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While parts 1 and 2 of this trilogy considered the mechanical power applied to the lung skeleton and the effects of lung inhomogeneity [i.e. ‘stress raisers’], respectively; this final installment will draw the reader towards the pulmonary vasculature as a key mediator of ventilator induced lung injury [VILI]. That the pulmonary vasculature participates in the pathogenesis and propagation of the acute respiratory distress syndrome [ARDS] has been known for decades . Highlighting the importance of the pulmonary vascular tree in ARDS, both a prediction score for acute cor pulmonale [ACP] in ARDS and an expert opinion on the hemodynamic management of ARDS have been – very recently – circulated [2, 3].
Blood Vessels and VILI
There are a plethora of ‘indirect’ insults to the pulmonary vasculature which raise resistance to blood flow [4, 5] during ARDS. These include microthrombi, hypoxemic vasoconstriction, hyperpcapnia and interstitial edema . Additionally, the ‘direct’ effect of augmented lung stress and airway mechanics upon the vasculature are also paramount . In a patient, fully adapted with the ventilator [e.g. paralyzed], a mechanical breath raises lung stress as detailed in part 1. Stress on the lung skeleton has opposing effects upon the two vascular populations within the lung . The alveolar vessels [e.g. the pulmonary capillaries] are exposed to the alveolar pressure and tend to collapse during lung inflation [i.e. because the alveolar pressure rises relative to the pleural pressure]. By contrast, within the bronchovascular bundles – which originate at the hila and invaginate into the lung parenchyma – lie the extra-alveolar vessels. When lung volume rises [even in response to a fully passive, ventilator-delivered breath] these conduits dilate. To the extent that these conduits increase in size, the interstitial pressure surrounding the extra-alveolar vessels falls; consequently, the extra-alveolar vessels tend to dilate and elongate .
There is a unique sub-population of blood vessels within the lung known as ‘corner vessels’ which are anatomically alveolar [they lie at the junction of at least 3 alveolar septae] but are physiologically extra-alveolar because they dilate when lung volume rises . Indeed, under West zone I conditions, the corner vessels are responsible for continued, local blood flow . When lung stress is abnormally high – as during ARDS – over-distention of inhomogeneous lung will result in excessive West Zone I, particularly during inflation. This will force excess blood through corner vessels, raise their transmural pressure and favor interstitial edema, particularly when vessels are abnormally leaky as in ARDS [3, 6]. While the Mead model detailed in part 2 discusses the effects of stress raisers on neighboring lung units during inflation, asymmetrical radial forces are exerted in an equal, but opposite direction during exhalation . Accordingly, the interstitial space adjacent to a stress raiser during alveolar emptying is predicted to experience traction forces multiplied by a factor of 4.5 [6, 9]. Thus, if alveoli begin to empty at an end-inspiratory pressure of 30 cm H2O, the interstitial pressure surrounding the corner vessel may fall by 140 cm H2O [or 100 mmHg]! It follows that the transmural pressure of the corner vessel can – in theory – raise to a level known to fracture capillaries  [see figure 1].
In summation, the mechanical power applied to the airways can exacerbate vascular injury via cyclical stress on the microvasculature. Empirically, increased pulmonary arterial blood flow, cycle time and pressure have all been demonstrated to exacerbate hemorrhagic edema and VILI [6, 11-14]. Additionally, in a VILI model, lowering left atrial pressure exacerbates lung injury . From above, it may be deduced that diminished left atrial and pulmonary venous pressure will increase the fraction of West zone I and II thereby exacerbating cyclical fluctuation in microvascular stress. By this reasoning, West zone III acts – in some ways – as ‘vascular PEEP.’
In response to the aforementioned vascular injury – and consequent high right ventricular [RV] afterload – the RV may suffer from dilation [i.e. diastolic dysfunction or volume overload] and paradoxical septal motion [i.e. systolic dysfunction or pressure overload]. When both RV diastolic and systolic dysfunction are present on an echocardiogram, ACP is diagnosed . Prior to lung protective ventilation [LPV], the incidence of ACP in ARDS was upwards of 60%, while in contemporary studies, it is about 20% . Fortunately, clinicians can now better predict the likelihood of ACP based on a recent evaluation  [see table 1]
[see reference ]
Non-invasive indices of fluid responsiveness in ARDS pose problems as RV output may vary in response to respiratory-induced augmentation in afterload, rather than decrement in preload . The use of trans-esophageal echocardiography may mitigate such error by continuous assessment of RV size, SVC collapsibility [i.e. in the paralyzed patient] and RV outflow mean acceleration time . The latter index is the ratio of the maximal velocity of RV outflow to the acceleration time; its fall is directly associated with RV systolic function and inversely related to RV afterload .
Another venerable monitoring utensil is the pulmonary artery catheter [PAC]. Importantly, because of the near-ubiquitous presence of tricuspid regurgitation during mechanical ventilation  [especially in ARDS ], thermodilution cardiac output should be abandoned. Similarly, pulmonary vascular resistance is likely a meaningless variable [21, 22]. Instead, untoward hemodynamic effects of mechanical ventilation upon the RV may be inferred from diminished pulmonary arterial pulse pressure and/or increased isovolumic contraction pressure [see figure 2] .
Ultimately, the above underscores the importance of LPV; adhering to the adage ‘what’s good for the lung is good for the RV’  certainly applies. Selection of optimal PEEP using driving pressure or the stress index as quantitative and qualitative surrogates – respectively – of alveolar distention, minimizing mechanical power applied to the lung, prone positioning, the use of norepinephrine to maintain right coronary artery perfusion in shocked ARDS patients as well as the judicious use of fluids are all initial considerations. Further, deliberation for pulmonary arterial vasodilators and extra-corporeal support should be part of one’s hemodynamic approach to severe ARDS [3, 5]. Nevertheless, what remains unanswered is whether specifically monitoring and treating ACP in ARDS will improve outcome.
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