Cardiopulmonary bypass (CPB) precipitates inflammation that causes marked pulmonary dysfunction. Leukocyte filtration has been proposed to reduce these deleterious effects. Other studies show an improvement with aprotinin. We proposed that a combination of these two therapies would synergistically improve pulmonary outcomes. Two hundred and twenty-five patients participated in a randomized prospective study comparing pulmonary microvascular function and pulmonary shunt fraction postcoronary artery bypass grafting (CABG). The study group underwent leukocyte depletion with aprotinin during the procedure. Pulmonary microvascular function was assessed by pulmonary microvascular pressure (PMVP), a measure of pulmonary capillary edema, and pulmonary function was evaluated by comparing pulmonary shunt fractions. Elevated PMVP and increased pulmonary shunting compromise pulmonary performance. The leukocyte-depleted group had significantly reduced PMVP and pulmonary shunt fraction for at least the first 24 hours postbypass. The combination of strategic leukocyte filtration and aprotinin therapy can effectively reduce postoperative decline in pulmonary function. Cardiopulmonary bypass precipitates a variety of inflammatory effects that can cause marked pulmonary dysfunction to the point of respiratory failure, necessitating prolonged mechanical ventilation. Leukocyte filtration has been investigated previously and appears to be beneficial in improving pulmonary outcome by preventing direct neutrophil-induced inflammatory injury. Recent studies of leukocyte reduction profiles suggest that leukoreduction via leukofiltration is short lived with filter saturation occurring 30-45 minutes after onset of filtration. This phenomenon may explain the limited utility observed with higher risk patients. These patients typically require longer pump runs, so leukocyte reduction capability is suboptimal at the time of pulmonary vascular reperfusion. To more effectively protect the lung from reperfusion injury, leukocyte filtration can be delayed so that reduction of activated neutrophils is maximal at the time of pulmonary vascular reperfusion. It is, thus, conceivable that a timely use of arterial line leukoreducing filters may improve, more substantially, pulmonary function postbypass. Two hundred and twenty-five isolated coronary revascularization patients participated in this prospective, randomized trial. The patients received moderately hypothermic CBP alone (control group: n = 110) or combined with leukocyte depletion, initiated 30 minutes before crossclamp release, with filters placed in the bypass circuit (study group: n = 115). All patients also received full Hammersmith aprotinin dosing during the operation. Pulmonary microvascular pressures were lower in the study group at three hours postbypass, and continued to fall until 24 hours postbypass. In contrast, the control group measured a rise in PMVP and a continued plateau throughout 24 hours postbypass (p < 0.028). The calculated pulmonary shunt fraction also was reduced sign...

This novel intraoperative treatment strategy of both mechanical (leukocyte filtration) and pharmacological (aprotinin) intervention appears to markedly reduce the incidence of postcardiopulmonary bypass atrial fibrillation. To our knowledge, this is the first study to combine these two treatment strategies. A previous study has noted a decline in atrial fibrillation with aprotinin in the animal model, but not to the extent observed in our study. The beneficial effects of the reduction of atrial fibrillation include reduced risk of emboli formation and the incidence of ischemia in the heart, lung and brain. In addition, a decrease in length of hospital stay, recovery time and overall cost occurred.

Cardiopulmonary bypass activates an array of cellular and humoral inflammatory mechanisms that culminate in diverse or organ-specific injury. A manifestation of inflammatory injury to the heart, atrial fibrillation ranks among the most frequent and potentially life-threatening postsurgical complications. Pulmonary manifestations of the inflammatory response are also of major concern. Neutrophils activated by passage through the extracorporeal circuit inflict local injury and provoke the inflammatory cascade by producing oxyradicals and proinflammatory factors. This study tested if a combination of leukocyte depletion and aprotinin suppression of neutrophils could minimize postbypass atrial fibrillation and pulmonary dysfunction. In part one, two randomized groups of 90 patients undergoing primary coronary artery bypass grafting received full Hammersmith aprotinin alone (control group) or combined with leukofiltration (study group) and were prospectively examined. The dual treatment decreased the incidence of postoperative atrial fibrillation (7 of 90, 7.8%) by 67% versus aprotinin alone (21 of 90, 23.3%). Respiratory gas exchange in these patients was assessed from pulmonary shunt fraction. In the first two hours postbypass, pulmonary shunt fraction in the dual treatment group increased 40% less than in the group receiving aprotinin alone (p = 0.002), and subsided more quickly and completely over the next six hours. In part two, the cardiopulmonary bypass group receiving aprotinin + leukofiltration was retrospectively compared with 45 patients undergoing off-pump coronary revascularization. A strong, albeit not statistically significant trend (p = 0.08) toward a lower incidence of atrial fibrillation was found in the dual treatment group versus the off-pump group (8 of 45, 17.8%). These findings suggest that combining mechanical and pharmacologic suppression of the systemic inflammatory response could mitigate its deleterious arrhythmic and pulmonary complications.

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