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HEMODYNAMIC MONITORING and support of circulation are at the center of acute intervention-based specialties such as anesthesiology and critical care. In spite of the general assumption that the understanding of basic and clinical hemodynamics is relatively complete, clinicians often invoke a number of reasons to explain away the discrepancies between the commonly used mental model of circulation and various pathophysiologic states. A cursory review of the literature on treatment modalities of various hemodynamic states over the past several decades suggests that this mental model has undergone a steady revision. For example, contrary to expectations, the results of a 2012 intra-aortic balloon pump (IABP)-Shock II randomized, open-label multicenter trial found no difference in 30-day mortality (40%) in patients with acute myocardial infarction associated with cardiogenic shock and treated with combined pharmacologic therapy, percutaneous intervention and IABP, or with pharmacologic therapy and percutaneous intervention only.
Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): Final 12 month results of a randomised, open-label trial.
On the basis of previously reported meta-analyses and conflicting evidence from data registries, joint American College of Cardiology and American Heart Association, together with the European Society of Cardiology, downgraded the class of recommendation for IABP use from class IB (should be used) to IIbB (may/can be used).
In the wake of these findings, some have questioned the recommendations of potentially harmful adjunct therapies, namely, the use of intra-aortic balloon pumps, in this high-risk group of patients based on “pathophysiologic assumptions and expert opinions” rather than on randomized clinical trials.
Moreover, in the editorial to this landmark study, O’Connor and Rogers submitted that “the results of the IABP-SHOCK II trial parallel those from many recent outcome trials that have challenged the understanding of the management of acute and chronic heart failure, including those regarding the use of pulmonary artery catheters and the role of revascularization in ischemic cardiomyopathy.”
Similarly, the emerging modalities in pharmacologic therapy of acute and chronic heart failure further question the fundamental understanding of the circulation. Most notable is a shift from the use of potent sympathomimetic amines (epinephrine, isoproterenol, and dopamine) in the 1960s and 1970s,
to a widespread use of vasodilators. On the contrary, the use of inotropes (dobutamine and milrinone) currently is reserved for the treatment of a minority of patients with severe systolic dysfunction who do not tolerate vasodilators due to hypotension.
The Acute Decompensated Heart Failure National Registry (ADHERE): Opportunities to improve care of patients hospitalized with acute decompensated heart failure.
In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: An analysis from the Acute Decompensated Heart Failure National Registry (ADHERE).
Practice guidelines of the Heart Failure Society of America (HFSA), the American College of Cardiology Foundation/American Heart Association (ACCF/AHA), as well as the European Society of Cardiology (ESA) therefore recommend the use of vasodilators and deemphasize the use of inotropes in the management of acute heart failure syndromes.
It is of note that, from the range of available inotropes, dobutamine and milrinone are chosen for their significant vasodilatory effect. In addition, the use of ß-blockers is recommended universally in all patients with stable mild, moderate, and severe heart failure with ischemic or non-ischemic cardiomyopathy and reduced LV ejection fraction.
Guidelines for the diagnosis and treatment of chronic heart failure: Executive summary (update 2005) The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology.
The question naturally arises as to whether or not the above-mentioned treatment modalities and recommendations arose from poorly designed trials or whether or not the understanding of pathophysiologic mechanisms involved is in need of “renewed growth and development.”
A number of other examples challenge the understanding of the basic tenets of circulation, such as the curious phenomenon of increase in cardiac output during aortic cross-clamp by up to 25% in a controlled experimental setting
The Fontan repair used for surgical correction of various hypoplastic right and left heart syndromes (HLHS) presents a yet-to-be explained hemodynamic paradox which, in the absence of the right heart complex, the single, often weakened, ventricle supposedly pumps the blood through systemic and pulmonary circulations.
There are a large amount of conflicting data from exercise physiology in which the concept of a muscle pump has been evoked in order to explain the greatly increased systemic blood flows that exceed theoretical limits of the heart’s pumping capacity. Review of literature suggests that increased cardiac outputs can neither be ascribed to the heart (on account of a greatly shortened diastole that precludes adequate filling) nor to contracting muscles.
From the physiologic perspective, the heart is considered to be a dual pump, driving the blood through pulmonary and systemic circuits arranged in series. In the course of an average life span of 75 years, the heart, weighing around 350 grams, pumps 400 million liters of blood (the amount that fills a lake 1 km long, 40 m wide and 10 m deep)
through a system of conduits with the total length of about 100,000 km. Considering the fact that the diameter of the red blood cells frequently exceeds the width of the capillary beds, the heart as a pump truly performs a prodigious task.
The idea that the heart is a pump providing the total mechanical energy for blood’s propulsion has dominated the field of cardiovascular physiology for well over a century. A detailed discussion of the history of the propulsion pressure circulation model is beyond the scope of this article,
but even a cursory look at the leading medical journals in the 1850’s showed that there was a lively debate among the proponents of the heart-centered circulation model who supported the view that the heart is the “motor” of the circulation, and those who maintained that the “capillary power,” or the force from behind (vis á tergo), played a principal role in blood’s propulsion.
It should be noted parenthetically that the classic concept, vis á tergo, goes back to antique medicine when it played only a secondary role to vis á fronte, or “force from the front,” which referred to suction forces (vacuum) working locally, (eg, ventricular diastolic suction) and at a distance, akin to gravity.
but, largely bereft of their original meaning, slowly acquired a new identity. The force from behind now assumes the dominant role as pressure generated by ventricular contraction, pushing the blood through the capillary beds back to the atria. A portion of this force is stored in vessel walls as elastic energy and is represented in the concept of the mean systemic pressure (Pms). The force from the front, on the other hand, became a generic term for a host of phenomena ranging from ventricular diastolic suction and/or respiratory pump, which facilitate filling of the heart, to a range of factors that impede venous return.
The latter became the mainstay of Guyton’s venous return model of circulation discussed in the following section.
Over time, the pressure-propulsion (PP) model has become deeply engrained in the collective subconscious and, with few exceptions, virtually has remained unchallenged. It is suggested that in the light of rapidly accumulating growth of information obtained with the help of in-vivo experimental and clinical imaging modalities, the number of discrepancies between the observed phenomena and the constraints imposed by the existent circulation model is likely to increase. It is the purpose of this article to present some of the recently collected evidence against the commonly accepted PP model of circulation and to propose the conceptual framework for a new, more complete understanding of the circulatory phenomena.
In the first part of the article a brief historic outline and the salient features of Guyton’s venous return (VR) model of circulation are discussed as well as the reason for its incongruence with the left ventricular (LV) model of circulation. Attention then is turned to the heart and to ways in which its mechano-energetic function compares to a standard hydraulic pump. Work on isolated heart preparations demonstrates that the heart is unable to maintain constant pressures or flow in face of the changing loading conditions and suggests that it is a rather inefficient pressure-propulsion pump. It is proposed that the heart functions by interrupting the flow of blood already in motion; that is, as an impedance pump, whose mechanical action can be compared to a hydraulic ram. It is further suggested that in place of the mechanistic PP model, the biologic model of circulation be adopted in which the blood is a self-moving agent driven by the metabolic demands of the tissues. The evidence in support of this model comes from observations of the embryonic circulation, through comparative anatomy and from phenomenology of the mature circulation. It is then shown that the conceptual framework for the PP model is rooted in the principles of a thermodynamically closed system, which, according to current understanding, no longer adequately describes the biologic phenomena in general and, as proposed in this article, the circulatory system in particular. Finally, the phenomenon of autonomous blood movement is discussed in the context of open-systems biology.
What Controls Cardiac Output?
In spite of the general assumption that the heart provides the total mechanical energy for blood propulsion, the experimental observations have polarized basic scientists and clinicians into 2 opposing views concerning the control of cardiac output (CO). While proponents of Guyton’s VR model contend that the peripheral circulation plays the dominant role in control of CO, adherents of the LV model ascribe this role, by default, to the heart.
Point:Counterpoint: The classical Guyton view that mean systemic pressure, right atrial pressure, and venous resistance govern venous return is/is not correct.
Since the ultimate source for blood propulsion in both models can be traced to the hydrodynamic equivalent of Ohm’s law (where the power source for the circulating blood clearly originates in the pump, ie, the heart), those seemingly opposing views differ only on the surface but not in essence. It is apparent that this central issue in cardiovascular physiology will not be resolved until the fundamental question (“What makes the blood go around?”)
Point:Counterpoint: The classical Guyton view that mean systemic pressure, right atrial pressure, and venous resistance govern venous return is/is not correct.
is considered not only in the light of the conventional model but also from the observed circulatory phenomena themselves.
Guyton’s Venous Return Model
Between the 1950s and 1970s, Arthur Guyton and coworkers developed a circulation model that has, in due course, become almost universally accepted. At the core of the model is the idea that venous circulation plays a central role in control of CO. The starting point for the VR model was a number of observations that convinced Guyton and his collaborators that cardiac output largely was unaffected by the activity of the heart.
did not cause an increase in CO. Similarly, experiments on dogs, in which the right heart was replaced by a bypass pump, showed that CO could be maintained at the baseline level only when the pump output matched the autonomous rate of venous return. The increase in pump flows above the baseline would result in collapse of the great veins without change in CO.
Significant to Guyton’s model is the division of the circulatory system into 2 parts. The first consists of the heart and lung and the second of the entire systemic circulation. Both parts were, in turn, investigated separately. The heart-lung segment was examined on the isolated heart preparation and in an intact animal under a variety of experimental settings. The isolated systemic circulation, on the other hand, was studied by replacing the heart with a bypass pump, and on intact animals by measuring pressure and flow at different points while stressing the circulation.
The other key component of the model is the role of elastic recoil pressure within the vessels that supplies potential energy to the circulating blood. This pseudostatic pressure, technically known as Pms, is defined as the equilibrium pressure generated by the elastic recoil of the vessels during no-flow state. Its value represents the filling of the vessels and is, according to the theory, the principal force for driving the circulation.
As the heart begins to pump, it transfers the blood from the highly compliant venous into the poorly compliant arterial limb of the circuit where the pressure increases with each increment in pump flow. Concomitantly, on the venous side, the right atrial pressure (Pra) begins to decrease until it reaches zero when the veins collapse and the flow ceases (Fig 1). According to the model, the right atrial pressure plays a dual role; viewed from the heart, Pra determines the degree of filling of the right heart and regulates its output according to the degree of its filling (Starling’s law). In respect to the blood returning to the heart (ie, venous return), the positive value of Pra acts as an impedance to venous return by exerting back pressure. Therefore, any value of Pra smaller than Pms allows for the flow of venous blood in accordance with the pressure gradient.
Fig 1Normal venous return curves obtained on 14 open-chest, anesthetized, areflex dogs during right-heart bypass experiments. Venous return reaches a maximum value and remains on a plateau at Pra less than−2 to−4 mmHg due to progressive collapse of the great veins and the right atrium. Decrease in pump flow causes a steady rise in Pra and results in decrease in venous return (sloped segment of the curve) until it reaches zero value, defined as the Pms. Note that points for construction of each curve were obtained during brief periods when Pra was kept at a desired level. Pra, right atrial pressure; Pms, mean systemic pressure. Adapted with permission.
In a simple analogy, the model has been compared to the flow of water from a bathtub (venous compartment) in which the rate of emptying is determined by the height of water in the tub (Pms) and the physical characteristics of the drain pipe, (ie, its resistance and downstream pressure [pressure difference between the Pms and Pra]). Importantly, the outflow from the tub does not depend on the force of stream issuing from the tap filling the tub, as represented by the action of the heart in generating arterial pressure.
Point:Counterpoint: The classical Guyton view that mean systemic pressure, right atrial pressure, and venous resistance govern venous return is/is not correct.
Guyton skillfully demonstrated the dual role of Pra in control of cardiac output by a composite diagram in which cardiac function and venous return curves are shown on the same coordinates. Guyton, moreover, maintained that venous return and cardiac function curves are complementary to each other and that the crossing of the 2 in the equilibrium point represents their solutions (Fig 2).
Fig 2Guyton’s combined plot of “normal cardiac output” and “normal venous return” curves crossing at a single level of Pra and flow, the “equilibrium point,” to show independent properties of the heart and vasculature. According to critics, such graphic representation implies that 1 of the functions necessarily is plotted backwards. Pra, right atrial pressure. Adapted with permission.
The value of Guyton’s emphasis on the role of peripheral circulation in the overall approach to studying the cardiovascular system has undoubtedly set the stage for progressive growth in knowledge about control of cardiac output. His unique graphic representations of dividing the circulation into systemic and cardiac segments (comprising of the heart and pulmonary circulations) has made it possible to visualize changes in hemodynamic variables in normal and pathologic conditions. They became a valuable tool in the hands of clinicians and educators and have been reproduced in virtually every text of basic and clinical hemodynamics. However, for reasons mentioned below, this model remains incomplete.
Critique of Guyton’s Model
Critics of the VR circulation model contend that the pivotal role played by the right atrium as back pressure in Guyton’s analysis is exactly its most controversial point.
At the core of the argument is the fact that simultaneous depiction of “cardiac function” and “venous return” curves on the same diagram presupposes that the 2 sets of experiments were performed on the same preparation, whereas they were obtained in two different sets of experiments.
Levy repeated the above-mentioned Guyton’s right-heart bypass experiment on a dog with arrested circulation in which the heart had been replaced by a bypass pump. He showed that over the range of pump flows from zero to maximal, the Pra progressively declined with a concomitant rise in arterial pressure, thus demonstrating a reciprocal relation between the two.
In the graphic representation of the experiment, Levy expressly stated that under conditions of this experiment, the venous return is clearly the dependent variable (Fig 3). He further argued that in a plot with joint representation of cardiac and vascular function curves, one of the curves necessarily is depicted backwards, giving the erroneous impression that Pra controls CO as back pressure rather than the bypass pump. It has, moreover, been pointed out that Guyton and coworkers recorded venous return curves and cardiac function curves at steady states where, for each point on the graph, the flow of the pump was adjusted manually (Fig 1). As such, the relationships do not record venous return in dynamic states, blur distinction between dependent and independent variables, and confuse mathematic abstraction with reality.
It also should be mentioned that the method by which these experiments were performed by Guyton and Levy, namely, on animal preparations with arrested hearts and abolished vasomotor reflexes, is essentially not compatible with life.
In this sense, the circulatory system of a nearly deceased experimental animal does approach a mechanical system subject to pressures and flows as demonstrated in Levy’s experiment, and it is superfluous to talk of Pms as the driving force for venous return. For methodologic difficulties with stopping the circulation and the measurement of mean systemic pressure, the reader is referred to reference
Fig 3The changes in the Pa and Pv produced by alterations in Q in canine right-heart bypass preparation with abolished cardiovascular reflexes. Stepwise changes in Q were produced by altering the rate at which blood was pumped mechanically from the right atrium to the pulmonary artery. Note reciprocity between Q and Pv; the preparation essentially behaves like a closed-loop hydraulic system. Pa, arterial pressure; Pv, central venous pressure; Q, systemic flow. Adapted with permission.
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In conclusion, it can be argued that for all its inconsistencies with the pressure-propulsion model, Guyton’s concept of right atrial pressure as an impedance to venous return finds its validation in numerous experimental and clinical studies. The intersection point of the cardiac and vascular function curves in his graphic analysis (Fig 2) is an ingenious attempt to represent dependence of the pulmonary and systemic circulations on right atrial pressure. However, by considering the heart and the pulmonary circulation as a single unit, rather than, in analogy with the systemic venous return, treating it independently as pulmonary arterial return, the real function of the pulmonary circulation and of the left heart complex had been obscured.
Implicit in the LV circulation model is the idea that, in addition to impelling the blood, the heart is also the chief regulator of cardiac output. The model further assumes that the circulation is a closed system of vessels in which the pressure gradient between the aorta and the right atrium determines the flow and where, during a steady state, the outputs of the left and right hearts are closely matched in accordance with the law of conservation of energy and matter.
The understanding of the physical laws governing the flow of fluids through hydraulic systems as described by Hagen-Poiseuille in the 19th century was the starting point for quantification of flow-related phenomena in biologic systems. The law describes the relation between pressure drop and volume flow in a rigid tube under steady conditions with laminar flow,
(Eq. 1)
where: ΔP is the pressure gradient along the tube, L is the length of tube, μ is the dynamic viscosity, Q is the volume flow rate, r is the radius, and π is the mathematic constant. However, since the physical dimensions of the circulatory system are not known, a simplified relation of variables in the form of Ohm’s law for fluids has been adopted:
where the pressure gradient (Pao-Pra) is the difference between the mean aortic and right atrial pressures, the flow is cardiac output (CO), and (Rp) is the peripheral resistance.
Assuming a zero value for right atrial pressure the equation can be re-written as:
(Eq. 3)
By analogy, the pressure difference between the right ventricle and left atrium is used to calculate resistance of the pulmonary circulation. It should be noted that pulmonary capillary wedge pressure (PCWP) is used as a surrogate for left atrial pressure.
The integration of the above concepts with the emerging technology of pulmonary artery pressure measurement in the 1970s ushered in a new era in the understanding of normal hemodynamics and of various pathophysiologic states. Simultaneous measurement of CO and right and left ventricular filling pressures with the use of Swan-Ganz catheters became an essential tool in the hands of sapient practitioners to observe trends and manipulate CO in terms of preload, afterload, and contractility. The presence of such a relationship may undoubtedly be applicable in a laboratory setting where the heart of an experimental animal has been replaced by a bypass pump and vascular reflexes have been abolished, as demonstrated in Levy’s experiment cited above.
The problem arises when a causal relationship among flow, pressure and resistance in a closed hydraulic system of known dimensions (where the source of pressure is unambiguous, and the flow and resistance are independently verifiable) is applied to a highly dynamic circulatory system. The difficulty of applying the concept of resistance to complex hemodynamic states recently has been reviewed.
The issue has been summarized eloquently by Fishman:The idea of resistance is unambiguous when applied to rigid tubes perfused by homogenous fluid flowing in a laminar stream…complexities are introduced when these concepts are extended to the pulmonary (as well as to systemic) circulation: the vascular bed is a non-linear, viscoelastic, frequency-dependent system, perfused by a complicated non-Newtonian fluid; moreover, the flow is pulsatile, so that the inertial factors, reflected waves, pulse-wave velocity, and interconversions of energy become relevant considerations…as a result of many active and passive influences that may affect the relationship between the pressure gradient and flow, the term “resistance” is bereft of its original physical meaning: instead of representing a fixed attribute of a blood vessel, it has assumed physiologic meaning as a product of a set of circumstances.
(Used by permission of the American Physiological Society)
Critics of the LV model ascribe its relative success to the erroneous assumption on the part of some practitioners that the right atrial pressure (and, in turn, RV filling pressure) is an index of circulatory volume, whereas it should be considered an impedance to venous return, as defined in Guyton’s circulation model.
Jacobsohn E, Chorn R, O’Connor M: The role of the vasculature in regulating venous return and cardiac output: Historical and graphical approach. Can J Anaesth 44:849-867
Accordingly, the LV model of circulation provides only limited information about the state of organ perfusion in various hyperdynamic or low-output states. For example, cardiac output can increase several-fold during aerobic exercise, with a drop in peripheral resistance to one-third without significant changes in blood pressure. Similarly, in patients with septic shock, cardiac output can be more than double, with increase in vascular resistance in non-reactive vascular beds, such as the skin, and decreases in the brain, heart and the skeletal muscle with the overall resistance unchanged. It hardly is surprising that a number of studies have failed to demonstrate a significant correlation between CO and ventricular filling pressures (CVP and PCWP) in a variety of physiologic and pathologic circulatory states.
Pulmonary artery occlusion pressure and central venous pressure fail to predict ventricular filling volume, cardiac performance, or the response to volume infusion in normal subjects.
Collectively, they demonstrate the weakness of the current circulation model and call for its revision. While it is intuitively obvious that during normal, steady-state conditions flow through the systemic and pulmonary circulations must be equal; the assumption, however, that this distribution is governed by pressure gradients alone is certainly an oversimplification.
Quantification of the Ventricular Pump
The notion that the heart is a pump has prompted researchers to characterize its mechano-energetic principles and compare it to a standard mechanical pump. The performance characteristic of a hydraulic pump typically is defined by a pump function graph that is obtained by measuring pressures while changing the resistance of the outflow tube at constant levels of inflow. The flow at which the pump operates at a particular steady state is said to be the working point of the pump (Fig 4). As is evident from the graph, an inverse relationship exists between flow and pressure generated by the pump when operating at constant power.
Fig 4Pump-function diagram for a fluid pump. The pump can operate at any point within the confines of its function curve. The working point of a pump denotes the maximal flow (B) the pump can generate at a given pressure (A). The pump is said to be a pressure source when it generates a range of flows at the same pressure and a flow source when a constant flow is generated irrespective of pressure. The “working point” of this particular pump is between the 2 limits.
To exclude the effects of neurogenic and humoral control mechanisms, Elzinga and coworkers carried out a number of studies in which the pumping capacity of the left ventricle in an isolated cat heart was compared to a mechanical pump and tested against a hydraulic impedance as represented by a model arterial tree, the 3-element Windkessel. (Lumped parameter models assume that circuit parameters [capacitance, resistance and impedance] that occur along the length of the arterial tree, are summed into single capacitance and resistance, which can be independently controlled.) The model has been used extensively to study pressure-volume relationships of the ventricle and has given results that closely match in vivo studies.
The experimental setup allowed for control of heart rate, ventricular filling, and contractility. The heart was ejecting against variable aortic loads (as determined by the investigators) by changing the resistance and compliance of the model arterial tree. The results of experiments were represented as mean aortic pressures, at which the heart was working, versus flow (Fig 5). In similarity to a mechanical pump operating at constant power, when ejecting at increasing arterial loads (mean aortic pressure), the left ventricle generates smaller stroke volumes until it reaches the state of isovolumic contraction when no blood is expelled. It is evident from the graph that, in the absence of increased contractility, the heart’s output changes significantly with loading conditions; its output decreases when pumping against higher pressures and vice versa. Thus, the ventricle is neither a “flow source” (ie, it cannot maintain the same flow [stroke volume] under different [aortic] loads) nor a “pressure source” (ie, it cannot maintain pressure independently of the load).
Fig 5Pump function graph of the isolated cat heart paced at a fixed rate of 120 beats per minute. The lower curve shows ventricular output under control conditions, and the upper during increased contractility. Note that under different loading conditions, the heart neither generates the same pressure nor flow (ie, it is neither flow nor pressure source but has a working point between the 2 limits). CO, cardiac output; SV, stroke volume. With kind permission from Springer Science and Business Media.
that the heart transfers the blood to the aorta with optimal power (calculated from pressure and flow) and efficiency (expressed as the ratio of external work and myocardial oxygen consumption) (Fig 6).
The control mechanism of this matching principle remains unknown and cannot readily is explained by the current knowledge of cardiovascular control. Since both power and efficiency have their maximum at some intermediate value of cardiac output, any value smaller than optimum would have to be registered twice (ie, at a smaller and at a higher output) (Fig 6).
Given the fact that in most mammals the arterial pressure is about the same, this value can be achieved at multiple settings. However, there is only 1 setting (working point) at which the heart “chooses” to operate.
Fig 6Left ventricular pump function graph of the isolated feline left ventricle (top) with its related external power (middle panel) and external efficiency (lower panel). Power output of the heart is measured at different arterial loads while ventricular filling, heart rate, and contractility are kept constant. The ventricle ejects with optimal power (the product of pressure and flow) at the physiologic arterial load that represents 58% of maximum cardiac output at zero pressure (middle panel) and with optimal efficiency at 69% of maximum cardiac output. Vertical lines demonstrate a close connection between the heart’s working point (arrow) and its optimal power and efficiency. Adapted with permission.
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An alternative way to determine ventricular performance can be obtained by simultaneous recording of ventricular pressure and volume during a series of cardiac contractions.
Similarly to the ventricular pump function graph, the end-systolic pressure-volume relationship (ESPVR) is obtained when the aortic pressure is varied over several beats and the family of end-systolic points is joined with a line (Fig 7). The slope of the line corresponds to maximal ventricular elastance (Emax) for each ventricular contraction. (Elastance is defined as a change in pressure for a corresponding change in volume.) It has been confirmed in numerous experiments that during a stable contractile state, the slope of the ESPVR line represents a sensitive, load-independent index of contractility and that the left ventricular oxygen consumption per beat corresponds linearly to the systolic pressure-volume area (PVA).
It is of note that for a given contractile state, the oxygen consumption per beat is independent of heart rate and of the type of contraction, whether ejecting or isometric (ie, when the aorta is occluded), and therefore, of cardiac output.
Fig 7Ventricular pressure-volume relationships. (A) When the ventricle contracts against increasing load, a series of P-V loops are generated whose left upper corner falls on a straight line with a slope of Emax. (B) Time-varying elastance model of left ventricular contraction. Ventricular performance of a single beat can be characterized in terms of elastance, which increases towards maximum (Emax) during end-systole and decreases with relaxation in diastole. (C) The PVA of a single beat represents the total mechanical energy, which the ventricle expends during EW and during PE. P, pressure; V, volume; V0, unstressed ventricular volume; ED, end-diastolic volume; ES, end-systolic volume; E(t), time-varying elastance; P-V, pressure volume; Emax, maximal elastance; PVA, pressure-volume area; EW, ejection; PE, isovolumic contraction. Adapted with permission.
However, this linear increase between myocardial oxygen consumption and mechanical load occurs in the absence of measurable changes in high-energy phosphates, ATP, and phosphocreatinine.
In comparison with the striated muscle, the non-beating myocardium exhibits about a ten-fold-higher metabolic rate, 30% of which is dissipated as heat. During contraction, the metabolic rate increases 3 to 4 times, with some 70% of consumed energy converted into heat. This accounts for a surprisingly low myocardial energetic efficiency (the ratio of the heart’s external work and consumed oxygen) in the range of 10% to 15%.
It is apparent from the previous discussion that in comparison with mechanical pumps engineered to maintain either constant pressure or flow under varying loading conditions, the heart is a rather poorly “designed” pressure-propulsion pump, or could it be that the heart, in fact, functions according to sound mechano-energetic principles emulated by a different type of pump? It is proposed that such a pump is the hydraulic ram.
The Heart as an Organ of Impedance
At the beginning of the 20th century, Steiner proposed a radically different circulation model by suggesting that rather than being an inert fluid propelled by the heart, the blood has autonomous movement that is closely linked to metabolic activity of the tissues. He further suggested that the heart creates pressure by rhythmically interrupting the flow of blood and, thus, primarily functions as an organ of impedance whose mechanical function conceptually can be compared to a hydraulic ram.
By all accounts, this theory was way ahead of its time and largely went unnoticed. (As discussed below, the first ideas about physics of the open systems appeared in the 1930s.) Over the years, sporadic studies appeared, mostly in German, such as a paper by Havlicek, who drew a mechanical and morphologic analogy between the heart and the hydraulic ram and even constructed a physiologic model of a hydraulic ram.
In the 1970s and 1980s, Manteuffel-Szoege, a cardiac surgeon, published a number of observational studies of the embryonic circulation and of patients in deep hypothermic arrest and made the following remark:Is it really true that the heart works like a pump? A pump sucks in fluid from a reservoir, which is a hydrostatic system and not a hydrodynamic one. In the circulation, on the other hand, not only is blood ejected from the heart, but it flows into the heart. The heart is a mechanism inserted into the blood circuit, and so it is a very peculiar kind of pump.
The impetus for his work came from work by Thompson who studied the effect of artificial ventilation on the blood circulation in asphyxiated dogs in which it was demonstrated that residual circulation persisted for up to 1 hour after the heart had stopped.
Repeat experiments showed that even in the absence of mechanical ventilation, significant movement of the blood continued in the asphyxiated animals for up to 2 hours.
On the basis of his work and existing evidence, Manteuffel-Szoege concluded that the blood possesses its own kinetic energy, which is intricately bound with the thermal conditions, (ie, metabolic state of the subject).
The hydraulic ram is a cyclical pump that converts kinetic energy of flowing water into pressure. The ingenious design of the pump allows the water to perform work on itself, thus obviating the need of additional external power for its operation (Fig 8.1). It is apparent that the hydraulic ram bears more than a casual resemblance to the isolated heart preparation, which is also “driven” by the inflowing blood (Fig 8.2). The reservoir represents the atrium, and the combination of drive pipe (A) and pressure vessel (D) represent the ventricle. The spill valve (B) corresponds to the A-V valve, the delivery valve (C) to the semilunar valve, and, finally, the delivery pipe (E) stands for the aorta/pulmonary artery. For the sake of simplicity, the ram’s operation will be compared to the function of the right heart. The blood accelerates from the right atrium (reservoir) into the right ventricle (combined compartments of drive pipe A and pressure vessel D) where it suddenly decelerates upon closure of the tricuspid valve (spill-valve B). A steep rise in ventricular pressure opens the pulmonic valve (delivery valve C) and impels the blood into the pulmonary artery (delivery pipe E). Like the heart, the ram only ejects a portion of its ventricular volume, and the pressure recordings of a model ram closely resemble ventricular pressures.
Fig 8Components and working cycle of a hydraulic ram. (1). Water from the reservoir accelerates with the force of gravity along the drive pipe (A) and escapes via the loaded spill valve (B). As the water flow reaches some critical velocity the spill valve (B) is suddenly closed, creating a back surge (water hammer) that opens the delivery valve (C) and forces the water into the pressure vessel (Windkessel) (D). Increased pressure in the vessel (D) forces water up the delivery pipe (E) and closes the delivery valve (C). The flow of water is once more redirected along the drive pipe (A) where it escapes via the opened waste valve (B), completing the cycle. Note similarity with the simple model of the isolated heart preparation; see text for explanation. With kind permission from Springer Science and Business Media.
(2). Isolated left heart preparation. Blood flowing from the venous reservoir enters the left atrium (LA) at a pressure determined by the height of the reservoir relative to that of the atrium (preload). The left ventricle (LV), when stimulated to contract, ejects the blood through the aorta (AO) into a tube; the height of the aortic outlet constitutes the ejection pressure (afterload). Note conceptual resemblance to the hydraulic ram. Adapted with permission.
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Morphologic features of the right ventricle with a thin, highly compliant wall and a long, curving outflow tract, suggest that its ram-like function is optimized for generation of low pressures. The opposite is the case with the left ventricle where a short, acutely-angled outflow tract (the angle between the long ventricular axis and the left ventricular outflow tract being less than 45º), and a thick, poorly compliant wall is “designed” to generate high pressures. It is noteworthy that, in a recent editorial, the function of the RV has been compared to a hydraulic ram.
It is significant that within given design constraints and experimental settings, the ram always operates at optimal power and efficiency since both are derived from the hydraulic energy of the driving flow.
This is not unlike the heart, which, as mentioned, also works at (hitherto unexplained) optimal power and efficiency. Thus, the missing link to understanding the isolated heart’s remarkable energetic stability and optimal matching of its work to the prevailing state of the arterial system can be explained by comparing its function to a hydraulic ram.
It is suggested that a number of other circulatory phenomena, such as the ones listed in the introduction, become intelligible in light of the proposed model. For example, beyond helping to maintain pressure by the weakened heart in patients with acute myocardial infarction, application of the aortic balloon pump would not be expected to increase CO. In addition to jeopardizing myocardial perfusion, the use of potent vasoconstrictors, such as norepinephrine and epinephrine, will further compromise the flow of the autonomously moving blood and contribute to an adverse outcome in patients with acute cardiogenic shock or other types of heart failure, all of which benefit at some level by the use of vasodilators. Similarly, the use of ß-blockers and vasodilators in a failing heart can improve hemodynamics in spite of reducing its inotropic state and pressure gradients, respectively.
The ram-like function of the heart, moreover, can explain the inimical intervention of aortic occlusion. Should the heart function as a pressure-propulsion pump, occlusion of the pump’s outflow would be expected to result in loss of arterial pressure and cardiovascular collapse. On the contrary, studies in dog models have shown that CO can increase from 20% to 40% during occlusion of the thoracic aorta.
Finally, the greatly increased COs that far exceed the theoretical pumping capacity of the heart during aerobic exercise can be understood as the acceleration of blood flow in response to increased metabolic demands. For extended discussion of the above and for other examples, see reference
Some of the best evidence in support of the new circulation model comes from the emerging field of embryonic hemodynamics. It could be argued that the minute scale of early embryonic circulation is far removed from the conditions (ie, pressures and flows) prevailing in the mature circulation. According to the proposed model, the forces for the circulating blood arise at the interface between the blood and the tissues (ie, at the level of the microcirculation). The movement of blood is, therefore, the primary phenomenon and is inextricably linked with the metabolic demands of the tissues (tissue and organ autoregulation), irrespective of the size of the organism. (For example, the flows in zebrafish embryo heart measuring the width of human hair are in the range of 0.5 cm/s. When adjusted for size, these flows exert a surprisingly large shear wall stress of about 75 Dyn/cm2, which is about half of that in the adult human aorta.) The comparative (evolutionary) model of circulation shows that the arterial circulation in lower vertebrates is preceded by a low-pressure venous circulation. With transition from water to land, the species undergo a profound change in physiology as they adapt to life in gravity and atmospheric pressure. A change from gill to lung respiration is tied closely with remodeling of the heart (ie, the emergence of the left-heart complex), and increased refinement of the reno-adrenal system, as the pressurized arterial circulation increasingly gains in importance (Fig 9). It has been suggested that the existence of pressure in the arterial compartment in warm-blooded vertebrates does not primarily serve blood propulsion but plays a different evolutionary role. Its magnitude depends on species, activity, posture, and a host of neurohumoral mechanisms and environmental factors.
Fig 9Comparative circulatory systems in fish, amphibians, mammals, and birds. In fish’s single-circuit circulation the gill and systemic circulations are placed in series. The heart has a single atrium and a single ventricle placed in the venous limb of the circuit. In addition to systemic, the amphibians also have a rudimentary lung circulation (bottom-heavy lemniscate) and a new heart chamber, the left atrium, which receives oxygenated blood from the primitive lung. Systemic and pulmonary circulation are placed in parallel and are served by a single ventricle. Complete adaptation to air respiration in mammals is associated with development of a new heart chamber, the left ventricle. The pulmonary and systemic circulations again are placed in series with a pulmonary-to-systemic flow ratio of 1:1 (balanced lemniscate). With adaptation to life in the air, the cardiorespiratory system in birds reaches a new level of development and surpasses the mammalian in efficiency, (top-heavy lemniscate). In comparison to mammals, the birds have higher metabolic rates (physiologic hyperthermia and hypertension) and aerobic capacity. With kind permission from Springer Science and Business Media.
The heart, the system of vessels, and the blood are the first functional organs to develop in the vertebrate embryo. They originate from the common mesodermal progenitors. Morphologic features of early embryonic hearts are almost identical across the vertebrate classes. The heart’s primordium is a capillary-sized tube which, in due course, undergoes a series of complex transformations (collectively known as looping) before it reaches the stage of a 2-chambered organ consisting of a single atrium and a ventricle. At this early stage, the heart contains no valves.
It traditionally has been assumed that the valveless embryo heart impels the blood by means of peristaltic contractions originating at the venous inflow and propagating along its length in analogy with the propulsive action of hollow organs such as the esophagus or the gut. This long-held view has been overturned by recent observations that demonstrated that the blood traverses the heart’s lumen at a rate that exceeds the velocity of the peristaltic wave,
How does the tubular embryonic heart work? Looking for the physical mechanism generating unidirectional blood flow in the valveless embryonic heart tube.
It has, therefore, been proposed that the embryonic heart functions as an organ of impedance and generates pressure by rhythmic interruption of the flow.
Additional evidence supporting the heart’s flow interrupting function is the presence of diastolic vortices in the embryonic heart chambers. It increasingly is recognized that intracardiac blood flow patterns play a key epigenetic role in the heart’s embryonic morphogenesis.
In fact, the final form of the vertebrate heart invariably assumes a vortex-like structure. It further has been proposed that, at least in the case of adult hearts, diastolic vortex flows perform an important energy dissipation function. By trapping kinetic energy of the inflowing blood and dissipating it as heat, diastolic vortices facilitate filling at lower intracavitary pressures,
thereby confirming the primary function of the heart as an organ of impedance.
Is the Circulation a Closed System?
The question arises as to whether or not the circulatory system indeed functions according to the principles of a mechano-energetically closed system? It still was assumed by 19th century biologists that the life of organisms was inexplicable within the confines of physicochemical laws postulated by the emerging new science of thermodynamics. Life supposedly was sustained by a vitalistic factor governed by a set of laws that essentially are different from the laws of inorganic nature. This outlook was to change with the arrival of a new generation of physiologists who made it their task to free organic sciences of vitalistic ideas and, in the words of one of the fathers of modern physiology, Carl Ludwig, “…to constitute physiology on chemico-physical foundation and give it equal scientific rank with physics.”
Moreover, Du Bois-Reymond, Ludwig’s collaborator, boldly proclaimed that “the more one advances in the knowledge of physiology, the more one will have reasons for ceasing to believe that the phenomena of life are essentially different from physical phenomena.”
As revolutionary as these statements sound, they were conceived within the framework of the Newtonian (deterministic) frame of reference that, in spite of tremendous advances in technologic and analytic methods, necessarily lead to a reductionist view in physiology.
The assumption implicit in the PP model, that energetically the circulation is a closed system where classical laws of conservation of mass and energy apply, is only an extension of this paradigm.
This view was changed radically in the middle of the 20th century with the advent of physics of open systems introduced by Prigogine and others, according to which closed or isolated systems are only a special case of time-dependent, irreversible processes.
Von Bertalanffy, one of the pioneers of the open-system biology, pointed to a profound difference between the open and closed systems in physics and biology. The maintenance of a constant inner environment (ie, of invariable form, growth, and reproduction), is said to constitute a time-dependent, self-emergent property of an organism. Homeostasis and numerous feedback controls known to exist in organisms all presuppose the theory of open systems.
Only on transition from steady state to equilibrium does an organism succumb to its environment, leading to illness, death, and disintegration of form.
According to the second law of thermodynamics, a closed system must attain a time-independent equilibrium state with maximum entropy (wasted heat) and minimum free energy (potential energy that could do more useful work). A chemical reaction where, at equilibrium, the final concentration of products depends on the initial conditions is an example of such a system. Living structures, on the other hand, are capable of just the opposite. Unlike in the closed systems in which useful energy continuously degrades into heat (entropy), a steady state is maintained in organisms through continuous exchange of substrate and energy with the environment under nonequilibrium conditions.
It is evident from the foregoing discussion that the PP model of circulation is construed on the principles of the closed system. For example, in his core text, Guyton explicitly stated how “special attempts have been made to remove all time-dependent factors in the construction of the curves in this book.”
Considered mechanistically, autonomous movement of the blood represents a violation of the second law of thermodynamics, which states that perpetual motion (machine) is impossible; such behavior, however, is predicted when an organism is considered a far-from-equilibrium, living system.
A long-recognized self-regulating form principle of the cardiovascular system originally was proposed in 1913 by Hess and formulated by Murray (1926). Murray’s law of optimal cardiovascular design predicts that there is a functional relationship between the vessel radius and the volumetric flow rate and that the energy required to maintain blood flow and vasculature is minimal.
It has been confirmed experimentally that a blood vessel responds to increase in flow by automatic adjustment of its diameter until the flow is stabilized at a new rate. Similarly, in a set of vessels in parallel, an optimal relationship is established during maximal flow between their radius and conductance.
Increased sheer stress on the vessel’s wall triggers the release of nitric oxide, a potent vasodilator, and a number of other flow-modulating factors by the endothelial cells. In the long term, increased shear stress stimulates endothelial cell proliferation, which results in adjustment of the vessel diameter to increased mean flow rate.
The endothelial cells literally will “sense” and respond to a set of flow “instructions” directly in accordance with their specific locations in the vascular system. They can be considered a prime example of a self-regulating structure.
What Moves the Blood?
The ability of vascular beds to sustain the metabolic demands of the tissues is known as tissue and organ autoregulation and is based on metabolic, myogenic, and endothelial processes. As mentioned, a number of factors have been identified that contribute to changes in vascular tone, such as intraluminal pressure (myogenic response), local metabolite concentrations, and the effect of shear stress on endothelial lining. Their common denominator is the maintenance of optimal flow across the capillary beds, often at minimal pressure gradient.
There is growing evidence that local biochemical and mechanical factors, in conjunction with red blood cells (RBCs), play a far more direct role in tissue metabolism than previously assumed. Ellsworth and others have shown that, in addition to convective flow and diffusive oxygen transfer, erythrocyte oxygen content is critical for the maintenance of tissue oxygen supply. It has been demonstrated that erythrocytes release ATP as they perfuse a region of tissue with a low oxygen saturation (SpO2) and, in turn, stimulate the production of endothelium-derived relaxing factors, including nitric oxide (NO-). Thus, the erythrocytes act as tissue oxygen sensors and suppliers and have emerged as the key regulators of tissue perfusion.
Significantly, the pivotal role of the erythrocytes in supplying oxygen to the metabolically active systemic vascular beds is complemented by the opposite effect in the pulmonary vessels. In contrast to the systemic vascular smooth muscle, which reacts to hypoxemia with vasodilation and increased blood flow, pulmonary vessels constrict in response to low levels of inspired oxygen. This important regulatory mechanism matches pulmonary ventilation with perfusion by diverting blood away from hypoxic lung regions. Nitric oxide, a potent vasodilator, is produced continuously by the pulmonary vascular and respiratory epithelium and acts as an inhibitor of pulmonary hypoxic vasoconstriction. Its powerful vasodilating activity is counteracted through irreversible binding to RBC hemoglobin.
In light of existing evidence, the RBCs increasingly are considered an important regulator of blood flow not only in systemic but also in pulmonary microvascular beds. It is estimated, for example, that the RBC-induced production of NO- by vascular endothelium accounts for 25% to 30% of basal human blood flow.
A number of other conditions can be listed in which this motor becomes unmasked and goes into overdrive though for a different pathophysiologic reason. Congenital heart defects with large, nonrestrictive communication between the systemic and pulmonary circulations at the level of the heart or the great vessels such as ASD, VDS, and PDA, share a number of similarities. Because of the anatomic defect, the heart is unable to separate the systemic and pulmonary circulations and maintain them at their normal ratios of 1:1. The short-circuited pulmonary circulation becomes subject to accelerated flows that far exceed the flows through the systemic circulation, a condition known as Eisenmenger syndrome. Pulmonary-to-systemic blood flow ratios as high as 5:1 have been reported.
Left uncorrected, they invariably lead to increased pulmonary resistance and equalization pressures between the pulmonary and systemic circulations and end with the patient’s demise.
Hyperdynamic circulation with disturbed balance between the pulmonary and systemic circulations also can be observed in the case of systemic arteriovenous fistulas. While smaller fistulas present with a range of peculiar phenomena such as flow reversal in the feeding arteries and arterializations of proximal fistula veins, large-volume fistula flows, on the other hand, result in high-output heart failure or lead to an increase in pulmonary vascular resistance and pulmonary hypertension. For a more detailed account of the above conditions, see reference
Since, according to the proposed model, the pressure sustained by the heart in the arterial vascular compartment, though essential for maintenance of normal physiology, can no longer be assumed to be the primary cause of blood’s movement, the question arises as to how the circulation can be understood not only locally, where it is self-regulated, but also at the level of the entire organism. Phenomenologic evidence suggests that a “dynamic tension” exists between the lung, as the supplier of oxygen, and the peripheral tissues, where it is consumed. This far-from-equilibrium state is bridged by the blood which, as a fluid organ with its own oxygen and metabolic demands, circulates between the two. (Here, a crude analogy can be drawn between the blood’s movement and the coil rotating between 2 poles of the magnetic field.) In this context, the heart, as a feedback organ of impedance, regulates and maintains the balance between the pulmonary and systemic circulations in accordance with global metabolic demands.
In summary, an attempt has been made to review some of the inconsistencies of the widely accepted pressure-propulsion circulation model that fails to explain an increasing number of observed circulatory phenomena and has, in due course, become increasingly complex and even self-contradictory. The model is construed on the basis of a closed hydraulic system functioning at a quasi-equilibrium state in which blood, an inert fluid, is propelled around the circuit by the pressure gradient created by the heart. Experimental and phenomenologic evidence suggest the opposite, namely that the blood possesses autonomous movement sustained by the metabolic demands of the tissues at the level of microcirculation. The heart plays a crucial role by maintaining the pressure in the pulmonary and systemic arterial circulations through rhythmic interruption of flow. It functions as an organ of impedance by exerting a negative feedback to the global metabolic demands, at the level of the macro-circulation. (See Fig 10 for comparison of circulation models.) This is supported by the biologic model of circulation (ontogenetic and phylogenetic) in which the circulatory system, comprising the heart, the vessels, and the blood, arises from the common mesodermal precursors and forms a unified, highly differentiated organ system functioning (oscillating) at a steady state that is far removed from equilibrium, and by numerous experimental and clinical observations.
Fig 10A comparison of the classic PP and biologic models of circulation. A defining feature of both PP models is that the pressure gradient created by the heart is the source of blood propulsion. In Guyton’s VR model, CO predominantly is regulated by the circuit parameters (ie, elastic and resistive properties of the blood vessels and blood volume). The Pra plays a dual role; viewed from the heart, increased Pra promotes ventricular filling, thereby increasing CO. Viewed from the circulation, increased Pra exerts back pressure, impedes venous return, and reduces CO. The LV model assumes that the CO is limited by the pump’s output and is proportional to the gradient between the mean aortic and Pra and inversely proportional to Rp. The blood is considered an inert, incompressible fluid, and the amount pumped into the arterial side of the circuit is equal to the amount of blood returning at the venous side. The biologic model assumes the existence of dynamic tension between the source of oxygen in the lung and its sink in the metabolically active tissues. The blood, a liquid self-moving organ, bridges this tension and plays a dual role by procuring oxygen and nutrients to the peripheral tissues and also to itself. The forces for blood propulsion thus originate at the level of the microcirculation. The heart plays a secondary role and exerts a negative feedback to the metabolic demands of the tissues by rhythmic interruption of the blood flow. Its ram-like function maintains pressure in the systemic and pulmonary arterial compartments and carries the rhythm of life. PP, pressure-propulsion; VR, venous return; LV, left ventricular; CO, cardiac output; Pra, right atrial pressures; Rp, peripheral resistance.
Science moves in spirals, and it appears that according to the current view of solid-state physics, du Bois-Reymond’s statement, “that phenomena of life indeed are no different from physical phenomena,”
is again within reach. The extent to which the explanation of circulatory phenomena, based on contemporary physics, will translate into a deeper understanding of physiology and lead to practical applications in clinical medicine presents, however, an ongoing challenge, the realization of which will, no doubt, depend on a closer collaboration between the 2 disciplines.
Acknowledgment
The author would like to thank Christina Porkert for her invaluable secretarial assistance.
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Guidelines for the diagnosis and treatment of chronic heart failure: Executive summary (update 2005) The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology.
Point:Counterpoint: The classical Guyton view that mean systemic pressure, right atrial pressure, and venous resistance govern venous return is/is not correct.
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Pulmonary artery occlusion pressure and central venous pressure fail to predict ventricular filling volume, cardiac performance, or the response to volume infusion in normal subjects.
How does the tubular embryonic heart work? Looking for the physical mechanism generating unidirectional blood flow in the valveless embryonic heart tube.
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