a strategic interface between blood and body and has many regulatory roles:
• modulation of immunoresponses
• regulation of vascular cell growth
• vasomotor control
• pro- and anti thrombotic mechanism
• metabolic and immunological functions.
Enzymes located on the endothelial surface control the level of circulating compounds, such as bradykinin, serotonin, angiotensin and adenine nucleotides. In addition, the endothelium releases substances which affect vascular tone and platelet function. Many endothelium-derived substances have now been characterized and play an important role in the physiological control of the coronary circulation through the production of endotheliumderived
relaxing and contracting factors.
One of the most powerful substances, endotheliumderived relaxing factor (EDRF), has now been identified as nitric oxide (NO). The release of NO can be triggered by sheer stress (flow) and by a number of autocoids including bradykinin, histamine, noradrenaline, substance P, platelet-derived products, serotonin and thrombin. NO evokes relaxation of vascular smooth muscle and
inhibits platelet function through activation of soluble guanylate cyclase, which leads to an increase in the intracellular levels of cyclic 3,5-guanosine monophosphate. The potent vasomotor and anti-platelet properties of NO suggest a functional role of the endothelium in the maintenance of an adequate organ blood flow. Dysfunction of endothelial cells in controlling the underlying smooth muscle is an early sign of vascular disease, such as atherosclerosis, hypertension and cerebral or coronary vasospasm.
The normal endothelium is a non-thrombogenic surface, which under physiological circumstances does not react with platelets or blood constituents. NO inhibits platelet aggregation, adhesion and secretion. Several other factors contribute to the antiaggregatory activity of the endothelium. Endothelial cells offer a negatively charged surface which repels the negatively charged platelets. The endothelial lining of blood vessels forms prostacyclin which inhibits platelet aggregation and formation of platelet derived growth factors.
In addition to their inhibitory effects on platelet function, prostacyclin and NO act together to antagonize procoagulant factors such as thrombin and thromboxane A2. Other endothelium-derived compounds are also specific antagonists of the procoagulant activity of thrombin. Endothelial cells generate specific thrombin inhibitors that remove thrombin from the circulation and convert its procoagulant activity into anticoagulant activity. Examples of these are thrombomodulin, a surface receptor and heparin sulphate, a glycosaminoglycan, which activates antithrombin III. The endothelium also modulates fibrinolysis by generation of fibrinolytic components.
The fetal circulation
In utero, the pulmonary circulation is largely unnecessary because fetal blood is oxygenated by placental blood flow, a parallel and integral element in the systemic circulation. In the fetus, systemic venous blood returning to the rightatrium is partly deflected through the foramen ovale to the left atrium. Blood that passes through the right ventricle is diverted away from the pulmonary arteries to the aorta through the ductus arteriosus. Thus, the systemic venous return, which is a mixture of oxygenated and deoxygenated blood, is mostly returned to the systemic arterial system.
At birth, inspiration dilates the pulmonary arterioles, resulting in a dramatic reduction of pulmonary vascular resistance. Blood therefore flows through the pulmonary circulation. The increased oxygen tension and reduced levels of prostaglandins trigger closure of the ductus arteriosus, and the reduced right atrial pressure and increasing left atrial pressure tend to close the foramen ovale. Thus, the circulation is divided into two separate circuits connected in series. In the fetus the left and right heart both propel blood from the systemic veins to the systemic arteries; thus, severe abnormalities of the heart may not compromise fetal blood flow.
The cardiac cycle
The first event in the cardiac cycle is atrial depolarization (a p wave on the surface ECG) followed by right atrial and then left atrial contraction. Ventricular activation (the QRS complex on the ECG) follows after a short interval (the PR interval). Left ventricular contraction starts and shortly thereafter right ventricular contraction begins. The increased ventricular pressures exceed the atrial pressures, and close first the mitral and then the tricuspid valves. Until the aortic and pulmonary valves open, the ventricles contract with no change of volume (isovolumetric contraction). When ventricular pressures rise above the aortic and pulmonary artery pressures, the pulmonary valve and then the aortic valve open and ventricular ejection occurs. As the ventricles begin to relax, their pressures fall below the aortic and pulmonary arterial pressures, and aortic valve closure is followed by pulmonary valve closure. Isovolumetric relaxation then occurs. After the ventricular pressures have fallen below the right atrial and left atrial pressures, the tricuspid and mitral valves open.
The cardiac cycle can be graphically depicted as the relationship between the pressure and volume of the ventricle. This is illustrated which illustrates the changing pressure-volume relationships in response to increased contractility and to exercise.