Ventilation during cardiopulmonary bypass: impact on neutrophil activation and pulmonary sequestration.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with neutrophil activation, pulmonary sequestration, and release of inflammatory mediators leading to pulmonary dysfunction. We investigate the effect of continuous ventilation during cardiopulmonary bypass on neutrophil activation and pulmonary sequestration. METHODS: Forty-six patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were prospectively randomized to continuous ventilation and nonventilation groups. Blood samples were collected, and bronchoalveolar lavage (BAL) was performed following induction of anesthesia and at 4 hr after aortic declamping. Differential white cell count was measured, and flow cytometry to determine cell count numbers and quantify CD45 and CD11b leukocyte cell surface adhesion molecule expression was performed on the blood and BAL samples. RESULTS: Twenty-three patients were randomized to standard nonventilated CPB and 23 patients to ventilation throughout CPB. Significant increases in blood and BAL neutrophil numbers were detected at 4 hr following aortic declamping in both groups (Blood: NV p < .0001, V p < .0001; BAL: NV p = .017, V p = .0007). No significant inter-group differences in BAL and blood neutrophil numbers were found. Significantly higher blood neutrophil CD11b mean fluorescent intensity levels were present 4 hr following declamping compared with baseline in both groups (NV Blood, p = .021; V Blood p < .0001). No significant inter- or intragroup differences in BAL neutrophil CD11b mean fluorescent intensity levels were found. There was no death or major complication. CONCLUSIONS: Cardiopulmonary bypass during coronary artery bypass grafting is associated with increased neutrophil pulmonary sequestration, and blood neutrophil CD11b activation. Continuous ventilation during cardiopulmonary bypass does not significantly reduce neutrophil pulmonary sequestration or activation.

The importance of aprotinin and pentoxifylline in preventing leukocyte sequestration and lung injury caused by protamine at the end of cardiopulmonary bypass surgery.

BACKGROUND: Protamine has adverse effects on pulmonary gas exchange during the postoperative period. The objective of this study was to investigate the importance of aprotinin and pentoxifylline in preventing the leukocyte sequestration and lung injury caused by protamine administered after the termination of cardiopulmonary bypass (CPB). METHODS: Participants (n = 39) were allocated into three groups at the termination of CPB: Group 1, (control group, n = 16); Group 2 (aprotinin group, n = 12), who received protamine + aprotinin (15,000 IU/kg); and Group 3 (Pentoxifylline group, n = 11), who received protamine + pentoxifylline (10 mg/kg). Leukocyte counts in pulmonary and radial arteries were determined after the termination of CPB and before any drug was given (t1), and 5 minutes (t2), 2 hours (t3), 6 hours (t4) and 12 hours (t5) after the administration of protamine. Alveolar-arterial O2 gradient (A-aO2) and dynamic pulmonary compliance were measured at t1, t2 and t3. RESULTS: In the control group, an increase in pulmonary leukocyte sequestration was observed 5 minutes and 2 hours after protamine administration, after which this difference disappeared. No significant degree of pulmonary sequestration was detected in any measurements after protamine was administered in the aprotinin and pentoxifylline (PTX) groups. Dynamic lung compliance was 50.1, 45.2 and 47.2 ml/cm H2O in the control group, 49.2, 61.1 and 56.3 ml/cm H2O in the aprotinin group, and 49.5, 54.5 and 50.4 ml/cm H2O in the PTX group. The A-aO2 gradient was 212.2, 263.3 and 254.3 mm Hg in the control group, 209.4, 257.1 and 217.3 mm Hg in the aprotinin group, and 211.3, 260.8 and 219.2 mm Hg in the PTX group. CONCLUSION: Aprotinin and PTX treatments have favourable effects on lung function by reducing protamine-induced leukocyte sequestration into lungs at the end of CPB.

Effects of hyperbaric oxygen treatment on neutrophil activation and pulmonary sequestration in intestinal ischemia-reperfusion in rats.

Treatment with hyperbaric oxygen (HBO) has shown promising results in some models of ischemia, the major effect being a reduction in the local ischemic damage. The present study investigated the effects of HBO treatment on neutrophil activation and leukosequestration during reperfusion following intestinal ischemia in a rat model. The superior mesenteric artery was clamped for 2 h and subsequently reperfused for 90 min. One group of male Sprague-Dawley rats (n = 9) was given HBO and another group (n = 9) served as controls. Prior to ischemia, leukocytes and erythrocytes were separated, radiolabelled with 111ln and 51Cr, respectively, and reinfused. Leukocyte transit factor, the ratio between the mean passage time of leukocytes and erythrocytes was used to quantitate leukosequestration and the fraction of circulating, spontaneously nitroblue tetrazolium (NBT)-reducing neutrophils was used to measure the degree of neutrophil preactivation. HBO treatment reduced the level of leukocyte pooling significantly, especially in the lungs but also, to a minor degree, in the systemic vascular bed. The percentage of NBT-positive cells increased in all animals after reperfusion, but the increase was significantly reduced by HBO treatment. In conclusion, HBO treatment reduces leukosequestration and neutrophil preactivation following intestinal ischemia-reperfusion.

Attenuation of pulmonary leukocyte sequestration during extracorporeal circulation by a new c-AMP phosphodiesterase inhibitor.

Activated leukocytes may have an important role in developing complement-related lung injury, with pulmonary leukocyte sequestration in the presence of blood-material interaction in cardiopulmonary bypass and hemodialysis. The authors evaluated the effects of a new cAMP phosphodiesterase inhibitor (DN-9693) on leukocyte aggregation in vitro, utilizing canine heparinized blood and pulmonary leukocyte sequestration during extracorporeal circulation (ECC) in dogs. On in vitro evaluation, DN-9693 inhibited the leukocyte aggregation response to leukotriene B4 in a dose response manner; the aggregation response elicited by contact with a membrane lung was inhibited by a 50% inhibition dose of approximately 0.2 mumol/L. Leukocyte kinetics were assessed in a venovenous bypass system with a silicone hollow fiber membrane lung. The control group (n = 6) without DN-9693 developed a reduction in the arterial leukocyte count of 55 +/- 17% at 2 minutes of ECC. The transpulmonary difference in leukocyte count (pulmonary artery count minus systemic artery count) was significantly increased (P less than 0.05) from -175 +/- 206/microliters at baseline to 1225 +/- 330/microliters after 2 minutes of ECC. In the DN-group (n = 4, DN-9693; 60-80 micrograms/kg/min), there was no significant reduction in the arterial leukocyte count during ECC, and the transpulmonary difference showed no significant increases (75 +/- 386/microliters; baseline, versus 125 +/- 263/microliters; 2 minutes of ECC). These results suggest that DN-9693 inhibits the aggregation of leukocytes in the presence of blood-material interaction in vitro, and also prevents pulmonary leukocyte sequestration induced by ECC, with attenuation of systemic leukocyte depletion.