Changing lung volume phasically alters autonomic tone and pulmonary vascular resistance. At very high lung volumes, the expanding lungs compress the heart in the cardiac fossa, limiting absolute cardiac volumes analogous to cardiac tamponade, except that with hyperinflation both pericardial pressure and ITP increase by a similar amount.
Although neurohumoral processes define a few immediate effects of ventilation on the heart, these neurohumoral processes probably play a primary role in all the long-term effects of ventilation on the cardiovascular system. Most of the immediate effects of ventilation of the heart are secondary to changes in autonomic tone. The lungs are richly enervated with somatic and autonomic fibers that originate, traverse through, and end in the thorax. These networks mediate multiple homeostatic processes through the autonomic nervous system altering instantaneous cardiovascular function. The most commonly known of these are the vagally mediated heart rate changes during ventilation.4,5 Inflation of the lung to normal tidal volumes (<10 mL/kg) induces vagal-tone withdrawal, accelerating heart rate. This phenomenon is known as respiratory sinus arrhythmia6 and can be used to document normal autonomic control,7 especially in patients with diabetes who are at risk for peripheral neuropathy.8 Inflation to larger tidal volumes (>15 mL/kg), however, decreases heart rate by a combination of both increased vagal tone9 and sympathetic withdrawal. Sympathetic withdrawal also creates arterial vasodilation.4,10–14 This inflation–vasodilation response can reduce LV contractility in healthy volunteers15 and in ventilator-dependent patients with the initiation of high-frequency ventilation4 or hyperinflation.12 This inflation–vasodilation response is presumed to be the cause of the initial hypotension seen when infants are placed on mechanical ventilation. It appears to be mediated at least partially by afferent vagal fibers, because it is abolished by selective vagotomy. Hexamethonium, guanethidine, and bretylium, however, also block this reflex.16,17 These data suggest that lung inflation mediates its reflex cardiovascular effects by modulating central autonomic tone. Interestingly, the almost total lack of measurable hemodynamic effects of unilateral hyperinflation in subjects with normal lungs receiving split-lung ventilation18 suggests that these autonomic cardiovascular effects require a general increase in lung volume to be realized. This is not a minor point because selective hyperinflation within lung units commonly occurs in patients with acute lung injury (ALI) and chronic obstructive pulmonary disease (COPD). If localized hyperinflation were able to induce cardiovascular impairment, these subjects would be profoundly compromised.
Humoral factors, including compounds blocked by cyclooxygenase inhibition,19 released from pulmonary endothelial cells during lung inflation may also induce this depressor response20–22 within a short (15 seconds) time frame. These interactions, however, do not appear to grossly alter cardiovascular status.23 Ventilation also alters the more chronic control of intravascular fluid balance via hormonal release. The right atrium functions as the body’s effective circulating blood-volume sensor. Circulating levels of a family of natriuretic peptides increase in heart failure states secondary to right-atrial stretch.24 These hormones promote sodium and water diuresis. The levels of these hormones vary directly with the degree of heart failure. Both positive-pressure ventilation and sustained hyperinflation decrease right-atrial stretch mimicking hypovolemia. During positive-pressure ventilation, plasma norepinephrine and renin increase,25,26 whereas atrial natriuretic peptide decreases.27 This humoral response is the primary reason why ventilator-dependent patients gain weight early in the course of respiratory failure, because protein catabolism is also usually seen. Interestingly, when patients with congestive heart failure (CHF) are given nasal continuous positive airway pressure (CPAP), plasma atrial natriuretic peptide activity decreases in parallel with improvements in blood flow.28,29 This finding suggests that some of the observed benefit of CPAP therapy in heart failure is mediated in part through humoral mechanisms, owing to the mechanical effects of CPAP on cardiac function.
Pulmonary Vascular Resistance
Changing lung volume alters pulmonary vascular resistance.3 Marked increases in pulmonary vascular resistance, as may occur with hyperinflation, can induce acute cor pulmonale and cardiovascular collapse. The reasons for these changes are multifactorial. They can reflect conflicting cardiovascular processes and almost always reflect both humoral and mechanical interactions.
Lung volume can only increase if its distending pressure increases. Lung-distending pressure, called the transpulmonary pressure, equals the pressure difference between alveolar pressure (Palv) and ITP. If lung volume does not change, then transpulmonary pressure does not change. Thus, occluded inspiratory efforts (Mueller maneuver) and expiratory efforts (Valsalva maneuver) cause ITP to vary by an amount equal to Palv, but do not change pulmonary vascular resistance. Although obstructive inspiratory efforts, as occur during obstructive sleep apnea, are usually associated with increased RV afterload, the increased afterload is caused primarily by either increased vasomotor tone (hypoxic pulmonary vasoconstriction) or backward LV failure.30,31
RV afterload is maximal RV systolic wall stress.32,33 By law of Laplace, wall stress equals the product of the radius of curvature of a structure and its transmural pressure. Systolic RV pressure equals transmural pulmonary artery pressure. Increases in transmural pulmonary artery pressure increases RV afterload, impeding RV ejection,34 decreasing RV stroke volume,35 inducing RV dilation, and passively causing venous return to decrease.19,21 If such acute increases in transmural pulmonary artery pressure are not reduced, or if RV contractility is not increased by artificial means, then acute cor pulmonale rapidly develops.36 If RV dilation and RV pressure overload persist, RV free-wall ischemia and infarction can develop.37 These concepts are of profound clinical relevance because rapid fluid challenges in the setting of acute cor pulmonale can precipitate profound cardiovascular collapse secondary to excessive RV dilation, RV ischemia, and compromised LV filling. Ventilation can alter pulmonary vascular resistance by either altering pulmonary vasomotor tone, via a process known as hypoxic pulmonary vasoconstriction, or mechanically altering vessel cross-sectional area, by changing transpulmonary pressure.
Hypoxic Pulmonary Vasoconstriction.
Unlike systemic vessels that dilate under hypoxic conditions, the pulmonary vasculature constricts. Once alveolar partial pressure of oxygen decreases below 60 mm Hg, or acidemia develops, pulmonary vasomotor tone increases.38 Hypoxic pulmonary vasoconstriction is mediated, in part, by variations in the synthesis and release of nitric oxide by endothelial nitric oxide synthase localized on pulmonary vascular endothelial cells, and in part by changes in intracellular calcium fluxes in the pulmonary vascular smooth muscle cells. The pulmonary endothelium normally synthesizes a low basal amount of nitric oxide, keeping the pulmonary vasculature actively vasodilated. Loss of nitric oxide allows the smooth muscle to return to its normal resting vasomotor tone. Nitric oxide synthesis is dependent on adequate amounts of O2 and is inhibited by both hypoxia and acidosis. Presumably, hypoxic pulmonary vasoconstriction developed to minimize ventilation–perfusion mismatches caused by local alveolar hypoventilation. Generalized alveolar hypoxia, however, increases global pulmonary vasomotor tone, impeding RV ejection.32 At low lung volumes, terminal bronchioles collapse, trapping gas in the terminal alveoli. With continued blood flow, these alveoli lose their O2 and also may collapse. Patients with acute hypoxemic respiratory failure have small lung volumes and are prone to both alveolar hypoxia and spontaneous alveolar collapse.39,40 This is one of the main reasons why pulmonary vascular resistance is increased in patients with acute hypoxemic respiratory failure.
Based on the above considerations, mechanical ventilation may reduce pulmonary vasomotor tone by a variety of mechanisms. First, hypoxic pulmonary vasoconstriction can be inhibited if the patient is ventilated with gas enriched with O2 increasing alveolar partial pressure of oxygen.41–44 Second, mechanical breaths and positive end-expiratory pressure (PEEP) can refresh hypoventilated lung units and recruit collapsed alveolar units, causing local increases in alveolar partial pressure of oxygen,3,45–47 especially if small lung volumes are returned to resting functional residual capacity (FRC) from an initial smaller lung volume.48 Third, mechanical ventilation often reverses respiratory acidosis by increasing alveolar ventilation.44 Fourth, decreasing central sympathetic output, by sedation or decreased stress of breathing against high-input impedance during mechanical ventilation, also reduces vasomotor tone.49,50 Importantly, these effects do not require endotracheal intubation to occur; they occur with mere reexpansion of collapsed alveoli.51,52 Thus, PEEP, CPAP, recruitment maneuvers, and noninvasive ventilation may all reverse hypoxic pulmonary vasoconstriction and may all improve cardiovascular function.
Volume-Dependent Changes in Pulmonary Vascular Resistance.
Changes in lung volume directly alter pulmonary vasomotor tone by compressing the alveolar vessels.39,46,47 The actual mechanisms by which this occurs have not been completely resolved, but appear to reflect vascular compression induced by a differential extraluminal pressure gradient. The pulmonary circulation lives in two environments, separated from each other by the pressure that surrounds them.46 The small pulmonary arterioles, venules, and alveolar capillaries sense Palv as their surrounding pressure, and are called alveolar vessels. The large pulmonary arteries and veins, as well as the heart and intrathoracic great vessels of the systemic circulation, sense interstitial pressure or ITP as their surrounding pressure, and are called extraalveolar vessels. Because the pressure difference between Palv and ITP is transpulmonary pressure, increasing lung volume increases this extraluminal pressure gradient. Increases in lung volume progressively increase alveolar vessel resistance by increasing this pressure difference once lung volumes increase much above FRC (Fig. 36-1).42,53 Similarly, increasing lung volume, by stretching and distending the alveolar septa, may also compress alveolar capillaries, although this mechanism is less well substantiated. Hyperinflation can create significant pulmonary hypertension and may precipitate acute RV failure (acute cor pulmonale)54 and RV ischemia.37 Thus, PEEP may increase pulmonary vascular resistance if it induces overdistension of the lung above its normal FRC.55
Schematic of the relationship between changes in lung volume and pulmonary vascular resistance (PVR), where the extraalveolar and alveolar vascular components are separated. Pulmonary vascular resistance is minimal at resting lung volume or functional residual capacity. As lung volume increases toward total lung capacity or decreases toward residual volume, pulmonary vascular resistance also increases. The increase in resistance with hyperinflation is caused by increased alveolar vascular resistance, whereas the increase in resistance with lung collapse is caused by increased extraalveolar vessel tone.
Extraalveolar vessels are also influenced by changes in transpulmonary pressure. Normally, radial interstitial forces of the lung, which keep the airways patent, only make the large vessels more distended as lung volume increases,45,56,57 just as increasing lung volume increases airway diameter. These radial forces also act upon the extraalveolar vessels, causing them to remain dilated, increasing their capacitance.58 This tethering is reversed with lung deflation, thereby increasing extraalveolar vascular resistance.42,45 Thus, pulmonary vascular resistance is increased at small lung volumes owing to the combined effect of hypoxic pulmonary vasoconstriction and extraalveolar vessel collapse, and at high lung volumes by alveolar compression.
The right ventricle, as opposed to the left ventricle, ejects blood into a low-pressure, high-compliance system: the pulmonary circulation. The pulmonary circulation is capable of accommodating high volumes of blood without generating high pressure, which is beneficial for the right ventricle. Despite being compliant, this circuit does pose resistance to the ejecting right ventricle as quantified by pulmonary artery pressure, which is the pressure limit the right ventricle has to overcome to open the pulmonary valve. RV afterload is conceptually similar to LV afterload and is determined by the wall tension of the right ventricle. RV afterload is highly dependent on the distribution of blood flow in the lung, namely, the proportion of West zones 1 and 2, as compared to zone 3, as originally described by Permutt et al.59 Zones 1 and 2 exist whenever the intraluminal pressure of juxtaalveolar capillaries is lower than the Palv during the respiratory cycle, thus collapsing vessels and increasing pulmonary vascular resistance. In contrast, zone 3 occurs when intraluminal capillary pressure is higher than Palv, decreasing pulmonary resistance. Importantly, intraluminal pressure of alveolar capillaries tracks changes in ITP,60 and thus decreases less than Palv during spontaneous inspiration, and increases less than Palv during positive-pressure inspiration. Consequently, both spontaneous and positive-pressure inspiration above FRC increase the afterload to the right ventricle as opposed to the LV afterload, which is reduced by increased ITP.
Because right ventricle output is linked to left ventricle output serially, if right ventricle output decreases, left ventricle output must eventually decrease. The two ventricles, however, are also linked in parallel through their common septum, circumferential fibers, and pericardium, which limits total cardiac volume. For this reason, the diastolic filling of the RV has a direct influence on the shape and compliance of the LV, and vice versa. This phenomenon is known as ventricular diastolic interdependence.61 The most common manifestation of ventricular interdependence is pulsus paradoxus. Changes in RV end-diastolic volume inversely alter LV diastolic compliance.62 Because venous return can and often does vary by as much as 200% between inspiration and expiration, owing to associated changes in the pressure gradient for venous return (infra vide, see the section “Systemic Venous Return”), right ventricle filling also changes in parallel. Increasing RV end-diastolic volume, as occurs during spontaneous inspiration and spontaneous inspiratory efforts, will reduce LV diastolic compliance, immediately decreasing LV end-diastolic volume. Positive-pressure ventilation may decrease venous return causing RV volumes to decrease, increasing LV diastolic compliance. Except in acute cor pulmonale or biventricular overloaded states, however, the impact of positive-pressure ventilation on LV end-diastolic volume is minimal.
Ventricular interdependence functions through two separate processes. First, increasing RV end-diastolic volume induces an intraventricular septal shift into the LV, thereby decreasing LV diastolic compliance (Fig. 36-2).63 Because left ventricle wall stress is unaltered, any change in LV output does not reflect a change in LV preload. Because spontaneous inspiration increases venous return, causing right ventricle dilation, LV end-diastolic compliance decreases during spontaneous inspiration. Whereas right ventricle volumes usually do not increase during positive-pressure inspiration, ventricular interdependence usually has less impact over the patient’s hemodynamic status. Second, if pericardial restraint or absolute cardiac fossal volume restraint limits absolute biventricular filling, then right ventricle dilation will increase pericardial pressure, with minimal to no septal shift because the pressure outside of both ventricles will increase similarly.64,65
Schematic of the effect of increasing right-ventricular (RV) volumes on the relationship between left-ventricular (LV) diastolic pressure and left ventricle volume (filling). Increases in right ventricle volumes decrease LV diastolic compliance, such that a higher filling pressure is required to generate a constant end-diastolic volume. (Adapted, with permission, from Taylor RR, Covell JW, Sonnenblick EH, Ross J Jr. Dependence of ventricular distensibility on filling the opposite ventricle. Am J Physiol. 1967;213:711–718.)
Positive-pressure ventilation, however, can still display right ventricle dilation-associated ventricular interdependence. If positive-pressure inspiration overdistends alveoli, as for example during lung recruitment maneuvers, pulmonary vascular resistance will increase. Despite the fact that hemodynamic changes elicited by recruitment maneuvers do not cause persistent cardiovascular insufficiency, transient right ventricle dilation and left ventricle collapse can occur during recruitment maneuvers.66 This is an important concept when treating patients with borderline RV failure. Thus, recruitment maneuvers should be used with caution and be restricted to 10 seconds or less of an end-inspiratory hold to avoid significant hemodynamic derangements.
The presence of ventricular interdependence can be assessed in mechanically ventilated patients based on heart–lung interactions. Using echocardiographic techniques, Mitchell et al67 and Jardin et al68 showed that positive-pressure breaths decrease RV dimensions, whereas both LV dimensions and LV flows increase. Still, the changes in RV output generated by positive-pressure inspiration are much less than the changes in LV output.69 If ventricular interdependence was the primary process driving hemodynamic interactions during a positive-pressure breath, then a phasic increase in LV stroke volume would occur during inspiration. If the primary process was a phasic decrease in venous return, however, a phasic decrease in LV stroke volume would be observed two to three beats later, usually during the expiratory phase, suggesting the right ventricle is preload responsive. These points underscore the use of LV stroke volume variation during positive-pressure ventilation to identify volume responsiveness.
Mechanical Heart–Lung Interactions Because of Lung Volume
With inspiration, the expanding lungs compress the heart in the cardiac fossa,70 increasing juxtacardiac ITP. Because the chest wall and diaphragm can move away from the expanding lungs, whereas the heart is trapped within this cardiac fossa, juxtacardiac ITP usually increases more than these external ITPs.71,72 This effect is a result of increasing lung volume. It is not affected by the means whereby lung volume is increased. Both spontaneous73 and positive-pressure-induced hyperinflation56,57 induce similar compressive effects on cardiac filling. If one measured only intraluminal LV pressure, then it would appear as if LV diastolic compliance was reduced, because the associated increase in pericardial pressure and ITP would not be seen.74–76 When LV function, however, is assessed as the relationship between end-diastolic volume and output, no evidence for impaired LV contractile function is seen77,74 despite the continued application of PEEP.78 These compressive effects can be considered as analogous to cardiac tamponade79–81 and are discussed further in the “The Effect of Intrathoracic Pressure.”
Effect of Intrathoracic Pressure
The heart lives within the thorax, a pressure chamber inside a pressure chamber. Thus, changes in ITP affect the pressure gradients for both systemic venous return to the right ventricle and systemic outflow from the left ventricle, independent of the heart itself (Fig. 36-3). Increases in ITP, by increasing right-atrial pressure (Pra) and decreasing transmural LV systolic pressure, will reduce the pressure gradients for venous return and LV ejection decreasing intrathoracic blood volume. Using the same argument, decreases in ITP will augment venous return and impede LV ejection, increasing intrathoracic blood volume. The increases in ITP during positive-pressure ventilation show marked regional differences; juxtacardiac ITP increases more than lateral chest wall ITP as inspiratory flow rate and tidal volume increase.71 Interestingly, lung compliance plays a minimal role in defining the positive-pressure-induced increase in ITP. For the same increase in tidal volume, ITP usually increases similarly if tidal volume is kept constant.82,83 If, however, chest wall compliance decreases, then ITP will increase for a fixed tidal volume.84,85
Schematic of the effect of increasing or decreasing intrathoracic pressure on the left-ventricular (LV) filling (venous return) and ejection pressure.
Guyton et al described the determinants of venous return more than 50 years ago.86,87 Blood flows back from the systemic venous reservoirs into the right atrium through low-pressure, low-resistance venous conduits. Pra is the backpressure, or downstream pressure, for venous return. Pressure in the upstream venous reservoirs is called mean systemic pressure, and, itself, is a function of blood volume, peripheral vasomotor tone, and the distribution of blood within the vasculature.88 Ventilation alters both Pra and mean systemic pressure. Many of the observed ventilation-induced changes in cardiac performance can be explained by these changes. Mean systemic pressure does not change rapidly during positive-pressure ventilation, whereas Pra does, owing to parallel changes in ITP (Fig. 36-4).89,90 Positive-pressure inspiration increases both ITP and Pra, decreasing venous blood flow,35 RV filling, and consequently, RV stroke volume.35,89–99 During normal spontaneous inspiration, the opposite effects occur. Spontaneous inspiration decreases ITP and Pra, accelerating venous blood flow, and increasing RV filling and RV stroke volume.35,36,64,93,96,100–102
A venous return curve, describing the relationship between the determinants of right-ventricular preload. Right atrial pressure inversely changes the magnitude of venous return and is influenced by changes in intrathoracic pressure (ITP). Positive-pressure ventilation shifts the ventricular function curve to the right (A), increasing right-atrial pressure but decreasing blood flow. Spontaneous inspiration decreases ITP and shifts the ventricular function curve to the left (B), decreasing right-atrial pressure but increasing blood flow. As right-atrial pressure becomes negative, as may occur during forced inspiratory efforts against resistance or impedance, a maximal blood flow is reached; further decreases in right-atrial pressure no longer augment venous return.
If changes in Pra were the only process that altered venous return, then positive-pressure ventilation would induce profound hemodynamic insufficiency in most patients. The decrease in venous return during positive-pressure ventilation, however, is often lower than one might expect based on the increase in Pra.
The reasons for this preload-sparing effect seen during positive-pressure ventilation are twofold. First, when cardiac output does decrease, increased sympathetic tone decreases venous capacitance, increasing mean systemic pressure, which tends to restore the pressure gradient for venous return, even in the face of an elevated Pra. Increases in sympathetic tone, however, would increase steady-state cardiac output and would not alter the phasic changes in venous return seen during positive-pressure ventilation. The decreased phasic reductions in venous return are caused by associated increases in mean systemic pressure during inspiration. Diaphragmatic descent and abdominal-muscle contraction increase intraabdominal pressure, decreasing intraabdominal vascular capacitance.103,104 Because a large proportion of venous blood is in the abdomen, the net effect of both inspiration and PEEP is to increase mean systemic pressure and Pra in a parallel but unequal fashion.105–107 Accordingly, the pressure gradient for venous return may not be reduced as much as predicted as predicted from a pure increase in Pra. This is an important adaptive response by the body to positive-pressure ventilation and PEEP, both of which produce this effect secondary to the associated increase in lung volume, which promotes diaphragmatic descent. This preload-sparing effect is especially well demonstrated in patients with hypervolemia. In fact, both the translocation of blood from the pulmonary to the systemic capacitance vessels,108 as well as abdominal pressurization secondary to diaphragmatic descent, may be the major mechanisms by which the decrease in venous return is minimized during positive-pressure ventilation.109–113 In fact, van den Berg et al114 documented that up to 20 cm H2O CPAP did not significantly decrease cardiac output, as measured 30 seconds into an inspiratory-hold maneuver, in fluid-resuscitated, postoperative cardiac surgery patients. Although CPAP induced an increase in Pra, intraabdominal pressure also increased, preventing a significant change in RV volumes (Fig. 36-5). Interest in inverse-ratio ventilation has raised questions as to its hemodynamic effect, because its application includes a large component of hyperinflation.
Effect of increasing levels of continuous positive airway pressure (CPAP) on the relations between increasing airway pressure (Paw) and right-atrial pressure (Pra) (left graph), Paw and intraabdominal pressure (Pabd) (center graph), and Paw and changes in right-ventricular end-diastolic volume (RVEDV) (right graph) in forty-three postoperative fluid-resuscitated cardiac surgery patients. (Data derived, with permission, from data in Van den Berg P, Jansen JRC, Pinsky MR. The effect of positive-pressure inspiration on venous return in volume loaded post-operative cardiac surgical patients. J Appl Physiol. 2002;92:1223–1231.)
Current data clearly show that detrimental effects of increased ITP and PEEP on venous return are far more complex than an effect on the pressure gradient between mean systemic pressure and Pra, and that geometric deformation of the venous vasculature and its flow distribution, which alter the resistance to flow, may be a better explanation.115 Animal data suggest that compression and deformation of capacitance vessels at the entrance of the thorax103 and compression of the portal circulation by diaphragmatic descent115 may account for these increments in venous resistance and thus decreased venous return.
Relevance of Intrathoracic Pressure on Venous Return.
It is axiomatic that the heart can only pump out that amount of blood that it receives and no more. Thus, venous return is the primary determinant of cardiac output and the two must be the same.88 Because Pra is the backpressure to venous return and because Pra is normally close to zero relative to atmospheric pressure, venous return is maintained near maximal levels at rest,12,87,94,98,99 because right ventricle filling occurs with minimal changes in filling pressure.81 Spontaneous inspiratory efforts usually increase venous return because of the combined decrease in Pra64,94–96,116 and increase in intraabdominal pressure.103,104 For Pra to remain very low, however, RV diastolic compliance must be high and RV output must equal venous return. Otherwise, sustained increases in venous blood flow would distend the RV and increase Pra. During normal spontaneous inspiration, although venous return increases, ITP decreases at the same time, minimizing any potential increase in Pra, which might otherwise occur if ITP were not to decrease.89 Aiding in this process of minimizing RV workload, the pulmonary arterial inflow circuit is highly compliant and can accept large increases in RV stroke volume without changing pressure.35,117 Thus, increases in venous return proportionally increase pulmonary arterial inflow without significant changes in RV filling or ejection pressures. Accordingly, this compensatory system fails if RV diastolic compliance decreases or if Pra increases independent of changes in RV end-diastolic volume. Figure 36-6 illustrates these differential effects of negative (spontaneous inspiration) and positive (positive-pressure inspiration) swings in ITP on dynamic RV and LV performance. In RV failure states, spontaneous inspiration does not decrease Pra and Pra actually increases. This results in the physical sign of increased jugular venous distension during spontaneous inspiration.
Strip chart recording of right and left-ventricular stroke volumes (SVrv and SVlv, respectively), aortic pressure (PaO), left-atrial, pulmonary arterial, and right-atrial transmural pressures (Platm, Ppatm, and Pratm, respectively), airway pressure (Paw), pleural pressure (Ppl), and right-atrial pressure (Pra) during spontaneous ventilation (left) and similar tidal volume positive-pressure ventilation (right) in an anesthetized, intact canine model. (Used, with permission, from Pinsky MR, Matuschak GM, Klain M. Determinants of cardiac augmentation by elevations in intrathoracic pressure. J Appl Physiol. 1985;58:1189–1198.)
Note further in Figure 36-6 that not only does RV stroke volume increase with spontaneous inspiration and decrease with positive-pressure inspiration, but also that LV stroke volume decreases only during spontaneous inspiration (ventricular interdependence); during positive-pressure inspiration, however, any change in LV stroke volume occurs late, as the decrease in RV output finally reaches the left ventricle. RV diastolic compliance can acutely decrease in the setting of acute RV dilation or cor pulmonale (pulmonary embolism, hyperinflation, and RV infarction). Importantly, acute RV dilation and acute cor pulmonale can not only induce rapid cardiovascular collapse, but they are singularly not responsive to fluid resuscitation. Because spontaneous inspiration and inspiratory efforts cause both ITP and Pra to decrease, RV dilation may occur in patients with occult heart failure. Accordingly, some patients who were previously stable and ventilator-dependent can develop acute RV failure during weaning trials.
Finally, with exaggerated negative swings in ITP, as occur with obstructed inspiratory efforts, venous return behaves as if abdominal pressure is additive to mean systemic pressure in augmenting venous blood flow.118–121 These findings have some investigators to suggest that obstructive breathing may be a therapeutic strategy in sustaining cardiac output in patients in hemorrhagic shock.122 Interestingly, negative pressure ventilation, by augmenting venous return, increases cardiac output by 39% in children following repair of tetralogy of Fallot.123 In this condition, impaired RV filling secondary to RV hypertrophy and reduced RV chamber size are the primary factors limiting cardiac output. This augmentation of venous return by spontaneous inspiration, however, is limited,119,120 because as ITP decreases below atmospheric pressure, venous return becomes flow-limited because the large systemic veins collapse as they enter the thorax.87 This vascular flow limitation is a safety valve for the heart, because ITP can decrease greatly with obstructive inspiratory efforts,13 and if not flow-limited, the RV could become overdistended and fail.124 Finally, having subjects breathe through an airway that selectively impedes inspiration will result in exaggerated negative swings in both ITP and Pra, and associated greater increases in intraabdominal pressure secondary to recruitment of accessory muscles of respiration (to sustain a normal tidal volume).122
Positive-pressure ventilation tends to create the opposite effect: increase in ITP increases Pra, thus decreasing venous return, RV volumes, and ultimately LV output. The detrimental effect of positive-pressure ventilation on cardiac output can be minimized by either fluid resuscitation, to increase mean systemic pressure,91,100,114,115,118 or by keeping both mean ITP and swings in lung volume as low as possible. Accordingly, prolonging expiratory time, decreasing tidal volume, and avoiding PEEP all minimize this decrease in systemic venous return to the right ventricle.1,89,93–97,125,126 Increases in lung volume during positive-pressure ventilation primarily compress the two ventricles into each other, decreasing biventricular volumes.127 The decrease in cardiac output commonly seen during PEEP is caused by a decrease in LV end-diastolic volume, because both LV end-diastolic volume and cardiac output are restored by fluid resuscitation128,129 without any measurable change in LV diastolic compliance.74
A common respiratory maneuver, called a Valsalva maneuver, which is forced expiration against an occluded airway, such as one may do while straining at stool, displays most of the hemodynamic effects commonly seen in various disease states and with different types of positive-pressure ventilation.
During a Valsalva maneuver, airway pressure (Paw) and ITP increase equally, and pulmonary vascular resistance remains constant. During the first phase of the Valsalva maneuver, right ventricle filling decreases because venous return decreases with no change in left ventricle filling, LV stroke volume, or arterial pulse pressure. Although LV stroke volume does not change, LV peak ejection pressure increases equal to the amount of the increase in ITP.30 As the strain is sustained, both LV filling and cardiac output both decrease owing to the decrease in venous return,70,131 which results in the second phase. During this second phase of the Valsalva maneuver, both RV and LV output are decreased; arterial pulse pressure is reduced, but peak systolic pressure sustained at an elevated level owing to the sustained increase in ITP. This phase delay in LV output decrease compared to RV output decrease is also seen during positive-pressure ventilation; it is exaggerated if tidal volumes increase or if the pressure gradient for venous return was already low, as is the case in hypovolemia.1,74–76,98,125,132–138 With release of the strain in phase three of the Valsalva maneuver, arterial pressure abruptly declines as the low LV stroke volume cannot sustain an adequate ejection pressure on its own. Furthermore, with the release of the increased ITP, venous return increases, increasing RV volume, and, through the process of ventricular interdependence, decreases LV diastolic compliance, making LV end-diastolic volume even less. Conceptually, then ventricular interdependence usually becomes apparent with sudden increases in RV volume from apneic baseline, as would occur during spontaneous inspiration, but less so when RV volumes decrease below these volumes. As described above, because RV volumes are usually decreased during positive-pressure ventilation, ventricular interdependence is not a prominent feature of this form of breathing (see Fig. 36-6).62,136–139 Although PEEP results in some degree of right-to-left intraventricular septal shift, echocardiographic studies demonstrate that the shift is small.77,132 It follows that positive-pressure ventilation decreases intrathoracic blood volume94 and PEEP decreases it even more140,141 without altering LV diastolic or contractile function.142 During spontaneous inspiration, however, RV volumes increase transiently shifting the intraventricular septum into the LV,63 decreasing LV diastolic compliance and LV end-diastolic volume.48,61,139 This transient RV dilation-induced septal shift is the primary cause of inspiration-associated decreases in arterial pulse pressure, which, if greater than 10 mm Hg or 10% of the mean pulse pressure, is referred to as pulsus paradoxus (see Fig. 36-6).64,143
Left-Ventricular Preload and Ventricular Interdependence.
Ventricular interdependence does not induce steady-state changes in left ventricle performance, only phasic ones. Thus, the associated rapid changes in right ventricle filling induced by phasic changes in ITP cause marked changes in LV output, which are a hallmark of ventilation-induced hemodynamic changes as described above (see Figure 36-6 Spontaneous ventilation).
LV afterload is defined as the maximal LV systolic wall tension, which equals the maximal product of LV volume and transmural LV pressure. Under normal conditions, maximal LV wall tension occurs at the end of isometric contraction, with the opening of the aortic valve. During LV ejection, as LV volumes rapidly decrease, LV afterload also decreases despite an associated increase in ejection pressure. Importantly, when LV dilation exists, as in CHF, maximal LV wall stress occurs during LV ejection because the maximal product of pressure and volume occurs at that time. LV ejection pressure is the transmural LV systolic pressure. This is the main reason why subjects with dilated cardiomyopathies are very sensitive to changes in ejection pressure, whereas patients with primarily diastolic dysfunction are not. Normal baroreceptor mechanisms, located in the extrathoracic carotid body, function to maintain arterial pressure constant with respect to atmosphere. Accordingly, if arterial pressure were to remain constant as ITP increased, then transmural LV pressure would decrease. Similarly, if transmural arterial pressure were to remain constant as ITP increased, then LV wall tension would decrease.144 Thus, increases in ITP decrease LV afterload, and decreases in ITP increase LV afterload.130,145 These two opposing effects of changes in ITP on LV afterload have important clinical implications.
The concept that increases in ITP decrease both LV preload and LV afterload can be clearly illustrated with the use of high-frequency jet ventilation, which can increase ITP but does not result in large swings in lung volume.135 When high-frequency jet ventilation is delivered in synchrony with the cardiac cycle, such that heart rate and ventilatory frequency are identical, one can dissect out the effects of ITP on preload and afterload. Under hypovolemic and normovolemic conditions with intact cardiovascular reserve, positive-pressure ventilation usually decreases steady-state cardiac output by decreasing the pressure gradient for venous return. When one compares the hemodynamic effects of high-frequency jet ventilation synchronized to occur during diastole (when ventricular filling occurs), cardiac output decreases to levels seen during end-inspiration for normal-to-large tidal-volume (10 mL/kg) ventilation. In the same subject, however, if the increases in ITP occur during systole, the detrimental effects of the same mean Paw, mean ITP, and tidal volume do not impede venous return (Fig. 36-7).146,147 Furthermore, in heart failure states, positive-pressure ventilation does not impede cardiac output because the same decreases in venous return do not alter LV preload. If these increases in ITP, however, reduce LV afterload, then cardiac output will also increase. These points are illustrated in Figure 36-8, wherein synchronous high-frequency jet ventilation is delivered either during preejection systole (presystolic) or ejection (systolic). The only difference between the two ventilatory states is that arterial pulse pressure does not change despite increases in LV stroke volume with presystolic increases in Paw, consistent with a decreased LV afterload, whereas with systolic increases in Paw, arterial pulse pressure increases, and peak arterial pressure increases by an amount equal to the increase in ITP, consistent with mechanically augmented LV ejection.
Strip chart recording of right- and left-ventricular stroke volumes (SVrv and SVlv, respectively), aortic pressure (PaO), left atrial, pulmonary arterial, and right atrial transmural pressures (Platm, Ppatm, and Pratm, respectively), airway pressure (Paw), and pleural pressure (Ppl) during apnea (left), and both systolic (systole) and diastolic (diastole) high-frequency jet ventilation (HFJV) (middle), and intermittent positive-pressure ventilation with similar mean Paw (right) in an anesthetized, intact canine model with normal cardiovascular function. Note that the cardiac cycle-specific increases in Paw created by systole HFJV minimally impede cardiac output, whereas diastole HFJV markedly decreases venous return (SVrv decreases first, then SVlv decreases). The rapid strip chart speed shown on the left is to illustrate the exact timing of synchronous HFJV. (Used, with permission, from Pinsky MR, Matuschak GM, Bernardi L, Klain M. Hemodynamic effects of cardiac cycle-specific increases in intrathoracic pressure. J Appl Physiol. 1986;60:604–612.)
Continuous strip chart recording of right- and left-ventricular stroke volumes (SVrv and SVlv, respectively), aortic pressure (PAO), left atrial, pulmonary arterial, and right-atrial transmural pressures (Platm, Ppatm, and Pratm, respectively), airway pressure (Paw), pleural pressure (Ppl), and right-atrial pressure (Pra) during intermittent positive-pressure ventilation (tidal volume [VT] 10 mL/kg), apnea (left), and then both preejection systole (presystolic) and LV ejection (systolic) synchronous high-frequency jet ventilation (HFJV) (middle), and then intermittent positive-pressure ventilation again (right) in an anesthetized, intact canine model with fluid-resuscitated acute ventricular failure. Note that the cardiac cycle–specific increases in Paw created by both presystolic and systolic HFJV increase steady-state SVrv and SVlv (i.e., cardiac output), but affect PAO differently. Presystolic HFJV does not change PAO pulse pressure despite an increase in SVlv (reduced afterload), whereas systolic HFJV increases PAO pulse pressure for a similar increase in SVlv. (Used, with permission, from Pinsky MR, Matuschak GM, Bernardi L, Klain M. Hemodynamic effects of cardiac cycle-specific increases in intrathoracic pressure. J Appl Physiol. 1986;60:604–612.)
Relevance of Intrathoracic Pressure on Myocardial Oxygen Consumption.
Decreases in ITP increase both LV afterload and myocardial O2 consumption. Accordingly, spontaneous ventilation not only increases global O2 demand by its exercise component,80,126,148 but also increases myocardial O2 consumption. Profound decreases in ITP commonly occur during spontaneous inspiratory efforts with bronchospasm, obstructive breathing, and acute hypoxemic respiratory failure. Under these conditions, the cardiovascular burden can be great and may induce acute heart failure and pulmonary edema.30 Because weaning from positive-pressure ventilation to spontaneous ventilation may reflect dramatic changes in ITP swings, from positive to negative, independent of the energy requirements of the respiratory muscles, weaning is a selective LV stress test.144,148–150 Similarly, improved LV systolic function is observed in patients with severe LV failure placed on mechanical ventilation.150 Very negative swings in ITP, as seen with vigorous inspiratory efforts in the setting of airway obstruction (asthma, upper airway obstruction, or vocal cord paralysis) or stiff lungs (interstitial lung disease, pulmonary edema, or ALI), selectively increase LV afterload, and may be the cause of LV failure and pulmonary edema,13,30,31,151 especially if LV systolic function is already compromised.152,153
Pulsus paradoxus seen during spontaneous inspiration under conditions of marked pericardial restraint reflects primarily ventricular interdependence.154–158 The negative swings in ITP, however, also increase LV ejection pressure, increasing LV end-systolic volume.130 Other systemic factors may influence LV systolic function during loaded inspiratory efforts. These associated factors also contribute to a greater or lesser degree to the inhibition of normal LV systolic function, including increased in aortic input impedance,159 altered synchrony of contraction of the global LV myocardium,160 and hypoxemia-induced decreased global myocardial contractility.161 Hypoxia also directly reduces LV diastolic compliance.162 Experimental repetitive periodic airway obstructions induce pulmonary edema in normal animals.30,31 Furthermore, removing the negative swings in ITP by applying nasal CPAP results in improved global LV performance in patients with combined obstructive sleep apnea and CHF.130
Relevance of Intrathoracic Pressure on Left-Ventricular Afterload.
If arterial pressure remains constant, then increases in ITP decrease transmural LV ejection pressure, decreasing LV afterload. These points are easily demonstrated in a subject with an indwelling arterial pressure catheter during cough or Valsalva maneuvers. During a cough, ITP increases rapidly without changes in intrathoracic blood volume. Arterial pressure also increases by a similar amount, as described above for phase 1 of the Valsalva maneuver. Thus, transmural LV pressure (LV pressure relative to ITP)130,163,164 and aortic blood flow70 would remain constant. Sustained increases in ITP, however, must eventually decrease aortic blood flow and arterial pressure secondary to the associated decrease in venous return.130 If ITP increased arterial pressure without changing transmural arterial pressure, then baroreceptor-mediated vasodilation would induce arterial vasodilation to maintain extrathoracic arterial pressure-flow relations constant.134 Because coronary perfusion pressure reflects the ITP gradient for blood flow and is not increased by ITP-induced increases in arterial pressure, such sustained increases in ITP can cause decreased coronary perfusion pressure-induced myocardial ischemia.165–167