Multiple sequential insults cause post-pump syndrome

Picone, Anthony; Lutz, Charles J.; Finck, Christine; Carney, David E.; Gatto, Louis A.; Paskanik, Andrew M.; Searles, Bruce; Snyder, Kathy; Nieman, Gary F.

doi:10.1016/s0003-4975(99)00093-4

Cited by 60 publications

(63 citation statements)

References 27 publications

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“…4,5 These findings support the theory that accepts the mechanism of postpump syndrome as a neutrophil-mediated destruction of the alveolar-capillary interface. In our model, CPB primes neutrophils, causing them to sequester in the lung, and subsequent exposure to low-dose LPS activates these primed neutrophils, causing degranulation and the release of oxygen radical species, serine proteases, and MMPs.…”

Section: Discussionsupporting

confidence: 72%

“…5 A short period of CPB alone is rather innocuous, but when it is combined with a subsequent, seemingly benign insult (ie, transient hypoxia, ischemia, endotoxemia), the result is an overwhelming inflammatory response leading to endothelial injury, pulmonary edema, and ARDS. It has been well documented that the lung injury in both ARDS 6,7 and specifically postpump syndrome [7][8][9] is neutrophil-mediated.…”

Section: See P 333mentioning

confidence: 99%

“…Our previous investigations support this concept, because we have shown an association between pulmonary neutrophil sequestration and physiological lung injury. 5 Thus, postpump syndrome provides an excellent model of ARDS, since it allows us to investigate the sequence of pathophysiological changes because the timing of the priming and activating stimuli are known.…”

Section: See P 333mentioning

confidence: 99%

“…5 Briefly, healthy Yorkshire hybrid pigs (15 to 20 kg) were anesthetized with sodium pentobarbital (50 mg/mL IV bolus, then 6 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 ) and bolus infusion of pancuronium bromide. Instrumentation included a tracheostomy and intravascular catheters to monitor both systemic and pulmonary arterial and venous pressures.…”

Section: Surgical Preparationmentioning

confidence: 99%

“…5 Briefly, with verification of adequate anticoagulation (activated clotting time Ͼ480 seconds), femoral cannulas were placed. The pump priming solution consisted of lactated Ringer's solution (1500 mL), mannitol (5 g), sodium bicarbonate (35 mEq), and porcine lung heparin (300 U/kg).…”

Section: Cardiopulmonary Bypassmentioning

confidence: 99%

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Matrix Metalloproteinase Inhibitor Prevents Acute Lung Injury After Cardiopulmonary Bypass

Carney¹,

Lutz²,

Picone³

et al. 1999

Circulation

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120

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Background-Acute lung injury (ALI) after cardiopulmonary bypass (CPB) results from sequential priming and activation of neutrophils. Activated neutrophils release neutral serine, elastase, and matrix metalloproteinases (MMPs) and oxygen radical species, which damage alveolar-capillary basement membranes and the extracellular matrix, resulting in an ALI clinically defined as adult respiratory distress syndrome (ARDS). We hypothesized that treatment with a potent MMP and elastase inhibitor, a chemically modified tetracycline (CMT-3), would prevent ALI in our sequential insult model of ALI after CPB. Methods and Results-Anesthetized Yorkshire pigs were randomized to 1 of 5 groups: control (nϭ3); CPB (nϭ5), femoral-femoral hypothermic bypass for 1 hour; LPS (nϭ7), sham bypass followed by infusion of low-dose Escherichia coli lipopolysaccharide (LPS; 1 g/kg); CPBϩLPS (nϭ6), both insults; and CPBϩLPSϩCMT-3 (nϭ5), both insults plus intravenous CMT-3 dosed to obtain a 25-mol/L blood concentration. CPBϩLPS caused severe lung injury, as demonstrated by a significant fall in PaO 2 and an increase in intrapulmonary shunt compared with all groups (PϽ0.05). These changes were associated with significant pulmonary infiltration of neutrophils and an increase in elastase and MMP-9 activity. Conclusions-All pathological changes typical of ALI after CPB were prevented by CMT-3. Prevention of lung dysfunction followed an attenuation of both elastase and MMP-2 activity. This study suggests that strategies to combat ARDS should target terminal neutrophil effectors. (Circulation. 1999;100:400-406.)

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Section: Discussionsupporting

confidence: 72%

Section: See P 333mentioning

confidence: 99%

Section: See P 333mentioning

confidence: 99%

Section: Surgical Preparationmentioning

confidence: 99%

Section: Cardiopulmonary Bypassmentioning

confidence: 99%

See 3 more Smart Citations

Matrix Metalloproteinase Inhibitor Prevents Acute Lung Injury After Cardiopulmonary Bypass

Carney¹,

Lutz²,

Picone³

et al. 1999

Circulation

Self Cite

120

View full text Add to dashboard Cite

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Preoperative prediction of postoperative edema and effusion in pediatric cardiac surgery by altered antigen expression patterns on granulocytes and monocytes

et al. 2001

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Postoperative edema and effusion (POEE) following cardiopulmonary bypass (CPB) surgery in children retards recovery and may aggravate postpericardiotomy (PPS), capillary leak syndrome (CLS), or multiorgan failure (MOF). Compared with complication-free children, POEE affected children have different preoperative serum levels of circulating cytokines and adhesion molecules. These levels may be used preoperatively to assess POEE, but their determination is time consuming, costly, and a substantial blood volume is required. Altered serum levels of cytokines and adhesion molecules also may be reflected in altered antigen expression on circulating blood leukocytes. The predictive potential of flow cytometric (FCM) leukocyte immunophenotyping was explored as a sensitive and fast method that required small blood samples. Blood samples taken 24 h preoperatively from 49 patients (3-18 years old) were stained with monoclonal antibodies for adhesion molecules (ICAM-1, LFA-1, Mac-1) or constitutive/activation markers (CD4, CD14, CD16, CD25, CD54, CD69, HLA-DR) and measured on a microbead calibrated FCM. Neutrophils, monocytes, and eosinophils from POEE patients express higher preoperative levels of LFA-1, monocytes, HLA-DR, and other activation markers (all P < 0.03). Over 89% of the patients were classified correctly by using two discriminant analysis methods (sensitivity, >76%; specificity, >86%; positive prediction, >80%; negative prediction, >83%). Granulocytes and monocytes of postoperative POEE patients exhibit significant preoperative immune activation, suggesting an increased risk for patients with atopic/allergic predisposition. Surgical trauma and CPB cause additional immune activation, leading to POEE by a summative response. Most patients at risk for POEE can be identified preoperatively by using data pattern analysis on FCM-derived parameters. Cytometry (Comm. Clin. Cytometry) 46:247-253, 2001.

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