Abstract
The Frank–Starling law (also known as Starling’s law of the heart) states that the strength of ventricular contraction is dependent on the length of the resting fibres. In other words, when all other factors are kept constant, an increase in left ventricular preload causes stroke volume (SV) to increase, without the need for extrinsic neural or humoral regulatory mechanisms. As left ventricular preload (i.e. left ventricular end-diastolic volume, LVEDV) is difficult to measure, left ventricular end-diastolic pressure (LVEDP) is often used as its surrogate marker. The relationship between SV and LVEDP is nonlinear (Figure 30.1).
What is Starling’s law of the heart?
The Frank–Starling law (also known as Starling’s law of the heart) states that the strength of ventricular contraction is dependent on the length of the resting fibres. In other words, when all other factors are kept constant, an increase in left ventricular preload causes stroke volume (SV) to increase, without the need for extrinsic neural or humoral regulatory mechanisms. As left ventricular preload (i.e. left ventricular end-diastolic volume, LVEDV) is difficult to measure, left ventricular end-diastolic pressure (LVEDP) is often used as its surrogate marker. The relationship between SV and LVEDP is nonlinear (Figure 30.1).
Figure 30.1 The Frank–Starling curve.
The mechanism of Starling’s law remains incompletely understood. It has been traditionally attributed to the degree of overlap of the actin and myosin myofilaments in diastole, which in turn determines the extent of crossbridge formation on activation. This is known as the length–tension relationship:
The maximal force of contraction occurs when the sarcomere is stretched to around 2.2 μm. This length corresponds to an optimal point where the number of actin and myosin crossbridges formed is high (Figure 30.2b) but there is no overlapping of the thin filaments. In a normal heart, this optimal sarcomere length corresponds to an LVEDP of approximately 10–12 mmHg.
When the sarcomere is shorter than 2.2 μm (i.e. end-diastolic volume is decreased and the sarcomere is less stretched), overlapping of thin filaments reduces the tension that may be generated (Figure 30.2a):
– Contractile energy is lost due to work against friction.
– The sarcomere becomes distorted.
When the sarcomere is stretched beyond 2.2 μm, fewer actin–myosin crossbridges are formed; the force of contraction is thus reduced (Figure 30.2c). This situation does not occur in the normal heart, but may occur in ventricular failure.
At 3.6 μm, there is no overlap between actin and myosin myofilaments; the active tension developed is zero (Figure 30.2d).
The most important consequence of the Frank–Starling mechanism is the matching of SV between the right and left sides of the heart. An increase in venous return to the right ventricle (RV) increases its SV, resulting in a greater pulmonary blood flow, a greater LVEDV and hence a greater left ventricular SV. If the left ventricle (LV) ejected just 1 mL of blood less than the RV per cycle, after an hour the pulmonary circulation would contain over 3 L of additional blood.
What is cardiac failure?
Cardiac failure (or heart failure) is said to occur when the heart is unable to provide sufficient cardiac output (CO) to meet the demands of the tissues. Heart failure may either be:
High-output heart failure: CO is normal, but the tissue O2 demand is high, such as in thyrotoxicosis and pregnancy.
Low-output heart failure: the tissue’s O2 demand is normal, but the CO is insufficient to meet it.
In low-output failure, either the RV or LV may be affected in isolation, resulting in right ventricular failure (RVF) or left ventricular failure, respectively. In addition, progressive pump failure of the LV may lead to RVF – this is known as congestive cardiac failure. Heart failure may be classified as follows:
Systolic heart failure, in which the pump function of the heart is impaired; that is, ejection fraction is reduced to below 45% (Figure 30.3). At 20%, the annual mortality of patients with systolic heart failure is higher than many cancers; patients also suffer considerable morbidity. Systolic heart failure occurs when the strength of myocardial contraction is inadequate due to:
– Dysfunction of myocytes as a result of ischaemia (coronary artery disease), inflammation (myocarditis), congenital disease (Duchenne muscle dystrophy) or following myocardial infarction and scar formation. The reduction in SV leads to an increased LVEDV, and in turn the size of the heart is increased; this pathological dilatation of the heart is known as cardiomegaly.
– Chronically raised afterload; for example, systemic hypertension or aortic stenosis. Chronically increased afterload causes a compensatory left ventricular concentric hypertrophy. Over time, further increases in afterload exceed the heart’s ability to compensate by hypertrophy. SV becomes reduced and LVEDV increased.
Whatever the cause, the heart must then expend more energy to achieve a normal SV. This increases myocardial O2 demand, thus reducing cardiac reserve. A vicious positive feedback ensues during periods of increased demand (e.g. during exercise), where increased myocardial O2 demand in the face of low output exacerbates the failure.
Diastolic heart failure, in which ventricular compliance is reduced, either as a result of impaired ventricular relaxation (e.g. in ischaemic heart disease, restrictive cardiomyopathy) or as a result of pathological ventricular hypertrophy (e.g. in hypertension, hypertrophic obstructive cardiomyopathy, aortic stenosis). Reduced ventricular compliance leads to impaired ventricular filling and thus reduced SV. Because atrial contraction makes a significant contribution to ventricular filling in these patients, a fourth heart sound may be heard. The development of atrial fibrillation significantly reduces ventricular filling; a high heart rate results in reduced diastolic filling time, thus reducing LVEDV further. Rate control using β-blockers or Ca2+ channel antagonists helps prevent this.
Diastolic heart failure is being recognised increasingly commonly, and often coexists with systolic heart failure. Annual mortality in diastolic heart failure is 8% – less than that of systolic heart failure. Again, these patients suffer significant morbidity.
