Granulocytes in bronchial lavage fluid after major vascular surgery

Increased numbers of polymorphonuclear granulocytes (PMN) in the airways, as measured by PMN content in bronchial lavage fluid (P less than 0.01), were found 3 h postoperatively in ten patients undergoing surgery for lumbar aortic aneurysms. An increase in plasma levels of the complement split product C3dg from 6 (0-19) AU/ml preoperatively to 20 (13-50) AU/ml 3 h after surgery (P less than 0.01), indicates an activation of the complement cascade. These changes were not accompanied by increased elastase activity in the bronchial lavage fluid or by major changes in pulmonary blood gas exchange or vascular resistance, indicating that massive PMN activation, analogous to that proposed in adult respiratory distress syndrome (ARDS) had not taken place. In conclusion, complement system activation and migration of PMN into the airways, as seen in connection with major vascular surgery, does not seem to contribute to ARDS-type pulmonary dysfunction.     

Complement activation following multiple injuries

Complement activation was evaluated by assay of plasma C3dg and the terminal complement complex (TCC) in 19 patients with multiple injuries. In the nine patients with thoracic involvement, statistically significant increase of plasma TCC was found at first sampling (average 90 min post-trauma), and of C3dg after 24 hours. Such increase was not found in the ten patients without thoracic involvement. Heightened granulocyte elastase activity was found in bronchial lavage fluid 90 min after the trauma in three patients with thoracic injury. Pulmonary insufficiency (pO2/FiO2 less than 16 kPa on intermittent positive-pressure ventilation) arose in four patients. All four had raised plasma levels of TCC or C3dg on arrival at the hospital. Six patients with complement activation did not show pulmonary insufficiency. Although the series was relatively small, the results indicate that thoracic injury is particularly associated with complement activation, and that complement activation alone does not suffice to produce post-traumatic pulmonary insufficiency.     

Pulmonary hypertension and polymorphonuclear leukocyte elastase after esophageal cancer operations

To evaluate the role of polymorphonuclear leukocyte (PMN) elastase in pulmonary impairment occurring after operation for esophageal cancer, 10 patients were randomized preoperatively into two equal groups. One group received a placebo infusion and the other, an infusion of the PMN elastase inhibitor ulinastatin. In the placebo group, the mean plasma PMN elastase level increased from 154 +/- 23 micrograms/L preoperatively to 449 +/- 56 micrograms/L at 6 hours postoperatively (p less than 0.01), whereas the mean plasma fibronectin concentration decreased from 490 +/- 70 micrograms/mL preoperatively to 265 +/- 81 micrograms/L on postoperative day 2 (p less than 0.01). The mean pulmonary vascular resistance increased markedly from 151 +/- 24 dynes.s.cm-5.m-2 preoperatively to 284 +/- 76 dynes.s.cm-5.m-2 at 6 hours postoperatively (p less than 0.01). In the group given ulinastatin, 150,000 units every 12 hours from the start of the operation, the mean PMN elastase value at 6 hours postoperatively was lower (275 +/- 66 micrograms/L; p less than 0.01) and the fibronectin level on postoperative days 1 and 2, higher (p less than 0.05). A lower pulmonary vascular resistance was noted into day 2 (p less than 0.05). Our results suggest that PMN elastase may participate in the development of postoperative pulmonary impairment.     

Granulocyte Superoxide Anion and Elastase Release During Cardiopulmonary Bypass

Abstract: Cardiopulmonary bypass (CPB) is known to induce several pathogenic responses in cardiovascular surgery. To explore leukocyte activation during PCB, we investigated superoxide anion (O₂^-) production by granulocytes in 6 patients undergoing aortocoronary bypass surgery. O₂^- production was determined with chemiluminescence amplified by a cypridina luciferin analogue. Granulocytes collected from the blood in the arterial site of the CPB circuit were stimulated by phorbol myristate acetate, n -formyl-methionyl-leucyl-phenylalanine, and opsonized zymosan. All the stimulators failed to disclose a significant difference between the magnitude of chemiluminescence during and after CPB. However, significant complement activation was detected, and the plasma level of granulocyte elastase increased gradually during and after CPB. This discrepancy between the unchanged O₂^- production by stimulated granulocytes and the increase in inflammatory mediators including granulocyte elastase may be due to sequestration of activated granulocytes in extravascular tissues. Namely, it was highly likely that activated granulocytes responsible for the increased plasma elastase level were sequestered and remained outside the blood circulation.     

Reduction of degranulation of polymorphonuclear leukocytes by immunosuppression in patients following cadaveric renal transplantation

Plasma levels of main granulocyte components of patients after cadaveric renal transplantation were compared 9 days postoperative with the plasma levels of patients undergoing aortofemoral and iliacofemoral bypass operation or abdominal surgery. Lactoferrin values were significantly lower in patients under immunosuppression with cyclosporine and prednisolone, whereas plasma levels of myeloperoxidase were comparable in all 3 groups of patients. Plasma E-alpha 1 PI values were significantly lower in patients undergoing bypass operation compared to abdominal surgery but did not differ from patients undergoing cadaveric kidney transplantation. Within 22 days postoperatively, there was no difference in the plasma levels of main granulocyte components in patients after kidney transplantation with and without postoperative complications. In vitro incubation of heparinized whole blood and isolated granulocytes obtained from healthy subjects in the presence of CsA, azathioprine, or prednisolone were performed. Only CsA caused inhibition of spontaneous degranulation of polymorphonuclear neutrophils showing significant lower elastase and lactoferrin release. However, in vivo administration of CsA and prednisolone in transplant patients displayed no effect on in vitro degranulation of both whole blood samples and isolated granulocytes. Our data demonstrate that CsA after in vitro incubation inhibits spontaneous granulocyte degranulation but not after in vivo administration. However, in vivo administration of CsA and prednisolone reduces lactoferrin release under certain conditions, e.g., postoperative stress or during hemodialysis therapy.     

The role of different types of corticosteroids on the inflammatory mediators in cardiopulmonary bypass.

In a placebo-controlled double-blind study on patients undergoing cardiopulmonary bypass (CPB) we studied the inhibiting effects of dexamethasone, a high dose of methylprednisolone, and a low dose of prednisolone on the inflammatory reaction induced by CPB. During CPB two episodes of blood activation were noticed. First, the blood-material interaction caused a significant increase in complement C3a and elastase concentrations after the start of bypass (p less than 0.01). Secondly, the reperfusion of the ischemic heart, lungs, and peripheral tissue, after release of the aortic cross-clamp, caused an additional increase in C3a and elastase concentration and a statistically significant increase in leukotriene B4 (LTB4) concentration and tissue plasminogen activator (t-PA) activity (p less than 0.01, p less than 0.05, respectively). Dexamethasone treatment effectively inhibited the increase in LTB4 concentration and t-PA activity after release of the cross-clamp (significant differences to the placebo group, p less than 0.01, p less than 0.05, respectively). High-dose methylprednisolone treatment was almost as effective as dexamethasone treatment, whereas low-dose prednisolone treatment was less effective than methylprednisolone in the inhibition of the inflammatory mediators (DM greater than MP greater than P). None of the corticosteroid regimens was able to inhibit the increase in complement C3a and elastase. We therefore conclude that corticosteroids do not have an effect on complement activation during CPB. However, leukocyte activation and t-PA activity after release of the aortic cross-clamp are effectively inhibited by corticosteroid treatment, in a dose-dependent way. The inhibition of this inflammatory reaction will have a favourable effect on the postoperative course in patients who have undergone CPB.     

Increase in lactoferrin and elastase α-1-proteinase inhibitor complexes but lack of complement activation and IL-6 response following thoracic surgery

Polymorphonuclear neutrophil (PMN) stimulation and degranulation can be mediated by the cytokines and by complement activation. The aim of the present study was to measure TNFa, IL-lα, IL-6 and C3d in relation to postoperative increase in lactoferrin and elastase α-1-proteinase inhibitor (E α-l-PI) levels. Eleven patients undergoing thoracic surgery took part in the study. Blood leucocytes, E α-l-PI, lactoferrin and C3d were measured preoperatively, at the end of surgery and postoperatively, at 4 h and on day 1, 2, 3 and 5. TNFa, IL-lα and IL-6 were measured preoperatively, at the end of surgery and postoperatively, at 4 h, and on days 1 and 5. The leucocyte count, lactoferrin and E α-l-PI levels increased significantly postoperatively (P < 0.01). There was no significant change in C3d values. Plasma IL-6 levels were unchanged in the postoperative period. Plasma TNFa and IL-lα were detectable at low levels in only two and four patients, respectively. Conclusion: The postoperative increase in blood levels of PMN lactoferrin and E α-l-PI complexes observed in the present study was not accompanied by complement activation, or increased blood levels of IL-6.     

The effects of glucocorticoid therapy on inflammatory responses to coronary artery bypass graft surgery

HYPOTHESIS: Delayed or reduced polymorphonuclear leukocyte (PMN) apoptosis may contribute to prolongation of systemic inflammation after cardiopulmonary bypass. BACKGROUND/OBJECTIVE: Preoperative administration of glucocorticoids has been used ostensibly to attenuate the systemic inflammation associated with cardiopulmonary bypass. Therefore, this study evaluated, in patients undergoing cardiopulmonary bypass, the efficacy of glucocorticoids in restoring peripheral blood PMN apoptosis and modulating PMN surface receptors (CD95, tumor necrosis factor receptor [TNFR]) known to be involved in proapoptotic or antiapoptotic signal transduction. DESIGN: Randomized control study. SETTING: Medical school and affiliated tertiary care hospital. PATIENTS: Thirteen patients undergoing coronary artery bypass grafting. INTERVENTION: Patients were randomly assigned to the control group (n = 7) or to receive 1 g of methylprednisolone sodium succinate on anesthetic induction (n = 6). MAIN OUTCOME MEASURES: Blood samples were drawn before induction, 20 minutes after sternotomy and bypass, immediately postoperatively, and on postoperative day 1. Isolated PMNs were incubated for 6 hours with or without the CD95 agonist CH 11. Polymorphonuclear leukocyte apoptosis was measured using propidium iodide-RNAase staining and flow cytometry. Levels of PMN cell-associated receptors (TNFR and CD95), cytokines (TNF-alpha, interleukin 6 [IL-6], IL-8, and IL-10), and soluble receptors (sTNFR1 and sTNFR2) were measured. RESULTS: In all 13 patients, spontaneous and Fas-mediated PMN apoptosis decreased more than 80% from baseline (P<.001) by postoperative day 1. Polymorphonuclear leukocyte CD95 increased (P<.003) by postoperative day 1 compared with baseline, whereas PMN TNFR was unchanged. Methylprednisolone administration did not modulate PMN apoptosis or immunocyte receptor expression; however, such treatment did decrease postoperative IL-6 secretion (P<.001) and increase postoperative IL-10 secretion (P<.001). CONCLUSIONS: The complications of major surgery include persistent inflammation, which can lead to multisystem organ failure. Polymorphonuclear leukocyte resistance to apoptosis may contribute to this process. A single preoperative dose of glucocorticoids did not effect PMN apoptosis or receptor phenotype.     

Complement activation during cardiopulmonary bypass: comparison between the use of large volumes of plasma and dextran 70

Cardiopulmonary bypass surgery may be complicated by a systemic inflammatory reaction, which has been ascribed to the activation of complement. For such activation, the choice of priming solution for the heart-lung machine may be of importance. The peripheral blood of two groups of 10 patients, either exposed to dextran 70 or to plasma as priming solutions, was therefore studied pre-, per-, and postoperatively. The study confirmed that activation of complement is a consistent phenomenon during cardiopulmonary bypass surgery and that the activation involves both the early and the late phase of the complement cascade. The increase in the plasma concentration of the C3 activation products C3c and C3dg was significantly higher in the plasma group than in the dextran group, while there was no difference in the increase in the concentration of the terminal complement complex SC5b-9.     

ARDS-like reactive respiratory failure after radical operation for esophageal cancer--with reference to PMN elastase and anaphylatoxin

In a study undertaken to elucidate the pathophysiology underlying reactive respiratory failure following surgery for esophageal cancer, postoperative esophageal cancer patients were divided into 2 groups, i.e. one with respiratory failure (defined as impairment of oxygenating capacity with a respiratory index (RI) value of 1.5 or above, lasting from more than 5 days after surgery) and the other without it, and between-group comparisons were made of respiratory & circulatory dynamics and biologic response system components, e.g., complement, anaphylatoxins and polymorphonuclear granulocytes (PMN) elastase. There were no differences between the two groups in patient's age at operation and pulmonary function test. The mean duration of endotracheal control was 5.1 days for the respiratory failure (+) group against 3.7 days for the respiratory failure (-) group. Assessments of respiratory & circulatory dynamics showed that the RI was significantly increase early in the postoperative course in the respiratory failure (+) group as compared with the respiratory failure (-) group, while the hydrostatic pressure of pulmonary circulation (pulmonary microvascular pressure (Pmv)-plasma colloid-osmotic pressure (COP] and pulmonary shunting rate (Qs/Qt) were also elevated in the former group. Among biologic response parameters, the leukocyte count, platelet count, CH5, C3, and C5 showed long-sustained decreases from the postoperative day 1 on in the repertory failure (+) group as compared to the respiratory failure (-) while PMN elastase activity and anaphylatoxin C3a were elevated from the postoperative day 1 on in the former group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preoperative plasmapheresis in patients undergoing cardiac surgery procedures

Donor plasmapheresis that is carried out weeks before the operation has proven to be of benefit in elective orthopedic patients with regard to reducing homologous blood consumption and preserving coagulation. In this study acute preoperatively performed plasmapheresis (APP) was investigated in cardiac surgery patients. Forty-five patients scheduled for elective aortocoronary bypass surgery were randomly divided into three groups of 15 patients each: 1) removal of platelet-poor plasma (PPP), 2) removal of platelet-rich plasma (PRP), and 3) no plasmapheresis (control group). Plasma volume removed was 10 ml/kg in all APP patients, and plasma was replaced by the same amount of low-molecular weight hydroxyethylstarch solution (6% HES 200/0.5). Various laboratory data were investigated before, during, and after extracorporeal circulation (ECC). Blood loss in control patients was more pronounced than in the two APP groups; two of the control patients needed packed red cells. APP itself did not affect coagulation variables, free hemoglobin, or polymorphonuclear (PMN) elastase. At the end of the operation, 5 h after ECC, and at the first postoperative day the number of platelets was significantly lower in the control group; PRP patients showed the highest values. Fibrinogen and AT-III levels were less compromised in APP patients than in the control group. Global coagulation parameters did not differ between the groups within the whole investigation period. PMN elastase increased significantly during ECC in all groups with the greatest increase in the control group (722%) and the smallest increase in PRP patients (280%), possibly due to the removal of cellular elements in this group.(ABSTRACT TRUNCATED AT 250 WORDS)     

PMN-elastase as a marker in diagnosis and follow-up of bone and joint infections]

PMN elastase, a proteolytic enzyme, is a biochemical marker for pathologic granulocyte stimulation. In the presence of sepsis, excessive neutrophil stimulation occurs and significant amounts of PMN elastase are released into the plasma and serve as an indicator for the severity of the disease and the prognosis. PMN elastase is also a useful parameter for preoperative diagnostic management and postoperative follow-up of bone and joint infections. In patients with osteomyelitis and joint empyema (n = 48) PMN elastase had a sensitivity of 77%, which was only exceeded by that of the unspecific erythrocyte sedimentation rate (sensitivity 89%). Sensitivities of other inflammation parameters were lower: C-reactive protein (CRP) 67%, fibrinogen 50%, neopterin 32% and leukocyte count 21%. Determination of PMN elastase levels was also helpful in postoperative follow-up of patients with bone and joint infections. In the early postoperative period PMN elastase levels normalized more quickly than the other parameters unless patients actually developed complications. At the first postoperative determination (day 2-4 after surgery) 38% of the patients (n = 24) already had PMN elastase levels within the normal range (less than or equal to 40 micrograms/l) (CRP 13%). After 10 days PMN elastase was normal in 57% and CRP in 30% of the patients. Later on both parameters reacted similarly: by the time of discharge from hospital levels of PMN elastase were normal in 70% and CRP levels in 74%.     

Complement activation during major operations with or without cardiopulmonary bypass

Plasma concentrations of the complement products C3dg and the terminal complement complex, as well as the number of granulocytes (polymorphonuclear neutrophils), were assessed in patients undergoing aorta-coronary bypass with extracorporeal circulation, abdominal aneurysmectomy with implantation of an aortic graft, or thoracotomy without the introduction of synthetic material into the circulation. The concentration of terminal complement complex increased significantly only in the group undergoing extracorporeal circulation, with a corresponding drop in the number of granulocytes. In contrast, the C3dg concentration increased during both extracorporeal circulation and abdominal aneurysmectomy, which indicates that other factors than extracorporeal circulation may affect C3 activation during major operations. In the thoracotomy group, where the most pronounced increase in granulocytes was found, no complement activation was recorded. It is concluded that extracorporeal circulation activates the terminal pathway of complement and that assays detecting activation of both the initial and the terminal parts should be included when the pathophysiology of complement is examined during major operations and extracorporeal circulation.     

Reduced complement activation during cardiopulmonary bypass does not affect the postoperative acute phase response.

OBJECTIVE: In the present study the relationship was evaluated between perioperative inflammation and the postoperative acute phase response in patients undergoing elective coronary artery bypass grafting (CABG) assisted by cardiopulmonary bypass (CPB). CPB circuits contained either non-coated- (UMS), Carmeda- (BPS) or Trillium-coated oxygenators (BAS). METHODS: Prospectively, 71 CABG patients were randomly allocated to one of the oxygenator groups (UMS: n=25, BPS: n=25 and BAS: n=21). Terminal complement complexes (TCC) and elastase were determined in plasma samples collected before, during and after bypass. Secretory phospholipase A2 (sPLA2) and C-reactive protein (CRP) were determined before and after bypass. RESULTS: Demographic, CPB and clinical outcome data were similar for the three groups. TCC and elastase increased during CPB, and decreased thereafter. Significant differences between the groups were present in the levels of TCC at the end of CPB (P=0.002) and at the first (P=0.012) and second (P<0.001) postoperative days, the BPS and BAS groups having reduced levels of TCC compared to the UMS group. Also elastase concentrations differed significantly between the groups at the end of CPB (P<0.001). The postoperative sPLA2 and CRP levels increased in all three groups on the first and second postoperative days, but no significant differences were present between the groups. CONCLUSIONS: Material-induced reduction of the inflammatory response during CPB does not affect the postoperative acute phase response. Thus, in CABG patients this response seems relatively unaffected by the composition and/or biocompatibility of the modern CPB circuit and rather to be evoked by surgical trauma, anesthetics and organ perfusion.     

Nafamostat mesilate reduces blood cell adhesion to cardiopulmonary bypass circuits: an in-vitro study

Nafamostat mesilate (FUT-175) is a protease inhibitor, working as an inactivator of coagulation, fibrinolysis and platelet aggregation. Although FUT-175 directly blocks contact factors in coagulation, it also may decrease activation of humoral cascade systems when used in cardiopulmonary bypass circuits. We performed an in vitro study using fresh human blood in the following cardiopulmonary bypass circuits: standard circuit (C), biosurfaced circuit (B) and standard circuit containing FUT-175 (F). Each circuit was primed with 500 ml of electrolyte solution and 500 ml of fresh blood. Cardiopulmonary bypass was performed using a roller pump for four hours in two sets of each circuit configuration. Platelet factors (platelet count and beta-thromboglobulin), coagulation factors (thrombin-antithrombin III complex and fibrinopeptide A), fibrinolysis factors (alpha 2-plasmin inhibitor complex and alpha 2-plasmin inhibitor), complement factors (C3a, C4a), free hemoglobin, and granulocyte elastase were measured at the beginning and end of the study. Hemocytograms were measured concurrently. The FUT-175 group showed significantly lower levels of the measured indices than the biosurfaced group in thrombin-antithrombin III complex (7.4 +/- 2.1 vs. 54.9 +/- 38.1 ng/ml), fibrinopeptide A (7.2 +/- 2.0 vs. 20.2 +/- 14.6 ng/ml), beta-thromboglobulin (1940 +/- 250 vs. 2438 +/- 314 ng/ml) and free hemoglobin (25.2 +/- 14.3 vs. 73.8 +/- 18.4 mg/dl). There were no significant differences between Group F and Group B in platelet count, C3a, C4a and granulocyte elastase, although these indices were significantly lower in Groups F and B when compared to Group C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neutrophil and macrophage activation and anaphylatoxin formation in orthotopic liver transplantation without the use of veno-venous bypass

Background. Activation of neutrophils and activation of complement may be an aetiologic factor behind circulatory insufficiency in association with reperfusion of the grafted liver.
Methods. Neutrophil and macrophage activation (determined as PMN elastase and neopterin release) and complement activation were evaluated in 15 consecutive patients undergoing orthotopic liver transplantation without the use of veno-venous bypass.
Results. The PMN elastase concentrations were increased at the end ot the anhepatic phase, 2, 5 and 30 min after start of reperfusion and 6 and 24 h postoperatively. There were significantly higher PMN elastase concentrations in patients with circulatory instability (postreperfusion syndrome) compared with those without postreperfusion syndrome. The neopterin concentration was increased 2 min after the start of reperfusion and remained elevated until 6 h postoperatively. The plasma complement C3a concentrations were increased at the end of the anhepatic phase and 2, 5 and 30 min after the start of reperfusion. The plasma C3a levels were higher in patients with postreperfusion syndrome compared to those without.
Conclusions. Activation of neutrophils and macrophages and of the complement cascade with the formation of biologically active substances may be one explanation for the circulatory instability often seen in patients undergoing orthotopic liver transplantation.     

The effects of prostaglandin E1 on the granulocyte elastase, white blood cells and platelets in head-neck surgery

We studied whether prostaglandin E1 (PGE1) inhibits the granulocyte elastase increase, white blood cell increase and platelet decrease caused by surgical stimuli in 30 head-neck surgical patients. The patients were divided into a group of no PGE1 infusion (C group) and two groups of PGE1 infusion (infusion of 10 ng.kg-1.min-1 in P 10 group and infusion of 30 ng.kg-1.min-1 in P 30 group). PGE1 was infused intravenously using a syringe pump during operation. The granulocyte elastase, white blood cells and platelets were measured at 4 points: before induction of anesthesia, before surgery, 4 hours after the start of surgery or the infusion of PGE1, and on the first postoperative day. Granulocyte elastase was maintained at significantly higher levels during and after surgery in 3 groups. White blood cells correlated with granulocyte elastase in 3 groups (especially in C group; Granulocyte elastase = 1.48 X white blood cells + 23.5, r = 0.672). Platelets decreased significantly in the first postoperative day in C and P 10 group. PGE1 has a tendency to inhibit dose-dependently the postoperative decrease in platelets. We conclude that 30 ng.kg-1.min-1 infusion of PGE1 did not inhibit granulocyte elastase release from white blood cells, but has a tendency to inhibit postoperative platelet decrease.     

Relationship between granulocyte elastase and C3a under protamine dosing in on-pump cardiac surgery.

OBJECTIVE: The complement cascade and granulocytes are activated in on-pump cardiac surgery. If activation of complement directly regulates granulocytes, granulocyte elastase (GEL) should increase significantly after protamine administration. We examined the effect of protamine on granulocytes by protamine administration and observation of the effect on GEL and C3a. METHODS: Thirty patients who underwent coronary artery bypass grafting were randomly assigned to two groups. In 15 patients, protamine was administered 5 min after the termination of cardiopulmonary bypass, and was administered 35 min after cardiopulmonary bypass in the other 15 patients. All patients were perfused with heparin-coated circuits and received 300 IU/kg heparin and 3 mg/kg protamine. GEL and C3a concentrations were measured at 7 time points. RESULTS: GEL concentrations increased significantly just before aortic declamping and did not increase significantly after protamine administration. C3a concentrations, however, did not increase during cardiopulmonary bypass and did increase significantly after protamine administration. CONCLUSIONS: This study indicates that GEL does not increase after protamine administration and that complement concentration does not directly affect GEL release.     

Cardiopulmonary bypass reduction of bronchial blood flow: a potential mechanism for lung injury in a neonatal pig model

BACKGROUND: During total cardiopulmonary bypass, blood flow to the lungs is limited to flow through the bronchial arteries. We tested the hypothesis that bronchial blood flow during cardiopulmonary bypass is insufficient to prevent ischemia of the lung and that perfusion of the pulmonary arteries with oxygenated blood during bypass would reduce lung injury. METHODS: Eighteen piglets (5.0 +/- 0.5 kg) were subjected to 120 minutes of normothermic total cardiopulmonary bypass, followed by 60 minutes of postbypass perfusion. Nine of them received continuous pulmonary perfusion with oxygenated blood during bypass. Six additional piglets served as a control group and were mechanically ventilated after sternotomy for 180 minutes only. We quantitated bronchial arterial blood flow, tissue lactate content, and alveolar septal thickness and surface area. We also obtained bronchioalveolar lavage fluid samples. RESULTS: With the beginning of cardiopulmonary bypass, bronchial arterial blood flow decreased to 13% of baseline (42.1 +/- 10.4 to 5.6 +/- 1.0 mL/min). It remained decreased until the end of bypass and returned to starting levels 60 minutes after bypass. The decrease in bronchial blood flow was associated with a 3-fold increase in tissue lactate content. At the end of reperfusion there was a 2-fold increase in alveolar septal thickness and significant accumulations relative to control in the bronchoalveolar lavage fluid of albumin, lactate dehydrogenase, neutrophils, and elastase. Controlled pulmonary perfusion significantly ameliorated all the observed changes. CONCLUSION: Cardiopulmonary bypass caused a reduction in bronchial arterial blood flow, which was associated with injury of the lung. Controlled pulmonary perfusion reduced injury to the lung during bypass. The inflammatory response, as evidenced by bronchoalveolar lavage fluid, may be caused by ischemia.     

Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis, complement, and renal function after cardiopulmonary bypass.

The use of aprotinin to reduce blood loss after cardiopulmonary bypass is under debate. Concern has been raised about the renal effects of aprotinin. We administered a mean aprotinin dose of 4.2 x 10(6) kallikrein-inhibiting units to 13 patients with coronary disease undergoing cardiopulmonary bypass for 74 +/- 5 minutes (mean +/- standard error of the mean); 13 comparable patients having cardiopulmonary bypass served as control subjects, and all were studied postoperatively for 24 hours. Aprotinin reduced postoperative blood loss by 50% (p = 0.0082). Two of the 13 patients who received aprotinin needed one red cell unit each versus a total of 18 units in eight of 13 control patients (p = 0.0096). Blood pressure, hemoglobin value and serum protein concentration were higher after operation in the aprotinin group (p less than 0.05 to p less than 0.01). Platelet counts did not differ, but plasma thromboxane was lower in aprotinin recipients (p less than 0.001). In control patients fibrinogen degradation products (D dimer) doubled, and alpha 2-antiplasmin activity was halved during and after cardiopulmonary bypass (p less than 0.01 to p less than 0.001), whereas aprotinin patients showed no changes. The complement breakdown products C4a, C3a, and C3dg as well as C9 neoantigen increased from prebypass baseline in both groups (p less than 0.001); the increment of C3a and C3dg was greater in the aprotinin than in the control patients (p less than 0.001). Serum electrolytes, osmolality, and creatinine remained normal in both groups of patients. Creatinine clearance was normal or above normal and virtually identical in both groups. Osmolar clearance and fractional sodium excretion were higher in the aprotinin group than in the control group shortly after cardiopulmonary bypass (p less than 0.05 to p less than 0.01); renal function was unremarkable the next morning. No adverse clinical effects attributable to aprotinin were seen. In summary, aprotinin offers advantages for cardiopulmonary bypass.