Multiple sequential insults cause post-pump syndrome

Background. We hypothesize that post-pump syndrome (PPS) following cardiopulmonary bypass (CPB) can be caused by multiple minor insults and that the mechanism of PPS is a priming and subsequent activation of polymorphonuclear (PMN) leukocytes. In this study extensive pathophysiologic and morphometric assessment was undertaken in a porcine model of sequential insult PPS. Methods. Pigs were anesthetized, placed on a ventilator, instrumented for measurements of hemodynamic function, and separated into five groups: (1) Control (n = 4)—surgery only, (2) CPB (n = 4)—placed on femoral-femoral hypothermic (28°C) bypass for 1 h, (3) LPS (n = 6)—underwent sham CPB followed by infusion of low dose endotoxin [E. colilipopolysaccharide (LPS-1 μg/kg)], (4) Heparin + protamine + LPS (HP + LPS, n = 4)—were heparinized without CPB for 1 h, following which protamine and LPS were infused and (5) CPB + LPS (n = 8)—subjected to both CPB and LPS. Results. Only CPB + LPS resulted in acute respiratory distress typical of PPS as indicated by a significant decrease in PaO2 and increase in intrapulmonary shunt fraction (p< 0.05). CPB + LPS significantly increased tissue density and the number of sequestered monocytes and PMNs (p< 0.05) above all other groups. Alveolar macrophages (AM) increased equally in all groups receiving LPS. Conclusions. CPB primes the inflammatory system causing pulmonary PMN sequestration without lung injury. Exposure to an otherwise benign dose of endotoxin results in activation of the sequestered PMNs causing PPS. This study confirms that PPS can be caused by multiple minor insults.Key words: Cardiopulmonary bypass, ARDS, endotoxin, sepsis, post-pump syndrome