Introduction: The Cardiac Cycle

A complete cardiac cycle occurs with each audible ‘lub-dub’ that is heard with a stethoscope. The purpose of the cardiac cycle is to effectively pump blood. During a heartbeat, both atria simultaneously contract followed by the contraction of the ventricles. Systole refers to the contractile phase of each chamber while diastole is the relaxation phase. The right heart delivers deoxygenated blood to the lungs. Here oxygen is picked up and carbon dioxide is breathed off. The left heart delivers oxygenated blood to the body. Normally, the volume of blood ejected by the right ventricle to the lungs is almost identical to the volume ejected by the left ventricle. A mismatch in volumes ejected by the ventricles (i.e. right ventricle pumps more blood than the left ventricle) can result in heart failure.

The synchronized actions of the atria and the ventricles are coordinated to maximize pumping efficiency. Rhythm disturbances can greatly impair this synchrony, resulting in a less effective cardiac cycle.

During ventricular systole, the tricuspid valve closes – otherwise, it remains open. At end atrial diastole and ventricular diastole, an open tricuspid valve provides a channel between the right atrium and the right ventricle. As a result, blood flows into both the right atrium and the right ventricle simultaneously. The ventricle receives up to 85% of its blood volume during this period.

Prior to ventricular systole, the atrium contracts. Since the atrium is about 1/3 the size of the ventricle, an atrial contraction only contributes an additional15-35% of blood volume to the ventricle. This ‘topping up’ of the ventricle by the atrium is called atrial kick. The conclusion of atrial systole coincides with the end of ventricular diastole. After ventricular end-diastole, the ventricle enters systole and contracts forcefully. As the pressure within the ventricle increases, the tricuspid valve closes to ensure forward blood flow. Very soon after, the pulmonic valve opens as pressure within the ventricle becomes greater than pulmonary artery pressure. Blood is then pumped into the pulmonary arteries.

As blood is ejected, ventricular pressure falls. When ventricular pressure is below the pulmonary artery pressure, the pulmonic valve closes to prevent back flow of blood into the right ventricle. The closure of the AV valves (tricuspid and mitral valves) normally produces the ‘lub’ heart sound. The closure of the semilunar valves (pulmonic and aortic valves) produces the ‘dub’ heart sound.
While ventricular systole ejects blood into either the pulmonary or systemic vascular systems, ventricular diastole is at least as important. Without a sufficient period of diastole, systole is ineffective. During diastole, the ventricles relax. But in relaxing, the ventricles open to regain their pre-contractile size, effectively dropping the chamber pressure below that of the vena cava. As a result, blood is drawn into the ventricle during ventricular (and atrial) diastole. Then the cardiac cycle begins again.
And this cardiac cycle is repeated over 100,000 times daily.

What is cardiac output?

Cardiac output (‘Q’ or ‘CO’) is the amount of blood ejected by the heart in a minute. It is pumped out of the left ventricle and is the product of stroke volume and heart rate. Sufficient cardiac output is necessary to sustain energy and life. The average cardiac output for an adult is about 5-8 litres blood in per minute.

Cardiac output is calculated via the following formula:

Cardiac Output (CO) = Stroke Volume (SV) x Heart Rate (HR)

With strenuous activity, the cardiac output of an adult can increase to 25 litres per minute to satisfy the body’s demands for oxygen and nutrients. Cardiac output is a product of heart rate (beats per minute) and stroke volume. Stroke volume is the amount of blood ejected by the left ventricle with each contraction.

The formula above can be used to find not only CO but also SV and HR. Let’s say a typical cardiac output is about 5000 ml (5 litres). We would like to find a patient named Sarah’s approximate stroke volume. Assuming Sarah has a pulse of 72/minute, we can identify her stroke volume by applying the formula:

5000 = ____(SV) X 72 (HR)

With a little math, Sarah’s stroke volume is calculated to be about 70 ml.

SV = 5000 / 72 = 70 ml

Therefore, each time Sarah’s left ventricle beats, it ejects about 70 ml of blood. This amount considered about average when it comes to stroke volume. A typical stroke volume for adults is 50-80 ml. How about your stroke volume?

Why is Cardiac Output important?

Cardiac output is essential to our wellbeing. Put simply, cardiac output is directly connected to energy production. Ample perfusion to the tissues produces an abundant energy supply. Poor tissue perfusion results in critical shortages of energy and often weakened function.

Blood, Oxygen and Aerobic Metabolism

On average, an adult has approximately 5-6 litres of blood (about 70 ml/kg). The blood has several functions in the human body as it delivers nutrients and removes wastes. Blood also transports messengers such as hormones between sites, thus facilitating communication and responsiveness between various organs. The continuous flow of oxygenated blood is therefore extremely important. This flow is vital to metabolism, the production of energy and other materials necessary for life. Energy production is synonymous with life. No energy…no life. Blood delivers oxygen and glucose to the tissues. One molecule of glucose is oxidized in the cell’s mitochondria to produce 36 adenosine triphosphate molecules (ATP).

O2 + Glucose = H2O + CO2

Metabolism that utilizes oxygen is called aerobic metabolism. The above equation is the balance of the much abbreviated Kreb’s cycle. The fact is that oxygen when combined with glucose produces a substantial amount of energy.

Note that ATP is the primary energy molecule for the body. Virtually every activity – thinking, movement, cardiac contraction, protein formation, etc. – requires ATP.
Without a constant production of ATP, each of these processes would cease.

Aerobic metabolism has by-products of water (H2O) and carbon dioxide (CO2). Water we can definitely use. In fact, about 2/5 of body fluids come from aerobic metabolism, from what is burned (or oxidized) rather than what is drank. And carbon dioxide is readily breathed off at about 20 times the rate that oxygen diffuses into the bloodstream. Aerobic metabolism is incredibly efficient and effective.
Sufficient cardiac output is necessary to deliver adequate supplies of oxygen and nutrients (glucose) to the tissues. This translates to the conclusion that cardiac output is directly related to energy production. Low cardiac output will reduce energy levels.

For example, if your cardiac output fell to 3.5 L/m (about 2/3 of normal) your oxygen -and hence your energy supply – would be decreased as well. Your brain with 1/3 less energy may be less sharp, confused or even unconscious. Your muscles with 1/3 less energy would feel weaker. In contrast, high cardiac output satisfies periods of high energy demand.

Anaerobic Metabolism

When energy demands exceed the supply of vital energy precursors such as oxygen, cells are left with the much less efficient anaerobic energy production – metabolism without oxygen. An insufficient supply of oxygen can occur due to hypoxia, obstructed blood vessels, anaemia or low cardiac output conditions.
Anaerobic metabolism is not an efficient energy producer

O2 + Glucose = LACTIC ACID

We have all experienced the effects of anaerobic metabolism after over-engaging in a strenuous activity. The next day our muscles are painful. This is because our blood vessels simply delivered insufficient amounts of oxygen and nutrients to satisfy the needs of these muscles. The muscles turned to anaerobic metabolism to boost the ATP supply. As a result, lactic acid accumulated in our tissues.

Ischemia

Anaerobic metabolism becomes increasingly important during periods of ischemia.
Ischemia results from an inadequate blood flow that fails to meet the oxygen demands (energy demands) of tissues. If tissues are subject to ischemia, they try to compensate by removing more oxygen from the blood. Tissue groups such as muscle or the intestines typically use only a third of the oxygen available to them.
The heart is the exception, extracting about 3/4 of the oxygen available to it through the coronary arteries. Because the heart does not have an abundance of extra oxygen available, it is extremely dependent on blood flow for sufficient oxygenation. With increased oxygen demand, the coronary arteries must dilate to increase this blood flow.

Organ Extracted O2 as Percentage of O2 Available

• Heart 75%
• Kidney 20%
• Skeletal Muscle 30%
• Intestine 35%
• Skin 8%

Note that the heart extracts most of the available oxygen from the blood even during periods when the body is at rest. The heart, then, has very little physiological reserve to respond to episodes of high energy demand. Rather, the heart depends almost entirely on increased coronary blood flow to satisfy high energy demand.
Anaerobic metabolism can buy some time for activities that occur sporadically (i.e. sprinting or weight lifting). Anaerobic metabolism does not produce enough
ATP to sustain the viability of cells that are engaged in rhythmic or continuous activity i.e. myocardial cells).

Low cardiac output can cause cardiac ischemia – perhaps more so for the heart than other organs because of the heart’s already high rate of oxygen extraction. A vicious cycle ensues. Cardiac ischemia forces a shift towards anaerobic metabolism (2 ATP) from the much more efficient aerobic metabolism (36 ATP). With less energy available and increased intercellular acidity, the force of contraction weakens, causing a further reduction in stroke volume and cardiac output.

The bottom line is that cardiac output is intimately coupled with energy production.
For the heart, low cardiac output may in turn cause ischemia. Cardiac ischemia weakens contractility, and directly affects cardiac output. Patients with cardiac ischemia, must assessed for signs and symptoms of poor cardiac output (shock).While patients experiencing shock states must be assessed for cardiac ischemia. Cardiac ischemia and poor cardiac output states often occur simultaneously.

Poor cardiac output tends to cause an increase in catecholamines (i.e. norepinephrine), which, combined with cardiac ischemia, can trigger serious dysrhythmias such as ventricular tachycardia and ventricular fibrillation.

Factors that affect cardiac output

Heart Rate

Heart rate and cardiac output have a direct relationship. As heart rate increases, so does cardiac output. As mentioned earlier, as energy demands rise (oxygen demands), cardiac output increases. A heart rate of 100/minute will almost always result in more blood ejected per minute than a heart rate of 80/minute. Take for example a person with an average stroke volume of 65 ml.
A 20% increase in heart rate (from 80 to 100/minute) yields a 20% increase in cardiac output (from 5.2 L/m to 6.5 L/m).
There is a definite limit to this logic. Heart rates of 260/minute are usually associated with signs and symptoms of shock, with a corresponding poor cardiac output. In fact, heart rates of more than 150/minute are often associated with a reduced cardiac output. Why? During diastole, the blood is drawn into the ventricle. This takes time, referred to as “filling time”. A very important parameter of cardiac output. Without an adequate filling time, the ventricle receives less blood. With less blood volume, stroke volume and cardiac output falls.

Heart Rate of 80/minute: CO = SV X HR = 65 X 80 = 5200
Heart Rate of 100/minute: CO = SV X HR = 65 X 100 = 6500

More realistically, stroke volume might also increase because catecholamine stimulation of the heart results in an increase in both heart rate and stroke volume. As a result, an increase in heart rate by 20% tends to increase cardiac output by more than 20%.
Parameters that Affect Cardiac Output 17
As heart rate increases, so does cardiac output – to a point. Cardiac output tends to fall when heart rate surpasses 150/minute due to inadequate filling time. Low cardiac output states also occur with low heart rates (<50/minute). Young and athletic people can have good cardiac outputs with heart rates greater than 150/minute and less than 50/minute. Those with cardiac disease often cannot tolerate heart rates as low as 50/minute or as high as 150/minute.
Conversely, if the heart rate is too low – say below 50/minute – cardiac output tends to fall quickly.
The ventricles have all the time they need to fill to the brim. Stroke volume is quite good. The problem is that there isn’t a sufficient heart rate.
Another example is in order here. Let’s continue with Henry. As Henry ages gracefully, unfortunately his sinus node begins to fail with a junctional escape rhythm resulting of only 40/minute. This long filling time might increase his stroke volume to 80 ml.

CO = SV X HR = 80 X 40 = 3200 ml/minute = 3.2 L/m

A cardiac output of 3.2 could leave Henry feeling quite unwell.

As a general rule, a patient with a heart rate that is too fast (>150/minute – not enough filling time) or too slow (< 50/minute – not enough rate) requires urgent assessment for signs and symptoms of shock. Both extreme rates can be associated with inadequate cardiac output. Signs and symptoms of shock include shortness of breath, chest pain, hypotension, and an altered level of consciousness (due to hemodynamic compromise).

As a general rule, patients with rates more than 150/minute or less than 50/minute are closely monitored for signs and symptoms of poor cardiac output. However, exceptions do exist. For example, peak performance athletes have very efficient, larger hearts with higher resting stroke volumes than the average population. A stroke volume of 100/minute and a heart rate of 50/minute would yield an acceptable cardiac output of 5 litres.
On the other side of the continuum, patients with a significant cardiac history (i.e. myocardial infarction and/or congestive heart failure) may have a low stroke volume.
Heart rates as high as 150/minute may be associated with cardiac ischemia and reduced cardiac output. A bradycardia of 50/minute combined with an already reduced stroke volume (i.e. 40 ml) could result in shock with a cardiac output of only 2000 ml.
The more pronounced a patient’s history of cardiac illness, generally the narrower is the range of heart rates that yield sufficient cardiac outputs. For example, a patient who becomes short of breath with minimal exertion i.e. walking to the bathroom.
These patients are often restricted to limited activities due to a narrow range inacceptable heart rates that yield sufficient cardiac outputs (i.e. 65-100/min). For this patient, a heart rate over 95/minute could cause a drop in cardiac output.
Heart rate is an important factor in any physical assessment, as is collecting a cardiac history. The seriousness of a cardiac rhythm is intimately connected with each.

Stroke Volume

While heart rate is an undisputed contributor to cardiac output, stroke volume is the other major player. As heart rates vary to changes in cardiac output demand, so does stroke volume. Stroke volume – the amount of blood ejected with each beat fluctuates with changes in preload, afterload, and catecholamine release.

Preload

The blood supply to the ventricle is often referred to as preload. Technically, the definition of preload is the volume or pressure in the ventricle at the end of diastole.
Note that atrial kick offers much to preload, especially for those getting on in years (contributing up to 35% of cardiac output). Preload is connected to stroke volume and cardiac output via the Frank-Starling law.

Parameters that Affect Cardiac Output

Most of us have heard of the Frank-Starling phenomenon (often referred to as
Starling’s Law). Frank and then Starling demonstrated that as cardiac muscle fibres stretch, contraction becomes more forceful. In other words, the more the stretch of the heart’s chambers, the more forceful the contraction (and indeed the greater the stroke volume).
Blood filling into the chambers increase pressures causing causes the heart’s chambers to stretch. Whether you refer to increased pressure or volume either way you are referring to preload. More preload causes more cardiac fibre stretch and increased contractility.

The resting healthy heart depicts the varying contractility of the myocardium with respect to changes in ventricular end diastolic pressure (preload).
The slope of each curve is the to this graph. Compare the healthy resting heart to the curves of both the diseased heart and the heart during strenuous activity. Notice how the effect of sympathetic stimulation (i.e. norepinephrine) during exercise results in a magnified effect of preload on contractility.
Compare the preload/contractility curve of the healthy heart with that of the diseased heart. While the healthy heart curves peak with a preload of about 12 mm of Hg, the diseased heart requires increased pressures to maximize contractility. The diseased heart depends more on preload than the healthy heart to drive an effective contraction.
Note that the higher the preload, the higher the myocardial workload. Therefore, high preload states (i.e. fluid overload) can make matters worse during ischemic episodes. And ischemia is one precursor to the development of serious dysrhythmias. Related to stroke volume is the term ‘ejection fraction’. An ejection fraction is determined by an echocardiogram or via a pulmonary artery catheter. Ejection fraction is the percentage of volume ejected from the left ventricle. The left ventricle has about 100 ml of blood just before contraction. Of this 100 ml, about 50-80 ml is normally ejected from the heart with each beat (stroke volume). Therefore, about 50 to 80 percent of blood is ejected. This is a normal ejection fraction.

Figure – Frank-Starling Curve

The Figure depicts the relationship between ventricular end diastolic pressure and contractility for a resting healthy heart, a resting diseased heart and a healthy heart during strenuous activity. Several points are evident here: 1) in general, the force of contraction (contractility) increases as the pressure within the ventricles increase (increases in pressure and volume increase both cardiac fiber stretch and contractility); 2)during strenuous activity, catecholamine release increases the force of contraction; 3) for the diseased heart (i.e. cardiomyopathies), the force of contraction is impaired; 4) increases in chamber pressure do not produce significant changes in contractility for the diseased heart; and 5) there is a limit to the affect of ventricular end-diastolic pressures (VEDP) on contractility. With high VEDP, contractility begins to fall. In other words, with high VEDP, contractility and stroke volumes tend to decrease.

Afterload

The resistance to the ejection of blood by the ventricle is called afterload. The left ventricle, for example, must create sufficient pressures during systole to overcome diastolic arterial pressure and systemic vascular resistance before any blood is ejected.
While preload enhances contractility and stroke volume, high pressures in the arterial vessels during ventricular end diastole is inversely related to stroke.

Similar to preload, increased afterload causes increased myocardial workload, a factor to consider for those with advanced cardiac disease and/or cardiac ischemia.
Afterload is also tied to cardiac hypertrophy. As the resistance to chamber contraction increases, the chamber adapts to this increased workload with the accumulation of increased fibre within the myocardial cells. This makes the cells stronger but also bulks up the cells, ultimately resulting in chamber hypertrophy. Unfortunately, these thicker chamber walls can be associated with additional complications such as decreased contractility, reduced stroke volume, and cardiac dysrhythmias.

Methods of Measuring Cardiac Output

There are several clinical methods for measuring and monitoring cardiac output each with strengths and limitations. Methods range from direct intracardiac catheterisation to non-invasive measurement of the arterial pulse. The value of Non-invasive methods of measuring cardiac output lies in its low-risk and convenient application to a variety of clinical settings.

• USCOM is an innovative ultrasonic monitor that measures safely and accurately beat by beat – the blood flow in a living person or animal and provides a measure of many other parameters of cardiac function. The USCOM monitor receives and analyses signals from an externally applied ultrasonic transducer (placed on the chest like a stethoscope). It responds immediately to any change that effects blood flow. Internal software translates the signals and the output can be seen in graphical format on a touch sensitive screen. No keyboard or mouse is required. The machine stores all its measurement results in individual patient records. These can be recalled and compared to study trend information.
• The Pulmonary Artery Catheter (PAC) has been, up until now, the Gold Standard of measurement for clinical use. This method measures how fast flowing blood can dilute an indicator substance introduced to the circulatory system. Early methods used a dye, the cardiac output being inversely proportional to the concentration of dye sampled downstream. A more modern technique is the use of injected cold saline with the change in temperature measured downstream. In the Swan-Ganz method (considered 80 -85% accurate) catheters are fitted with a heated filament, which heats the blood and measures the resultant thermodilution trace.
• Pulse Contour devices (considered 65-70 % accurate) calculate cardiac output by analysis of arterial pulse waveforms. Because waveform analysis cannot account for unmeasured variables such as compliance of the vascular tree, an independent technique must be used initially (and at regular intervals) to calibrate the software. Calibration is usually carried out using one of the methods of indicator dilution (cold saline or lithium chloride solution). A more recent development, yet to be extensively evaluated, can derive cardiac output from the arterial waveform without the need for an independent method of calibration.
• The Fick Principle (Adolf Eugen Fick (1829 -1901) is the basis of a number of other measurement methods. These rely on the uptake of an indicator gas from the lungs. Pulmonary blood flow can be calculated, if the amount of gas taken up in unit time and the solubility of the gas in blood is known. Acetylene, nitrous oxide and oxygen have all been used in the past. Current commercial devices use carbon dioxide.
• Impedance cardiography is a non-invasive method that monitors changing impedance in the chest, as the heart beats, to calculate cardiac output. A correction factor for sex, height and weight is required. The technique utilizes four pairs of electrodes placed in proscribed positions on the neck and thorax. Some indirect inferences about cardiac performance can be made from the impedance time waveform. It is of limited value in the critically ill, who often have very low baseline thoracic impedances due to increased lung water.
• Echocardiography (diagnostic ultrasound) produces an ultrasound image of the heart, it evaluates morphology (structure). It should not be confused with USCOM which measures the Doppler Shift in an ultrasound beam. Echocardiography is expensive and difficult to use accurately to calculate cardiac output. It is not really a viable option for serial haemodynamic assessments.
• Trans-oesophageal Doppler measurement of cardiac output, is in some ways similar to the USCOM monitor, in that it uses an ultrasound probe. However this is required to be placed in the mid-oesophagus via the nose or mouth. Although the probe is small, it is not well tolerated by conscious patients and its use is confined to sedated or anaesthetized patients.