Venous Return

The mean systemic pressure of the circulation (P_ms) is thought to be the inflow pressure driving blood toward the right ventricle.² This driving pressure is not measurable in the intact patient, but it can be thought of as the static mean pressure that might exist throughout the circulation if there were no blood flow.³ P_ms approximates the weighted average of pressures in venous reservoirs throughout the body during the circulation of blood.⁴ The backpressure that opposes flow toward the right heart is the right atrial pressure (P_ra). The impact of these pressures on return of venous blood to the heart is described by the venous return curve (Figure 26-1, A). Picture the systemic circulation as compliant arteries and veins separated by high-resistance arterioles and a pump that receives venous return and propels it into the arteries (Figure 26-1, B). The faster the pump circulates the blood, the more blood piles up before the arterioles and the higher the arterial pressure will be. In contrast, the faster the pump moves blood from vein to artery, the less blood resides on the venous side of the circuit and the lower the venous pressure will be. As the pump is slowed down, venous pressure rises until flow reaches zero and pressure equilibrates throughout the circulation at P_ms. Resistance to venous return (R_vr) is the reciprocal of the slope of the linear part of the venous return curve. Simply stated:

Figure 26–1 A, Systemic venous return curve. Flow (Q_pump) is plotted on the ordinate, but is treated as the independent variable. Right atrial pressure (P_ra), the dependent variable, is plotted on the abscissa. B, Circulation is treated as though a pump transferred blood from veins to arteries, generating arterial pressure sufficient to overcome peripheral arterial resistance. Arterial compliance (C_a) and venous compliance (C_v) determine the volume of blood distending arteries and veins at any Q_pump. When there is no flow, pressure equilibrates throughout the circulation at the mean systemic pressure of the circulation P_ms. As pump flow is progressively increased, venous pressure falls and arterial pressure rises because of the net transfer of blood from veins to arteries by the pump and because of the accumulation of blood before the peripheral resistance. When venous pressure falls to P_c, the critical closing pressure of the venous system, no further increase in pump flow is possible.

(Modified from Guyton AC: Determination of cardiac output by equating venous return curves with cardiac response curves, Physiol Rev 35:123, 1955.)

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P_ms is sensitive to the volume of blood in the circulation and to the capacitance of the venous reservoir. It can be altered by transfusion, volume infusion, hemorrhage, and diuresis. It also is sensitive to changes in venous tone. P_ms is an extrathoracic measurement and is less sensitive than P_ra to changes in intrathoracic pressure.⁵ P_ra, in contrast, is quite sensitive to changes in intrathoracic pressure.

At functional residual capacity (FRC), the thorax exerts recoil force, tending to spring outward, whereas the lung exerts recoil force (mostly as a result of alveolar surface tension), tending to collapse inward. These forces result in subambient pleural pressure. The cardiac fossa, or juxtacardiac space, which surrounds the pericardium and heart, shares in this balance of forces and has slightly negative pressure at apneic FRC. At any right atrial volume, P_ra is influenced by juxtacardiac pressure because these two forces act together to oppose the right atrium’s balloonlike tendency to recoil inward. Therefore it is not surprising that all of these pressures (pleural, juxtacardiac, and right atrial) are influenced by the respiratory cycle.^6–8

During spontaneous breathing, lung volume rises from FRC to end-inspiratory volume by expansion of the rib cage and descent of the diaphragm. This reshaping of the thorax stretches the lung, increasing its recoil tension, so pleural pressure and juxtacardiac pressure both become more negative (subambient). At any right atrial volume, this process reduces P_ra. Therefore spontaneous inspiration reduces pleural, juxtacardiac, and right atrial pressures. By the mathematical relationship in Equation 1, this augments venous return.⁹ Over the course of passive spontaneous expiration, all three pressures return toward their values at FRC. It follows that intrathoracic pressure, during relaxed spontaneous breathing, is always least negative at end-inspiration and falls continuously throughout the rest of the respiratory cycle.

Right Ventricular Preload and Stroke Volume

Transmural pressure is the pressure difference across (inside to outside) a hollow structure. This pressure difference and the wall tension of the structure determine its radius. P_ra approximates the pressure within the right ventricle during cardiac filling. Juxtacardiac pressure approximates the pressure surrounding the ventricle. During spontaneous inspiration, systemic venous return to the right atrium and ventricle are augmented (Equation 1), and end-diastolic ventricular volume rises. P_ra falls, but not as much as juxtacardiac pressure falls. Transmural pressure is, therefore, increased by spontaneous inspiration. Despite the falling P_ra, right ventricular stroke volume normally rises during spontaneous inspiration; hence, there is a paradoxical inverse relationship between P_ra and right ventricular stroke volume over the spontaneous respiratory cycle (Figure 26-2).¹⁰ If transmural P_ra is plotted against right ventricular stroke volume during various respiratory maneuvers, the expected positive slope is revealed (Figure 26-3).¹¹

Figure 26–2 During spontaneous inspiration, right atrial pressure (P_ra) falls, but this decline is associated with an increase in right ventricular stroke volume (SVRV). Shown at two different mean P_ra.

(From Pinsky MR: Instantaneous venous return curves in an intact canine preparation, J Appl Physiol 56:765, 1984.)

Figure 26–3 Over a wide range of respiratory maneuvers, right ventricular stroke volume (SVRV) varies directly with transmural right atrial pressure (Pra_tm). IPPB, Intermittent positive pressure breathing; MM, Müller maneuver; SPONT, spontaneous breathing; VSM, Valsalva maneuver.

(From Pinsky MR: Determinants of pulmonary arterial flow variation during respiration, J Appl Physiol 56:1237, 1984.)

Positive Pressure Mechanical Ventilation and Right Ventricular Preload

The effects of positive pressure ventilation on pleural, juxtacardiac, and right atrial pressure are opposite those of spontaneous breathing. A common goal in the application of positive end-expiratory pressure (PEEP) is restoration of normal end-expiratory lung volume (normal FRC). All other things being equal, pleural pressure, which opposes thoracic recoil, should be the same at end-expiration whether breathing is spontaneous or mechanical. Pleural pressure is, after all, determined by thoracic volume.

During spontaneous inspiration, active reshaping of the thorax by the respiratory muscles and diaphragm inflates the lungs by reducing pleural pressure. In contrast, throughout positive pressure mechanical inspiration, pleural pressure rises because the passive thorax is pushed outward (from FRC to end-inspiratory volume) by the expanding lungs. Passive expiration restores pleural pressure to that of FRC. Averaged over the entire respiratory cycle, pleural pressure is higher during positive pressure breathing than it would be during spontaneous breathing (Figure 26-4). (This elevation of pleural pressure during positive pressure mechanical ventilation is generally called transmission of airway pressure to the pleural space.) Positive pressure ventilation, therefore, reverses the effects of spontaneous breathing on venous return¹² and right ventricular transmural pressure.

Figure 26–4 Over the course of the respiratory cycle, if spontaneous and positive pressure breaths both begin and end at the same functional residual capacity (FRC), spontaneous breathing takes place at lower pleural pressure than does positive pressure ventilation.

Positive pressure inspiration impedes venous return by raising P_ra. Right ventricular stroke volume declines over positive pressure inspiration because right ventricular transmural pressure is reduced. Averaged over the entire respiratory cycle, P_ra is raised and right ventricular stroke volume and cardiac index are reduced by positive airway pressure relative to their expected values during spontaneous breathing (Figure 26-5).

Figure 26–5 Relationship between the percentage change in cardiac index and the percentage change in right atrial pressure that was produced by the application of graded levels of positive airway pressure in adults.

(From Jellinek H, Krafft P, Fitzgerald RD, et al: Right atrial pressure predicts hemodynamic response to apneic positive airway pressure, Crit Care Med 28:672, 2000.)

It is easy to argue from these observations that positive pressure ventilation will invariably decrease venous return to the right heart, but this is not always the case. PEEP tends to elevate intrathoracic pressure over the entire respiratory cycle and opposes venous return. However, it may also displace blood from the pulmonary circulation and from the abdominal viscera (by descent of the diaphragm), thereby raising P_ms. Positive airway pressure may also have favorable effects on left heart function (see the section on left ventricular afterload). In patients whose left heart function improves, both left and right ventricular inflow pressures fall, enhancing venous return.

Critical Illness and Effects of Positive Pressure Breathing on the Right Heart

Among the effects of critical illness are capillary leak, chest wall edema, pulmonary edema, surfactant dysfunction, abnormal blood volume, and abdominal distension. Each modifies the effects of positive pressure breathing on the right heart. Capillary leak alters the compliance of the atrial and ventricular chambers, modifying the responsiveness of the heart to changes in preload. Sepsis and inflammation decrease cardiac contractility, directly altering the way the heart responds to changes in preload. Chest wall edema, pulmonary edema, surfactant dysfunction, and abdominal distension alter thoracic and pulmonary compliances, which in turn alter pleural and juxtacardiac pressures.

Reduced respiratory system compliance diminishes the transmission of alveolar pressure to the juxtacardiac space.¹³ The change in intrathoracic pressure that occurs with a change in static airway pressure is essentially the same as the change observed in pulmonary artery wedge pressure,¹⁴ which is readily measured. Recognizing this relationship in adults has made it possible to estimate percent transmission of airway pressure to the juxtacardiac space by measurement of respiratory system compliance (Figure 26-6).

Figure 26–6 Relationship between the static compliance of the respiratory system (C_st,rs) and the index of transmission (I_t, decimal fraction) of a change in static airway pressure to the pulmonary circulation in adults. I_t values for pleural and juxtacardiac spaces are presumed to be comparable.

(From Teboul JL, Pinsky MR, Mercat A, et al: Estimating cardiac filling pressure in mechanically vented patients with hyperinflation, Crit Care Med 28:3631, 2000.)

Both abnormal blood volume and abnormal vascular compliance can change P_ms and thereby alter venous return. Vascular hypovolemia can exaggerate the adverse effects of positive pressure ventilation on preload.

Lung Volume

The alveolar septae are highly vascular (Figure 26-7). More than 90% of the alveolar surface makes contact with alveolar capillaries. These vessels can be separated into two categories according to their location or their response to lung inflation. Most alveolar vessels are capillaries and lie in septa, which separate adjacent alveoli. Other alveolar vessels are termed corner vessels because they are located at the intersection of alveolar septa. These corner vessels are generally larger and most likely will divide later in their course to become alveolar capillaries located in septa between adjacent alveoli. When the lung is stretched, either by spontaneous inspiration or by positive pressure distension, corner vessels are pulled open by radial traction and their resistance to blood flow is reduced. When alveolar septa are stretched, alveolar capillaries thin and restrict flow. The net effect of these factors is a U-shaped relation of PVR to lung volume (Figure 26-8)^15–18; PVR is least at FRC and rises with either atelectasis or overdistension.

Figure 26–7 Alveolus is encased in a network of capillaries. Alveolar vessels are those that lie between adjacent alveoli. Corner vessels are those that lie at the intersection of alveolar septa. RBC, Red blood cell.

Figure 26–8 Effects of lung volume on pulmonary vascular resistance (PVR). As whole lung is distended from functional residual capacity (FRC) toward total lung capacity (TLC), PVR rises, predominantly by increasing resistance to flow through the small alveolar vessels that course between adjacent alveoli (alveolar vessels). As whole lung is collapsed from FRC toward residual volume, PVR rises, predominantly by effects on corner vessel that traverse the intersection of alveolar septa. (Modified from Cassidy SS, Schwiep F: Cardiovascular effects of positive end-expiratory pressure. In Scharf SM, Cassidy SS, editors: Heart lung interactions in health and disease, vol 42, Lung biology in health and disease, New York, 1989, Dekker.)

Alveolar Pressure

When alveolar pressure is greater than ambient, as it is during positive pressure ventilation, the vessels that course through alveolar septae between adjacent alveoli can be compressed.^19,20 This behavior is akin to that of a Starling resistor, a collapsible tube traversing a rigid housing (Figure 26-9). Flow (Q) is propelled through the tube by inflow pressure (P_i) and is opposed by outflow pressure (P_o). The tubing has some intrinsic resistance (R). If the housing is pressurized to a surrounding pressure (P_s), flow through the tube is determined as follows:

Figure 26–9 Starling resistor is a compressible conduit traversing a rigid housing, which is pressurized to a surrounding pressure (P_s). Flow (Q) traverses the conduit, propelled by inflow pressure (P_i) and opposed by outflow pressure (P_o) such that driving pressure is (P_i − P_o) for P_s < P_o. As P_s is increased, it begins to influence flow, but only after it exceeds P_o. At P_s > P_o, the driving force for flow becomes (P_i − P_s).

(Modified from Knowlton FP, Starling EH: The influence of variations in temperature and blood pressure on performance of the isolated mammalian heart, J Physiol 44(3):206-219, 1912.)

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Except when P_s < P_o, alveolar pressure appears to modulate local pulmonary blood flow as though it surrounds the pulmonary capillary (Figure 26-10).

Figure 26–10 Pulmonary capillaries are, in essence, surrounded by gas-filled alveoli. The influence of alveolar pressure (P_A) on regional lung blood flow is similar to the influence of surrounding pressure on flow through a Starling resistor. At ambient values of P_A, pulmonary vein pressure (PV) opposes inflow. As P_A rises, it begins to oppose inflow only after P_A > PV. It modulates inflow until P_A reaches hydrostatic inflow pressure (PA), at which point flow ceases.

From this discussion, the degree to which P_s affects pulmonary blood flow is influenced by the magnitude of inflow pressure, which, for the pulmonary capillary, must be adjusted for vertical height. Alveolar pressure causes greater reduction in flow at low pulmonary artery pressure than it does at high pressure. Pulmonary hypertension (high P_i) dampens this cardiopulmonary interaction, whereas hypovolemia (low P_i) accentuates it.

Hydrostatic pressure in the lung is a function of vertical height (see Chapter 20).²¹ To estimate the hydrostatic inflow pressure of a pulmonary capillary, a pressure equivalent to that exerted by a water column extending from the left atrium to the capillary must be subtracted from the pressure within the main pulmonary artery. The greater the vertical height of the pulmonary capillary, the lower its inflow pressure and the greater the attenuation of flow by alveolar pressure. This can produce areas of no flow, especially at peak inspiration, high in the supine lung. These high ventilation/perfusion ratio (Va/Q) alveolar capillary units waste ventilation and can cause hypercarbia (see Chapter 40). Vertical height (h) of the capillary also alters the backpressure to flow. At a left atrial pressure of 10 cm H₂O (7 mm Hg), for example, there is (10 − h) cm H₂O opposing flow up to a vertical height 10 cm above the heart. Above that, there is no back pressure, and P_i and P_s determine flow through the capillary. Compression of pulmonary capillaries is a local phenomenon. It can divert pulmonary blood flow away from normal lung segments toward consolidated or atelectatic lung segments whose airways do not effectively transmit airway pressure to the alveolus.²² By this mechanism, the application of high PEEP in the presence of lobar pneumonia may increase blood flow through unventilated lung and worsen hypoxemia (Figure 26-11). From a more positive perspective, PEEP may relieve atelectasis and improve ventilation, thereby relieving alveolar hypoxic vasoconstriction. Whether PEEP benefits or impairs pulmonary blood flow may depend on the balance of its effect on atelectasis and its effect on alveolar capillaries.

Figure 26–11 Blood flow to the left lower lobes (LLL) of dogs with LLL pneumonia, measured at zero positive end-expiratory pressure (PEEP) (C₁), 6−12 cmH₂O PEEP (P), and on cessation of applied PEEP (C₂). PEEP diverted blood flow away from more normal lung toward the consolidated LLL.

(From Mink SN, Light RB, Cooligan T, et al: Effect of PEEP on gas exchange and pulmonary perfusion in canine lobar pneumonia, J Appl Physiol 50:517, 1981.)

Regulation of Pulmonary Vascular Resistance

The resistance to flow through a vessel is described by the following:

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where η is viscosity, l is length, and r is radius. It follows that PVR can be effectively controlled by active changes in vessel radius. Mechanical ventilation may alter blood pH and alveolar oxygen tension (pO₂), both of which influence vessel tone and radius (Figure 26-12).^23,24

Figure 26–12 Pulmonary vascular resistance (PVR) is a function of both pH and arterial pO₂.

(From Rudolph AM, Yuan S: Response of the pulmonary vasculature to hypoxia and H⁺ ion concentration changes, J Clin Invest 45:399, 1966.)

Hypoxic pulmonary vasoconstriction is a powerful mechanism for sustaining systemic oxygenation in the face of lung disease.^25–28 Relief of atelectasis and restoration of segmental ventilation not only increases the fraction of the lung that is ventilated but also restores blood flow to those segments by several mechanisms. Segmental alveolar hypoxia is relieved. Segmental volume is restored, which returns segmental vascular resistance toward its volume-dependent nadir. Gas exchange is also improved, favorably altering pH, pCO₂, and pO₂, and thereby reducing global PVR.

Direct Effects of Airway Pressure on Pulmonary Vascular Tone

Pulmonary vessels are stretched by lung inflation. The lung of infant lambs responds to abrupt changes in airway pressure with changes in vascular tone. Abrupt distension of one lung of the intact infant lamb increases the PVR of that lung alone.²⁹ The resistance change is sensitive to the waveform of the lung distension³⁰ and persists for some time after relief of distending pressure and return of lung volume to baseline.³¹ This effect is calcium channel dependent³² and resembles a myogenic reflex whereby direct vessel stretch causes constriction.

Decreased Venous Return

The reduction in venous return to the right heart seen at high airway pressure should directly reduce filling of the left heart. But there is a trap in this line of reasoning. Venous return, when averaged over several respiratory cycles, equals cardiac output. If other cardiopulmonary interactions and compensatory mechanisms restore cardiac output to normal, then right and left heart venous return will not be diminished.