Effects of Cardiac Arrest on Arterial and Venous Pressure

Figure 19-2, B, shows the circulation at the very beginning of an episode of cardiac arrest; that is, Q_h = 0. In the instant immediately after arrest of the heart, the volume of blood in the arteries (V_a) and veins (V_v) has not had time to change appreciably. Because arterial pressure and venous pressure depend on V_a and V_v, respectively, these pressures are identical to the respective pressures in Figure 19-2, A (i.e., P_a = 102 and P_v = 2). This arteriovenous pressure gradient of 100 mm Hg forces a flow (Q_r) of 5 L/min through the peripheral resistance of 20 mm Hg/L/min. Thus, although cardiac output (Q_h) now equals 0 L/min, flow through the microcirculation equals 5 L/min because the potential energy stored in the arteries by the preceding pumping action of the heart causes blood to be transferred from arteries to veins. This transfer occurs initially at the control rate, even though the heart can no longer transfer blood from the veins to the arteries.

As the heart continues in arrest, blood flow through the resistance vessels causes the blood volume in the arteries to decrease progressively and the blood volume in the veins to increase progressively at the same absolute rate. Because the arteries and veins are elastic structures, arterial pressure falls gradually and the venous pressure rises gradually. This process continues until arterial and venous pressures become equal (Fig. 19-2, C). Once this condition is reached, flow (Q_r) from the arteries to the veins through the resistance vessels is zero, as is Q_h.

When the effects of cardiac arrest reach this equilibrium state (Fig. 19-2, C), the pressure attained in the arteries and veins depends on the relative compliance of these vessels. If arterial compliance (C_a) and venous compliance (C_v) are equal, the decline in P_a would equal the rise in P_v because the decrease in arterial volume would equal the increase in venous volume (principle of conservation of mass). Both P_a and P_v would attain the average of their combined values in Figure 19-2, A; that is, P_a = P_v = (102 + 2)/2 = 52 mm Hg. However, C_a and C_v in a living subject are not equal. Veins are much more compliant than arteries; the compliance ratio (C_v/C_a) is approximately 19, the ratio that we have assumed for the model. When the effects of cardiac arrest reach equilibrium in an intact subject, the pressure in the arteries and veins is much less than the average value of 52 mm Hg that occurs when C_a and C_v are equal. Hence, transfer of blood from arteries to veins at equilibrium induces a fall in arterial pressure 19 times greater than the concomitant rise in venous pressure. As Figure 19-2, C, shows, P_v would increase by 5 mm Hg (to 7 mm Hg), whereas P_a would fall by 19 × 5 = 95 mm Hg (to 7 mm Hg). This equilibrium pressure, which prevails in the absence of flow, is referred to as either mean circulatory pressure or static pressure. The pressure in the static system reflects the total blood volume in the system and the overall compliance of the system.

The example of cardiac arrest aids our understanding of the vascular function curve. One can now begin to assemble a vascular function curve (Fig. 19-3). The independent variable (plotted along the x axis) is cardiac output, and the dependent variable (plotted along the y axis) is central venous pressure. Two important points on this curve can be derived from the example in Figure 19-2. One point (A in Fig. 19-3) represents the control state; that is, when cardiac output is 5 L/min, P_v is 2 mm Hg (as depicted in Fig. 19-2, A). Then, when the heart is arrested (cardiac output = 0), P_v becomes 7 mm Hg at equilibrium (Fig. 19-2, C); this pressure is the mean circulatory pressure (P_mc in Fig. 19-3).

Figure 19-3 Changes in central venous pressure produced by changes in cardiac output. The mean circulatory pressure (or static pressure), P_mc, is the equilibrium pressure throughout the cardiovascular system when cardiac output is 0. Points B and A represent the values of venous pressure at a cardiac output of 1 and 5 L/min, respectively.

The inverse relationship between P_v and cardiac output simply denotes that when cardiac output is suddenly decreased, the rate at which blood flows from arteries to veins through the capillaries is temporarily greater than the rate at which the heart pumps blood from the veins back into the arteries. During that transient period, a net volume of blood is transferred from arteries to veins; hence, P_a falls and P_v rises.

Now let us suddenly increase cardiac output. This example will illustrate how a third point (B in Fig. 19-3) on the vascular function curve is derived. Consider that the arrested heart is suddenly restarted and immediately begins pumping blood from the veins into the arteries at a rate of 1 L/min (Fig. 19-2, D). When the heart first begins to beat, the arteriovenous pressure gradient is zero, and no blood is transferred from the arteries through the capillaries and into the veins. Thus, when beating resumes, blood is depleted from the veins at the rate of 1 L/min, and arterial blood volume is repleted from venous blood volume at that same absolute rate. Hence, P_v begins to fall and P_a begins to rise. Because of the difference in arterial and venous compliance, P_a will rise at a rate 19 times faster than the rate at which P_v will fall.

The resultant arteriovenous pressure gradient causes blood to flow through the peripheral resistance. If the heart maintains a constant output of 1 L/min, P_a will continue to rise and P_v will continue to fall until the pressure gradient becomes 20 mm Hg. This gradient will force a flow of 1 L/min through a resistance of 20 mm Hg/L/min. This gradient will be achieved by a 19–mm Hg rise (to 26 mm Hg) in P_a and a 1–mm Hg fall (to 6 mm Hg) in P_v. This equilibrium value of P_v = 6 mm Hg for a cardiac output of 1 L/min also appears on the vascular function curve of Figure 19-3 (point B). The 1–mm Hg reduction in P_v reflects a net transfer of blood from the venous to the arterial side of the circuit.

The reduction in P_v that can be evoked by a sudden increase in cardiac output is limited. At some critical maximal value of cardiac output, sufficient fluid will be transferred from the venous to the arterial side of the circuit for P_v to fall below ambient pressure. In a system of very distensible vessels, such as the venous system, the vessels will be collapsed by the greater external pressure (see Chapter 17). This venous collapse impedes venous return to the heart. Hence, it limits the maximal value of cardiac output to 7 L/min in this example (Fig. 19-3), regardless of the capabilities of the pump.

Factors That Influence the Vascular Function Curve

Blood Volume

The vascular function curve is affected by variations in total blood volume. During circulatory standstill (zero cardiac output), mean circulatory pressure depends only on total vascular compliance and blood volume. For a given vascular compliance, mean circulatory pressure is increased when blood volume is expanded (hypervolemia) and is decreased when blood volume is diminished (hypovolemia). This relationship is illustrated by the y axis intercepts in Figure 19-4, where mean circulatory pressure is 5 mm Hg after hemorrhage and 9 mm Hg after transfusion, as compared with a value of 7 mm Hg at normal blood volume (normovolemia or euvolemia).

Figure 19-4 Effects of increased blood volume (transfusion curve) and decreased blood volume (hemorrhage curve) on the vascular function curve. Similar shifts in the vascular function curve can be produced by increases and decreases, respectively, in venomotor tone.

IN THE CLINIC

Cardiac output may decrease abruptly when a major coronary artery suddenly becomes occluded in a human patient. The acute heart failure that occurs as a result of myocardial infarction (death of myocardial tissue) is usually accompanied by a fall in arterial blood pressure and a rise in central venous pressure.

From Figure 19-4 it is also apparent that the cardiac output at which P_v = 0 varies directly with blood volume. Therefore, the maximal value of cardiac output becomes progressively more limited as the total blood volume is reduced. However, the central venous pressure at which the veins collapse (illustrated by the sharp change in slope of the vascular function curve) is not significantly altered by changes in blood volume. This pressure depends only on the ambient pressure surrounding the central veins. Ambient pressure is the pleural pressure in the thorax (see Chapter 21).

Peripheral Resistance

The changes in the vascular function curve induced by alterations in arteriolar tone are shown in Figure 19-5. The amount of blood in the arterioles is small—they contain only about 3% of total blood volume (see Chapter 15). Changes in the contractile state of arterioles do not significantly alter mean circulatory pressure. Thus, vascular function curves that represent different peripheral resistances converge at a common point on the abscissa.

Figure 19-5 Effects of arteriolar dilation and constriction on the vascular function curve.

P_v varies inversely with total peripheral resistance (TPR) when all other factors remain constant. Physiologically, the relationship between P_v and TPR can be explained as follows: if cardiac output is held constant, a sudden increase in TPR causes a progressively greater volume of blood to be retained in the arterial system. Blood volume in the arterial system continues to increase until P_a rises sufficiently to force a flow of blood equal to cardiac output through the resistance vessels. If total blood volume does not change, this increase in arterial blood volume is accompanied by an equivalent decrease in venous blood volume. Hence, an increase in TPR diminishes P_v proportionately. This relationship between TPR and P_v, together with the inability of peripheral resistance to affect mean circulatory pressure, accounts for the clockwise rotation of the vascular function curves in response to increased arteriolar constriction (see Fig. 19-5). Similarly, arteriolar dilation produces a counterclockwise rotation from the same vertical axis intercept. A higher maximal level of cardiac output is attainable when the arterioles are dilated than when they are constricted (Fig. 19-5).

Coupling between the Heart and the Vasculature

In accordance with Starling’s law of the heart, cardiac output depends closely on right atrial (or central venous) pressure. Furthermore, right atrial pressure is approximately equal to right ventricular enddiastolic pressure because the normal tricuspid valve acts as a low-resistance junction between the right atrium and ventricle. Graphs of cardiac output as a function of central venous pressure (P_v) are called cardiac function curves; extrinsic regulatory influences may be expressed as shifts in such curves.

A typical cardiac function curve is plotted on the same coordinates as a normal vascular function curve in Figure 19-6. The cardiac function curve is plotted according to the usual convention; that is, the independent variable (P_v) is plotted along the abscissa, and the dependent variable (cardiac output) is plotted along the ordinate. From the Frank-Starling mechanism, the cardiac function curve reveals that a rise in P_v increases cardiac output.

Figure 19-6 Typical vascular and cardiac function curves plotted on the same coordinate axes. Note that to plot both curves on the same graph, the x and y axes for the vascular function curves had to be reversed; compare the assignment of axes with that in Figures 19-3, 19-4, and 19-5. The coordinates of the equilibrium point, at the intersection of the cardiac and vascular function curves, represent the stable values of cardiac output and central venous pressure at which the system tends to operate. Any perturbation (e.g., a sudden increase in venous pressure to point A) institutes a sequence of changes in cardiac output and venous pressure that restore these variables to their equilibrium values.

Conversely, the vascular function curve describes an inverse relationship between cardiac output and P_v; that is, a rise in cardiac output diminishes P_v. P_v is the dependent variable (or response) and cardiac output is the independent variable (or stimulus) for the vascular function curve. Therefore, to plot a vascular function curve in the conventional manner, P_v should be scaled along the y axis and cardiac output along the x axis.

To plot the cardiac and vascular function curves on the same set of axes requires a modification of the plotting convention for one of these curves. We arbitrarily violate the convention for the vascular function curve. Note that the vascular function curve in Figure 19-6 is intended to reflect how P_v (scaled along the x axis) varies in response to a change in cardiac output (scaled along the y axis).

When the cardiovascular system is represented by a given pair of cardiac and vascular function curves, the intersection of these two curves defines the equilibrium point of that system. The coordinates of this equilibrium point represent the values of cardiac output and P_v at which the system tends to operate. Only transient deviations from such values of cardiac output and P_v are possible, as long as the given cardiac and vascular function curves accurately describe the system.

The tendency to operate about this equilibrium point may best be illustrated by examining the response to a sudden change. Consider the changes caused by a sudden rise in P_v from the equilibrium point to point A in Figure 19-6. This change in P_v might be caused by the rapid injection, during ventricular diastole, of a given volume of blood on the venous side of the circuit and simultaneous withdrawal of an equal volume from the arterial side of the circuit. Thus, although P_v rises, total blood volume remains constant.

As defined by the cardiac function curve, this elevated P_v would increase cardiac output (from A to B) during the next ventricular systole. The increased cardiac output would then transfer a net quantity of blood from the venous to the arterial side of the circuit, with a consequent reduction in P_v. In one heartbeat the reduction in P_v would be small (from B to C) because the heart would transfer only a fraction of the total venous blood volume to the arterial side. As a result of this reduction in P_v, cardiac output during the very next beat diminishes (from C to D) by an amount dictated by the cardiac function curve. Because D is still above the intersection point, the heart will pump blood from the veins to the arteries at a rate greater than that at which blood will flow across the peripheral resistance from arteries to veins. Hence, P_v will continue to fall. This process will continue in diminishing steps until the point of intersection is reached. Only one specific combination of cardiac output and venous pressure—the equilibrium point, denoted by the coordinates of the point at which the curves intersect—will simultaneously satisfy the requirements of the cardiac and vascular function curves. Stable operation of the system at the equilibrium point (A, in Fig. 19-6) indicates that cardiac output equals venous return.

Myocardial Contractility

Combinations of cardiac and vascular function curves also help explain the effects of alterations in ventricular contractility on cardiac output and P_v. In Figure 19-7, the lower cardiac function curve represents the control state, whereas the upper curve reflects the influence of increased myocardial contractility. This pair of curves is analogous to the “family” of ventricular function curves shown in Figure 18-12. The enhanced ventricular contractility represented by the upper curve in Figure 19-7 can be produced by electrical stimulation of the cardiac sympathetic nerves. When the effects of such neural stimulation are restricted to the heart, the vascular function curve is unaffected. Therefore, only one vascular function curve is needed for this hypothetical intervention (Fig. 19-7).

Figure 19-7 Enhancement of myocardial contractility, as by cardiac sympathetic nerve stimulation, causes the equilibrium values of cardiac output and central venous pressure (P_v) to shift from the intersection (point A) of the control vascular and cardiac function curves (continuous curve) to the intersection (point D) of the same vascular function curve with the cardiac function curve (dashed curve) that represents the response to sympathetic stimulation.

During the control state of the model, the equilibrium values for cardiac output and P_v are designated by point A in Figure 19-7. Cardiac sympathetic nerve stimulation abruptly raises cardiac output to point B because of the enhanced myocardial contractility. However, this high cardiac output increases the net transfer of blood from the venous to the arterial side of the circuit, and consequently, P_v subsequently begins to fall (to point C). The reduction in P_v then leads to a small decrease in cardiac output. However, cardiac output is still sufficiently high to effect the net transfer of blood from the venous to the arterial side of the circuit. Thus, P_v and cardiac output both continue to fall gradually until a new equilibrium point (D) is reached. This equilibrium point is located at the intersection of the vascular function curve and the new cardiac function curve. Point D lies above and to the left of the control equilibrium point (A) and indicates that sympathetic stimulation can evoke greater cardiac output despite the lower level of P_v.

The biological response to enhancement of myocardial contractility is mimicked by the hypothetical change predicted by our model. As depicted in Figure 19-8, sympathetic nerves innervating the heart are stimulated during the time denoted by the two arrows. During neural stimulation, cardiac output (aortic flow) rose quickly to a peak value and then fell gradually to a steady-state value significantly greater than the control level. The increased aortic flow was accompanied by reductions in right and left atrial pressure (P_RA and P_LA).

Figure 19-8 During electrical stimulation of the cardiac sympathetic nerve fibers, aortic blood flow (cardiac output) increased while pressure in the left atrium (P_LA) and right atrium (P_RA) diminished. These data conform to the conclusions derived from Figure 19-7, in which the equilibrium values of cardiac output and venous pressure are observed to shift from point A to point D (i.e., cardiac output increased, but central venous pressure decreased) during cardiac sympathetic nerve stimulation.

(Redrawn from Sarnoff SJ et al: Circ Res 8:1108, 1960.)

Blood Volume

Changes in blood volume do not directly affect myocardial contractility, but they do influence the vascular function curve in the manner shown in Figure 19-4. Thus, to understand how changes in blood volume affect cardiac output and P_v, the appropriate cardiac function curve is plotted along with the vascular function curves that represent the control and experimental states (Fig. 19-9).

Figure 19-9 After a blood transfusion, the vascular function curve is shifted to the right. Therefore, cardiac output and venous pressure are both increased, as denoted by translocation of the equilibrium point from A to B.

When blood volume is increased by a blood transfusion, the equilibrium point (B), which denotes the values of cardiac output and P_v after transfusion, lies above and to the right of the control equilibrium point (A). Thus, transfusion increases both cardiac output and P_v. Hemorrhage causes the opposite effect. Mechanistically, the change in ventricular filling pressure (central venous pressure) evoked by a given change in blood volume alters cardiac output by changing the sensitivity of the contractile proteins to the prevailing concentration of intracellular Ca⁺⁺ (see Chapters 17 and 18). For reasons explained earlier, pure increases or decreases in venomotor tone elicit responses that are like those evoked by increases or decreases, respectively, in total blood volume.

IN THE CLINIC

Heart failure is a general term that applies to conditions in which the pumping capability of the heart is impaired to the extent that the tissues of the body are not adequately perfused. In heart failure, myocardial contractility is impaired. Heart failure may be acute or chronic. Consequently, in a graph of cardiac and vascular function curves, the cardiac function curve is shifted downward and to the right, as depicted in Figure 19-10.

Figure 19-10 Moderate or severe heart failure shifts the cardiac function curves downward and to the right. Before changes in blood volume, cardiac output decreases and central venous pressure rises (from control equilibrium point A to point B or point C). After the increase in blood volume that usually occurs in heart failure, the vascular function curve is shifted to the right. Hence, central venous pressure may be elevated with no reduction in cardiac output (point D) or (in severe heart failure) with some reduction in cardiac output (point E).

Acute heart failure may be caused by toxic concentrations of drugs or by certain pathological conditions such as coronary artery occlusion. In acute heart failure, blood volume does not change immediately. In Figure 19-10, therefore, the equilibrium point shifts from the intersection (A) of the normal curves to the intersection (B or C) of the normal vascular function curve with one of the curves that depict depressed cardiac function.

Chronic heart failure may occur in conditions such as essential hypertension or ischemic heart disease. In chronic heart failure, both the cardiac function and vascular function curves shift. The vascular function curve shifts because of an increase in blood volume caused in part by fluid retention by the kidneys. The fluid retention is related to the concomitant reduction in glomerular filtration rate and the decreased renal excretion of NaCl and water (see also Chapter 34). The resultant hypervolemia is reflected by a rightward shift of the vascular function curve, as shown in Figure 19-10. Hence, with moderate degrees of heart failure, P_v is elevated, but cardiac output may be normal (D). With more severe degrees of heart failure, P_v is still greater, but cardiac output is subnormal (E).

Peripheral Resistance

Analysis of the effects of changes in peripheral resistance on cardiac output and P_v is complex because both the cardiac and vascular function curves shift. When peripheral resistance increases (Fig. 19-11), the vascular function curve is rotated counterclockwise, but it converges on the same P_v axis intercept as the control curve does. Note that vasoconstriction causes a counterclockwise rotation of the vascular function curve in Figure 19-11 but a clockwise rotation in Figure 19-5. The direction of rotation differs because the axes for the vascular function curves were reversed in these two figures, as explained earlier. The cardiac function curve in Figure 19-11 is also shifted downward because at any given P_v, the heart is able to pump less blood against the greater cardiac afterload imposed by the increased peripheral resistance. Because both curves in Figure 19-11 are displaced downward, the new equilibrium point, B, falls below the control point, A; that is, an increase in peripheral resistance diminishes cardiac output.

Figure 19-11 An increase in peripheral resistance shifts the cardiac and vascular function curves downward. At equilibrium, cardiac output is less (B) when peripheral resistance is high than when it is normal (A).

Whether point B falls directly below point A or lies slightly to the right or left of it depends on the magnitude of the shift in each curve. For example, if a given increase in peripheral resistance shifts the vascular function curve more than it does the cardiac function curve, equilibrium point B will fall below and to the left of A; that is, both cardiac output and P_v will diminish. Conversely, if the cardiac function curve is displaced more than the vascular function curve, point B falls below and to the right of point A; that is, cardiac output decreases, but P_v rises.