Cardiopulmonary Bypass (CPB) and endotoxin synergistically induce the Adult Respiratory Distress Syndrome (ARDS)

PURPOSE: It is well established that CPB causes the sequestration of neutrophils in the lung and other organs, and that cellular damage does not occur until these 'primed' neutrophils are activated. We hypothesized that a second stimulus (endotoxin) would activate the 'primed' neutrophils resulting in ARDS. METHODS: Certified healthy pigs were anesthetized, placed on a ventilator and instrumented for measurements of pulmonary and systemic hemodynamics, peak airway pressure (Pap, mmHg), blood chemistry [gases (torr), αTNF], and lung function. Ventilatory Efficiency Index (VEI) and pulmonary shunt (Qs/Qt, %) were calculated. Following baseline measurements animals were separated into three groups: CPB Only (Gp I, n=4)-placed on femoral-femoral bypass for 1 hr during which time they were oxygenated (membrane), cooled (28-30°C), and re-warmed. CPB was followed by sham endotoxin infusion; Endotoxin Only (Gp II, n=5)-underwent sham CPB followed by endotoxin [E. coli lipopolysaccharide (LPS) 1μg/kg] infusion; and CPB+Endotarin (Gp III, n=6)-subjected to both CPB and LPS. Animals were euthanized 3 hours following LPS or sham LPS. Pulmonary edema, bronchoalveolar lavage (white cell differential, αTNF and protein content) and pulmonary histology supported the findings presented below. RESULTS: CPB or LPS alone caused little changes in lung function whereas CFB+LPS resulted in severe lung injury. The parameter values at the end of the study were as follows: (Data are mean±SEM) Pap PO₂ Qs/Qt VEI GpI 11±0.5 253±4 3±0.2 0.91±0.10 GpII 11±1.0 194±12 9±1.3 0.93±0.07 GpIII 15±1.3* 125±37† 22±6.5† 0.37±0.07* *=P<0.05 vs Gps I&II; †=p<0.05 vs GpI. CONCLUSIONS: These findings suggest that CPB 'primes' the inflammatory system such that subsequent exposure to an otherwise benign dose of endotoxin results in ARDS. CLINICAL IMPLICATIONS: Following CPB the patient is highly susceptible to the development of ARDS if exposed to a secondary challenge that, by itself, would not be of clinical significance.