Mechanics and Function of the Pulmonary Vasculature: Implications for Pulmonary Vascular Disease and Right Ventricular Function

Abstract

The relationship between cardiac function and the afterload against which the heart muscle must work to circulate blood throughout the pulmonary circulation is defined by a complex interaction between many coupled system parameters. These parameters range broadly and incorporate system effects originating primarily from three distinct locations: input power from the heart, hydraulic impedance from the large conduit pulmonary arteries, and hydraulic resistance from the more distal microcirculation. These organ systems are not independent, but rather, form a coupled system in which a change to any individual parameter affects all other system parameters. The result is a highly nonlinear system which requires not only detailed study of each specific component and the effect of disease on their specific function, but also requires study of the interconnected relationship between the microcirculation, the conduit arteries, and the heart in response to age and disease. Here, we investigate systems-level changes associated with pulmonary hypertensive disease progression in an effort to better understand this coupled relationship.

Figure 1

Normal blood pressures of the systemic and pulmonary circulatory systems. Pulmonary circulation has much lower pressures and pulsations extend into the capillaries. (Redrawn, with permission, by Devon Scott.)

Figure 2

Diagram of pulmonary vascular tree.

Figure 3

Impedance modulus in healthy (A) and pulmonary hypertensive (B) children. As with other clinical studies of impedance, pulmonary hypertensive individuals displayed both larger values of Z₀, corresponding to higher PVR and larger values of the first several harmonics of impedance. Further, the first minimum of the curve is shifted rightward in the PH patients, corresponding to higher pulse-wave velocities (56).

Figure 4

Changes in mean blood pressure (MBP) (solid circle) and aortic pulse wave velocity (PWV) (open circle) for survivors and nonsurvivors of systemic hypertension in end-stage renal disease. Patients underwent antihypertensive therapy and were tracked from inclusion to end of follow-up (45).

Figure 5

Mechanisms of arterial stiffening. Panels A, B, C, and D are discussed in detail in the text.

Figure 6

Average hydraulic power of the inlet (IN, MPA) and outlet (OUT, pulmonary vein, near left atrium) of the pulmonary bed of anesthetized, open-chest dogs. Regions above and below the hydraulic power = 0 line are both positive valued. Upper region contains pressure-potential and kinetic energy terms associated with oscillatory component of blood flow. Lower region contains analogous terms for the steady-flow component. Input and output hydraulic power values are shown in their respective columns with the difference between the two being the power dissipated (DISS) throughout the pulmonary bed during the cardiac cycle (87).

Figure 7

Power dissipated as a function of heart rate for a constant pulmonary flow of 42.0 cm³/s measured in anesthetized dogs (87).

Figure 8

Oscillatory component of input power (ordinate) at different levels of pulmonary blood flow (abscissa) for three different heart rates at constant stroke volume (solid line) and for three different stroke volumes at constant heart rate (solid line). Constant stroke volume curves are shown for three volumes (S = 10, 20, and 30 cm³/stroke) and constant heart rate curves are shown for three rates (f = 1.0, 2.0, and 3.0 beats/s). Constant stroke volume and constant heart rate curves are nearly equal for heart rates above 3 beats/s. Plot shows that pulmonary blood flow can be increased more efficiently by increasing heart rate than by increasing stroke volume (87).

Figure 9

Effect of graded exercise on the increment in stroke volume (A), vascular resistance (B), aortic characteristic impedance (C), and external power (D) represented as mean change from resting values for young and old dogs at three different levels of exercise, *P = 0.05 (between young and old) (155).

Figure 10

Schematic of pressure-controlled isolated supported ventricle (PCISV). R, central reservoir; C2, C3, and C4, stopcocks; SL, supply container; OL, overflow system; RL, small reservoir; RP peripheral resistance; F, filter; RC characteristic impedance; and C capacitance (33).

Figure 11

Schematic of volume controlled isolated supported ventricle (VCISV). A, coronary perfusion tube; AV, air vent; B, sealed box in which heart was placed for testing; BC, Bellofram cylinder; C, comparator; E, error signal; EDV, end diastolic volume; ESV, end systolic volume; HE, heat exchanger; LT, linear displacement transducer; LV, left ventricle; NP, negative pressure applied behind the diaphragm to reduce the compliance of the rolling diaphragm; PA, power amplifier; V, coronary venous return tube; VP, ventricular pressure measured by a miniature gage; VV, ventricular volume signal; W, hydraulic fluid (water) (136).

Figure 12

Diagram of the Windkessel controlled isolated supported ventricle (WCISV). A linear motor and piston-pump assembly allows for precise control of instantaneous ventricular volume. Loading system computes instantaneous ventricular pressure-flow data in real time. Control system imposed real time pressure flow relationship based on three-element Windkessel model through control of the linear motor (137).

Figure 13

Example of typical Windkessel controlled isolated supported ventricle (WCISV) dataset. Experimental protocol consisted of first determining control values for the distal vascular resistance, characteristic impedance, and arterial compliance of the normal animal; which were 3.0 mmHg-s/ml, 0.2 mmHg-s/ml, and 0.4 ml/mmHg, respectively, for dogs weighing 20 to 22 kg. Arterial compliance and resistance were varied by 50% and 200% of control values while P-V loops were generated at four end-diastolic volumes for each experimental condition. Characteristic impedance was kept at control value. Heart rate was kept constant during all experiments (127 ± 9 beats/min) by pacing. Solid line at control indicates P-V relationship at control conditions, dashed lines in other panels indicate transcribed P-V relationship line from control. (B) and (C) End-systolic pressure versus stroke with varying resistance and capacitance, symbols represent experimental data (137).

Figure 14

pressure-controlled isolated supported ventricle (PCISV) model showing the effect that changes in resistance and compliance have on the left ventricular pressure, aortic pressure, and aortic flow measured from cat left ventricle. Distal resistance was increased from a control value of 28.5 g/(cm⁴s) to 61 and 137 g/(cm⁴s). Aortic compliance was decreased from a control value of 43 cm⁴s²/g to 14 and 3.6 cm⁴s²/g. Heart rate was maintained constant at 153 beats/min by pacing. Results from this model for aggregated data from six feline PCISV hearts exposed to a 208% increase in resistance and a 21% decrease in compliance are given in Table 3. Similar results were obtained for changes in the resistance and compliance parameters of PCISV hearts from dogs (33).

Figure 15

The experimental approach was to increase the distal resistance from a control value of 28.5 g/(cm⁴s) to 61 and 137 g/(cm⁴s) and to decrease the aortic compliance from a control value of 43 cm⁴s²/g to 14 and 3.6 cm⁴s²/g while maintaining a constant heart rate of 153 beats/min.

Figure 16

Stiff arteries may extend high flow pulsatility into the pulmonary microcirculation, whereas in a normal compliant artery the capillaries experience semisteady flow.