Complement activation during cardiopulmonary bypass. Comparison of bubble and membrane oxygenators

A prospective randomized trial involving 91 patients undergoing cardiopulmonary bypass compared the effects of bubble oxygenators (with and without methylprednisolone sodium succinate) and membrane oxygenators on complement activation and transpulmonary sequestration of leukocytes. Patients were divided as follows: Group I, 30 patients, bubble oxygenator; Group II, 31 patients, bubble oxygenator and methylprednisolone sodium succinate (30 mg/kg); Group III, 30 patients, membrane oxygenator. In Group I, C3a increased from 323 +/- 171 ng/ml during cardiopulmonary bypass to 1,564 +/- 785 ng/ml at 25 minutes after bypass (p less than 0.0001). A significant decrease in C3a was found in Groups II and III compared to Group I (p less than 0.0001). C5a did not change significantly during cardiopulmonary bypass in any group. Reestablishment of pulmonary circulation at the end of bypass produced significant transpulmonary leukocyte sequestration in Group I; the median cell difference was 1,700/microliter. Transpulmonary sequestration was significantly (p less than 0.0001) less in Group II (median cell difference = 200/microliter) and in Group III (median cell difference = 400/microliter) than in Group I. We conclude that cardiopulmonary bypass with a bubble oxygenator alone initiates significantly (p less than 0.0001) more C3a activation and leukocyte sequestration than when methylprednisolone sodium succinate (30 mg/kg) is given 20 minutes before the start of cardiopulmonary bypass with a bubble oxygenator or when a silicone membrane oxygenator is used.     

Significance of the concentrated red cell and albumin priming method with particular reference to anaphylatoxin generation.

Anaphylatoxins generated by cardiopulmonary bypass were observed in basic and clinical studies (n = 120 in the latter). In vitro immunoglobulin fractions denatured by oxygen bubbling produced C4a, C3a, and C5a, but albumin identically treated did not. Therefore concentrated red cells with albumin were used to prime homologous blood for clinical application during cardiopulmonary bypass. Complement levels were compared with type of oxygenator (bubble or membrane) and the ratio of primed homologous blood to circulating autologous blood volume. With the bubble oxygenator at a low ratio of homologous to autologous blood (arbitrarily defined as less than 20%), C3a levels during cardiopulmonary bypass tended to be lower in the concentrated red cells plus albumin priming group than in the ordinary priming group (p less than 0.1, at 60 and 90 minutes of cardiopulmonary bypass). C4a and C3a levels increased less after protamine administration with concentrated red cells plus albumin priming (p less than 0.05, p less than 0.01, respectively, 90 minutes after protamine) than with ordinary priming. Such changes in the membrane oxygenator group were less remarkable. Thus C3a levels were approximately the same in both oxygenator groups primed with concentrated red cells plus albumin. The higher the homologous to autologous ratio, the steeper the C4a and C3a increase from the beginning of cardiopulmonary bypass with the bubble oxygenator. This tendency was less remarkable in the membrane oxygenator group. Early postoperative pulmonary function was improved by concentrated red cells plus albumin priming, especially in the bubble oxygenator group. In conclusion, (1) oxygenator systems primed with concentrated red cells plus albumin produced less anaphylatoxin than those with homologous blood, especially with the bubble oxygenator, and (2) our clinical results support the importance of immunoglobulin denatured by oxygen bubbling in anaphylatoxin generation (by means of the classical pathway), as shown by our in vitro study.     

Retinal microembolism and neuropsychological deficit following clinical cardiopulmonary bypass: comparison of a membrane and a bubble oxygenator. A preliminary communication

To observe and quantify cerebrovascular microembolic events in the central nervous system during cardiopulmonary bypass, 40 patients having elective uncomplicated coronary surgery had retinal fluorescein angiograms 5 min before bypass was discontinued. Each patient also had 10 neuropsychological tests before and after surgery. A Harvey H1700 bubble oxygenator was used for 23 patients and a Cobe CML sheet membrane oxygenator was used for 17 patients. All 23 (100%) of patients in the bubble oxygenator group had retinal microvascular occlusions consistent with microembolism compared to 8/17 (47%) in the membrane oxygenator group (P less than 0.001). In those retinas with occlusions, the mean resultant area of non-perfusion was less in the membrane oxygenator group (0.11 mm2; n = 8) than in the bubble oxygenator group (0.29 mm2; P less than 0.01). Arterial PO2 levels during bypass were similar in both groups at moderate hypothermia, but the mean PaO2 during rewarming was higher in the bubble oxygenator group (27 kPa) than in the membrane group (13 kPa; P less than 0.001). Neuropsychological deficits were more common and more severe after bubble oxygenation than after membrane oxygenation, but in this small patient group, the difference was not statistically significant. We conclude that flat sheet membrane oxygenation during cardiopulmonary bypass may confer significant protection against cerebrovascular microembolism.     

A Comparison of the Effects of Membrane and Bubble Oxygenators on Platelet Counts and Platelet Size in Elective Cardiac Operations

To compare the effects of membrane and bubble oxygenators on platelet counts and the size of circulating platelets, serial hematocrits, platelet counts, and platelet sizing were measured in 23 patients undergoing elective cardiac operations. In 10 patients a bubble oxygenator was used and in 13, a SciMed membrane oxygenator. The two groups were statistically similar with respect to age, weight, time on bypass, and mean blood flow rates during bypass.It was found that platelet counts, when corrected for hemodilution, did not fall from control levels during or up to 24 hours after cardiopulmonary bypass in either group. In both groups, the relative number of platelets per gram of hemoglobin increased slightly during and after bypass, and this increase was significant in the bubble oxygenator group. The average size of circulating platelets increased only in the bubble oxygenator group, and then only in the one-day postoperative sample. These findings suggest that the membrane oxygenator offers no advantage with respect to preservation of platelets during cardiopulmonary bypass lasting up to 2 to 3 hours.     

Different oxygenators for cardiopulmonary bypass lead to varying degrees of human complement activation in vitro

Complement activation was studied in vitro with six different membrane and bubble oxygenators for cardiopulmonary bypass. There was a similar increase in terminal (C5 to C9) activation with all oxygenators (p less than 0.001), ranging from 281% (117% to 444%) to 453% (225% to 680%) after 60 minutes (median and 95% confidence intervals). C3 activation was not observed with a hollow fiber membrane and a soft shell bubble oxygenator. On the other hand, a capillary membrane, a sheet membrane, a nonporous membrane, and a hard shell bubble oxygenator all induced a similar increase in C3 activation (p less than 0.01), ranging from 107% (23% to 346%) to 272% (88% to 395%) after 60 minutes. The differences in C3 activation could not be explained by the blood contact materials or any other single factor known to induce activation, which suggests that overall complement activation during cardiopulmonary bypass is a multifactorial effect. The tubing set per se induced only minor C3 activation but contributed to the overall formation of terminal complement complex. The study further indicates that an arterial line blood filter prevents activated neutrophils from being reinfused to the patient and should be used regardless of type of oxygenator.     

Blood conservation with membrane oxygenators and dipyridamole

Cardiopulmonary bypass induces platelet activation and dysfunction, which result in platelet deposition and depletion. Reduced platelet numbers and abnormal platelet function may contribute to postoperative bleeding. A membrane oxygenator may preserve platelets and reduce bleeding more than a bubble oxygenator, and the antiplatelet agent dipyridamole may protect platelets intraoperatively and reduce bleeding postoperatively. A prospective randomized trial was performed in 44 patients undergoing elective coronary artery bypass grafting to assess the effects of the membrane oxygenator and dipyridamole on platelet counts, platelet activation products, and postoperative bleeding. Patients who were randomized to receive a bubble oxygenator and no dipyridamole had the lowest postoperative platelet counts, the greatest blood loss, and the most blood products transfused. Platelet counts were highest and blood loss was least in patients randomized to receive a membrane oxygenator and dipyridamole (p less than .05). A bubble oxygenator with dipyridamole and a membrane oxygenator without dipyridamole resulted in intermediate postoperative platelet counts and blood loss. Arterial thromboxane B2 and platelet factor 4 concentrations were elevated on cardiopulmonary bypass in all groups. Both the membrane oxygenator and dipyridamole were independently effective (by multivariate analysis) in preserving platelets. Optimal blood conservation was achieved with a membrane oxygenator and dipyridamole.     

Influence of oxygenator type on the prevalence and extent of microembolic retinal ischemia during cardiopulmonary bypass. Assessment by digital image analysis

We have previously reported the occurrence of microembolic ischemia in the retina during cardiopulmonary bypass, as revealed by fluorescein angiography. This method has been extended by digital image analysis to include quantification of the extent of retinal ischemia and has been applied to a prospective comparative study of 64 patients undergoing elective coronary operations with either a bubble or a membrane oxygenator. Patients with diabetes or clinically evident cerebrovascular disease were excluded. Bypass procedures were standardized in all cases with pulsatile flow and a 40 microns arterial line filter (Pall EC Plus). Thirty patients had bypass with a bubble oxygenator (Harvey H1700) and 34 patients had bypass with a flat sheet membrane oxygenator (COBE CML). In each case retinal fluorescein angiograms were obtained preoperatively and 5 minutes before the end of bypass and were processed with a digital image analyzer (Context Vision GOP-302). Microembolic perfusion defects were identified by digital subtraction of preoperative and end-bypass angiograms and their total area was computed. Results. In the bubble oxygenator group retinal perfusion defects indicative of microembolism occurred in all 30 (100%) patients. In contrast, over half the patients in the membrane oxygenator group had normal retinal perfusion, and the prevalence of perfusion defects (44%; 70% confidence limits 34% to 54%) was significantly less than in the bubble group (p less than 0.001). In addition, those patients in the membrane group had significantly fewer lesions (median 0; 70% confidence limits 0 to 1) than patients in the bubble group (median 2; 70% confidence limits 2 to 2; p less than 0.001) and also had significantly smaller total areas of retinal ischemia (median 0 mm2; 70% confidence limits 0 to 0.16 mm2) than the bubble group (median 0.22 mm2; 70% confidence limits 0.21 to 0.27 mm2; p less than 0.001). There was no relationship between the extent of retinal ischemia and bypass time, arterial blood gas concentrations, volume of cardiotomy suction or donor blood returned to the pump, or recent medication with aspirin. Inferences. Digital image analysis of retinal fluorescein angiograms may provide a method of quantifying microembolic ischemia in the central nervous system during cardiopulmonary bypass. Flat sheet membrane oxygenation appears to provide significantly better protection against microembolic ischemia than bubble oxygenation.     

Complement activation with bubble and membrane oxygenators in aortocoronary bypass grafting

Thirty-three patients admitted for coronary bypass grafting were randomized to cardiopulmonary bypass with a bubble oxygenator (Cobe or Polystan) or a membrane oxygenator (SciMed). Plasma concentrations of C3 activation products and the terminal complement complex were measured using enzyme immunoassays. Both variables increased almost linearly after onset of cardiopulmonary bypass, with maximal concentrations at closure of the sternum. From a baseline of 7.5 to 12.0 arbitrary units (AU)/mL (medians), the concentrations of C3 activation products increased by 117.5 AU/mL (Cobe), 120.5 AU/mL (Polystan), and 213.3 AU/mL (SciMed). The increase in the membrane group was significantly higher than in the two bubble oxygenator groups (p less than 0.01). From a baseline of 0.9 to 1.3 AU/mL, the concentrations of terminal complement complex increased by 5.4 AU/mL (Cobe), 6.6 AU/mL (Polystan), and 7.7 AU/mL (SciMed) (differences not significant). The higher C3 activation caused by the membrane oxygenator may be explained by differences in flow profile and surface area in contact with blood. The study cannot confirm the general assumption that membrane oxygenators lead to lower complement activation than do bubble oxygenators.     

Pressure drop, shear stress, and activation of leukocytes during cardiopulmonary bypass: a comparison between hollow fiber and flat sheet membrane oxygenators

The membrane oxygenator is known to be superior to the bubble oxygenator, but little information is available about the difference between the hollow fiber and flat sheet membrane oxygenators with regard to pressure drop, shear stress, and leukocyte activation. In this study, we compared these 2 types of membrane oxygenators in patients undergoing cardiopulmonary bypass (CPB) surgery with special focus on leukocyte activation and pressure drop across the oxygenators. Plasma concentration of elastase, a marker indicating leukocyte activation, increased to 593+/-68% in the flat sheet oxygenator group versus 197+/-42% in the hollow fiber oxygenator group (p<0.01) at the end of CPB compared to their respective baseline concentrations before CPB. Pressure drop across the oxygenator was significantly higher in the flat sheet group than in the hollow fiber group throughout the entire period of CPB (p<0.01). High pressure drop across the oxygenator as well as the calculated shear stress was positively correlated with the release of elastase at the end of CPB (r = 0.760, p<0.01, r = 0.692, p<0.01). However, this positive correlation existed in the flat sheet oxygenator but not in the hollow fiber oxygenator. Clinically, both membrane oxygenators have satisfactory performance in O2 and CO2 transfer. These results suggest that a higher pressure drop across the flat sheet oxygenator is associated with more pronounced activation of leukocytes in patients undergoing cardiopulmonary bypass.     

Pulmonary artery perfusion with protective solution reduces lung injury after cardiopulmonary bypass

BACKGROUND: The inflammatory response and higher temperature of lung tissue during cardiopulmonary bypass can result in lung injury. This study was to evaluate the protective effect of pulmonary perfusion with hypothermic antiinflammatory solution on lung function after cardiopulmonary bypass. METHODS: Twelve adult mongrel dogs were randomly divided into two groups. The procedure was carried out through a midline sternotomy, cardiopulmonary bypass was established using cannulas placed in the ascending aorta, superior vena cava, and right atrium near the entrance of the inferior vena cava. After the ascending aorta was clamped and cardioplegic solution infused, the right lung was perfused through a cannula placed in the right pulmonary artery with 4 degrees C lactated Ringer's solution in the control group (n = 6) and with 4 degrees C protective solution in the antiinflammation group (n = 6). Antiinflammatory solution consisted of anisodamine, L-arginine, aprotinin, glucose-insulin-potassium, and phosphate buffer. Plasma malondialdehyde, white blood cell counts, and lung function were measured at different time point before and after cardiopulmonary bypass; lung biopsies were also taken. RESULTS: Peak airway pressure increased dramatically in the control group after cardiopulmonary bypass when compared with the antiinflammation group at four different time points (24 +/- 1, 25 +/- 2, 26 +/- 2, 27 +/- 2 cm H2O versus 17 +/- 2, 18 +/- 1, 17 +/- 1, 18 +/- 1 cm H2O; all p < 0.01). Pulmonary vascular resistance increased significantly in the control group than in the antiinflammation group at 5 and 60 minutes after cardiopulmonary bypass (1,282 +/- 62 dynes x s x cm(-5) versus 845 +/- 86 dynes x s x cm(-5) and 1,269 +/- 124 dynes x s x cm(-5) versus 852 +/- 149 dynes x s x cm(-5), p < 0.05). Right pulmonary venous oxygen tension (PvO2) in the antiinflammation group was higher than in the control group at 60 minutes after cardiopulmonary bypass (628 +/- 33.3 mm Hg versus 393 +/- 85.9 mm Hg, p < 0.05). The ratio of white blood cells in the right atrial and the right pulmonary venous blood was lower in the antiinflammation group than in the control group at 5 minutes after the clamp was removed (p < 0.05). Malondialdehyde were lower in the antiinflammation group at 5 and 90 minutes after the clamp was removed (p < 0.01 and p < 0.05, respectively). Histologic examination revealed that the left lung from both groups had marked intraalveolar edema and abundant intraalveolar neutrophils, whereas the right lung in the control group showed moderate injury and the antiinflammation group had normal pulmonary parenchyma. CONCLUSIONS: Pulmonary artery perfusion using hypothermic protective solution can reduce lung injury after cardiopulmonary bypass.     

Deleterious effects of cardiopulmonary bypass. A prospective study of bubble versus membrane oxygenation

A number of hematologic and immunologic parameters that reflect erythrocyte and platelet damage and host defense mechanisms against infection were studied in 20 patients undergoing cardiopulmonary bypass during coronary operations. The patients were randomly assigned to a group in which a bubble oxygenator or a hollow-fiber membrane oxygenator was used. Hemolysis, thrombocytopenia, and significant release of beta thromboglobulin occurred in patients from the bubble oxygenator group and, to much lesser extent, in patients from the membrane oxygenator group. Polymorphonuclear leukocytes and monocytes from bubble oxygenator patients demonstrated increased generation of reactive oxygen species in the resting state and in the presence of the stimulating agents N-formyl-methionyl-leucyl-phenylalanine, concanavalin A, and opsonized zymosan, as compared with cells from membrane oxygenator patients. No difference was found between bubble and membrane oxygenator patients in the time of occurrence or intensity of leukopenia during bypass, of leukocytosis at the end of bypass, nor in the rate of complement activation, as assessed by quantitation of plasma C3a antigen. Complement activation was dependent on the alternative pathway. Immunoglobulin M concentration significantly decreased during bypass in both groups of patients. The serum opsonizing capacity for endotoxin and serum bactericidal activity for Serratia marcescens were decreased in both groups, mainly because of hemodilution, although they were additionally affected by bubble oxygenation. Several deleterious hematologic consequences of cardiopulmonary bypass can be minimized by the use of a membrane oxygenator. However, complement activation remains a potential risk factor even in membrane oxygenator patients and requires further investigation to obtain better hemocompatible materials for cardiopulmonary bypass circuits.     

Leukocyte depletion ameliorates free radical-mediated lung injury after cardiopulmonary bypass

Activated leukocytes and oxygen free radicals have been implicated in the pathogenesis of lung injury associated with cardiopulmonary bypass. To determine whether leukocyte depletion could prevent this injury, we used a dog model simulating routine cardiac operations. Mongrel dogs (11 to 17 kg) were subjected to cardiopulmonary bypass with a bubble oxygenator and cooled to 27 degrees C. After aortic crossclamping and cardioplegic arrest for 90 minutes, control animals (n = 5) were rewarmed and weaned from bypass, and their condition was then stabilized for 90 minutes. Leukocyte-depleted animals (n = 5) had a leukocyte filter incorporated in the bypass circuit. During bypass, circulating leukocyte counts decreased by 60% in control dogs, and by 97% in leukocyte-depleted animals. Free radical generation (estimated by spectrophotometric assay of plasma conjugated dienes) was significantly reduced by leukocyte depletion during and after bypass. Total hemolytic complement activity and the titer of C5 decreased markedly immediately after the onset of bypass in both the control and leukocyte-depleted animals. Pulmonary function after bypass was better preserved in leukocyte-depleted animals. These data suggest that depletion of circulating leukocytes contributes to lung injury during cardiopulmonary bypass and is associated with increased oxygen radical activity, pulmonary edema, and vasoconstriction. Leukocyte depletion substantially reduced the pulmonary injury seen after cardiopulmonary bypass.     

Platelet changes during heart surgery with extracorporeal circulation

The changes in the number of platelets during anesthesia and operation were evaluated in 24 patients (8 females and 16 males) scheduled for cardiac surgery with cardiopulmonary bypass. There was a significant (p less than 0.05) thrombopenia at the beginning of perfusion, which persisted 60 minutes after the end of cardiopulmonary bypass. There were no significant differences when these changes were evaluated depending on the type of oxygenator, the need for transfusion or the duration of cardiopulmonary bypass. There was a reduction in the platelet count at the beginning of the bypass (207 to 124 x 10(9).1(-1), when blood contacts with the synthetic surfaces of the circuits and the oxygenator, al though-the most marked reduction was found at the end of bypass (95.9 x 10(9).1-1), coinciding with protamine administration. The function and number of platelets tended to become normal in the first hours of the postoperative period.     

The safety and efficacy of ten percent pentastarch as a cardiopulmonary bypass priming solution. A randomized clinical trial.

Ten percent pentastarch is a low-molecular-weight hydroxyethyl starch with greater oncotic pressure and shorter intravascular persistence than 6% hetastarch. To evaluate its safety and efficacy as a component of cardiopulmonary bypass priming solution, we prospectively studied 90 patients undergoing coronary artery bypass grafting or valve replacement necessitating cardiopulmonary bypass (bubble oxygenator and moderate systemic hypothermia). Sixty patients were randomized to receive 75 gm of either 10% pentastarch (group P) or 25% albumin (group A), and 30 patients received lactated Ringer's solution alone (group C). Intravascular colloid osmotic pressure during cardiopulmonary bypass was highest with either of the colloid primes (15-minute measurement: group P, 15.7 +/- 2.2 mm Hg (mean +/- standard deviation); group A, 15.2 +/- 2.0 mm Hg; group C, 11.3 +/- 1.7 mm Hg; p less than 0.05, groups P and A compared with group C). This was associated with a lower volume requirement during cardiopulmonary bypass to maintain the venous reservoir (group P, 333 +/- 318 ml; group A, 483 +/- 472 ml; group C, 1332 +/- 1013 ml; p less than 0.05, groups P and A compared with group C). Urine output during cardiopulmonary bypass was similar in each group. Net intraoperative fluid balance was lowest in the colloid groups (groups P and A, 5.7 +/- 1.4 L; group C, 6.9 +/- 1.3 L; p less than 0.05, groups P and A compared with group C). Cardiac index shortly after weaning from cardiopulmonary bypass was greatest in group P (group P, 3.2 +/- 0.9; group A, 2.8 +/- 0.8; group C, 2.7 +/- 0.6 dyne.sec.cm-5; p less than 0.05, group P compared with group C). Changes in alveolar-arterial oxygen gradients, shunt fraction, and effective compliance were similar in all groups. During cardiopulmonary bypass, pentastarch appeared to cause the greatest degree of hemodilution, as suggested by the lowest hemoglobin, factor VII and IX levels and platelet count. The activated partial thromboplastin time was significantly prolonged during and immediately after cardiopulmonary bypass in group P relative to groups A and C (p less than 0.05), although there were no significant differences in the activated clotting time before cardiopulmonary bypass, during cardiopulmonary bypass, or after heparin neutralization. As well, clinical indices of hemostasis, including mediastinal drainage, red cell, platelet, and fresh frozen plasma requirements, and reoperation for excessive postoperative bleeding, were similar. We conclude that pentastarch, when used in cardiopulmonary bypass prime, is as safe as either albumin or Ringer's solution alone.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cardiac ischemic preconditioning improves lung preservation in valve replacement operations

BACKGROUND: Previous work has shown that cardiac ischemic preconditioning reduces cardiac reperfusion injury. We investigated whether cardiac ischemic preconditioning can improve lung preservation in patients who undergo valve replacement. METHODS: Forty patients with rheumatic heart disease requiring valve replacement were randomly divided into two groups. Twenty patients received two cycles of 3 minutes of aortic cross-clamping and 2 minutes of reperfusion before cardioplegic arrest (group IP), and 20 patients underwent 10 minutes of cardiopulmonary bypass (group C, control group). Blood samples from the pulmonary vein were collected to measure levels of polymorphonuclear leukocytes, superoxide dismutase, malonedialdehyde, and thromboxane B2, and arterial oxygen tension. Blood samples from the coronary sinus were used to measure calcitonin gene-related peptide values. Hemodynamic data were recorded by a pulmonary artery Swan-Ganz catheter. Lung tissue was collected after 1 hour of reperfusion to evaluate morphology. Clinical outcome data were recorded. RESULTS: In group C (cardiopulmonary bypass and cardioplegic arrest), the levels of polymorphonuclear leukocytes, thromboxane B2, malonedialdehyde, and calcitonin gene-related peptide were increased after 1 hour of reperfusion, whereas the value for superoxide dismutase was decreased. In group IP, preconditioning attenuated the increase in polymorphonuclear leukocytes, thromboxane B2, and malonedialdehyde (p < 0.05) and increased superoxide dismutase and calcitonin gene-related peptide levels (p < 0.05). Preconditioning also increased arterial oxygen tension and cardiac index compared with controls (p < 0.05) and decreased mean pulmonary artery pressure and pulmonary vascular resistance index (p < 0.05). Histologic findings showed less lung injury and a lower polymorphonuclear leukocyte count in group IP than in group C (p < 0.05). Group IP had fewer postoperative pulmonary complications and a shorter intubation time. CONCLUSIONS: Cardiac ischemic preconditioning improves lung preservation in patients having valve replacement. The mechanism may be that cardiac ischemic preconditioning reduces the accumulation of polymorphonuclear leukocytes in lung tissue and decreases the formation of oxygen free radicals.     

Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest. I. Gaseous microemboli.

OBJECTIVES: Recent studies suggest that myocardial reperfusion injury is exacerbated by free radicals when pure oxygen is used during cardiopulmonary bypass. Partial replacement of the oxygenator gas mixture with nitrogen, however, such as has already been adopted clinically in many centers, could increase the risk of gaseous nitrogen microembolus formation and therefore of brain damage because of the low solubility of nitrogen, particularly under conditions of hypothermia. METHODS: Ten 7- to 10-kg piglets were cooled for 30 minutes to 15 degrees C on cardiopulmonary bypass and then rewarmed for 40 minutes to 37 degrees C. In 5 piglets cardiopulmonary bypass was normoxic and in 5 it was hyperoxic. In each group 3 bubble oxygenators without arterial filters and 2 membrane oxygenators with filters were used. Cerebral microemboli were monitored continuously by carotid Doppler ultrasonography (8 MHz) and intermittently by fluorescence retinography. RESULTS: Embolus count was greater with lower rectal temperature (P <.001), use of a bubble oxygenator (P <.001), and lower oxygen concentration (P =.021) but was not affected by the temperature gradient between blood and body during cooling or rewarming. CONCLUSIONS: Gaseous microemboli are increased with normoxic perfusion, but this is only important if a bubble oxygenator without a filter is used.     

Biocompatibility of extracorporeal circulation with autooxygenation.

Platelet damage, complement activation and neutropenia during cardiopulmonary bypass are the result of blood contact with artificial surfaces, mainly in the oxygenator. To evaluate biocompatibility of this kind of bypass we compared two techniques of extracorporeal circulation in 40 patients undergoing elective coronary bypass operations. In 20, a standard technique with a bubble oxygenator was used (group 1), and in the remaining 20 patients with autooxygenation, the patients' own lungs were included in the perfusion circuit (group 2). Several blood samples were taken before, during and after perfusion to estimate the corrected platelet numbers and pulmonary leucocyte sequestration in all patients, and additionally in 6 patients from each group, complement C3a and C5a anaphylatoxins were measured (radioimmunoassay). At the end of cardiopulmonary bypass, the decline of platelet number corrected to haematocrit platelet number in group 1 was significantly higher than in group 2 (P less than 0.01). There was a significant increase in circulating white blood cells when compared to pre-bypass time in both groups (P less than 0.05). However, comparison of differences between leucocyte counts in the blood of the patients' right and left atria showed enhanced leucocyte sequestration in group 1, 1.46 +/- 0.5 x 10(3)/mm3 vs only 0.34 +/- 0.2 x 10(3)/mm3 in group 2. The C3a rose progressively during extracorporeal circulation: in group 1 from 268 +/- 46 ng/l to 521 +/- 65 ng/l, and in group 2 from 244 +/- 46 ng/l to 418 +/- 34 ng/l (P less than 0.05). No characteristic changes in C5a activation were observed in either group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of L-arginine or nitroglycerine during deep hypothermic circulatory arrest in neonatal lambs

BACKGROUND: The role of nitric oxide (NO) in ischemia-reperfusion injury remains controversial. This study evaluated the effects of L-arginine (NO precursor) or nitroglycerine (NO donor) on cardiac and lung function after deep hypothermic circulatory arrest in neonatal lambs. METHOD: Three groups of anesthetized lambs underwent cardiopulmonary bypass, deep hypothermic circulatory arrest (120 minutes at 18 degrees C), and rewarming (40 minutes). During reperfusion, L-arginine (5 mg/kg per minute), nitroglycerine (2 microg/kg per minute), or saline (control group) was infused for 100 minutes. All animals were separated from cardiopulmonary bypass and observed for 3 additional hours. Preload recruitable stroke work, cardiac index, pulmonary vascular resistance, alveolar-arterial oxygen difference, and lung compliance plasma nitrate/nitrite levels (NO metabolites) were measured before and after cardiopulmonary bypass. Malondialdehyde in heart tissue and lung tissue was measured 3 hours after cardiopulmonary bypass. RESULTS: Recovery of preload recruitable stroke work and cardiac index were significantly higher in the L-arginine and nitroglycerine groups than in the control group (p < 0.05). Pulmonary vascular resistance was significantly lower in the L-arginine and nitroglycerine groups than in the control group (p < 0.05). Levels of NO metabolites and issue malondialdehyde did not differ among groups. CONCLUSIONS: L-arginine and nitroglycerine improved recovery of left ventricular function and reduced pulmonary vascular resistance after deep hypothermic circulatory arrest. The mechanism of beneficial action could involve increased NO levels, but we did not find higher levels of NO metabolites compared with controls. Tissue malondialdehyde levels were not affected by L-arginine or nitroglycerine. These results show that, at these dosage levels, provision of substrate for NO production or provision of an NO donor were beneficial to the recovery of myocardial and pulmonary vascular function.     

Disadvantages of prostacyclin infusion during cardiopulmonary bypass: a double-blind study of 50 patients having coronary revascularization

Prostacyclin (PGI2) has been suggested for use in cardiopulmonary bypass (CPB) because of its positive effects on platelet number and function. Fifty patients who underwent coronary artery bypass grafting using a bubble oxygenator received heparin, 3 mg per kilogram of body weight, and then were randomly assigned to receive PGI2, 25 ng/kg/min, beginning 5 minutes before and until the end of CPB (26 patients) or a placebo (24 patients). Both groups were similar in sex, age, heparin dose, protamine dose, and CPB time. During CPB, mean arterial pressure fell significantly with PGI2 (76 +/- 2 mm Hg to 53 +/- 2 mm Hg; p less than 0.05) and necessitated pressor substances. Platelet counts fell significantly in both groups with the start of CPB, but after 60 minutes were similar in both groups (118 +/- 9 X 10(3) versus 130 +/- 8 X 10(3); not significant [NS]) and were unchanged 3 hours after CPB. Total chest tube output was 647 +/- 51 ml (placebo group) versus 576 +/- 34 ml (PGI2 group) (NS); 18 of the patients given PGI2 required 26 transfusions compared with 16 transfusions in 8 of the patients given a placebo (p less than 0.05). In PGI2 patients, arterial oxygen tension on 100% oxygen fell from 281 +/- 18 mm Hg before CPB to 223 +/- 17 mm Hg immediately after CPB (p less than 0.05). The placebo patients did not show a change in this variable.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postperfusion lung syndrome. Comparison of Travenol bubble and membrane oxygenators.

To examine the role of the oxygenator in the postperfusion lung syndrome, we studied 16 patients undergoing aorta-coronary bypass with a bubble oxygenator and 14 similar patients with a membrane oxygenator both before and for 2 days after the operation. To maintain the same pulmonary artery occluded pressure and hemoglobin level at the end of the surgical procedure, significantly more blood was required in the bubble than in the membrane group. Postoperative pulmonary dysfunction in the bubble group was characterized by increased pulmonary vascular resistance (PVR) and lung water. The increase in lung water was present after bubble oxygenation on three successive measurements, whereas there was no increase in lung water above control value at any measurement time in the membrane group. The bubble group had a significantly greater increase in PVR at the immediate postoperative study time than did the membrane group. PVR returned to control value for the duration of study. These differences in lung water and PVR measurements may be related to greater blood component trauma with a Travenol bubble oxygenator than with a membrane lung.