CARDIOPULMONARY BYPASS PRIMES POLYMORPHONUCLEAR LEUKOCYTES

Polymorphonuclear leukocyte (PMN) superoxide (. O-2(-)) production has been implicated in the pathogenesis of cardiopulmonary bypass (CPB)-r elated end organ injury. PMN ''priming'' has been described as an even t which enhances the release of . O-2(-) following a second, activatin g insult. We hypothesized that PMN priming occurs during CBP and is te mporally related to the plasma level of complement (C3a), interleukin (IL)-6, and IL-8. PMNs were isolated from 10 CPB patients pre-bypass ( preCPB), 5 min after protamine administration (PROT), and at 6 and 24 h post-CPB. PMN . O-2(-) production was measured by a cytochrome c red uction assay in the presence or absence of either phorbol 12-myristate -13-acetate (PMA, 0.4 mu g/ml) or N-formyl-methionyl-leucyl-phenylalan ine (FMLP, 1 mu M) and also after priming with 2000 nM platelet-activa ting factor (PAF) followed by activation with either PMA or FMLP. Plas ma levels of C3a, IL-6, and IL-8 were determined by enzyme-linked immu nosorbent assay. PMA-activated PMN . O-2(-) production was significant ly elevated at 6 h post-CPB compared to preCPB levels (11.04 +/- 0.9 v s 7.62 +/- 0.57, P = 0.009), indicating that CPB is associated with in vivo PMN priming. When PMNs were primed in vitro with PAF and then ac tivated with PMA or FMLP, O-2(-) release at 6 h post-CPB was also sign ificantly greater than pre-CPB levels (16.04 +/- 0.74 vs 12.2 +/- 0.92 , P = 0.038; and 17.33 +/- 1.38 vs 13.33 +/- 1.35, P < 0.05), indicati ng that CPB acts synergistically with PAF to prime PMNs. Levels of C3a rose significantly over pre-CPB levels at PROT (P = 0.001), and IL-6 and IL-8 rose over pre-CPB levels at 6 h post-CPB (P = 0.01 and P = 0. 006, respectively). These findings demonstrate that CPB not only direc tly primes PMNs, but also potentiates priming of PMNs by PAF. This ''p rimed'' PMN state, which coincided with the increased plasma levels of inflammatory mediators, may suggest a mechanism of predisposition to organ dysfunction following CPB. (C) 1998 Academic Press.