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Ann Thorac Surg 1999;68:1107-1115
© 1999 The Society of Thoracic Surgeons

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Current Review

Lung injury and acute respiratory distress syndrome after cardiopulmonary bypass

^a Cardiothoracic Unit, Imperial College School of Medicine at Hammersmith Hospital, London, England, UK

Address reprint requests to Dr Taylor, Cardiothoracic Unit, Imperial College School of Medicine at Hammersmith Hospital, Du Cane Rd, London W12 0NN, England
e-mail: scarroll{at}rpms.ac.uk

	Abstract

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
Cardiopulmonary bypass is often followed by pulmonary dysfunction as assessed by measuring the alveolar-arterial oxygenation gradient, intrapulmonary shunt, degree of pulmonary edema, pulmonary compliance, and pulmonary vascular resistance. It is also regarded as a risk factor for development of acute respiratory distress syndrome. On the other hand, cardiopulmonary bypass is associated with a whole body inflammatory response, which involves activation of complement, leukocytes, and endothelial cells with secretion of cytokines, proteases, arachidonic acid metabolites, and oxygen free radicals. Leukocyte adhesion to microvascular endothelium, leukocyte extravasation, and tissue damage are the final steps. Although the inflammatory response to cardiopulmonary bypass often remains at subclinical levels, it can also lead to major organ dysfunction and multiple organ failure. This review article summarizes the recent literature on the molecular and cellular mechanisms involved in the phenomenon of pulmonary dysfunction after cardiopulmonary bypass. It also summarizes reports on the prevalence and mortality of acute respiratory distress syndrome after cardiac surgery.

	Introduction

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
Since the early days of cardiac surgery, it has been recognized that cardiopulmonary bypass (CPB) is associated with systemic inflammation, and that occasionally this leads to major organ dysfunction. When organ dysfunction cannot be directly attributed to a specific cause, such as infection or ischemia, the concept of the "postpump syndrome" or "systemic inflammatory response syndrome to CPB" is used as an alternative explanation. The term systemic inflammatory response syndrome signifies the presence of a clinical syndrome that results from the inflammatory reaction of the body to a variety of different types of tissue injury [1]. In cardiac surgery, systemic inflammatory response syndrome is thought to be the result of four main forms of injury: (1) contact of the blood components with the artificial surface of the bypass circuit, (2) ischemia–reperfusion injury, (3) endotoxemia, and (4) operative trauma.

Pulmonary dysfunction after CPB was described 40 years ago [2] and continues to be the subject of a considerable amount of experimental and clinical research. Many studies have focused on the pathophysiologic mechanisms of lung injury after CPB, of which the most severe form is the acute (or adult) respiratory distress syndrome (ARDS). Although pulmonary complications after CPB have been attributed primarily to cardiogenic or infective origin, a systemic inflammatory response through contact of blood with the artificial material of the bypass circuit, leading to contact activation of leukocytes and platelets, is regarded as a major contributing factor [3].

Our knowledge about the molecular mechanisms that are involved in systemic inflammatory response syndrome and lung injury has increased considerably over the last two decades; inasmuch as these mechanisms appear to follow similar pathways irrespective of cause, much of the new information may be applied to the cardiac surgical patient. This review article summarizes the expanding literature about acute lung injury and ARDS in patients undergoing CPB. Questions to be answered are (1) which inflammatory mechanisms may be related to lung injury after cardiac surgery, and (2) what is the incidence, and relation to systemic inflammation, of ARDS after cardiac surgery.

	Methods

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
A search of English-language articles featured in MEDLINE during the last 10 years was undertaken. Key words used were lung injury, acute and adult respiratory distress in various combinations with endothelium, neutrophil(s), monocyte(s), platelet(s), cytokine(s), and complement. In addition, relevant publications mentioned in the reference lists or articles selected from the MEDLINE search were considered. All articles reporting studies in humans and animals were reviewed. With few exceptions, reports from pediatric and transplant cardiac surgery were excluded. Reports of purely in vitro work, review publications, and in vivo trials unrelated to CPB were reviewed only when we believed that we contributed significantly to answering the main questions of this current review article. Although many interesting relevant studies, pertinent to the pathophysiology of acute lung injury and ARDS in general, have been published recently, a detailed presentation of the basic science literature in these areas would reach beyond the scope of this review article.

	Pulmonary dysfunction after cardiopulmonary bypass

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
The American–European Consensus Conference on ARDS [4] defined the term acute lung injury, which could be applied to a wide spectrum of pathologic processes, and recommended that the term ARDS be reserved for the most severe form of this spectrum, using an arbitrary cutoff point (Table 1).

On a molecular and cellular level, the exact mechanisms leading to acute lung injury and ARDS are not yet fully clarified. A review of work performed in the 1980s concluded that the relationship between inflammatory response and CPB-related lung injury was still unclear [6]. Recent research, however, underlines the importance of cell activation during inflammatory lung injury. Neutrophils, monocytes, and macrophages, as well as endothelial cells, undergo activation, resulting in local and systemic secretion of humoral inflammatory mediators. Similarly, CPB-induced lung injury has been associated with the activation of complement, leukocytes, and endothelial cells and secretion of cytokines and other soluble inflammatory mediators.

	Complement

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
Complement is a system of proteins that becomes activated at an early stage of the inflammatory response (Fig 1 ), although the exact role of complement in this process is not completely understood. The chemotactic effects of the complement component C3a and the ability of C3a and C5b–C9 (membrane attacking complex) to activate leukocytes and endothelial cells [7, 8] are important factors leading to inflammatory tissue injury. There is also the suggestion that complement activation leads to neutrophil accumulation in the lung and that it may be involved in the cascade of events leading to lung injury in at-risk patients. Thus, blockade of C5a by anti-C5a antibodies suppressed an increase in membrane permeability and neutrophil accumulation in a rat model of acute lung injury [9]. It is unlikely, however, that specific complement components alone can be used as a predictor of ARDS [10].

View larger version (13K): [in this window] [in a new window]   Fig 1. The complement cascade. Contact between complement components and the artificial surface of the bypass circuit activates the alternative pathway. Activation of the classic pathway also occurs, probably as a result of administration of protamine. Membrane attacking complex (MAC) is the final product of the reaction.

Although activation of complement during CPB is not always associated with pulmonary epithelial injury, as measured through the radioaerosol lung clearance of technetium 99m-labeled diethylenetriaminepentaacetic acid [14], reduction of the respiratory index correlated with C3a levels in one study [17]. In an earlier study, patients requiring prolonged respiratory support after cardiac surgery were shown to have C3a plasma levels that were nearly twice that of patients who were uneventfully weaned from the ventilator [18]. Gillinov and colleagues [19] showed that after CPB, lung myeloperoxidase content and expression of neutrophil integrin subunit CD18 were lower in C3-deficient dogs, compared with control dogs, whereas impairment in lung function was similar between groups. These findings suggest that C3a may mediate neutrophil activation but is not an essential component of inflammatory lung injury after CPB. The same group of investigators also found that treatment of pigs during CPB with soluble human complement receptor type 1, an inhibitor of C3 and C5, resulted in a reduction of pulmonary vascular resistance [20]. These findings may underline the significance of C5 in CPB-induced pulmonary dysfunction, with tissue damage probably caused by the direct effect of C5a and the membrane attacking complex C5b–C9 on the pulmonary endothelium, neutrophils, and cytokine-producing monocytes.

	Neutrophils

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
Neutrophils may be activated by complement or by a complement-independent mechanical mechanism. This activation leads to increased neutrophil interaction with similarly activated endothelium, resulting in enhanced neutrophil–endothelial cell adhesion and neutrophil sequestration. The adhesion molecule family of selectins mediates the initial rolling phase of neutrophil attachment to endothelium. Subsequently, interaction between the adhesion molecule families of integrins and immunoglobulins facilitate firm binding of neutrophils to the activated endothelium [21]. Adherent neutrophils are then subjected to further activation through the action of chemokines, such as interleukin-8. Thus, oxygen free radicals and enzymes, such as proteases (eg, elastase and metalloproteinases) and myeloperoxidase, are generated by the adherent neutrophils, exacerbating damage to endothelial cells and to subendothelial matrix proteins and inducing tissue injury [22] (Fig 2). There is, furthermore, a positive correlation between elastase plasma concentrations after CPB and postoperative respiratory dysfunction, as shown by changes in the respiratory index and increases in the intrapulmonary shunt [23, 24]. Inhibition of elastase with ulinastatin ameliorates the increase of intrapulmonary shunt [25].

View larger version (25K): [in this window] [in a new window]   Fig 2. Leukocytes, endothelial cells (EC), and humoral inflammatory mediators have been shown to play an important role in the cardiopulmonary bypass-induced lung injury. Complement activation and complement-independent mechanical injury activates leukocytes, which, in their turn, secrete several inflammatory mediators, such as proteases and cytokines. Complement, cytokines, and ischemia–reperfusion also activate endothelial cells. Endotoxin, probably released from intestinal bacteria, exerts similar effects on leukocytes and endothelium. This process leads to disruption of endothelial and epithelial integrity and allows albumin, plasma, and activated leukocytes to enter the interstitial and alveolar space, causing tissue edema and reducing pulmonary compliance and blood oxygenation. (AAM = arachidonic acid metabolites; ICAM-1 = intercellular adhesion molecule-1; IL = interleukin; IS = interstitial space; LPS = lipopolysaccharide; M = monocyte; Mg = macrophage; MPO = myeloperoxidase; N = neutrophil; NO = nitric oxide; O2-DFR = oxygen-derived free radicals; P = platelet; PAF = platelet-activating factor; PDGF = platelet-derived growth factor; Pn = pneumocyte; TGF = tumor growth factor; TNF = tumor necrosis factor.)

Although in endotoxin-induced lung injury, monocytes appear to precede neutrophils with regard to infiltration into the alveoli, in ischemia–reperfusion this phenomenon may be reversed. Indeed, large numbers of neutrophils infiltrated the alveoli at 4 hours of reperfusion during lung injury of the ischemia–reperfusion type in rats [27].

In CPB-associated lung injury, in which endotoxemia may coexist with ischemia–reperfusion and activation of complement, neutrophils appear to play a significant role. After the administration of protamine, the neutrophil count in the pulmonary artery exceeds the count in the systemic arterial blood, suggesting that neutrophils are sequestrated in the lungs, rendering them prone to injury [24, 28]. Concentrations of neutrophils in bronchial lavage fluid was higher after CPB in comparison with a control group of patients [29]. Positive end-expiratory pressure ventilation after CPB also contributes to pulmonary neutrophil entrapment, possibly because of the compression of alveolar capillaries in response to raised alveolar pressure [30].

The significance of leukocyte activation in CPB-induced lung injury was demonstrated by the finding that pentoxifylline, an inhibitor of leukocyte activation, reduced lung dysfunction in cardiac surgical patients [31]. Similarly, leukocyte depletion with an arterial filter was shown to attenuate lung injury after CPB in humans [32].

It is likely that the mechanism of acute lung injury by neutrophils involves an upregulation of neutrophil integrins and, more specifically, of the ß2 integrin Mac-1 (CD11b/CD18). Indeed, lung dysfunction after CPB was reduced when animals were treated with the Mac-1 inhibitor NPC 15669 [33] or with an anti-CD18 monoclonal antibody [34].

The above findings have established a neutrophil-dependent model for CPB-related lung dysfunction. Activation of neutrophils, with upregulation of adhesion molecules, neutrophil adhesion to the endothelium of lung vessels, and endothelial damage through proteases, appears to be the main step of the underlying pathophysiologic mechanism.

	Macrophages, monocytes, and cytokines

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
Within the complicated network that interconnects different inflammatory pathways involved in CPB-induced lung injury, the role of pulmonary macrophages, activated monocytes, and monocyte-secreted proinflammatory cytokines is increasingly recognized (Fig 2). Monocytes are known to migrate out of the pulmonary vessels into the lung interstitial and alveolar space, where they may be transformed into macrophages during pulmonary inflammation [35]. Pulmonary macrophages can be found in the airways, the alveolar spaces, the interstitium, the pleura space, and in the lumen of noninflamed pulmonary capillaries [36].

Macrophages play an important role in the evolution of the inflammatory acute lung injury through the secretion of cytokines, cytotoxic metabolites, and chemoattractants for leukocytes. Alveolar macrophages are activated at an early stage (within 30 minutes) of acute lung injury [27] when they secrete the chemoattractant for neutrophils (macrophage inflammatory protein-2) and the monocyte chemoattractant protein-1, which is specific for monocyte chemotaxis and activation. Expression of rat lung mRNA for monocyte chemoattractant protein-1 can be induced by tumor necrosis factor- (TNF-), interleukin-1 (IL-1), endotoxin, and ischemia–reperfusion [27, 37]. In humans, serum levels of monocyte chemoattractant protein-1 were elevated during CPB in one study [38].

By combining these data it is reasonable to suggest that, after the onset of endotoxin- or ischemia-induced acute lung injury, activated lung macrophages secrete chemoattractants for monocytes and neutrophils. Subsequently, activated neutrophils adhere to pulmonary endothelium, but it is the monocytes that migrate first into the tissue and exert their toxic effects directly or are transformed into new macrophages. The effect of the initial injury may be amplified by cytokines released by activated blood monocytes and endothelial cells.

During and after CPB, however, endotoxemia and ischemia–reperfusion may coexist with factors, such as complement activation, that activate neutrophils directly. In this case, the mechanisms leading to lung inflammation may be more complicated than in models of CPB-unrelated ischemia, and the lung injury may be led by neutrophils, as suggested in the previous section.

The importance of the monocyte in CPB-induced lung injury requires further investigation. Cardiopulmonary bypass induces monocyte activation, as measured through tissue factor expression on monocyte surface and tissue factor procoagulant activity [39, 40]. Plasma levels of TNF- and IL-1 were increased during CPB in some studies [41, 42]. Tumor necrosis factor- and IL-1 are the main proinflammatory cytokines that are secreted by activated monocytes and, in their turn, activate endothelial cells, neutrophils, and macrophages. Endotoxin plasma levels are also known to increase during CPB [43], but the degree of their contribution to macrophage/monocyte activation is uncertain.

In addition to activation of plasma monocytes, inflammatory lung injury also involves alveolar macrophages and monocytes. In one recent study, there was significant increase of integrin expression on alveolar macrophages obtained after cross-clamp release, as compared with alveolar macrophages obtained before CPB. Alveolar macrophages, but not peripheral monocytes, produced high levels of TNF- and the inflammatory cytokine IL-8 when cultured postoperatively in vitro in the same study [44]. Concentrations of IL-8 in bronchial lavage fluid, which is produced by activated monocytes and endothelial cells, increased after CPB as compared with controls [29].

	Platelets

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
The role of platelets in acute lung injury is not completely known. Platelet sequestration in pulmonary capillaries occurs during severe lung injury [45]. These platelets may contribute to endothelial injury and tissue edema by secretion of cytotoxic metabolites. Experimental studies, however, have often produced inconsistent results and suggest that activated platelets may, in contrast, have protective effects on endothelium. Wang and associates [46] reported that a combined infusion of platelets and of the neutrophil and platelet activator phorbol myristate acetate induced lung injury in isolated rat lungs. Other studies, however, showed that circulating platelets exerted a protective effect against phorbol myristate acetate-induced lung injury in sheep [47] and suggested that infusion of lungs with platelets preserved endothelial integrity in models of lung injury [48].

Similarly, platelets have been shown to collect in the small vessels of the lung during bypass. The use of uncoated bypass circuits in pigs resulted in reduced platelet and neutrophil accumulation in major organs, including the lungs. In the same study, more biocompatible materials caused a reduction of platelet accumulation in the circuit with a corresponding increase in platelet deposition within internal organs [49]. The use of the platelet aggregation-inhibiting drug prostacyclin in dogs undergoing CPB resulted in preservation of platelet numbers, reduction in platelet aggregation, and reduction in occlusive fibrin, leukocytes, and small platelet-based microaggregates obstructing pulmonary arterioles [50]. The precise pathophysiologic importance of these platelet aggregates in the lungs during CPB is, however, still unknown.

	Endothelial cells

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
Although CPB is thought to be associated with increased endothelial permeability, the injury to endothelial cells is not yet fully characterized. Although blood components, and not endothelial cells, come into direct contact with the artificial surface of the bypass circuit, endothelium is potentially activated by complement, cytokines, endotoxin, and ischemia–reperfusion. Increases in plasma levels of molecules derived from activated endothelium have been demonstrated after CPB. Plasma levels of von Willebrand factor, a marker of endothelial injury, were elevated in patients undergoing cardiac surgery [51]. Levels of IL-8, which is produced by activated monocytes and endothelial cells, also increase significantly after CPB [52]. The specific organs of origin of these mediators is, however, still uncertain.

Levels of thromboxane, an arachidonic acid metabolite that is secreted by activated endothelial cells and causes vasoconstriction, are increased in left atrial plasma after total but not partial CPB in animals. Inhibition of thromboxane synthesis in sheep undergoing CPB resulted in elimination of lung injury [53].

With regard to potential markers of lung injury, nitric oxide (NO) has recently attracted significant attention. Another endothelial-derived molecule, NO exerts a protective effect toward the endothelium. It is known to inhibit leukocyte–endothelial cell adhesion and to reduce vascular tone [54, 55]. The protective effect of NO may also be mediated through scavenging of oxygen-derived free radicals [56]. Reduced release of NO is an early event in reperfusion injury, and the use of NO gas or NO donors has been shown to attenuate neutrophil infiltration in animal models of ischemia–reperfusion [57].

There is a large amount of recent literature investigating the effects of CPB on endogenous production of NO and also the effect of exogenous NO on pulmonary function in patients undergoing CPB. There is some inconsistency in the literature, however, with regard to endogenous NO production. Nitric oxide was shown to increase in the airways of adults, [58] but to decrease in the airways [59] and to remain unaffected in plasma [60] in children after CPB. It is reasonable to assume, however, that if endogenous NO were produced by CPB-induced inflammatory activation of endothelial cells, it would exert protective effects toward the cells that produce it. Inhaled NO has been used as a pulmonary vasodilator in adult cardiac surgical patients [61].

	Acute respiratory distress syndrome

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
Increased plasma and airway concentrations of markers of pulmonary endothelial injury often correlate with impairment of pulmonary function in patients undergoing CPB. It is interesting that several characteristics of the CPB-related lung injury bear, at least qualitatively, resemblance to changes occurring during ARDS. Indeed, CPB appears on lists of risk factors for the development of ARDS [4, 62].

Acute respiratory distress syndrome can be caused by a variety of direct and indirect lung injuries [4]. It is an acute, noncardiogenic, high-permeability lung injury that is characterized by interstitial and alveolar edema, epithelial damage, and rapid onset of pulmonary fibrosis, resulting in significant reduction in pulmonary gas exchange and hypoxemia. It was first described 30 years ago [63] and is still associated with high mortality.

Acute respiratory distress syndrome represents an inflammatory response of the lung to a variety of insults, and therefore, its pathophysiology may be explained by the complement- and neutrophil-based inflammatory theory described for lung injury. An early study demonstrated the significance of complement activation in neutrophil activation leading to ARDS [64]. Increased concentrations of neutrophils and neutrophil-derived proteases were found in bronchoalveolar lavage fluid of patients with ARDS, and the percentage of neutrophils correlated directly with the severity of lung injury [65]. The role of the activated neutrophil in ARDS has been established through further studies that showed increased elastase activity in plasma and the alveoli before and during ARDS [66]. Furthermore, the importance of mechanisms suggestive of systemic inflammation has been demonstrated by descriptive studies showing that plasma and lavage fluid levels of inflammatory mediators, such as TNF-, IL-1ß, IL-6, and, in particular, IL-8, increase during ARDS and correlate with adverse outcomes [67–69]. The predictive value of inflammatory mediator levels in the condition was summarized comprehensively in a recent review article [10].

A crucial step in the neutrophil-initiated pulmonary dysfunction is the release of free radicals, which put the endothelium under significant oxidative stress and contribute to the endothelial disruption characteristic of ARDS [70, 71]. A subpopulation of neutrophils, with an increased capacity to generate the oxygen free radical hydrogen peroxide after stimulation ex vivo, was found in patients with severe pneumonia or ARDS [72].

On the other hand, despite the above evidence supporting the inflammatory theory, it has also been shown that animals depleted of neutrophils may also suffer acute lung injury and that complement infusion does not cause severe lung injury. The complexity of the inflammatory network that participates in ARDS was outlined in recent review articles [73, 74].

At the clinical level, ARDS is often only one part of multiorgan failure [75], and lung injury should be seen as part of a more general state of systemic inflammation. Furthermore, despite our improved understanding of the pathophysiology of lung injury, the exact mechanisms involved in the progression in some individuals from acute lung injury to ARDS remain uncertain.

Treating ARDS in the adult is extremely problematic. In the neonatal respiratory distress syndrome, isolated lung failure occurs as a result of surfactant depletion. The mechanism of the lung injury is well understood, and specific treatment can be effective. On the other hand, ARDS in the adult is often only one part of a complex multiorgan failure in which death is not necessarily primarily related to pulmonary damage. To date, several multicenter randomized trials of specific treatment in ARDS have been conducted, none of which showed a definite survival benefit [76].

In patients undergoing uncomplicated CPB, the use of investigation techniques that can differentiate cardiac from noncardiac pulmonary edema revealed changes in the integrity of the alveolar endothelium that resemble ARDS-type lung injury, albeit at a smaller scale [77]. It is not clear why this low-grade lung injury, detectable in the majority of patients undergoing cardiac surgery, is only followed by severe lung injury in a very small number of cases. It is also not proved whether ARDS after CPB is an extreme form of the spectrum of CPB-related lung injury or whether it occurs after cardiac surgery through a CPB-unrelated mechanism

	Incidence and mortality of acute respiratory distress syndrome after cardiopulmonary bypass

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
Because of the lack of a standard definition for ARDS, different centers have reported a wide range of incidences of this condition in the general population [78]. To our knowledge, there are only four studies documenting the prevalence of ARDS after CPB in the literature [62, 79–81]. Although the American–European Consensus Conference on ARDS published a consensus definition of ARDS and acute lung injury in an attempt to assist standardization of future research [4], three of these studies used a more-complicated scoring system proposed by Murray and associates [82] (Tables 1 and 2 ). The reported prevalence of ARDS after CPB in these studies was 0.5% to 1.7%. The lowest incidence of 0.5% was reported from our institution and was the most recent [81]. This figure may reflect improvement in current primary care, resulting in a reduced number of patients who had ARDS without concomitant failure of other major organs. On the other hand, mortality in our cases of ARDS appears to be high (91.6%), albeit mainly in patients with multiorgan failure. A recent study from Switzerland reports similarly high mortality in patients with ARDS as part of multiorgan failure after CPB [80]. Frank multiorgan failure occurs in approximately 70% of patients with ARDS unrelated to cardiac surgery and also carries high mortality [76].

	Therapeutic considerations

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
As pulmonary impairment after cardiac surgery appears to be related to the systemic inflammatory response to CPB, it is reasonable to approach a strategy to reduce the degree of lung injury by suppressing secretion and function of various inflammatory mediators.

Studying the response of pulmonary function during and after CPB to treatments that affect one or more stages of the inflammatory cascade allows us to understand better the mechanisms involved and sometimes to monitor the severity of the injury. It is hoped that by understanding the significance of each individual inflammatory mediator we may become capable of modifying the inflammatory process by selectively inhibiting, or occasionally promoting, its function.

In recent years, many trials have investigated strategies that aim to reduce the inflammatory response that also takes place during and after CPB. Elimination of inflammation-induced postoperative morbidity is one of the potential benefits of minimally invasive cardiac surgery without CPB. Results of a randomized trial of patients undergoing coronary artery bypass grafting with or without CPB for single-vessel disease suggested that plasma neutrophil elastase levels, complement component C3a levels, and platelet degranulation were reduced when CPB was not used [83].

Heparin-coating of the bypass circuit has been shown to reduce complement activation [5]. Redmond and co-workers [84] showed that the use of heparin-coated circuits was associated with improved pulmonary function in comparison with uncoated circuits, as assessed through arterial oxygen tension, pulmonary vascular resistance, and static lung compliance, in pigs undergoing hypothermic CPB. Neutrophil expression of the integrin subunit CD18 and leukocyte counts, however, were similar in the two groups.

As mentioned previously, studies investigating the effects of leukocyte depletion on pulmonary function after CPB have contributed significantly to our belief that the neutrophil plays a major role in the CPB-induced lung injury. Despite some conflicting results, the majority of research demonstrates that leukocyte depletion during CPB improves lung function in the immediate postoperative period in animals and humans [32, 85].

The use of monoclonal antibodies directed specifically against certain inflammatory mediators is a relatively novel and promising antiinflammatory strategy. Recent experiments demonstrated significant reduction in the degree of myocardial reperfusion injury in animals treated with monoclonal antibodies against adhesion molecules, in particular ß2-integrins and selectins [86]. Similarly, inhibition of neutrophil adhesion to pulmonary endothelium is a potential method of obstructing the development of postoperative lung injury. Inhibition of the integrin Mac-1 could reduce adhesion of activated neutrophils to endothelium and the subsequent tissue injury. As mentioned previously, the Mac-1 inhibitor NPC 15669 was shown to reduce pulmonary leukocyte sequestration and lung injury in animal trials, by reducing adhesion of activated neutrophils [33, 87].

Many of these antiinflammatory strategies have so far been used only in animal experiments. Disappointingly, none of the human studies has as yet demonstrated any benefit with regard to mortality and major morbidity, probably because the studied populations were small and mainly included uncomplicated cases. However, some of the results have been promising and suggest that some of these techniques may well be applicable to the treatment or prevention of the inflammatory lung damage caused by CPB.

	Summary

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 
There is considerable evidence that CPB is associated with deterioration of pulmonary function as assessed by measuring the alveolar-arterial oxygenation gradient, intrapulmonary shunt, degree of pulmonary edema, pulmonary compliance, and pulmonary vascular resistance. Cardiopulmonary bypass leads to activation of complement, neutrophils, monocytes, macrophages, platelets, and endothelial cells. As suppression of activation of these inflammatory mediators correlates with reduction of pulmonary dysfunction, it is reasonable to suggest that pathways of systemic inflammatory response are of paramount importance in the development of CPB-related pulmonary dysfunction. This pulmonary dysfunction remains clinically insignificant in the vast majority of cardiac patients, including most patients who participated in relevant clinical trials. There is a definite prevalence after CPB, however, of a more significant lung injury, of which the most severe form is ARDS.

Although, at least qualitatively, similar pulmonary endothelial abnormalities are observed both in patients undergoing uncomplicated CPB and patients with ARDS, the majority of the former do not develop a clinically significant lung injury. It is only a small minority who demonstrate an intermediate degree of pulmonary impairment and an even smaller minority who have ARDS. Thus, the incidence of ARDS after CPB in current practice is about 1%. The mortality of ARDS is, however, extremely high, in particular when ARDS is part of multiorgan failure.

Our increasing understanding of some of the mechanisms that regulate the inflammatory response to CPB has already allowed the development of several potentially therapeutic techniques that aim to inhibit the adverse effects of inflammation. Definite clinical benefit has yet to be demonstrated, but results from animal work are promising. Further research in cardiac surgery, as an area of surgery in which the phenomenon of clinically significant inflammation is routinely present, can assist the basic sciences in the understanding of the mechanisms involved and the development of promising therapeutic strategies.

	Acknowledgments

 
We are indebted to Dr R. Clive Landis, PhD, for his support and useful comments on the manuscript. George Asimakopoulos is supported by the British Heart Foundation, grant no. FS/96081.

	References

Top Abstract Introduction Methods Pulmonary dysfunction after... Complement Neutrophils Macrophages, monocytes, and... Platelets Endothelial cells Acute respiratory distress... Incidence and mortality of... Therapeutic considerations Summary References

 

1. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Crit Care Med 1992;20:864-868.[Medline]
2. Kolff W.J., Effler D.B., Groves L.K. Pulmonary complications of open heart operations. Their pathogenesis and avoidance. Cleve Clin Q 1958;25:65-83.[Medline]
3. Byrick R.J., Noble W.H. Postperfusion lung syndrome. Comparison of Travenol bubble and membrane oxygenators. J Thorac Cardiovasc Surg 1978;76:685-693.[Abstract]
4. Bernard G.R., Artigas A., Brigham K.L., et al. The American–European Consensus Conference on ARDS. Am J Respir Crit Care Med 1994;149:818-824.[Abstract]
5. Gott J.P., Cooper W.A., Schmidt F.E., Jr, et al. Modifying risk for extracorporeal circulation. Ann Thorac Surg 1998;66:747-754.[Abstract/Free Full Text]
6. Royston D. Surgery with cardiopulmonary bypass and pulmonary inflammatory responses. Perfusion 1996;11:213-219.[Free Full Text]
7. Gerard C., Gerard N.C. C5a anaphylatoxin and its seven transmembrane signal receptors. Annu Rev Immunol 1994;12:775-808.[Medline]
8. Hansch G.M., Seitz M., Betz M. Effect of the late complement component C5b-9 on human monocytes. Int Arch Allergy Appl Immunol 1987;82:317-320.[Medline]
9. Mulligan M.S., Schmid E., Beck-Schimmer B., et al. Requirement and role of C5a in acute inflammatory injury in rats. J Clin Invest 1996;98:503-512.[Medline]
10. Connelly K.G., Repine J.E. Markers for predicting the development of acute respiratory distress syndrome. Annu Rev Med 1997;48:429-445.[Medline]
11. Chenoweth D.E., Cooper S.W., Hugli T.E., Stewart R.W., Blackstone E.H., Kirklin J.W. Complement activation during cardiopulmonary bypass. N Engl J Med 1981;304:497-502.[Abstract]
12. Boyle E.M., Jr, Pohlman T.H., Johnson M.C., Verrier E.D. The systemic inflammatory response. Ann Thorac Surg 1997;64:S31-S37.
13. Howard R.J., Crain C., Franzini D.A., Hood I., Hugli T.E. Effects of cardiopulmonary bypass on pulmonary leukostasis and complement activation. Arch Surg 1988;123:1496-1501.[Abstract/Free Full Text]
14. Tennenberg S.D., Clardy C.W., Bailey W.W., Solomkin J.S. Complement activation and lung permeability during cardiopulmonary bypass. Ann Thorac Surg 1990;50:597-601.[Abstract]
15. Kluft C., Dooijewaard G., Emeis J.J. Role of the contact system in fibrinolysis. Semin Thromb Hemost 1987;13:50-68.[Medline]
16. Foreman K.E., Vaporciyan A.A., Bonish B.K., et al. C5a-induced expression of P-selectin in endothelial cells. J Clin Invest 1994;94:1147-1155.
17. Nagamine S., Tabayashi K., Haneda K., Mohri H. A clinical study of respiratory complication after cardiopulmonary bypass, with special reference to complement activation, white blood count and granulocyte elastase. Nippon Geka Gakkai Zasshi 1994;95:348-353.[Medline]
18. Moore F.D., Jr, Warner K.G., Assousa S., Valeri C.R., Khuri S.F. The effects of complement activation during cardiopulmonary bypass. Ann Surg 1988;208:95-103.[Medline]
19. Gillinov A.M., Redmond J.M., Winkelstein J.A., et al. Complement and neutrophil activation during cardiopulmonary bypass. Ann Thorac Surg 1994;57:345-352.[Abstract]
20. Gillinov A.M., DeValeria P.A., Winkelstein J.A., et al. Complement inhibition with soluble complement receptor type 1 in cardiopulmonary bypass. Ann Thorac Surg 1993;55:619-624.[Abstract]
21. Albelda S.M., Smith C.W., Ward P.A. Adhesion molecules and inflammatory injury. FASEB J 1994;8:504-512.[Abstract]
22. Weiss S.J. Tissue destruction by neutrophils. N Engl J Med 1989;320:365-376.[Medline]
23. Tonz M., Mihaljevic T., von Segesser L.K., Fehr J., Schmid E.R., Turina M. Acute lung injury during cardiopulmonary bypass. Are the neutrophils responsible?. Chest 1995;108:1551-1556.[Abstract/Free Full Text]
24. Hashimoto K., Miyamoto H., Suzuki K., et al. Evidence of organ damage after cardiopulmonary bypass. The role of elastase and vasoactive mediators. J Thorac Cardiovasc Surg 1992;104:666-673.[Abstract]
25. Hiyama A., Takeda J., Kotake Y., Morisaki H., Fukushima K. A human urinary protease inhibitor (ulinastatin) inhibits neutrophil extracellular release of elastase during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1997;11:580-584.[Medline]
26. Domenici-Lombardo L., Adembri C., Consalvo M., et al. Evolution of endotoxin induced acute lung injury in the rat. Int J Exp Pathol 1995;76:381-390.[Medline]
27. Eppinger M.J., Deeb G.M., Bolling S.F., Ward P.A. Mediators of ischemia–reperfusion of rat lung. Am J Pathol 1997;150:1773-1784.[Abstract]
28. Braude S., Nolop K.B., Fleming J.S., Krausz T., Taylor K.M., Royston D. Increased pulmonary transvascular protein flux after canine cardiopulmonary bypass. Am Rev Respir Dis 1986;134:867-872.[Medline]
29. Jorens P.G., Van Damme J., De Backer W., et al. Interleukin-8 in the bronchoalveolar lavage fluid from patients with the adult respiratory distress syndrome (ARDS) and patients at risk for ARDS. Cytokine 1992;4:592-597.[Medline]
30. Loick H.M., Wendt M., Rotker J., Theissen J.L. Ventilation with positive end-expiratory airway pressure causes leukocyte retention in human lung. J Appl Physiol 1993;75:301-306.[Abstract/Free Full Text]
31. Turkoz R., Yorukoglu K., Akcay A., et al. The effect of pentoxifylline on the lung during cardiopulmonary bypass. Eur J Cardiothorac Surg 1996;10:339-346.[Abstract]
32. Hachida M., Hanayama N., Okamura T., et al. The role of leukocyte depletion in reducing injury to myocardium and lung during cardiopulmonary bypass. ASAIO J 1995;41:M291-M294.[Medline]
33. Friedman M., Wang S.Y., Sellke F.W., Franklin A., Weintraub R.M., Johnson R.G. Pulmonary injury after total or partial cardiopulmonary bypass with thromboxane synthesis inhibition. Ann Thorac Surg 1995;59:598-603.[Abstract/Free Full Text]
34. Dreyer W.J., Michael L.H., Millman E.E., Berens K.L., Geske R.S. Neutrophil sequestration and pulmonary dysfunction in a canine model of open heart surgery with cardiopulmonary bypass. Evidence for a CD18-dependent mechanism. Circulation 1995;92:2276-2283.[Abstract/Free Full Text]
35. Van Furth R., Cohn Z., Hirsch J. The mononuclear phagocyte system. Bull WHO 1972;46:845-855.[Medline]
36. Warner A.E. Pulmonary intravascular macrophages. Role in acute lung injury. Clin Chest Med 1996;17:125-135.[Medline]
37. Brieland J.K., Flory C.M., Jones M.L., et al. Regulation of monocyte chemoattractant protein-1 gene expression and secretion in rat pulmonary alveolar macrophages by lipopolysaccharide, tumor necrosis factor-, and interleukin-1ß. Am J Respir Cell Mol Biol 1995;12:104-109.[Abstract]
38. Fujiwara T., Seo N., Murayama T., Hirata S., Kawahito K., Kawakami M. Transient rise in serum cytokines during coronary artery bypass graft surgery. Eur Cytokine Netw 1997;8:61-66.[Medline]
39. Barstad R.M., Ovrum E., Ringdal M.A., et al. Induction of monocyte tissue factor procoagulant activity during coronary artery bypass surgery is reduced with heparin-coated extracorporeal circuit. Br J Haematol 1996;94:517-525.[Medline]
40. Kappelmeyer J., Bernabei A., Edmunds L.H., Jr, Edgington T.S., Colman R.W. Tissue factor is expressed on monocytes during simulated extracorporeal circulation. Circ Res 1993;72:1075-1081.[Abstract/Free Full Text]
41. Lahat N., Zlotnick A.Y., Shtiller R., Bar I., Merin G. Serum levels of IL-1, IL-6 and tumour necrosis factor in patients undergoing coronary artery bypass grafts or cholecystectomy. Clin Exp Immunol 1992;89:255-260.[Medline]
42. Menasche P., Haydar S., Peynet J., et al. A potential mechanism of vasodilatation after warm heart surgery. J Thorac Cardiovasc Surg 1994;107:293-299.[Abstract/Free Full Text]
43. Andersen L.W., Landow L., Baek Jansen E., Baker S. Association between gastric intramucosal pH and splanchnic endotoxin, antibody to endotoxin, and tumor necrosis factor-alpha concentrations in patients undergoing cardiopulmonary bypass. Crit Care Med 1993;21:210-217.[Medline]
44. Tsuchida M., Watanabe H., Watanabe T., et al. Effects of cardiopulmonary bypass on cytokine release and adhesion molecule expression in alveolar macrophages. Preliminary report in six cases. Am J Respir Crit Care Med 1997;156:932-938.[Abstract/Free Full Text]
45. Schneider R.C., Zapol W.M., Carvalho A.C. Platelet consumption and sequestration in severe acute respiratory failure. Am Rev Respir Dis 1980;122:445-451.[Medline]
46. Wang D., Chou C.-L., Hsu K., Chen H.I. Cyclooxygenase pathway mediates lung injury induced by phorbol and platelets. J Appl Physiol 1991;70:2417-2421.[Abstract/Free Full Text]
47. Nakano T., Miyamoto K., Aida A., Saito S., Nishimura M., Kawakami Y. Effects of platelet depletion on PMA-induced acute lung injury in awake sheep. Respir Physiol 1995;101:207-217.[Medline]
48. Heffner J.E., Baron D.A. Effects of prostaglandin E₁ on platelet attenuation of oxidant-induced edema in isolated rabbit lungs. J Lab Clin Med 1990;116:797-804.[Medline]
49. Bhujle R., Li J., Shastri P., et al. Influence of cardiopulmonary bypass on platelets and neutrophil accumulations in internal organs. ASAIO J 1997;43:M739-M744.[Medline]
50. Fessatidis I.T., Brannan J.J., Taylor K.M., Kanallaki-Kyparissi M., Abdulla A.K., Olsen E.C. Effect of prostacyclin PGI₂ on cardiopulmonary bypass-induced lung injury. Perfusion 1994;9:23-33.[Abstract/Free Full Text]
51. Tsang G.M.K., Allen S., Pagano D., Wong C., Graham T.R., Bonser R.S. von Willebrand factor and urinary albumin excretion are possible indicators of endothelial dysfunction in cardiopulmonary bypass. Eur J Cardiothor Surg 1998;13:385-391.[Abstract/Free Full Text]
52. Sawa Y., Shimazaki Y., Kadoba K., et al. Attenuation of cardiopulmonary bypass-derived inflammatory reduction reduces myocardial reperfusion injury in cardiac operations. J Thorac Cardiovasc Surg 1996;111:29-35.[Abstract/Free Full Text]
53. Friedman M., Wang S.Y., Sellke F.W., Cohn W.E., Weintraub R.M., Johnson R.G. Neutrophil adhesion blockade with NPC 15669 decreases pulmonary injury after total cardiopulmonary bypass. J Thorac Cardiovasc Surg 1996;111:460-468.[Abstract/Free Full Text]
54. Fullerton D.A., Eisenach J.H., McIntyre R.C., et al. Inhaled nitric oxide prevents lung neutrophil accumulation and pulmonary endothelial dysfunction after mesenteric ischemia–reperfusion injury. Am J Physiol 1996;271:L326-L331.[Abstract/Free Full Text]
55. McIntyre R.C., Moore F.A., Moore E.E., Piedalue F., Haenel J.B., Fullerton D.A. Inhaled nitric oxide variably improves oxygenation and pulmonary hypertension in patients with acute respiratory distress syndrome. J Trauma 1995;39:418-425.[Medline]
56. Gryglewski R.J., Palmer R.M.J., Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 1986;320:454-456.[Medline]
57. Novick R.J., Gehman K.E., Ali I.S., Lee J. Lung preservation. Ann Thorac Surg 1996;62:302-314.[Abstract/Free Full Text]
58. Hill G.E., Snider S., Galbraith T.A., Forst S., Robbins R.A. Glucocorticoid reduction of bronchial epithelial inflammation during cardiopulmonary bypass. Am J Respir Crit Care Med 1995;152:1791-1795.[Abstract]
59. Beghetti M., Silkoff P.E., Caramori M., Holtby H.M., Slutsky A.S., Adatia I. Decreased exhaled nitric oxide may be a marker of cardiopulmonary bypass-induced injury. Ann Thorac Surg 1998;66:532-534.[Abstract/Free Full Text]
60. Seghaye M.C., Duchateau J., Bruniaux J., et al. Endogenous nitric oxide and atrial natriuretic peptide biological activity in infants undergoing cardiac operations. Crit Care Med 1997;25:1063-1070.[Medline]
61. Rich G.F., Murphy G.D., Roos C.M., Johns R.A. Inhaled nitric oxide. Anesthesiology 1993;78:1028-1035.[Medline]
62. Fowler A.A., Hamman R.F., Good J.T., et al. Adult respiratory distress syndrome. Ann Intern Med 1983;98:593-597.
63. Ashbaugh D.G., Bigelow D.B., Petty T.L., Levine B.E. Acute respiratory distress in adults. Lancet 1967;2:319-323.[Medline]
64. Hammerschmidt D.E., Weaver L.J., Hudson L.D., Craddock P.R., Jacob H.S. Association of complement activation and elevated plasma C5a with adult respiratory distress syndrome. Lancet 1980;1:947-949.[Medline]
65. Weiland J.E., Davis W.B., Holter J.F., Mohammed J.R., Dorinsky P.M., Gadek J.E. Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiological significance. Am Rev Respir Dis 1986;133:218-225.[Medline]
66. Lee C.T., Fein A.M., Lippmann M., Holtzman H., Kimbel P., Weinbaum G. Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory distress syndrome. N Engl J Med 1981;304:192-196.[Abstract]
67. Headley A.S., Tolley E., Meduri G.U. Infections and the inflammatory response in acute respiratory distress syndrome. Chest 1997;111:1306-1321.[Abstract/Free Full Text]
68. Goodman R.B., Strieter R.M., Martin D.P. Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome. Am J Respir Crit Care Med 1996;154:602-611.[Abstract]
69. Ikuta N., Taniguchi H., Kondoh Y., Takagi K., Hayakawa T. Sustained high levels of circulatory interleukin-8 associated with a poor outcome in patients with adult respiratory distress syndrome. Intern Med 1996;35:855-860.[Medline]
70. Chabot F., Mitchell J.A., Gutteridge J.M.C., Evans T.W. Reactive oxygen species in acute lung injury. Eur Respir J 1998;11:745-757.[Abstract]
71. Quinlan G.J., Lamb N.J., Tilley R., Evans T.W., Gutteridge J.M.C. Plasma hypoxanthine levels in ARDS. Am J Respir Crit Care Med 1997;155:479-484.[Abstract]
72. Chollet-Martin S., Montravers P., Gibert C., et al. Subpopulation of hyperresponsive polymorphonuclear neutrophils in patients with adult respiratory distress syndrome. Role of cytokine production. Am Rev Respir Dis 1992;146:990-996.[Medline]
73. Fulkerstone W.J., MacIntyre N., Stamler J., Crapo J.D. Pathogenesis and treatment of adult respiratory distress syndrome. Arch Intern Med 1996;156:29-38.[Abstract/Free Full Text]
74. Luce J.M. Acute lung injury and the acute respiratory distress syndrome. Crit Care Med 1998;26:369-376.[Medline]
75. Moore F.A., Moore E.E. Evolving concepts in the pathogenesis of post injury multiple organ failure. Surg Clin North Am 1995;75:257-277.[Medline]
76. Baudouin S.V. Surfactant medication for acute respiratory distress syndrome. Thorax 1997;52(Suppl 3):S9-S15.[Free Full Text]
77. Sinclair D.G., Haslam P.L., Quinlan G.J., Pepper J.R., Evans T.W. The effect of cardiopulmonary bypass on intestinal and pulmonary endothelial permeability. Chest 1995;108:718-724.[Abstract/Free Full Text]
78. Zaccardelli D.S., Pattoshall E.N. Clinical diagnostic criteria of the adult respiratory distress syndrome in the intensive care unit. Crit Care Med 1996;24:247-251.[Medline]
79. Messent M., Sullivan K., Keogh B.F., Morgan C.J., Evans T.W. Adult respiratory distress syndrome following cardiopulmonary bypass. Anaesthesia 1992;47:267-268.[Medline]
80. Christenson J.T., Aeberhard J.M., Badel P., et al. Adult respiratory distress syndrome after cardiac surgery. Cardiovasc Surg 1996;4:15-21.[Medline]
81. Asimakopoulos G., Taylor K.M., Smith P.L.C., Ratnatunga C.P. Prevalence of acute respiratory distress syndrome after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1999;117:620-621.[Free Full Text]
82. Murray J.F., Matthay M.A., Luce J.M., Flick M.R. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 1988;138:720-723.[Medline]
83. Gu Y.J., Mariani M.A., van Oeveren W., Grandjean J.G., Boonstra P.W. Reduction of the inflammatory response in patients undergoing minimally invasive coronary artery bypass grafting. Ann Thorac Surg 1998;65:420-424.[Abstract/Free Full Text]
84. Redmond J.M., Gillinov A.M., Stuart R.S., et al. Heparin-coated bypass circuits reduce pulmonary injury. Ann Thorac Surg 1993;56:474-479.[Abstract]
85. Gu Y.J., deVries A.J., Boonstra P.W., van Oeveren W. Leukocyte depletion results in improved lung function and reduced inflammatory response after cardiac surgery. J Thorac Cardiovasc Surg 1996;112:494-500.[Abstract/Free Full Text]
86. Lefer A.M., Lefer D.J. The role of nitric oxide and cell adhesion molecules on the microcirculation in ischaemia–reperfusion. Cardiovasc Res 1996;32:743-751.[Medline]
87. Gillinov A.M., Redmond J.M., Zehr K.J., et al. Inhibition of neutrophil adhesion during cardiopulmonary bypass. Ann Thorac Surg 1994;57:126-133.[Abstract]

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				V. Casati, P. Della Valle, S. Benussi, A. Franco, C. Gerli, P. Baili, O. Alfieri, and A. D'Angelo Effects of tranexamic acid on postoperative bleeding and related hematochemical variables in coronary surgery: Comparison between on-pump and off-pump techniques J. Thorac. Cardiovasc. Surg., July 1, 2004; 128(1): 83 - 91. [Abstract] [Full Text] [PDF]

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				J. B. Celik, N. Gormus, S. Okesli, Z. I. Gormus, and H. Solak Methylprednisolone prevents inflammatory reaction occurring during cardiopulmonary bypass: effects on TNF-{alpha}, IL-6, IL-8, IL-10 Perfusion, May 1, 2004; 19(3): 185 - 191. [Abstract] [PDF]

				T. Nakano, H. Kado, Y. Shiokawa, K. Fukae, Y. Nishimura, K. Miyamoto, Y. Tanoue, H. Tatewaki, and N. Fusazaki The low resistance strategy for the perioperative management of the Norwood procedure Ann. Thorac. Surg., March 1, 2004; 77(3): 908 - 912. [Abstract] [Full Text] [PDF]

				W. Eichler, M. J. Bechtel, S. Klaus, M. Heringlake, M. Hernandez, K. Toerber, K.-F. Klotz, and C. Bartels Na+/H+exchange inhibitor cariporide: effects on respiratory dysfunction after cardiopulmonary bypass Perfusion, January 1, 2004; 19(1): 33 - 40. [Abstract] [PDF]

				E. D. Moloney, S. E. Mumby, R. Gajdocsi, J. H. Cranshaw, S. A. Kharitonov, G. J. Quinlan, and M. J. Griffiths Exhaled Breath Condensate Detects Markers of Pulmonary Inflammation after Cardiothoracic Surgery Am. J. Respir. Crit. Care Med., January 1, 2004; 169(1): 64 - 69. [Abstract] [Full Text] [PDF]

				N. Eren, O. Cakir, A. Oruc, Z. Kaya, and L. Erdinc Effects of N-acetylcysteine on pulmonary function in patients undergoing coronary artery bypass surgery with cardiopulmonary bypass Perfusion, December 1, 2003; 18(6): 345 - 350. [Abstract] [PDF]

				Z. K. Su, Y. Sun, Y. M. Yang, H. B. Zhang, and Z. W. Xu Lung Function After Deep Hypothermic Cardiopulmonary Bypass in Infants Asian Cardiovasc Thorac Ann, December 1, 2003; 11(4): 328 - 331. [Abstract] [Full Text] [PDF]

				D. L. Ngaage Off-pump coronary artery bypass grafting: the myth, the logic and the science Eur. J. Cardiothorac. Surg., October 1, 2003; 24(4): 557 - 570. [Abstract] [Full Text] [PDF]

				P. Giomarelli, S. Scolletta, E. Borrelli, and B. Biagioli Myocardial and lung injury after cardiopulmonary bypass: role of interleukin (IL)-10 Ann. Thorac. Surg., July 1, 2003; 76(1): 117 - 123. [Abstract] [Full Text] [PDF]

				T. Kovesi, D. Royston, M. Yacoub, and N. Marczin Basal and nitroglycerin-induced exhaled nitric oxide before and after cardiac surgery with cardiopulmonary bypass Br. J. Anaesth., May 1, 2003; 90(5): 608 - 616. [Abstract] [Full Text] [PDF]

				R Fink, M Al-Obaidi, S Grewal, M Winter, and J Pepper Monocyte activation markers during cardiopulmonary bypass Perfusion, March 1, 2003; 18(2): 83 - 86. [Abstract] [PDF]

				W. Eichler, J F M. Bechtel, J. Schumacher, J. A Wermelt, K.-F. Klotz, and C. Bartels A rise of MMP-2 and MMP-9 in bronchoalveolar lavage fluid is associated with acute lung injury after cardiopulmonary bypass in a swine model Perfusion, March 1, 2003; 18(2): 107 - 113. [Abstract] [PDF]

				A. J de Vries, Y J. Gu, W. J Post, P. Vos, I. Stokroos, H. Lip, and W. van Oeveren Leucocyte depletion during cardiac surgery: a comparison of different filtration strategies Perfusion, January 1, 2003; 18(1): 31 - 38. [Abstract] [PDF]

				C. A. Anderson, R. J. Rizzo, and L. H. Cohn Ascending Aortic Aneurysms Card. Surg. Adult, January 1, 2003; 2(2003): 1123 - 1148. [Full Text]

				H.-H Sievers, C. Freund-Kaas, S. Eleftheriadis, T. Fischer, H. Kuppe, E. G. Kraatz, and J.F. M. Bechtel Lung protection during total cardiopulmonary bypass by isolated lung perfusion: preliminary results of a novel perfusion strategy Ann. Thorac. Surg., October 1, 2002; 74(4): 1167 - 1172. [Abstract] [Full Text] [PDF]

				B. Meyns, R. Autschbach, A. Boning, W. Konertz, K. Matschke, F. Schondube, K. Wiebe, and E. Fischer Coronary artery bypass grafting supported with intracardiac microaxial pumps versus normothermic cardiopulmonary bypass: a prospective randomized trial Eur. J. Cardiothorac. Surg., July 1, 2002; 22(1): 112 - 117. [Abstract] [Full Text] [PDF]

				X. M. Mueller, D. Jegger, M. Augstburger, J. Horisberger, G. Godar, and L. K. von Segesser A new concept of integrated cardiopulmonary bypass circuit Eur. J. Cardiothorac. Surg., May 1, 2002; 21(5): 840 - 846. [Abstract] [Full Text] [PDF]

				A. Pereszlenyi, G. Lang, H. Steltzer, H. Hetz, A. Kocher, P. Neuhauser, W. Wisser, and W. Klepetko Bilateral lung transplantation with intra- and postoperatively prolonged ECMO support in patients with pulmonary hypertension Eur. J. Cardiothorac. Surg., May 1, 2002; 21(5): 858 - 863. [Abstract] [Full Text] [PDF]

				C. S.H. Ng, S. Wan, A. P.C. Yim, and A. A. Arifi Pulmonary Dysfunction After Cardiac Surgery* Chest, April 1, 2002; 121(4): 1269 - 1277. [Abstract] [Full Text] [PDF]

				A. J. Alcaraz, L. Sancho, L. Manzano, F. Esquivel, A. Carrillo, A. Prieto, E. D. Bernstein, and M. Alvarez-Mon Newborn patients exhibit an unusual pattern of interleukin 10 and interferon {gamma} serum levels in response to cardiac surgery J. Thorac. Cardiovasc. Surg., March 1, 2002; 123(3): 451 - 458. [Abstract] [Full Text] [PDF]

				M. A. Chaney Corticosteroids and Cardiopulmonary Bypass : A Review of Clinical Investigations Chest, March 1, 2002; 121(3): 921 - 931. [Abstract] [Full Text] [PDF]

				J. C. Cleveland Jr, A. L. W. Shroyer, A. Y. Chen, E. Peterson, and F. L. Grover Off-pump coronary artery bypass grafting decreases risk-adjusted mortality and morbidity Ann. Thorac. Surg., October 1, 2001; 72(4): 1282 - 1289. [Abstract] [Full Text] [PDF]

				G. B. Luciani, T. Menon, B. Vecchi, S. Auriemma, and A. Mazzucco Modified Ultrafiltration Reduces Morbidity After Adult Cardiac Operations: A Prospective, Randomized Clinical Trial Circulation, September 18, 2001; 104 (2009): I-253 - I-259. [Abstract] [Full Text] [PDF]

				G. Asimakopoulos Systemic inflammation and cardiac surgery: an update Perfusion, September 1, 2001; 16(5): 353 - 360. [Abstract] [PDF]

				G. Asimakopoulos, E. A. Lidington, J. Mason, D. O. Haskard, K. M. Taylor, and R. C. Landis Effect of aprotinin on endothelial cell activation J. Thorac. Cardiovasc. Surg., July 1, 2001; 122(1): 123 - 128. [Abstract] [Full Text] [PDF]

				I. Schulze-Neick, J. Li, D. J. Penny, and A. N. Redington Pulmonary vascular resistance after cardiopulmonary bypass in infants: Effect on postoperative recovery J. Thorac. Cardiovasc. Surg., June 1, 2001; 121(6): 1033 - 1039. [Abstract] [Full Text] [PDF]

				W. G. Kim, B.-H. Lee, and J. W. Seo Light and electron microscopic analyses for ischaemia-reperfusion lung injury in an ovine cardiopulmonary bypass model Perfusion, May 1, 2001; 16(3): 207 - 214. [Abstract] [PDF]

				J. A. Burns, T. B. Issekutz, H. Yagita, and A. C. Issekutz The {beta}2, {{alpha}}4, {{alpha}}5 Integrins and Selectins Mediate Chemotactic Factor and Endotoxin-Enhanced Neutrophil Sequestration in the Lung Am. J. Pathol., May 1, 2001; 158(5): 1809 - 1819. [Abstract] [Full Text] [PDF]

				K. D. Chinsky Critical Interactions : Man and Machine Chest, April 1, 2001; 119(4): 996 - 997. [Full Text] [PDF]

				M. A. Chaney, R. A. Durazo-Arvizu, M. P. Nikolov, B. P. Blakeman, and M. Bakhos Methylprednisolone does not benefit patients undergoing coronary artery bypass grafting and early tracheal extubation J. Thorac. Cardiovasc. Surg., March 1, 2001; 121(3): 561 - 569. [Abstract] [Full Text] [PDF]

				V. R. Conti Pulmonary Injury After Cardiopulmonary Bypass Chest, January 1, 2001; 119(1): 2 - 4. [Full Text] [PDF]

				D. P. Taggart Effects of a platelet-activating factor antagonist on lung injury and ventilation after cardiac operation Ann. Thorac. Surg., January 1, 2001; 71(1): 238 - 242. [Abstract] [Full Text] [PDF]

				A. Rahman, B. Ustunda, O. Burma, I. H. Ozercan, A. Cekirdekci, and M. K. Bayar Does aprotinin reduce lung reperfusion damage after cardiopulmonary bypass? Eur. J. Cardiothorac. Surg., November 1, 2000; 18(5): 583 - 588. [Abstract] [Full Text] [PDF]

				G. Asimakopoulos, A. Kohn, D. C. Stefanou, D. O. Haskard, R. C. Landis, and K. M. Taylor Leukocyte integrin expression in patients undergoing cardiopulmonary bypass Ann. Thorac. Surg., April 1, 2000; 69(4): 1192 - 1197. [Abstract] [Full Text] [PDF]

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