Kenneth M. Taylor

Hemoglobin Scavenger Receptor CD163 Mediates Interleukin-10 Release and Heme Oxygenase-1 Synthesis: Antiinflammatory Monocyte-Macrophage Responses In Vitro, in Resolving Skin Blisters In Vivo, and After Cardiopulmonary Bypass Surgery

Abstract— The recently described hemoglobin scavenger receptor CD163 mediates the endocytosis of hemoglobin:haptoglobin (Hb:Hp) complexes and thereby counters Hb-induced oxidative tissue damage after hemolysis. Although CD163 has been indirectly associated with antiinflammatory and atheroprotective activity, no ligand-receptor-effector pathway has yet been described for this receptor. To understand the significance of CD163 and more clearly define downstream pathways linked to inflammatory resolution, we studied the expression and function of CD163 in human monocytes/macrophages using both in vitro and in vivo models. Differentiation of human blood monocytes into macrophages either by in vitro culture or in resolving cantharidin-induced skin blisters led to an equivalent increase (>15×) in CD163 expression. Elevated CD163 levels were also noted on circulating monocytes in cardiac surgical patients during the resolution phase of the systemic inflammatory response to cardiopulmonary bypass surgery. In each case, binding of Hb:Hp to CD163-bearing cells elicited potent interleukin-10 secretion, and this was inhibited by the anti-CD163 antibody RM3/1. Release of interleukin-10, in turn, induced heme oxygenase-1 stress protein synthesis via an autocrine mechanism. Such induction of heme oxygenase-1 was observed in vivo 24 to 48 hours after the onset of cardiopulmonary bypass surgery. These results identify novel antiinflammatory and cytoprotective effector pathways in human monocytes/macrophages related to Hb scavenging and metabolism, which may have relevance in atheroprotection, wound healing, and patient recovery postoperatively.

Lung injury and acute respiratory distress syndrome after cardiopulmonary bypass

Cardiopulmonary bypass is often followed by pulmonary dysfunction as assessed by measuring the alveolar-arterial oxygenation gradient, intrapulmonary shunt, degree of pulmonary edema, pulmonary compliance, and pulmonary vascular resistance. It is also regarded as a risk factor for development of acute respiratory distress syndrome. On the other hand, cardiopulmonary bypass is associated with a whole body inflammatory response, which involves activation of complement, leukocytes, and endothelial cells with secretion of cytokines, proteases, arachidonic acid metabolites, and oxygen free radicals. Leukocyte adhesion to microvascular endothelium, leukocyte extravasation, and tissue damage are the final steps. Although the inflammatory response to cardiopulmonary bypass often remains at subclinical levels, it can also lead to major organ dysfunction and multiple organ failure. This review article summarizes the recent literature on the molecular and cellular mechanisms involved in the phenomenon of pulmonary dysfunction after cardiopulmonary bypass. It also summarizes reports on the prevalence and mortality of acute respiratory distress syndrome after cardiac surgery.

Brain swelling in first hour after coronary artery bypass surgery.

Six patients undergoing routine coronary artery bypass surgery were examined by magnetic resonance imaging of the brain before surgery, immediately afterwards, and 6-18 days later. Brain swelling was visible in all six patients on the immediate postoperative scan. In five patients who had later scans the swelling had subsided. No major neurological deficits were seen, and the patients were extubated successfully within 3 h of the operation. The mechanism of the cerebral swelling is uncertain, but it may provide insight into the cause of neurophysiological deficits seen after coronary artery surgery.

Generic, Simple Risk Stratification Model for Heart Valve Surgery

Background—Heart valve surgery has an associated in-hospital mortality rate of 4% to 8%. This study aims to develop a simple risk model to predict the risk of in-hospital mortality for patients undergoing heart valve surgery to provide information to patients and clinicians and to facilitate institutional comparisons. Methods and Results—Data on 32 839 patients were obtained from the Society of Cardiothoracic Surgeons of Great Britain and Ireland on patients who underwent heart valve surgery between April 1995 and March 2003. Data from the first 5 years (n=16 679) were used to develop the model; its performance was evaluated on the remaining data (n=16 160). The risk model presented here is based on the combined data. The overall in-hospital mortality was 6.4%. The risk model included, in order of importance (all P<0.01), operative priority, age, renal failure, operation sequence, ejection fraction, concomitant tricuspid valve surgery, type of valve operation, concomitant CABG surgery, body mass index, preoperative arrhythmias, diabetes, gender, and hypertension. The risk model exhibited good predictive ability (Hosmer-Lemeshow test, P=0.78) and discriminated between high- and low-risk patients reasonably well (receiver-operating characteristics curve area, 0.77). Conclusions—This is the first risk model that predicts in-hospital mortality for aortic and/or mitral heart valve patients with or without concomitant CABG. Based on a large national database of heart valve patients, this model has been evaluated successfully on patients who had valve surgery during a subsequent time period. It is simple to use, includes routinely collected variables, and provides a useful tool for patient advice and institutional comparisons.

Aortic valve replacement in patients 80 years of age and older: survival and cause of death based on 1100 cases: collective results from the UK Heart Valve Registry.

BACKGROUND Aging of the population and advances in preoperative and postoperative care are reflected in an increasing number of patients > or = 80 years of age undergoing aortic valve replacement (AVR) in the United Kingdom. The present study presents data on postoperative 30-day mortality, actuarial survival, and cause of death based on a large collective patient population. METHODS AND RESULTS Data were extracted from the UK Heart Valve Registry. From January 1986 to December 1995, 1100 patients > or = 80 years of age underwent AVR and were reported to the registry. Six hundred eleven patients (55.5%) were women. The mean follow-up time was 38.9 months. The 30-day mortality was 6.6%. Of the 73 early deaths, 42 were due to cardiac reasons. The actuarial survival was 89%, 79.3%, 68.7%, and 45.8% at 1, 3, 5, and 8 years, respectively. After the first 30 postoperative days, 144 of the 205 deaths were due to noncardiac reasons. Malignancy, stroke, and pneumonia were the most common causes of late death. Bioprosthetic valves were implanted in 969 patients (88%) and mechanical valves in 131 (12%) patients. There was no difference in early mortality and actuarial survival between the two groups (P>.05). CONCLUSIONS The above results suggest that under the selection criteria for AVR currently applied in the United Kingdom, patients > or = 80 years of age show a satisfactory early postoperative outcome and moderate medium-term survival benefit.

Effects of cardiopulmonary bypass on leukocyte and endothelial adhesion molecules

During the inflammatory response, triggered by cardiopulmonary bypass, interaction between activated leukocytes, platelets, and endothelial cells is mediated through the expression of three main groups of adhesion molecules: the selectins, the integrins, and the immunoglobulin superfamily. The selectins, which mediate the initial rolling of the leukocyte on the endothelium, are divided in three subgroups: L-selectin is expressed on all three leukocyte types, P-selectin is expressed on platelets and endothelial cells, and E-selectin is only expressed on endothelial cells. Integrins can be found on most cell types, consist of an alpha and a beta subunit and mediate firm adhesion of the leukocyte and migration into the tissues. They are classified into subgroups according to the type of their beta subunit. Immunoglobulins such as ICAM-1 and VCAM-1 are expressed mainly on endothelium and act as ligands for certain integrins. This review article summarizes the existing, and rapidly expanding, literature concerning the effects of cardiopulmonary bypass on the expression of leukocyte and endothelial adhesion molecules. Deeper understanding of the, behavior and the role of adhesion molecules during cardiopulmonary bypass may facilitate effective intervention in the inflammatory response process and suppression of its adverse effects.

Cardiopulmonary bypass impairs small intestinal transport and increases cut permeability

Gastrointestinal damage occurs in 0.6% to 2% of patients after cardiopulmonary bypass (CPB), and carries a mortality of 12% to 67%. The incidence of subclinical gastrointestinal damage may be much greater. We examined the effects of nonpulsatile, hypothermic CPB on intestinal absorption and permeability in 41 patients. Bowel mucosal saccharide transport and permeation were evaluated using 100 mL of an oral solution containing 3-O-methyl-D-glucose (0.2 g), D-xylose (0.5 g), L-rhamnose (1.0 g), and lactulose (5.0 g) to assess active carrier-mediated, passive carrier-mediated, transcellular, and paracellular transport, respectively, with a 5-hour urine analysis. Patients were studied before, immediately after, and 5 days after CPB. Immediately after CPB there was a decrease in urinary excretion of 3-O-methyl-D-glucose (from 34% +/- 2.2% to 5.2% +/- 0.7%; p < 0.0001), D-xylose (from 25.4% +/- 1.4% to 4.1% +/- 0.8%; p < 0.0001), and L-rhamnose (from 8.3% +/- 0.6% to 2.6% +/- 0.4%; p < 0.0001). The permeation of 3-O-methyl-D-glucose and D-xylose returned to normal levels 5 days after CPB, but that of L-rhamnose remained significantly below pre-CPB values at 6.6% +/- 0.5% (p = 0.004). However, the permeation of lactulose increased after CPB (from 0.35% +/- 0.04% to 0.59% +/- 0.1%; p = 0.018), and the lactulose/L-rhamnose gut permeability ratio increased markedly (from 0.045 +/- 0.04 to 0.36 +/- 0.08; normal = 0.06 to 0.08; p = 0.004). Patients who had a CPB time of 100 minutes or more had a greater increase in gut permeability (p = 0.049).(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Damage During Cardiopulmonary Bypass

The development of systems that allow cardiopulmonary bypass have been responsible for the growth of our specialty. In recent years continuing reduction in the mortality associated with cardiac operations has reinforced our confidence in the reliability and safety of perfusion equipment. Cardiac surgeons are aware that the mortality for most cardiac surgical procedures has decreased dramatically and overall morbidity has been reduced significantly. However, it is still clear that cardiopulmonary bypass techniques are not perfect. Indeed, it is fair to say that the period of bypass still contributes to significant morbidity in most patients. In particular, cerebral injury, the focus of this review, is a significant problem for patients and their caregivers and for funding of health-care systems. Incidence rates for stroke are around 2% to 3%, with increased risk in elderly patients and other high-risk groups. This relatively low incidence of what is universally recognized as a serious complication may be contrasted with the much higher reported incidence of cognitive defects assessed by neuropsychologic testing. The incidence of cognitive defects is as high as 60% at 8 days postoperative with reduction to 25% to 30% incidence at 8 weeks and 12 months. There are a variety of ways, at least potentially, in which the brain may be injured during an operation with cardiopulmonary bypass, including reduced cerebral blood flow, microembolism and macroembolism, and a systemic inflammatory response. These mechanisms interrelate and produce synergistic, cumulative effects on brain function during and after the operation. Reducing the incidence and effects of this altered brain function will rely on both preventive and therapeutic strategies. These, in turn, must be based on an understanding of the pathophysiology of these mechanisms of cerebral injury and directed toward ways to optimize cerebral perfusion, minimize embolic vascular occlusion, and develop pharmacologic approaches to modify the systemic inflammatory response.

The platelet in cardiopulmonary bypass

Platelets are the smallest of the blood cells and are known to be activated during cardiopulmonary bypass. They play a role in many associated complications. Both quantitative and qualitative platelet defects have been demonstrated, resulting in microvascular hemorrhage and thromboembolism. As their interactions with endothelium and other blood cells are unraveled, the important contribution they make toward the systemic inflammatory response to operation seen in cardiopulmonary bypass is increasingly evident. In this review, we consider platelet activation during cardiopulmonary bypass, the resultant clinical effects, and potential approaches to therapy and prevention.

Aprotinin therapy in cardiac operations : a report on use in 41 cardiac centers in the United Kingdom

Aprotinin, a serine protease inhibitor, has recently been shown to reduce blood loss in cardiac surgical patients. Data on the safety and efficacy of aprotinin therapy administered to 671 cardiac surgical patients in 41 United Kingdom cardiac surgical units have been submitted to interim analysis. The patients studied were in high-risk categories for excessive bleeding, including 457 redo operations and 79 patients with active infective endocarditis. Overall mortality was 12% in redo cases and 5.1% in first-time operations. Adverse events were reported in only 20 patients (3%). Median blood loss at 24 hours after operation was 400 mL, and median transfusion volume throughout the operative and postoperative period was 2 units. These data confirm that the use of aprotinin therapy in high-risk cardiac surgical patients is associated with a low incidence of adverse events.