Magnitude of pumping ability is an arbitrary measure that determines heart contractility. It depends on many factors, some of them being: degree of sympathetic stimulation, myocardial damage, effect of drugs etc.
Volume depicts the body blood volume in the intravascular compartment, which is about 75 mL/kg of body weight or about 5.5 L on average.
Resistance to venous return is the quality of the circulation which impacts the flow of blood from the periphery to the heart. It can be postulated that one half of resistance to venous return is fixed due to a relatively stable venous resistance and one half is proportional to the systemic vascular resistance.
The cardiovascular system is a close circuit, which means that under steady state conditions cardiac output, blood that exits the heart via the aorta, and venous return, blood that enters the heart via the venae cavae, are virtually equal . One of the ways one can depict physiologic haemodynamics is by coupling the cardiac function with the vascular function, where researchers like Guyton in 1955, tried this approach to determine the cardiac output. Although there are several ongoing debates, some of them available in the Journal of Physiology’s Crosstalks,, whether his experiments are appropriate, the graphs used in this simulator are adopting his approach using some newer studies.
As mentioned before, the graph is a coupling of the cardiac function curve (shown in orange) and the vascular function curve (shown in green). The independent variable is the right atrial pressure measured in mmHg (represented on the x-axis) and the dependent variable is total blood flow measured in L/min (represented on the y-axis). Total blood flow can represent either cardiac output in the cardiac function curve or venous return in the vascular function curve. At equilibrium, the levels of cardiac output and right atrial pressure are defined by the point of intersection of the two independent curves .
The cardiac function curve, also known as the cardiac response curve, is a relationship of cardiac output and right atrial pressure and is one of the forms in which Starling’s law can be expressed. It can depend on many factors and can be changed from beat to beat or from time to time: a) the phase of respiration at onset of cardiac contraction; b) the interval of time elapsing between two successive heart beats; c) the degree of sympathethic stimulation; d) the effect of many drugs on the heart, such as epinephrine, digitalis, cholinergic drugs, etc.; e) myocardial damage; f) cardiac fatique; g) the degree of oxygenation of blood, etc. However, when the heart is operating under constant and non-strenuous conditions, the cardiac response curve remains relatively constant from beat to beat .
In general, blood flow varies directly with venous pressure and inversely with arterial pressure. As the arterial pressure is dependent on the blood vessels, all the heart can do to change cardiac output is change right arterial pressure . Changes in either heart rate or myocardial contractility result in a shift to a new response surface, where an increase in contractility or decrease in afterload will result in an upward shift and vice versa . To sum up, cardiac output is generally determined by four variables: preload, afterload, contractility, and heart rate .
When a fluid is pumped through a system of tubes, the flow is characterised as the pressure gradient, which would be arteriovenous pressure gradient in the systemic vascular system, divided by total resistance. The change that occurs at each of the two terms, arterial pressure and venous pressure, with a given change in total blood flow, is determined by the elastic characteristics of the circulation and by the blood volume. The elastic characteristics can be represented as arterial or venous capacitance, which are defined as a change in volume per change in pressure. Because venous capacitance is much higher than arterial capacitance, Levy used the ratio of 19:1, the change in blood flow, which is the same in a closed circuit, elicits a very different change in pressure on the venous and arterial side, and causes approximately 70% of the blood volume to reside in the venules and small veins region. With the mean systemic filling pressure at 7 mmHg and total blood flow of 5 L/min, the arterial pressure rises to 102 mmHg and venous pressure falls to 2 mmHg [1,3].
In the vascular function curve, the pressure gradient is defined as a difference between mean systemic filling pressure, theoretic systemic pressure when no blood flow is present, and right atrial pressure, and total resistance is defined as resistance to venous return .
Interestingly, not all blood volume contributes to the mean systemic pressure. Volume that contributes to the mean systemic pressure is called stressed volume and the volume that does not is called unstressed volume. Animal studies suggest that 70-80% of the volume is unstressed . A change in blood volume shifts the vascular function curve to different right atrial pressures. An increase in blood volume shifts the curve to higher right atrial pressures (right). A change in arteriolar tone (which also affects resistance to venous return), alters the slope of the curve, where an increase in resistance results in lowering the slope of the curve. After volume change, there is a change in the mean systemic filling pressure, whereas after a change in resistance, the mean systemic filling pressure remains the same . To sum up, venous return is generally determined by five variables: stressed vascular volume, venous compliance, venous resistance, the distribution of flow, and right atrial pressure .
Mean systemic pressure represents a value in the circulation that is independent of cardiac function, because on a beat to beat basis, the heart can only provide the end-systolic volume as something to rise the stressed volume, and so provides a useful parameter for studying the characteristics of the peripheral circulation. However, the heart can utilise the blood from the pulmonary veins as an autotransfusion with raising the cardiac output and lowering the left atrial pressure.
With each heartbeat, the volume is transferred from the veins to the arteries, which creates a pressure gradient which generates venous flow. So, the only way the heart can affect this relationship is by lowering right atrial pressure. When the pressure in the right atrium is 0 mmHg, the veins collapse and further changes in flow are limited. The flow is then termed maximum venous flow, which is independent from the heart.
The three determinants of maximum venous flow are stressed volume, vascular resistance, and vascular compliance. One way to look at the resistance and compliance is by distribution of flow, which separates the circulation into regions with slow and fast time constants of venous drainage. If the fraction of flow increased to a region with slow time constant, fluid would accumulate there and lower the venous return. Under resting conditions approximately 60% of the blood goes to the fast time constant regions (blood takes 4 to 6 sec to pass) and 40% to the slow time constant regions (blood takes 18 to 24 sec to pass) .
Circular reasoning is an attempt to explain steady state changes in cardiac output in response to certain conditions (e.g. blood loss) by invoking changes in venous return. The conditions that affect total blood flow, provoke equal changes in cardiac output and venous return at equilibrium. It is the same as explaining a change in total blood flow based on a change in blood flow .
Guyton’s interpretation that right atrial pressure provides a back pressure restricting venous return provided a lot of confusion to physiologists and doctors. This is because Guyton’s model assumed a constant blood volume in the systemic circulation and they observed a rise in right atrial pressure as the cardiac output dropped . This lead to a faulty misinterpretation that flow is generated from a difference between mean systemic filling pressure and right atrial pressure , when in fact it is generated from a difference in mean arterial pressure and right atrial pressure .
Newer analysis’ made it clear, that cardiac output is the independent variable when considering venous return curves and not right atrial pressure, which occurs due to redistribution of blood volume. This is important clinically, because following Guyton’s interpretation, in case of compromised cardiac output, one should withhold intravenous fluids and keep the right atrial pressure low to avoid compromising venous return .
Cardiac output is the consequence of the interaction of the heart as a pump and the return of blood to the heart; therefore, a low cardiac output could be due primarily to a decrease in cardiac function, which acts by increasing right atrial pressure, or by a decrease in one of the factors that determine venous return. A cardiac output that is inadequate for tissue needs can be defined as shock. Interestingly, this can occur not only with a low cardiac output, but also with a normal or high cardiac output . In this section, we are going to focus on low cardiac output caused by cardiac failure.
The pathogenesis of heart failure comprises three phases: phase I – vascular redistribution, phase II – ventricular re-equilibration, and phase III – neurohormonal activation.
The higher pressure generated on the arterial side of the circulation in normal function is generated from the volume taken from the venous side. In phase I, during reduced ventricular pumping capacity, the cardiac output and mean arterial pressure are lowered, which returns the taken volume to the venous side, rising the right atrial pressure.
In heart failure (phase II), ventricular dysfunction typically affects the left ventricle more than the right ventricle. This causes the blood to accumulate before entering the left side of the heart, raising the left atrial pressure, which compensatory raises cardiac output. Because of the raised right atrial pressure, which acts as an afterload on the right ventricle, the right ventricle output decreases. Biventricular output re-equilibrates at an intermediate output below normal.
In phase III, the remaining cardiac output shortfall activates neurohormonal mechanisms to retain salt and water reduce venous capacitance and increase vascular resistance. This increases mean systemic filling pressure, right atrial pressure and right ventricular output, which in turn increases mean pulmonary pressure, left atrial pressure and left ventricular output to restore cardiac output back to normal. When normalisation of cardiac output is not possible, incessant neurohormonal activation causes a rise in right atrial pressure to such extent that the right ventricle distends and compresses the left ventricle, decreasing its stroke volume. This ends up stimulating even greater neurohormonal activation in a futile and counterproductive attempt to restore normal cardiac output .
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