9.4 Cardiac Physiology

Resting Cardiac Output

Cardiac output (CO) is a measurement of the amount of blood pumped by each ventricle in one minute. To calculate this value, multiply stroke volume (SV), the amount of blood pumped by each ventricle, by heart rate (HR), in contractions per minute (or beats per minute, bpm). It can be represented mathematically by the following equation:

CO = HR × SV

SV is normally measured using an echocardiogram to record EDV and ESV and calculating the difference: SV = EDV – ESV. SV can also be measured using a specialised catheter, but this is an invasive procedure and far more dangerous to the patient.

In humans, the mean CO is 5.25 L/min, with a range of 4.0–8.0 L/min (Note: CO from each ventricle separately, not the total for the heart). Various factors influence CO (Figure 9.23).

SVs are also used to calculate ejection fraction, which is the portion of the blood that is pumped or ejected from the heart with each contraction. To calculate ejection fraction, SV is divided by EDV. Despite the name, the ejection fraction is normally expressed as a percentage. Ejection fractions range from approximately 55–70 percent.

Correlation Between Heart Rates and Cardiac Output

Initially, physiological conditions that cause HR to increase also trigger an increase in SV. During exercise, the rate of blood returning to the heart increases. However, as the HR rises, there is less time spent in diastole and consequently less time for the ventricles to fill with blood. Even though there is less filling time, SV will initially remain high. However, as HR continues to increase, SV gradually decreases due to decreased filling time. CO will initially stabilise as the increasing HR compensates for the decreasing SV, but at very high rates, CO will eventually decrease as increasing rates are no longer able to compensate for the decreasing SV.

Cardiovascular Centres

Nervous control over HR is centralised within the two paired cardiovascular centres of the medulla oblongata (Figure 9.24). The cardioaccelerator regions stimulate activity via sympathetic stimulation of the cardioaccelerator nerves, and the cardioinhibitory centres decrease heart activity via parasympathetic stimulation as one component of the vagus nerve, cranial nerve X. During rest, both centres provide slight stimulation to the heart, contributing to autonomic tone.

Both sympathetic and parasympathetic stimulations flow through a paired complex network of nerve fibres known as the cardiac plexus near the base of the heart. Sympathetic stimulation causes the release of the neurotransmitter noradrenaline (NA) at the neuromuscular junction of the cardiac nerves. NA shortens the repolarisation period, thus speeding the rate of depolarisation and contraction, which results in an increase in HR. It opens chemical- or ligand-gated sodium and calcium ion channels, allowing an influx of positively charged ions.

Parasympathetic stimulation originates from the cardioinhibitory region with impulses traveling via the vagus nerve (cranial nerve X). The vagus nerve sends branches to both the SA and AV nodes, and to portions of both the atria and ventricles. Parasympathetic stimulation releases the neurotransmitter acetylcholine (ACh) at the neuromuscular junction. ACh slows HR by opening chemical- or ligand-gated potassium ion channels to slow the rate of spontaneous depolarisation, which extends repolarisation and increases the time before the next spontaneous depolarisation occurs. Decreasing parasympathetic stimulation decreases the release of ACh, which allows HR to increase (Figure 9.25).

Input to the Cardiovascular Centre

The cardiovascular centre receives input from a series of visceral receptors with impulses traveling through visceral sensory fibres within the vagus and sympathetic nerves via the cardiac plexus. Among these receptors are various proprioreceptors, baroreceptors, and chemoreceptors, plus stimuli from the limbic system. Collectively, these inputs normally enable the cardiovascular centre to regulate heart function precisely, a process known as cardiac reflexes. Increased physical activity results in increased rates of firing by various proprioreceptors located in muscles, joint capsules, and tendons. Any such increase in physical activity would logically warrant increased blood flow. The cardiac centre monitor these increased rates of firing and suppress parasympathetic stimulation and increase sympathetic stimulation as needed in order to increase blood flow.

Similarly, baroreceptors are stretch receptors located in the aortic sinus, carotid bodies, the venae cavae, and other locations, including pulmonary vessels and the right side of the heart itself. Rates of firing from the baroreceptors represent blood pressure, level of physical activity, and the relative distribution of blood. The cardiac centre monitor baroreceptor firing to maintain cardiac homeostasis, a mechanism called the baroreceptor reflex. With increased pressure and stretch, the rate of baroreceptor firing increases, and the cardiac centre decrease sympathetic stimulation and increase parasympathetic stimulation. As pressure and stretch decrease, the rate of baroreceptor firing decreases, and the cardiac centre increase sympathetic stimulation and decrease parasympathetic stimulation.

There is a similar reflex, called the atrial reflex or Bainbridge reflex, associated with varying rates of blood flow to the atria. Increased venous return stretches the walls of the atria where specialised baroreceptors are located. However, as the atrial baroreceptors increase their rate of firing and as they stretch due to the increased blood pressure, the cardiac centre responds by increasing sympathetic stimulation and inhibiting parasympathetic stimulation to increase HR. The opposite is also true.

Increased metabolic by-products associated with increased activity, such as carbon dioxide, hydrogen ions, and lactic acid, plus falling oxygen levels, are detected by a suite of chemoreceptors innervated by the glossopharyngeal and vagus nerves. These chemoreceptors provide feedback to the cardiovascular centre about the need for increased or decreased blood flow, based on the relative levels of these substances.

The limbic system can also significantly impact HR related to emotional state. During periods of stress, it is not unusual to identify higher than normal HRs, often accompanied by a surge in the stress hormone cortisol.

Other Factors Influencing Heart Rate

Using a combination of autorhythmicity and innervation, the cardiovascular centre can provide relatively precise control over HR. However, there are a number of other factors that have an impact on HR as well, including adrenaline, noradrenaline and thyroid hormones; levels of various ions including calcium, potassium, and sodium; body temperature; hypoxia (low oxygen); and pH balance (Table 9.1 and Table 9.2).

Table 9.1 Major factors increasing heart rate and force of contraction

Table 9.2 Factors decreasing heart rate and force of contraction

Adrenaline (A) and Noradrenaline (NA)

The catecholamines, adrenaline and noradrenaline, secreted by the adrenal medulla form one component of the extended fight-or-flight mechanism. The other component is sympathetic stimulation. Adrenaline and NA have similar effects: binding to the beta-1 receptors, and opening sodium and calcium ion chemical- or ligand-gated channels. The rate of depolarisation is increased by this additional influx of positively charged ions, so the threshold is reached more quickly and the period of repolarisation is shortened.

Thyroid Hormones

Increased levels of thyroid hormone (or thyroxine), increases cardiac rate and contractility. The impact of thyroid hormone is typically of a much longer duration than that of the catecholamines.

Calcium

Calcium ion levels have great impacts upon both HR and contractility; as the levels of calcium ions increase, so do HR and contractility. High levels of calcium ions (hypercalcaemia) may be implicated in a short QT interval and a widened T wave in the ECG. The QT interval represents the time from the start of depolarisation to repolarisation of the ventricles and includes the period of ventricular systole.

Factors Decreasing Heart Rate

HR can be slowed when a person experiences altered sodium and potassium levels, hypoxia, acidosis, alkalosis and hypothermia (Table 9.2). The relationship between electrolytes and HR is complex but maintaining electrolyte balance is critical to the normal wave of depolarisation. Of the two ions, potassium has the greater clinical significance. Initially, both hyponatraemia (low sodium levels) and hypernatraemia (high sodium levels) may lead to tachycardia. Severely high hypernatraemia may lead to fibrillation, which may cause CO to cease. Severe hyponatraemia leads to both bradycardia and other arrhythmias. Hypokalaemia (low potassium levels) also leads to arrhythmias, whereas hyperkalaemia (high potassium levels) causes the heart to become weak and flaccid, and ultimately to fail.

Heart muscle relies exclusively on aerobic metabolism for energy. Hypoxia (an insufficient supply of oxygen) leads to decreasing HRs, since metabolic reactions fuelling heart contraction are restricted.

Acidosis is a condition in which excess hydrogen ions are present, and the patient’s blood expresses a low pH value. Alkalosis is a condition in which there are too few hydrogen ions, and the patient’s blood has an elevated pH. Normal blood pH falls in the range of 7.35–7.45, so a number lower than this range represents acidosis and a higher number represents alkalosis. Recall that enzymes are the regulators or catalysts of virtually all biochemical reactions; they are sensitive to pH and will change shape slightly with values outside their normal range. These variations in pH and accompanying slight physical changes to the active site on the enzyme decrease the rate of formation of the enzyme-substrate complex, subsequently decreasing the rate of many enzymatic reactions, which can have complex effects on HR. Severe changes in pH will lead to denaturation of the enzyme.

The last variable is body temperature. Elevated body temperature is called hyperthermia, and suppressed body temperature is called hypothermia. Slight hyperthermia results in increasing HR and strength of contraction. Hypothermia slows the rate and strength of heart contractions. This distinct slowing of the heart is one component of the larger diving reflex that diverts blood to essential organs while submerged. If sufficiently chilled, the heart will stop beating, a technique that may be employed during open heart surgery. In this case, the patient’s blood is normally diverted to an artificial heart-lung machine to maintain the body’s blood supply and gas exchange until the surgery is complete, and sinus rhythm can be restored. Excessive hyperthermia and hypothermia will both result in death, as enzymes drive the body systems to cease normal function, beginning with the central nervous system.

Preload

Preload is another way of expressing EDV. Therefore, the greater the EDV is, the greater the preload is. One of the primary factors to consider is filling time, or the duration of ventricular diastole during which filling occurs. The more rapidly the heart contracts, the shorter the filling time becomes, and the lower the EDV and preload are. This effect can be partially overcome by increasing the second variable, contractility, and raising SV, but over time, the heart is unable to compensate for decreased filling time, and preload also decreases.

With increasing ventricular filling, both EDV or preload increase, and the cardiac muscle itself is stretched to a greater degree. At rest, there is little stretch of the ventricular muscle, and the sarcomeres remain short. With increased ventricular filling, the ventricular muscle is increasingly stretched and the sarcomere length increases. As the sarcomeres reach their optimal lengths, they will contract more powerfully, because more of the myosin heads can bind to the actin on the thin filaments, forming cross bridges and increasing the strength of contraction and SV. If this process were to continue and the sarcomeres stretched beyond their optimal lengths, the force of contraction would decrease. However, due to the physical constraints of the location of the heart, this excessive stretch is not a concern.

Any sympathetic stimulation to the venous system will increase venous return to the heart, which contributes to ventricular filling, and EDV and preload. While much of the ventricular filling occurs while both atria and ventricles are in diastole, the contraction of the atria, the atrial kick, plays a crucial role by providing the last 20–30 percent of ventricular filling.

Contractility

It is virtually impossible to consider preload or ESV without including an early mention of the concept of contractility. Indeed, the two parameters are intimately linked. Contractility refers to the force of the contraction of the heart muscle, which controls SV, and is the primary parameter for impacting ESV. The more forceful the contraction is, the greater the SV and smaller the ESV are. Less forceful contractions result in smaller SVs and larger ESVs. Factors that increase contractility are described as positive inotropic factors, and those that decrease contractility are described as negative inotropic factors (ino- = “fibre;” -tropic = “turning toward”).

Sympathetic stimulation increases heart contractility (positive inotropy) by releasing norepinephrine and adrenaline, which bind to cardiac receptors, raise metabolic activity, and enhance calcium influx—resulting in stronger contractions and increased stroke volume. In contrast, parasympathetic stimulation, primarily via acetylcholine from the vagus nerve, reduces contractile strength (negative inotropy), especially in the atria, by hyperpolarising the membrane and lowering preload. Positive inotropic agents include catecholamines, thyroid hormones, glucagon, dopamine, and digitalis, all of which boost intracellular calcium to strengthen contractions. Negative inotropes, such as beta blockers, calcium channel blockers, hypoxia, acidosis, and hyperkalaemia, reduce contraction strength and stroke volume.

Afterload

Afterload refers to the tension that the ventricles must develop to pump blood effectively against the resistance in the vascular system. Any condition that increases resistance requires a greater afterload to force open the semilunar valves and pump the blood. Damage to the valves, such as stenosis, which makes them harder to open will also increase afterload. Any decrease in resistance decreases the afterload. Figure 9.26 summarises the major factors influencing SV, Figure 6.4.5 summarises the major factors influencing CO, and Table 9.3 and Table 9.4 summarise cardiac responses to increased and decreased blood flow and pressure in order to restore homeostasis.

Table 9.3 Cardiac response to decreasing blood flow and pressure due to decreasing cardiac output

Table 9.4 Cardiac response to increasing blood flow and pressure due to increasing cardiac output

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