As Knausgaard reminds us, life is easy for the heart: It beats for as long as it can, then it stops. In fact, a person may expect to have their heart beat more than two billion times over the course of an average life span. But within each beat is a complex cycle of contraction and relaxation, known as systole and diastole, respectively, allowing the heart to push blood from its four chambers and to receive blood in preparation for the next cycle. The hearts sole obligation to us and to our body is to pump blood along two vascular pathways. The first of these pathways is organized into the pulmonary circuit, a network of vessels that carry blood to and from the gas exchanging surfaces of the lungs. The second pathway is called the systemic circuit and it is along this path that blood is transported to the rest of the body. Both of these circuits begin and end at the heart as blood courses first from one circuit then to the other then back again in sequence. A schematic representation of these pathways and their relationship to the heart can be seen in Figure 1.1.
Of the four chambers of the heart, the two on top, called atria, can be thought of as blood receivers, and the two on bottom, called ventricles, can be thought of as the blood pushers. Starting from a persons right atrium, blood is received by the heart from the systemic circuit, then pushed to the right ventricle. From the right ventricle blood is pushed into the pulmonary circuit, the blood becomes oxygenated, and returns to the heart via the left atrium. The left atrium collects the blood and empties it into the left ventricle, which then pumps the blood into the systemic circuit, and the whole process begins anew. (For graphical representation of this flow pattern, please review Figure 1.2) As the heart beats, first the atria contract, emptying their contents into their respective ventricles, then the ventricles contract. Normally this ventricular contraction occurs in both ventricles simultaneously and with equal volumes of blood being ejected into the pulmonary and systemic circuits. This, however, is not always the case.
Blood leaving the left ventricle passes into the ascending aorta (the largest vessel in the human body) through a valve, a thick membrane designed to open and close with respect to pressure, in this case, the aortic valve, also know as the aortic semilunar valve. Similar valves exist between the atria and the ventricles in the heart. On the right side of the heart lies a set of three fibrous flaps that constitute the right atrioventricular valve, also known as the tricuspid valve. On the left side of the heart is a pair of fibrous flaps referred to variously as the left arterioventricular valve, the bicuspid valve (as distinct from the rights tricuspid valve), and the mitral valve. Each of these valves is meant to serve the same purpose: to prevent blood from flowing in an undesired direction. Said conversely, it is meant to keep blood flowing in the correct direction through the heart and into the vascular circuits. To understand why we must first consider a basic aspect of fluids and their movements: fluids, be they water through a pipe or blood through the cardiovascular system, move down pressure gradients, moving from areas of higher pressure to ones of lower pressure. This basic principle allows blood to flow from the high-pressured aorta down to the arteries, into the arterial and ventricles, up the veins, back into the heart. (For a basic representation of the pressures throughout the body see 1.6) In the heart itself, the pressure in each chamber rises during systole, falls in diastole, forcing blood to move around and through and into the heart. The valves of the heart, between the chambers and at the aorta, ensure blood flows in the correct direction, by opening to positive pressure gradients in one direction and closing to positive pressure gradients in the opposite direction. In this way, the valves attempt to establish a consistent unidirectional pressure gradient throughout the entire circulatory system.
To maintain correct pressure relationships throughout the body, the cardiovascular reacts quickly to changes in volume and velocity via mechanotransduction occurring along and within vessel walls. The specifics of this maintenance will be elaborated in the coming sections on the vasculature itself.
For now, let us begin by imagining the start of an average idealized cardiac cycle with a resting heart rate of about 75 beats per minute, a systolic blood pressure of 120 mmHg, and a diastolic blood pressure of 80 mmHg. All four chambers are relaxed and the ventricles are partially filled with blood. First, the atria contract, increasing atrial pressure, causing the ventricles to fill completely with blood. Because atrial pressure exceeds venous pressure blood does not flow into the atria during this time. At the end of atrial systole, each ventricle contains the maximum amount of blood that it will hold during a cycle, a quantity known as end diastolic volume (EDV). Next the atria relax, entering a period of atrial di- astole that lasts until the next cardiac cycle. Starting at the same time as this atrial diastole is ventricular systole, the period of ventricle contraction. During this stage ventricles begin by contracting isometrically, inducing a pressure rise ultimately reaching a point of isovolumetric contraction where all heart valves are closed, the volumes of the ventricles remain constant, and ventricular pressures rise above the atrial. Once pressure in the ventricles exceeds that in the arterial trunks, the semilunar valves of the heart open and blood flows into the pulmonary and aortic trunks, marking the beginning of ventricular ejection. During ventricular ejection, each ventricles will eject some volume of blood (typically 70-80 mL, but can range anywhere from about 60-100 mL), known as the stroke volume of the heart. The ratio of this stroke volume to the end-diastolic volume is known as the ejection fraction and varies in response to the changing demands on the heart (to be discussed at a later point). At this point the ventricles contract isotonically. Having reached a peak, ventricular pressures decline rapidly and blood in the aorta and pulmonary trunks starts to flow back toward the ventricles, causing the semilunar valves to close. As these valves closes, there is a small temporary rise in pressure as the elastic arterial walls recoils, producing a distinct valley pressure tracings known as the dicrotic notch. The amount of blood that remains in the ventricle when the valve closes is known as the end-systolic volume (ESV). The heart then enters a period of ventricular diastole for the final stage of the cardiac cycle. The ventricles enter a period of isovolumetric relaxation until ventricular pressures fall below those of their atrial counterparts and the AV valves are forced open. The pressures in the ventricles are far below that of major veins, allowing blood to pour into the relaxed atria and ventricles, passively filling the chambers of the heart before the whole process is repeated.
The consistent cycling of the heart produces many possible signals to measure. From the pressures within the atria, ventricles, and the vessel feeding them and the volume of blood present in the heart at any given time to the electrical potentials caused by the heart’s shifting dipole and even the sounds it makes, this process generates each of the signals that are of interest to this work. It is therefore instructive to note here the relationship between these parameters as a function of the cardiac cycle. One method of doing so was developed by Carl J. Wiggers, a cardiovascular physiologist working at (Case) Western Reserve University in the early half of the twentieth century, where each of these signals is plotted graphically in parallel across time. A representative example of this Wiggers diagram can be seen in Figure 1.3, from which one can appreciate the synchronicity of the electrical, volumetric, and pressure changes constantly occurring across the heart. Special attention should be paid to the pressure and volume shifts as it is from these that much of this work builds from.
Ultimately of greatest concern in the pumping of the heart is how much blood is expelled from the ventricles for each beat. This quantity, known as the stroke volume, is equivalent to the end-systolic volume (the amount of blood remaining in each ventricle at the end of systole) subtracted from the end-diastolic volume (the volume of blood in each ventricle at the end of diastole). For a single cardiac cycle, stroke volume may be the single most important factor to examine because this is fundamentally a quantification of the hearts single beat efficiency.
To gauge a hearts efficiency over a longer period of time than a single cardiac cycle, physicians will often refer to a quantity known as the cardiac output, the amount of blood pumped by the left ventricle per some unit time. This value, a measure of ventricular efficiency over time, is often calculated by multiplying the heart rate (in beats per minute) by the stroke volume (in mL per beat) and generally falls within the range of 4-8 L/min . Cardiac output is essentially the volumetric flow rate of blood through peripheral tissues, indicative of what the heart and body perceive to be necessary to maintain homeostasis. To keep the body stable throughout many different activity levels (from resting to running) and health states (from picture perfect to pathological), the heart adjusts its cardiac output to balance the needs of the systems. A schematic representation of the factors affecting cardiac output are shown in Figure 1.4.
Broadly speaking there are two ways the heart is able to adjust its output, either through the heart rate or the stroke volume. Though an area of intense research and clinical relevance, the electrochemical generation of heart contractions and therefore one of the principle components of the heart rate will not be discussed here at any great length. Going still further, in our haste we will also forgo discussions of cardiac reflexes and autonomic tone on the heart rate. An exception will exist in the case of atrial reflex, which is the hearts response to the walls of the right atrium stretching in response to increased venous return. This reflex, also known as the Bainbridge reflex, is one case where volume is mechanically transduced by the system to cause a rate change, rather than another volume change. That both types of change, be they rate or volume, indirectly affect pressure gradients and flows should not go unnoticed. These factors are intrinsically bound in the body’s feedback-control system of regulation and more often than not, all else being equal, one will affect the other in some way. It might be intuitive for some readers to consider these two parameters, rate and change, as equivalent to a frequency and amplitude, respectively, of some ideal signal the heart is attempting to create. However, our concerns for this work will lie primarily with the effects of volumes on hemodynamic parameters. Therefore, we will concern ourselves primarily with those factors affecting stroke volume.
Stroke volume, as previously mentioned, is the difference between the end-diastolic volume and the end-systolic volume. How these volumes change in response to a myriad of conditions has been the subject of decades of intense medical research. For now a brief overview of the factors affecting each should suffice.
End-diastolic volume is affected by two main factors: the filling time and venous return. The filling time is simply the time it takes to complete ventricular diastole, itself a function of heart rate. As the heart rate increases, filling time decreases. To go back to my previously hinted at metaphor, this would be equivalent to adjusting the frequency of the ideal cardiac signal. To adjust the amplitude of this signal, one would turn to venous return. Strictly speaking venous return is merely the rate of blood flow returning to the heart during this diastolic period and it changes in response to cardiac output, blood volume, patterns of peripheral circulation, and intrathoracic pressures . By increasing the volume of blood returning to the heart, and holding all other parameters constant, one could increase the volume of blood exiting the heart. Increasing venous return tends to increase end-diastolic volume, which can lead to an increase in stroke volume.
Augmenting filling time and venous return changes a parameter of the heart itself known as the cardiac preload. Depending on the parlance, this preload refers to either the end diastolic pressure responsible for or the degree to which the ventricles of the heart stretch (alter their greatest geometric dimensions) under variable physiologic demands [4, 5]. Put simply, preload is the measure of myocardial stretching in the ventricles during diastole. This amount varies with the demands of the heart and is directly proportional to the end-diastolic volume itself. Increasing preload increases the end-diastolic volume. All else being equal, stroke volume should increase with preload. And within normal physiological limits this is generally true. First proposed by Ernest Starling and Otto Frank, this relationship of more in equals more out is essence of the Frank-Starling law of the heart . How end-diastolic volume and right atrial pressure affect stroke volume and cardiac output (and therefore venous return) is shown in Figure 1.5. There are of course instances where the Frank-Starling law does not hold [6, 7], but for the majority of cases, it is deemed reliable enough for clinical decision making.
As popularized by Guyton, the operation of the heart at any given time is determined by the intersection of the Frank-Starling cardiac output curve with the blood volume return curve of the patient as seen in Figure 1.5. There are many factors affecting the shapes, slopes, and intercepts of these two curves, but generally speaking contractility and blood volume play a significant role in their behavior. As the volume of blood is increased, we can see that preload and output increase in turn and is the foundation for fluid replacement therapy. The converse is true and demonstrates the dangerous consequences of hemorrhage and massive blood loss. A similar direct relationship can be seen with increased contractility increasing the operating point of the heart and decreased contractility decreasing the operating point. Add the myriad other factors that can alter these curves’ behaviors in conjunction with the fact that similar values of preload can give wildly varying values for cardiac output and some the problems of hemodynamic monitoring become apparent.
End-systolic volume, the amount of blood remaining in the ventricle at the end of ventricular systole, is subjected to three main factors. The first is preload which we have discussed previously. How this affects the ending volume is obvious: the amount that is left over is necessarily a function of the amount initially available. The second major factor is the contractility of the ventricle. Contractility, represented by the force required for contraction at a given preload, represents the intrinsic ability of the myocardium to contract. Under normal circumstances, the ability to produce force during contractions is altered by autonomic innervation and many circulating hormones, each acting on the degree to which myosin and actin in these muscles are bound, a relationship itself determined by the calcium ion concentrations in the cardiac cells. Both sympathetic and parasympathetic stimulation affect the contractility of the heart and can be thought of as either a positive inotropic action, if it increases contractility, or a negative inotropic action, if it decreases contractility. As contractility increases, end-systolic volume decreases and vice versa. The final factor affecting end-systolic volume is the afterload, the amount of tension the contracting ventricles must produce to open the semilunar valve and eject blood. Afterload relates directly to the period of isovolumetric contraction (the greater the afterload, the longer the period of contraction) and somewhat inversely to the duration of ventricular ejection (the greater the afterload, the shorter the period of ejection). As such, increased afterload tends to increase end-systolic volume and thereby decrease stroke volume.
Multiplying the volume ejected by each pump of the heart by the rate at which each pump occurs, yields the aforementioned cardiac output in terms of a volumetric flow rate. It is this volumetric flow that will be pushed to every portion of the body, providing nutrients, giving oxygen, and removing waste from every single living cell of our bodies. How this flow is created by the heart is crucial to understanding how the vasculature operates: flow from the heart is the primary input to the blood vessels system of transportation. With this basic understanding of how the heart operates, we can now proceed through the pump into the pipes, where blood volumes flow, perfuse, and are returned to whence they came. We can now begin to understand the role of the vasculature.