Rhythmic excitation

For a muscular pump to provide continuous blood flow through the circulation there must be a system that guarantees generation of muscle action potentials at regular intervals. The normal rhythm generator or pacemaker is a small group of cells that lies high in the wall of the right atrium, constituting the so-called sinoatrial node. The membranes of these cells have an unusually high sodium conductance and contain metabolic pumps that progressively reduce potassium conductance. These two properties together result in the membrane potential depolarizing gradually towards zero in what is termed the pacemaker potential, rather than them having a stable resting membrane potential of around −70 mV as is characteristic of the normal cardiac muscle cells. Since the threshold membrane potential for action potential initiation is around −40 mV, the pacemaker cells fire an action potential as soon as they depolarize to this threshold. As in any excitable cell, the action potential activates a delayed potassium efflux and this repolarizes the cells to around −70 mV but, once these voltage-gated potassium channels close, the membrane starts to depolarize once more and initiates another action potential.

The period between successive action potentials in a sinoatrial node cell at 37° C (98.5° F) is around 600 ms, giving an inherent frequency of cardiac excitation of about 100 beats/min. In the intact body, however, the slope of the pacemaker potential is subject to tonic influences by thoracic sympathetic nerves that increase the slope and speed up heart rate (tachycardia) and vagal parasympathetic nerves that reduce the slope and slow the heart down (bradycardia). In a resting subject, both of these neural inputs are continuously active but the bradycardic effect of the parasympathetic input predominates, so that resting heart rate is normally less than 100 beats/min and typically around 65–75 beats/min.

Duration of pressurization

It takes only about 50 ms to pressurize the blood contained within the cardiac chambers, but physical movement of that blood out into the arterial system takes several times longer and so ventricular compression needs to be maintained for much longer than in other types of muscle cell. This maintained pressurization is due to the presence of slow voltage-gated calcium channels whose opening follows the fast sodium-dependent rising phase of the action potential and which remain open for several hundred ms. Inward movement of calcium through these channels produces the characteristic plateau phase of the cardiac action potential. The calcium channel cycle time and the action potential plateau phase are shorter in atrial than in ventricular muscle cells, reflecting the fact that ejection from the ventricles has to overcome a greater downstream resistance than that faced by the atria and so movement of the same volume of fluid takes longer.

Delay between atrial and ventricular activation

For impulses from the sino-atrial node to produce synchronized contractions of the whole heart, the cardiac myocytes need to be coupled into an electrical syncytium. The position of the sinoatrial node within the atria means that action potential spread necessarily activates the atrial muscle first and only then gains access to the ventricles. This provides the correct sequence required for pumping of blood from atria to ventricles, but a single syncytium encompassing atria and ventricles would be impracticable, since ventricular pressurization would begin almost immediately after atrial contraction, allowing insufficient time for ventricular filling to be completed. Instead, the syncytium of the atria and the syncytium of the ventricles are separated by an insulative layer of connective tissue, with electrical continuity between atria and ventricles only via the specialized cells of the atrioventricular (A/V) node. These cells are very small in diameter and, therefore, conduct action potentials very slowly, conferring a delay of 120–200 ms between the beginning of atrial muscle depolarization and the arrival of action potentials in the ventricular muscle.

Direction of ventricular pressure gradient

The ventricular chambers are elongated, with the outlets into the arterial system lying at their rostral ends adjacent to the A/V margin. Efficient blood ejection, therefore, requires progressive development of pressure from the ventricular apex towards the exit site, although the apical region is furthest away from the point of entry of action potentials through the A/V node. To achieve the appropriate sequence of ventricular activation, the ventricular end of the A/V node is connected to a branching system of large-diameter (that is, fast-conducting) cells forming the Purkinje system. This conducting system travels down each side of the interventricular septum, bypassing the more rostral regions of the ventricular muscle and directing excitation directly to the endocardial surface of the ventricular apices. Excitation then propagates back through the syncytium towards the A/V margin, pushing the ventricular contents towards its arterial exit points. The efficiency of ejection is further enhanced by the fact that the muscle making up the outer ventricular walls is arranged spirally, so that when it contracts it produces a wringing movement.

Guaranteed time for filling

After ventricular contraction finishes and the heart relaxes, there must be time for the ventricles to relax completely so that they can refill. Thus, a safety mechanism must exist to guard against another action potential causing re-excitation while some muscle cells are still contracted. To achieve this the voltage-gated calcium channels in the endocardial muscle cells nearest to the conducting system have longer cycle times than those in the more superficial muscle layers, with correspondingly longer plateau phases and refractory periods. Thus, the cells that are coupled to the Purkinje system will remain electrically non-excitable until the rest of the ventricular muscle has repolarized and relaxed. The difference in channel cycle time between endocardium and epicardium is due at least partly to the higher pressure that is exerted on membranes of the endocardial cells when the heart wall contracts.

An additional safety factor is that the action potential plateau of the Purkinje fibres themselves is significantly longer than that of any ventricular myocardial cell, so that a second impulse is unlikely even to reach the ventricular myocardium until this has relaxed entirely.

Existence of a finite relaxation period is a prerequisite for nutritional perfusion of the ventricular myocardium. The coronary arteries that supply the heart arise from the aorta and so the pressure gradient responsible for coronary blood flow is essentially identical to that generated by the left ventricle. Because ventricular ejection must involve at least equivalent pressure being developed within the left ventricular wall, the left coronary arteries are mechanically occluded during the ejection phase of the cardiac cycle (termed systole) and nutritional perfusion can occur only during the relaxation phase (termed diastole). As will be discussed in Chapter 8 (p. 95), coronary perfusion of the right ventricle is more continuous, since the ventricular pressure developed there is much lower than systemic arterial pressure, and so the vasculature is perfused during systole as well as diastole.

Coordination of right and left outputs

Since the systemic and pulmonary circulations are in series, they must each pump identical volumes of blood per unit time. It is, therefore, essential that both ventricles eject blood simultaneously. This coordinated timing is ensured by the fact that the Purkinje system conveys action potentials simultaneously to the apices of both ventricles. Even with exact timing, however, the left ventricle needs to generate a far greater ejection pressure than the right ventricle in order to eject the same volume of blood, because the systemic vasculature has a much higher resistance than does the pulmonary vasculature. To provide the extra degree of pressurization, the left ventricle is wrapped with an additional spiral layer of muscle.

Increased venous return, for example in response to lying down, will produce a corresponding rise in end-diastolic ventricular volume. If the volume of blood ejected with each systolic contraction (the stroke volume) remained constant, there would be progressive pooling of blood in the heart and a progressive fall in cardiac output, so it is important that stroke volume can be matched automatically to ventricular filling. This is achieved by the resting length of all ventricular muscle fibres being substantially below the length that would correspond to optimal actin/myosin crossbridging and development of maximal active shortening. With increased filling, the increased resting sarcomere length that results from passive stretch of the ventricular wall will therefore result in increased active tension. This phenomenon is known as the Frank-Starling relationship.

Basis of the electrocardiogram