Inhibition of neutrophil activity improves cardiac function after cardiopulmonary bypass

Abstract

Background: The arterial in line application of the leukocyte inhibition module (LIM) in the cardiopulmonary bypass (CPB) limits overshooting leukocyte activity during cardiac surgery. We studied in a porcine model whether LIM may have beneficial effects on cardiac function after CPB.

Methods: German landrace pigs underwent CPB (60 min myocardial ischemia; 30 min reperfusion) without (group I; n = 6) or with LIM (group II; n = 6). The cardiac indices (CI) and cardiac function were analyzed pre and post CPB with a Swan-Ganz catheter and the cardiac function analyzer. Neutrophil labeling with technetium, scintigraphy, and histological analyses were done to track activated neutrophils within the organs.

Results: LIM prevented CPB-associated increase of neutrophil counts in peripheral blood. In group I, the CI significantly declined post CPB (post: 3.26 +/- 0.31; pre: 4.05 +/- 0.45 l/min/m2; p < 0.01). In group II, the CI was only slightly reduced (post: 3.86 +/- 0.49; pre 4.21 +/- 1.32 l/min/m2; p = 0.23). Post CPB, the intergroup difference showed significantly higher CI values in the LIM group (p < 0.05) which was in conjunction with higher pre-load independent endsystolic pressure volume relationship (ESPVR) values (group I: 1.57 +/- 0.18; group II: 1.93 +/- 0.16; p < 0.001). Moreover, the systemic vascular resistance and pulmonary vascular resistance were lower in the LIM group. LIM appeared to accelerate the sequestration of hyperactivated neutrophils in the spleen and to reduce neutrophil infiltration of heart and lung.

Conclusion: Our data provides strong evidence that LIM improves perioperative hemodynamics and cardiac function after CPB by limiting neutrophil activity and inducing accelerated sequestration of neutrophils in the spleen.

Figure 1

Boxplot depiction of Cardiac index values obtained for the control group and for the LIM group, pre- and postoperatively. In the control group but not in the LIM group, the difference between pre- and post CPB values was statistically significant (p < 0.01). The post-CPB intergroup difference was also statistically significant (p < 0.05).

Figure 2

Boxplot depiction of pre-load independent (A) end systolic pressure volume relationship (ESPVR) and (B) end diastolic pressure volume relationship (EDPVR) obtained for the control group and for the LIM group, pre- and postoperatively. In the control group but not in the LIM group, the differences between pre- and post CPB values for ESPVR and EDPVR were statistically significant (p < 0.001). The post-CPB intergroup differences were also statistically significant (p < 0.01).

Figure 3

Boxplot depiction of hemodynamic parameters (A) systemic vascular resistance index (SVRi) and (B) pulmonary vascular resistance index (PVRi) obtained for the control group and for the LIM group, pre- and postoperatively. Post CPB intergroup differences for PVRi but not for SVRi were statistically significant (p < 0.01).

Figure 4

Chloroacetate esterase staining of heart and lung paraffin sections. Representative tissue samples for untreated healthy animals, animals undergoing CPB, and animals undergoing CPB with LIM. Magnification is 200-fold.

Figure 5

Electron microscopic microphotographs of accumulated neutrophils within the epicardium (A) and within the left ventricular heart muscle (B) after CPB.

Figure 6

Whole body scintigraphy pictures from an animal without LIM or with LIM following injection of HMPAO-labeled neutrophils (A). High radioactivity was found in the spleen of LIM-treated animals. An internal control with subcutanously injected E.coli (control pig with CPB) confirmed the neutrophil activity over time (B). Data for the accumulation of radioactivity in the myocardium and musle tissue of control and LIM-treated animals is shown (C) as mean ± SD (CPB: n = 7; CPB + LIM: n = 8).