Introduction

The thorax and the heart within in it each vary their pressures and volumes cyclically, and there is an inescapable mechanical linkage between the two. Pressure and volume are the two dominant variables by which the thorax physically alters biventricular preload and afterload.1 The relationship between respiratory loads, intrathoracic pressure and volume in sickness and in health can be shown on a Campbell diagram (Figure 1).

When a patient is removed from mechanical ventilation, the elastic and resistive loads of the respiratory system are augmented; this becomes especially pronounced in patients with preexisting pulmonary pathology.2 Spontaneous breathing efforts may generate exaggerated swings in intrathoracic pressure and volume that stress the cardiovascular system and in turn increase respiratory load. The means by which pathophysiology in the cardiovascular system, respiratory system or a combination of the two initiate and perpetuate abnormalities in each other can explain the rapid deterioration seen in some patients following removal from mechanical ventilation.3 Knowledge of these injurious interactions may help the clinician anticipate and correct perturbations in cardiorespiratory load prior to liberating a patient from the ventilator.

This review will not discuss the neurohormonal and autonomic abnormalities that complicate the transition from mechanical ventilation to spontaneous ventilation.4 The concepts in respiratory physiology outlined here are reviewed further in the online supplement at the author’s website (www.heart-lung.org).

Figure 1. Campbell diagram illustrating the relationship between respiratory loads, intrathoracic pressure and volume.

Respiratory load: airway resistance and thoracic compliance

The load placed upon the respiratory system is typically divided into dynamic and static components. Each of these aspects of respiratory physiology are represented on the Campbell diagram2,5,6 and will be discussed in turn, followed by discussion of the pathophysiological load which may arise when a patient is liberated from the ventilator.

Dynamic respiratory pressure

Ohm’s law of electrical current is the model after which gas flow within the tracheobronchial tree is typically modeled. Resistance is defined mathematically by the relationship of pressure and flow. This model of resistance predicts a linear relationship between pressure and flow, but in the tracheobronchial tree, the pressure-flow relationship “bends” at high flows because of the production of transitional and turbulent flows which have higher effective resistances than laminar flow.7,8 Laminar flow can be thought of as an orderly flowing motion of gas molecules in concentrically arranged parabolas with the innermost molecules flowing with the highest velocity.

Changes in airways resistance or flow pattern alter absolute values of pleural pressure. In the spontaneously breathing patient, dynamic pressure properties are depicted as a curve to the left of the static pressure-volume relationship of the lung (figure 2).

Figure 2. Changes in pleural pressure (due to airway resistance, flow, etc.) result in changes in the pulmonary compliance curve.

Static respiratory pressure

The static pressure invested in respiration represents the intrathoracic pressure required to effect a change in volume of the lung and thorax; it says nothing about gas flow. This pressure can be represented by the lateral distance between the static lung and chest wall compliance curves for the volume of interest (figure 3).

Figure 3. Static respiratory pressure.

The slope of both the pulmonary and chest wall compliance curves will shift with different disease states. A down-left shift of the pulmonary compliance curve represents poor pulmonary compliance while a down-right shift of the chest wall compliance curve depicts worsening chest wall compliance (figure 4). The main determinant of pulmonary compliance is the presence and activity of surfactant9; a less prominent influence is the collagen and elastin composition of the lungs.10 The effectors of chest wall compliance are the compliances of the bony thorax, and the abdomen as well as the activity of the muscles of respiration.2,11,12

Figure 4. Relationship between pulmonary and chest wall compliance.

Extubation and respiratory load

Positive pressure reduces expiratory airways resistance and facilitates emptying of the lung, putatively by stenting open distal airways.13,14,15,16,17 Decreased pulmonary elastic recoil, a common phenomenon in patients with obstructive airways disease,18 contributes to a decrement in the pressure gradient from the alveolus down the airway during active expiration. As a consequence, a more distal equal pressure point is generated in the airway at which the pleural pressure exceeds the airway pressure, leading to dynamic airway collapse.19,20 This physiology predicts the phenomena of auto-PEEP and air-trapping21,22 which may complicate the post-extubation period. While dynamic hyperinflation and air-trapping are often used interchangeably, there is a subtle distinction. Hyperinflation is classically associated with impaired pulmonary elastic recoil and emphysema, while air-trapping can occur in disease states typified even by high elastic recoil such as pulmonary edema and the acute respiratory distress syndrome (ARDS). The air-trapping that occurs in the setting of excess lung water and ARDS is the result of high airway resistance which may occur as a result of edema, inflammation and high closing volumes in the lower lobe.23,24

As air-trapping progresses, the transpulmonary pressure increases. The transpulmonary pressure is the pressure within the alveolus minus the pleural pressure; it is the gradient which determines lung volume. High lung volume stretches the pulmonary parenchyma to a poorly compliant portion of its pressure-volume relationship.25,26

In summary, respiratory load increases as a consequence of high airway resistance, while the high airway resistance favors low pulmonary compliance in response to air-trapping. Together these factors generate a dynamic environment whereby the heart is exposed to exaggerated biventricular outflow impedance and increases in ventricular wall tension27,28,29,30,31 as elaborated in the following sections.

Right ventricular outflow impedance

Arterial impedance may be modeled as the geometric summation of two biophysical properties: resistance and reactance. Vascular resistance tends to obey Poiseuille’s law, which states that resistance is inversely proportional to the radius of the vessel raised to the fourth power.32,33 Reactance is inversely related to both vascular compliance and cycle frequency; thus reactance helps account for vascular elasticity.34 While a single measure of right ventricular (RV) afterload is elusive,35,36 there is evidence that increases in pulmonary vascular resistance37, decreases in pulmonary arterial compliance38 and increases in transmural vascular pressure all may effectively increase RV afterload31, though the relative contributions of the resistive versus compliance components to total impedance may differ.29,36

The abnormally low pleural pressure that accompanies augmented respiratory load has differing effects on extra-alveolar versus intra-alveolar vessels. The extra-alveolar vessels (the large pulmonary arteries, veins and tributaries that lie outside of the alveolar wall) are directly exposed to pleural pressure. The bronchovascular bundle enters the lungs at the hila via an invagination of the visceral pleura. To the extent the transpulmonary pressure exceeds the vascular transmural pressure, the extraalveolar vessel will dilate during inspiration39 thereby facilitating a lower vascular resistance; this effect predominates at lung volumes less than FRC.40,41

The intra-alveolar vessels, in contradistinction, are exposed to alveolar pressure. West and colleagues proposed lung zones to describe the relationship between alveolar pressure and pulmonary vascular pressure.42 Zone II physiology occurs when alveolar pressure is greater than left atrial pressure. Zone II predominates when alveolar pressure is high, and/or left atrial pressure is low (e.g. dynamic hyperinflation with auto-PEEP). In this circumstance, the alveolar pressure becomes the pressure against which the right ventricle ejects.43

This relationship between air-trapping and right ventricular load was illustrated in a study by Harris and colleagues44. They found that exercise and voluntary hyperventilation in patients with obstructive airways disease led to increased pulmonary vascular resistance when compared to healthy controls and the degree to which this occurred was directly related to the severity of pulmonary disease.45,46

While the increased impedance to right ventricular outflow seems mostly mediated by increased vascular resistance as a consequence of increased lung volume, large negative deflections in thoracic pressure also appear to retard right ventricular ejection, though the underlying mechanisms are beyond the scope of this review.29,47,48

Ventricular interdependence

Transitioning from mechanical ventilation to spontaneous breathing can adversely affect the function of both ventricles and their interaction, through the phenomenon of ventricular interdependence. The filling status of one cardiac chamber can affect the filling properties of each of the other three chambers49, and filling one ventricle alters the pressure-volume relationship of the contralateral ventricle, in essence generating a dynamic diastolic dysfunction. The mechanism behind this effect is thought to be mediated via septal shift.50

Ventricular interdependence may be clinically relevant in acute exacerbations of obstructive airways disease31 or in any form of pulmonary hypertension.51 As right ventricular outflow impedance increases, a tendency to increase RV volume is established; this may diminish left ventricular stroke volume and raise the left ventricular end-diastolic pressure. To the extent that change in RV geometry impairs LV compliance and raises the left atrial pressure (which opposes RV ejection) the RV preload can become its own afterload.48

Interdependence is facilitated when the ventricular free walls or pericardium become stiff, and is mitigated when the ventricular septum becomes poorly compliant.52,53,54 Because the time-constants of the lower lobes tend to be higher,55 increased airways resistance promote gas-trapping preferentially near the heart. Butler and colleagues demonstrated that this can raise biventricular filling pressure and facilitate ventricular interdependence as the heart is squeezed by the increased volume of the lower lobes56; in effect, this physiology mirrors pericardial constriction.

The respiratory load imposed on a patient removed from positive pressure ventilation can thus raise right ventricular afterload and exaggerate right ventricular volume. Equally important is facilitation of right heart preload, also favored by removal of positive intrathoracic pressure. Spontaneous inspiration is marked by an increase in transdiaphragmatic pressure, that is, intra-abdominal pressure increases while intrathoracic pressure is diminished. Compression of the abdominal splanchnic vessels by abdominal pressurization augments the upstream pressure for venous return – the mean systemic filling pressure.57,58,59 Simultaneously, spontaneous ventilation decreases the downstream pressure for venous return – the right atrial pressure.60,61 Because the gradient for venous return is typically less than 10 mmHg, small changes in either the upstream or downstream pressure magnify total blood flow back to the right heart. Importantly, a high right atrial pressure at the onset of spontaneous ventilation establishes a great potential for venous return58,62 and this will heighten ventricular interdependence.

Respiratory load and the left ventricle

Reducing the pressure surrounding the left ventricle and thoracic aorta relative to the extrathoracic compartment impairs the egress of blood from the thorax.27,29,63 This physiology is typically explained using the modified law of LaPlace28, that is, as the ambient pressure falls relative to the intraluminal pressure of the left ventricle, the transmural wall stress is increased; this retards ventricular systole. An exaggerated fall in intrathoracic pressure impairs left ventricular output by both diastolic (e.g. ventricular interdependence) and systolic (e.g. augmentation of afterload) events.64,65,66,67 When the greatest drop in pleural pressure coincides with ventricular diastole, the diminution in left ventricular stroke volume is primarily a consequence of the right heart impairing left heart compliance. By contrast, a plunge in intra-thoracic pressure which occurs during ventricular systole impairs left ventricular stroke volume as a result of high impedance to flow.

Enhanced pulmonary venous return accompanying each inspiratory rise in lung volume may further compound the situation. As the transpulmonary pressure is rises above functional residual capacity, the capacitance of the alveolar blood vessels is diminished. This tends to raise the pressure head for pulmonary venous return; in effect the left heart is bolused which each inspiration. In an analogous physiology to the abdomen’s68, the fraction of West Zone III physiology determines the degree of pulmonary venous return. In a lung that is relatively fluid overloaded (i.e., with a high West Zone III fraction), the inspiratory increase in pulmonary venous return will be accordingly large.

Thus, an inspiratory drop in intrathoracic pressure leads to both diastolic and systolic events that impair left ventricular stroke volume. In conjunction with enhanced pulmonary venous return as lung volume increases, a milieu is created that favors increases in the left ventricular filling pressure and the development of pulmonary edema.

Excess cardiorespiratory load and the formation of pulmonary edema

The aforementioned pathophysiological pathways ultimately result in high left ventricular filling pressure. This effect will diminish the gradient for pulmonary venous return and favor excess lung water. Historically, the investigation into the pathogenesis of pulmonary congestion and edema concentrated upon isolated stages of fluid overload.69,70 Both decreased pulmonary compliance, increased airway resistance and therefore high breathing work have been noted in each of these stages. The stages of increased lung water, in order of sequence, have been considered to be: pulmonary vascular engorgement, bronchovascular interstitial edema, alveolar interstitial edema followed by frank alveolar flooding.70

Pulmonary vascular engorgement, the first stage of excess lung water is clinically marked by ‘cephalization’ of the pulmonary vasculature on a simple chest radiograph.71 Even during this early stage there is an associated drop in pulmonary compliance in humans, though this effect tends to be minimal.72 The mechanism of impaired compliance is felt to be the result of auto-regulatory active vascular tension according to the myogenic theory of blood flow. The greatest decrement in pulmonary compliance occurs during the later stages of pulmonary edema, especially with frank alveolar flooding.73 Along with alveolar and airway edema, there is an accumulation of intraluminal bubble froth, which reduces pulmonary compliance by decreasing alveolar radius and interfering with surfactant function.74

Respiratory load is increased not only by impaired pulmonary compliance during states of excess lung water. Airway resistance is increased with pulmonary vascular engorgement and edema.73,74 Animal models75 propose that in the early stages of increased lung water, the vagus nerve mediates a reflex increase in airway resistance; bronchovascular interstitial edema progresses and physically impinges upon the airways.76,77,78 With frank alveolar edema, bubble froth plugs the small airways and leads to the greatest increase in resistance.74

Conclusion

The schema in figure 5 illustrates the possible interactions between the respiratory and cardiovascular systems in conditions of both “obstructive-lung” and “congested-lung” pathophysiology as described in this review. Primary perturbations in right ventricular outflow can facilitate left ventricular dysfunction, whereas states of impaired left ventricular function and excess lung water can facilitate and worsen right heart function. Although not each of these mechanisms is at play in every patient relieved from mechanical ventilation, the diagram does highlight the interrelationship between respiratory and cardiovascular pathophysiology. In addition to pulmonary resistance and thoracic compliance, biventricular preload and afterload should be contemplated and optimized when considering a patient for liberation from mechanical ventilation. Respect for these pathophysiologic mechanisms, especially in patients with chronic cardiopulmonary illness, may help prevent cardiorespiratory collapse following liberation from mechanical ventilation, an infrequent but potentially catastrophic scenario.3

Figure 5. Potential cardiorespiratory system interactions in the “obstructed lung” and “congested lung” states.