Stable Defects in Semiconductor Nanowires.

Semiconductor nanowires are commonly described as being defect-free due to their ability to expel mobile defects with long-range strain fields. Here, we describe previously undiscovered topologically protected line defects with null Burgers vector that, unlike dislocations, are stable in nanoscale crystals. We analyze the defects present in semiconductor nanowires in regions of imperfect crystal growth, i.e., at the nanowire tip formed during consumption of the droplet in self-catalyzed vapor-liquid-solid growth and subsequent vapor-solid shell growth. We use a form of the Burgers circuit method that can be applied to multiply twinned material without difficulty. Our observations show that the nanowire microstructure is very different from bulk material, with line defects either (a) trapped by locks or other defects, (b) arranged as dipoles or groups with a zero total Burgers vector, or (c) have a zero Burgers vector. We find two new line defects with a null Burgers vector, formed from the combination of partial dislocations in twinned material. The most common defect is the three-monolayer high twin facet with a zero Burgers vector. Studies of individual nanowires using cathodoluminescence show that optical emission is quenched in defective regions, showing that they act as strong nonradiative recombination centers.

Complete characterization of the edited transcriptome of the mitochondrion of Physarum polycephalum using deep sequencing of RNA.

RNAs transcribed from the mitochondrial genome of Physarum polycephalum are heavily edited. The most prevalent editing event is the insertion of single Cs, with Us and dinucleotides also added at specific sites. The existence of insertional editing makes gene identification difficult and localization of editing sites has relied upon characterization of individual cDNAs. We have now determined the complete mitochondrial transcriptome of Physarum using Illumina deep sequencing of purified mitochondrial RNA. We report the first instances of A and G insertions and sites of partial and extragenic editing in Physarum mitochondrial RNAs, as well as an additional 772 C, U and dinucleotide insertions. The notable lack of antisense RNAs in our non-size selected, directional library argues strongly against an RNA-guided editing mechanism. Also of interest are our findings that sites of C to U changes are unedited at a significantly higher frequency than insertional editing sites and that substitutional editing of neighboring sites appears to be coupled. Finally, in addition to the characterization of RNAs from 17 predicted genes, our data identified nine new mitochondrial genes, four of which encode proteins that do not resemble other proteins in the database. Curiously, one of the latter mRNAs contains no editing sites.

Lagrange L4/L5 points and the origin of our Moon and Saturn's moons and rings.

The current standard theory of the origin of the Moon is that the Earth was hit by a giant impactor the size of Mars causing ejection of debris from its mantle that coalesced to form the moon; but where did this Mars-sized impactor come from? Isotopic evidence suggests that it came from 1 AU radius in the solar nebula, and computer simulations are consistent with its approaching Earth on a zero-energy parabolic trajectory. How could such a large object form at 1 AU in a quiescent disk of planetesimals without having already collided with the Earth at an earlier epoch before having the chance to grow large? Belbruno and Gott propose that the giant impactor could have formed in a stable orbit from debris at the Earth's Lagrange point L(5) (or L(4)). It would grow quietly by accretion at L(5) (or L(4)), but eventually gravitational perturbations by other growing planetesimals would kick it out into a horseshoe orbit and finally into a chaotic creeping orbit, which Belbruno and Gott show would, with high probability, hit the Earth on a near zero-energy parabolic trajectory. We can see other examples of this phenomenon occurring in the solar system. Asteroid 2002AA29 is in a horseshoe orbit relative to the Earth that looks exactly like the horseshoe orbits that Belbruno and Gott found for objects that had been perturbed from L(4)/L(5). The regular moons of Saturn are made of ice and have the same albedo as the ring particles (ice chunks, plus some dust). We (J. R. Gott, R. Vanderbei, and E. Belbruno) propose that the regular icy moons of Saturn (out to the orbit of Titan), which are all in nearly circular orbits, formed out of a thin disk of planetesimals (ice chunks) rather like the rings of Saturn today only larger in extent. In such a situation formation of objects at L(4)/L(5) might be expected. Indeed, Saturn's moon Dione is accompanied by moons (Helene and Polydeuces) at both L(4) and L(5) Lagrange points, and Saturn's moon Tethys is also accompanied by moons (Telesto and Calypso) at both L(4) and L(5) Lagrange points. Epimetheus is in a horseshoe orbit relative to Janus that is exactly like the horseshoe orbit expected for an object that has been perturbed from a location at L(4)/L(5). We propose that the rings of Saturn visible today are all that remains of this original disk; they lie inside the Roche limit where tidal forces have simply prevented the formation of large moons by accretion. Further out, the icy particles have accumulated into icy moons. Objects in external solar systems on horseshoe orbits (like those of Epimetheus relative to Janus) could be detected by a slow sinusoidal variation with time of the calculated mass of a planet from radial velocity measurements.

Clinical outcomes, angiographic patency, and resource utilization in 200 consecutive off-pump coronary bypass patients.

BACKGROUND: This retrospective study compared clinical outcomes and resource utilization in patients having off-pump coronary artery bypass grafting (OPCAB) versus conventional coronary artery bypass grafting (CABG). Angiographic patency was documented in the OPCAB group. METHODS: From April 1997 through November 1999, OPCAB was performed in 200 consecutive patients, and the results were compared with those in a contemporaneous matched control group of 1,000 patients undergoing CABG. Patients were matched according to age, sex, preexisting disease (renal failure, diabetes, pulmonary disease, stroke, hypertension, peripheral vascular disease, previous myocardial infarction, and primary or redo status. Follow-up in the OPCAB patients was 93% and averaged 13.4 months. RESULTS: Hospital death (1.0%), postoperative stroke (1.5%), myocardial infarction (1.0%), and re-entry for bleeding (1.5%) occurred infrequently in the OPCAB group. There were reductions in the rates of transfusion (33.0% versus 70.0%; p < 0.001) and deep sternal wound infection (0% versus 2.2%; p = 0.067) in the OPCAB group compared with the CABG group. Angiographic assessment of 421 grafted arteries was performed in 167 OPCAB patients (83.5%) prior to hospital discharge. All but five were patent (98.8%) (93.3% FitzGibbon A, 5.5% FitzGibbon B, 1.2% FitzGibbon O). All 163 internal mammary artery grafts were patent. Off-pump coronary artery bypass grafting reduced postoperative hospital stay from 5.7 +/- 5.3 days in the CABG group to 3.9 +/- 2.6 days (p < 0.001), with a decrease in hospital cost of 15.0% (p < 0.001). CONCLUSIONS: Off-pump coronary artery bypass grafting reduces hospital cost, postoperative length of stay, and morbidity compared with CABG on cardiopulmonary bypass. Off-pump coronary bypass grafting is safe, cost effective, and associated with excellent graft patency and clinical outcomes.

Leukodepletion and aprotinin improve clinical outcome after extracorporeal circulation.

Most cardiac operations involve the use of extracorporeal circulation with its attendant systemic inflammatory response syndrome. Many anti-inflammatory strategies hold promise for reducing the associated morbidity of cardiopulmonary bypass. The application of pharmacological and mechanical strategies to control this inflammatory response now has demonstrable clinical benefit. The additional costs of these successful strategies are offset by the economic savings and improved quality of care.

Non-templated addition of nucleotides to the 3' end of nascent RNA during RNA editing in Physarum.

RNAs in Physarum: mitochondria contain extra nucleotides that are not encoded by the mitochondrial genome, at least in the traditional sense. While it is known that insertion of non-encoded nucleotides is linked to RNA synthesis, the exact nature of this relationship remains unclear. Here we demonstrate that the efficiency of editing is sensitive not only to the concentration of the nucleotide that is inserted, but also to the concentration of the nucleotide templated just downstream of an editing site. These data strongly support a co-transcriptional mechanism of Physarum: RNA editing in which non-encoded nucleotides are added to the 3' end of nascent RNAs. These results also suggest that transcription elongation and nucleotide insertion are competing processes and that recognition of editing sites most likely involves transient pausing by the Physarum: mitochondrial RNA polymerase. In addition, the pattern of nucleotide concentration effects, the context of editing sites and the accuracy of the mitochondrial RNA polymerase argue that the mechanism of Physarum: editing is distinct from that of other co-transcriptional editing systems.

In vivo hemodynamic, histologic, and antimineralization characteristics of the Mosaic bioprosthesis.

BACKGROUND: Performance of bioprosthetic valves is limited by tissue degeneration due to calcification with reduced performance and longevity. The Mosaic bioprosthetic valve (Medtronic Heart Valves, Inc, Minneapolis, MN) combines zero pressure fixation, antimineralization properties of alpha-amino oleic acid (AOA), and a proven stent design. We tested the hypothesis that AOA treatment of Mosaic valves improves hemodynamics, antimineralization properties, and survival in a chronic ovine model. METHODS: Mitral valves were implanted in juvenile sheep with Mosaic valves with AOA treatment (n = 8) or without AOA treatment (non-AOA, n = 8), or Hancock I (HAN, n = 4) tissue valves, and explanted at 20 postoperative weeks. RESULTS: Survival was equivalent in AOA and non-AOA (140 +/- 0.4 and 129 +/- 30 days), but was significantly less in HAN (82 +/- 35). Leaflet calcium (microgCa/mg tissue) was less in AOA (9.6 +/- 13.9; p < 0.05 versus non-AOA and HAN) than non-AOA (96.3 +/- 63.8) and HAN (130.8 +/- 43.2). Explant valve orifice area (cm2) was significantly preserved in the AOA group compared with the non-AOA group (1.5 +/- 0.7 vs 0.8 +/- 0.3; p < 0.05 versus non-AOA and HAN). CONCLUSIONS: We conclude that AOA treatment of Mosaic valves reduces leaflet calcification and valve gradient in juvenile sheep, and that the Mosaic design and fixation features may offer survival advantages that must be confirmed in extended trials.

Functions and mechanisms of RNA editing.

RNA editing can be broadly defined as any site-specific alteration in an RNA sequence that could have been copied from the template, excluding changes due to processes such as RNA splicing and polyadenylation. Changes in gene expression attributed to editing have been described in organisms from unicellular protozoa to man, and can affect the mRNAs, tRNAs, and rRNAs present in all cellular compartments. These sequence revisions, which include both the insertion and deletion of nucleotides, and the conversion of one base to another, involve a wide range of largely unrelated mechanisms. Recent advances in the development of in vitro editing and transgenic systems for these varied modifications have provided a better understanding of similarities and differences between the biochemical strategies, regulatory sequences, and cellular factors responsible for such RNA processing events.

Influence of concomitant CABG and urgent/emergent status on mitral valve replacement surgery.

BACKGROUND: Outcomes and resource utilization of patients undergoing mitral valve replacement (MVR) with or without concomitant coronary artery bypass grafting (CABG) were reviewed. METHODS: Data for 1,844 patients undergoing isolated primary MVR at Emory University Hospitals between 1980 and 1997 were recorded prospectively in a computerized database. RESULTS: The four groups included patients undergoing elective MVR with (n = 360) or without CABG (n = 1332) and urgent/emergent MVR with (n = 66) or without CABG (n = 86). Length of stay was significantly higher in patients undergoing elective MVR with CABG (15 days) than in those without CABG (11 days) but was not significantly different in patients undergoing urgent/emergent MVR with CABG (17 days) than in those without CABG (19 days). In-hospital mortality was significantly higher for patients undergoing elective (14%) or urgent/emergent (41%) MVR with CABG than in those undergoing MVR without CABG (elective:6%; urgent/emergent:20%). The 19-year survival rate was 32% for patients undergoing elective MVR with CABG compared with 51% for those without CABG and 28% for patients undergoing urgent/emergent MVR with CABG compared with 46% for those without CABG. Multivariate correlates of long-term mortality included older age, concomitant CABG, and urgent/emergent status. Hospital costs were significantly higher for patients undergoing elective MVR with ($33,216) than for those without ($23,890) CABG. No significant difference in cost were noted between patients undergoing urgent/emergent MVR with ($40,535) and without ($31,981) CABG. CONCLUSIONS: The addition of CABG or urgent/emergent status to patients undergoing MVR significantly increases morbidity, mortality, and costs. Careful scrutiny of the benefits versus resource utilization is required for patients undergoing high risk MVR.

Transcription and RNA editing in a soluble in vitro system from Physarum mitochondria.

The dissection of RNA editing mechanisms in PHYSARUM: mitochondria has been hindered by the absence of a soluble in vitro system. Based on our studies in isolated mitochondria, insertion of non-encoded nucleotides into PHYSARUM: mitochondrial RNAs is closely linked to transcription. Here we have fractionated mitochondrial lysates, enriching for run-on RNA synthesis, and find that editing activity co-fractionates with pre-formed transcription elongation complexes. The establishment of this soluble transcription-editing system allows access to the components of the editing machinery and permits manipulation of transcription and editing substrates. Thus, the availability of this system provides, for the first time, a means of investigating roles for cis-acting elements, trans-acting factors and nucleotide requirements for the insertion of non-encoded nucleotides into PHYSARUM: mitochondrial RNAs. This methodology should also be broadly applicable to the study of RNA processing and editing mechanisms in a wide range of mitochondrial systems.

Stroke after coronary artery operation: incidence, correlates, outcome, and cost.

BACKGROUND: Stroke is a major complication of coronary operation, with reported rates of postoperative cerebral dysfunction ranging from 0.4% to 13.8%. In this report, the incidence, correlates, outcomes, and costs of stroke in coronary operation were evaluated at Emory University between 1988 and 1996. METHODS: Data were entered prospectively into a dedicated computerized database at Emory University and analyzed retrospectively. Univariate and multivariate analyses were utilized where appropriate. RESULTS: Data from 10,860 patients undergoing primary coronary operation between 1988 and 1996 were analyzed. There were 250 patients not entered into the database. Stroke occurred in 244 (2.2%). Univariate predictors of stroke (p<0.05) included age, female gender, hypertension, diabetes, prior stroke, prior transient ischemic attack (TIA), and carotid bruits. Multivariate correlates included age (odds ratio 1.07) previous TIA (odds ratio 2.2), and carotid bruits (odds ratio 1.9), although the area under the Receiver Operating Characteristics (ROC) curve was only 0.69, suggesting limited ability to predict stroke. One and 5 year survival rates were 64% and 44% with stroke, and 94% and 81% without stroke, respectively. Among the stroke group, 23% of the patient population died before hospital discharge. The stroke group had a significantly longer length of hospital stay, as well as higher costs. CONCLUSIONS: Stroke is a devastating complication of coronary operation, significantly increasing morbidity, mortality, and cost. Three independent variables were identified for predicting stroke, including age, previous TIA, and carotid bruits. Patients should be carefully screened for cerebrovascular disease to help prevent stroke and its associated morbidity.

Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis.

BACKGROUND: Multiple organ failure after deep hypothermic circulatory arrest (DHCA) may occur secondary to endothelial dysfunction and apoptosis. We sought to determine if DHCA causes endothelial dysfunction and apoptosis in brain, kidney, lungs, and other tissues. METHODS: Anesthetized pigs on cardiopulmonary bypass were: (1) cooled to 18 degrees C, and had their circulation arrested (60 minutes) and reperfused at 37 degrees C for 90 minutes (DHCA, n = 8); or (2) time-matched normothermic controls on bypass (CPB, n = 6). Endothelial function in cerebral, pulmonary, and renal vessels was assessed by vasorelaxation responses to endothelial-specific bradykinin (BK) or acetylcholine (ACh), and smooth muscle-specific nitroprusside. RESULTS: In vivo transcranial vasorelaxation responses to ACh were similar between the two groups. In small-caliber cerebral arteries, endothelial relaxation (BK) was impaired in CPB vs DHCA (maximal 55% +/- 2% [p < 0.05] vs 100% +/- 6%). Pulmonary artery ACh responses were comparable between CPB (110% +/- 10%) and DHCA (83% +/- 6%), but responses in pulmonary vein were impaired in DHCA (109% +/- 3%, p < 0.05) relative to CPB (137% +/- 6%). In renal arteries, endothelial (ACh) responses were impaired in DHCA (71% +/- 13%) relative to CPB (129% +/- 14%). Apoptosis (DNA laddering) occurred primarily in duodenal tissue, with a greater frequency in DHCA (56%, p < 0.05) compared with normothermic CPB (17%) and nonbypass controls (0%). CONCLUSIONS: DHCA is associated with endothelial dysfunction in cerebral microvessels but not in the in vivo transcranial vasculature; in addition, endothelial dysfunction was noted in large-caliber renal arteries and pulmonary veins. DHCA is also associated with duodenal apoptosis. Vascular endothelial dysfunction and apoptosis may be involved in the pathophysiology of multisystem organ failure after DHCA.

Risk neutralization in cardiac operations: detection and treatment of associated carotid disease.

BACKGROUND: A screening and treatment protocol was implemented to extend the benefit of prophylactic carotid endarterectomy to patients who had open heart operations. METHODS: Patients aged 65 or older or who at any age had left main coronary disease, transient ischemic attack, or stroke were eligible for preoperative carotid duplex screening. Carotid endarterectomies and open heart operations were planned as a staged (n = 59) or combined procedure (n = 55) for angiographically confirmed carotid stenosis of at least 80%. RESULTS: Duplex scans were obtained in 1,719 of 7,035 open heart surgical patients over 8 years. The overall stroke rate was 1.5% (108 of 7,035). Seven of these were strokes of carotid origin (0.1%). There were 129 patients with at least 80% stenosis. One hundred fourteen had carotid endarterectomy preceding open heart operation, and none had carotid artery stroke. Twelve patients with at least 80% carotid stenosis by duplex scan had open heart operations without prophylactic carotid endarterectomies. There were four carotid strokes in these 12 patients (p = 0.0001; odds ratio, 20.2). Stroke risk remained significantly elevated (16.8%, p = 0.005) in the 50% to 79% group. The changes associated with the reduced risk afforded by this screening and treatment strategy amounted to $346 for each patient in the study. CONCLUSIONS: The risk of carotid stroke at the time of cardiac operation can be defined by duplex screening. Prophylactic carotid endarterectomy neutralizes the risk in those with at least 80% stenosis. Consideration for lowering the threshold for assessment and treatment of carotid stenoses appears warranted. The economic investment is recouped by the savings in system resources that would have been depleted through care for carotid stroke and its sequelae.

A randomized trial of endoscopic versus open saphenous vein harvest in coronary bypass surgery.

BACKGROUND: The purpose of this study was to determine whether or not endoscopic vein harvest is a reliable, beneficial, and cost-effective method for saphenous vein harvest in coronary bypass surgery (CABG). METHODS: A total of 100 patients having primary CABG were prospectively randomized to either endoscopic (EVH; n = 47) or open saphenous vein harvest (OVH; n = 50). Three patients in the EVH group required both techniques and were excluded from analysis. RESULTS: The groups did not differ in preoperative characteristics, including: age, gender, left ventricular function, height, weight, percent over ideal body weight, incidence of diabetes, peripheral vascular disease, or preoperative laboratory values (creatinine, albumin, or hematocrit). The EVH group had longer vein harvest and preparation times than the OVH group, while the incision length was significantly shorter. There was no difference between groups in mortality, perioperative myocardial infarction, intensive care unit or postoperative length of stay, blood product utilization, or discharge laboratory measures. There was more drainage noted from leg incisions at hospital discharge in the OVH (34%) versus EVH group (8%; p = 0.001), but more ecchymosis in the EVH group. Although there was a trend towards reduced leg incision pain in the EVH group, there was no statistically significant difference in pain or in the quality of life measure at any point in time. There was no difference between groups in readmission to hospital, administration of antibiotics, or incidence of leg infection. While mean hospital charges for the EVH group were approximately $1,500 greater than for OVH, this difference did not reach statistical significance. CONCLUSIONS: EVH is a safe, reliable, and cost-neutral method for saphenous vein harvest. The best indication for EVH may be in patients who are at increased risk for wound infection and in those for whom cosmesis is a major concern.

601 octogenarians undergoing cardiac surgery: outcome and comparison with younger age groups.

BACKGROUND: Cardiac valve replacement and coronary artery bypass graft surgery (CABG) are being applied with increasing frequency in patients 80 years of age and older. METHODS: Six hundred one consecutive patients older than 80 years, undergoing cardiac surgery between 1976 and 1994 (CABG with saphenous vein graft, 329 [54.7%]; CABG with left internal mammary artery, 101 [16.8%]; CABG + valve, 80 [13.3%]; isolated aortic valve replacement, 71 [11.8%]; isolated mitral valve replacement, 18 [3.0%]), were studied retrospectively to assess short- and long-term survival. They were compared with 11,386 patients aged 60 to 69 years and 5,698 patients aged 70 to 79 years undergoing similar procedures during the same time interval. RESULTS: In comparison with patients 60 to 69 years old, more octogenarians were women (44.4% versus 25.6%, p<0.0001), had class IV angina (54.1% versus 38.9%, p<0.0001), and had congestive heart failure class IV (4.9% versus 3.0%, p = 0.0001). In-hospital death rates (9.1% versus 3.4%, p<0.0001) and stroke (5.7% versus 2.6%, p<0.0001) reflected these adverse clinical risk factors. However, Q-wave infarction tended to be less frequent (1.5% versus 2.6%, p = 0.102). Interestingly, hospital mortality (9.1% versus 6.7%, p = 0.028) was only slightly increased, and stroke (5.7% versus 4.7%, p = 0.286) was not more common in octogenarians than in patients 70 to 79 years old. Late-survival curves have similar slopes for the first 5 years in all clinical subgroups. However, after 5 years there is a more rapid decline in octogenarians than in younger age groups. Median 5-year survival was 55% for patients older than 80 years, 69% for patients 70 to 79 years, and 81% for patients 60 to 69 years old. CONCLUSIONS: When appropriately applied in selected octogenarians, cardiac surgery can be performed with acceptable mortality and excellent 5-year survival.

Clinical outcomes and angiographic patency in 125 consecutive off-pump coronary bypass patients.

BACKGROUND: This study compared clinical outcomes, length of stay, and hospital costs in patients having off-pump coronary bypass (OPCAB) versus conventional bypass surgery (CABG). METHODS: From November 1996 through April 9, 1999, OPCAB was performed for 125 consecutive patients and compared with a contemporaneous, matched control group of 625 CABG patients. Patients were matched according to age, gender, incidence of renal failure, diabetes, pulmonary disease, stroke (CVA), hypertension, peripheral vascular disease, and previous myocardial infarction. Follow-up in the OPCAB patients was 100% and averaged 15 months. RESULTS: An average of 2.0 grafts per patient were performed in the OPCAB group (range 1-5). Ninety-four OPCAB patients (75.2%) had a total of 179 grafts assessed angiographically prior to hospital discharge. All but 4/179 grafts (2.2%) were patent, including 94 of 94 IMA grafts (100%). There were no in-hospital deaths in the OPCAB group compared to a mortality rate of 1.4% in the CABG group. OPCAB reduced postoperative hospital stay from 5.5 days in the traditional CABG group to 3.3 days (p=.002), with a decrease in hospital cost of 24% (p = .01). In addition, there was a significant reduction in the rate of transfusion in the OPCAB group (29.6%) compared to the CABG group (56.5%, p = .0001). Two OPCAB patients required postoperative intervention to improve graft patency during the follow-up period. No internal mammary grafts required revision. There was one perioperative CVA and one myocardial infarction in the OPCAB group. CONCLUSIONS: OPCAB surgery reduces hospital cost, postoperative length of stay, and transfusion rate compared to CABG. OPCAB is safe, cost effective, and associated with excellent graft patency and clinical outcomes.

Improving cost and outcome of coronary surgery.

BACKGROUND: There has been increasing interest in improving the outcome of coronary surgery while also seeking to minimize cost. It was the purpose of the present study to determine changes in the outcome and cost of CABG between 1988 and 1996. METHODS AND RESULTS: The outcome and costs for 12,266 patients undergoing CABG were evaluated. Clinical data were gathered from the Emory Cardiovascular Database, and financial data were obtained from the UB92 formulation of the hospital bill. Charges were reduced to cost through the use of departmental cost-to-charge ratios. Costs were inflated to 1996 costs by using the medical care inflation rate. The patients became sicker, especially with increased incidences of hypertension, diabetes, and prior myocardial infarctions and a decrease in ejection fraction over the study period. Mortality rates tended to decrease from 4.7% to 2.7% (P = 0.07). After accounting for increasing indexes of severity of disease over the period, there was a significant decrease in death (OR, 0.90/y; P = 0.0001). Q-wave myocardial infarction rate fell from 4.1% to 1.3% (P < 0.0001). Mean hospital cost decreased from $22,689 to $15,987. Length of stay after surgery decreased from 9.2 to 5.9 days. After accounting for other variables, cost decreased by $1118 per year, and annual length of stay decreased by 0.55 day. CONCLUSIONS: The outcome of CABG continues to improve with declines in mortality rate and Q-wave myocardial infarction. This was accomplished while decreasing costs and length of stay. Whether these favorable trends will continue remains to be seen.

Modifying risk for extracorporeal circulation: trial of four antiinflammatory strategies.

BACKGROUND: Despite recent rediscovery of beating heart cardiac surgical techniques, extracorporeal circulation remains appropriate for most heart operations. To minimize deleterious effects of cardiopulmonary bypass, antiinflammatory strategies have evolved. METHODS: Four state-of-the-art strategies were studied in a prospective, randomized, preoperatively risk stratified, 400-patient study comprising primary (n = 358), reoperative (n = 42), coronary (n = 307), valve (n = 27), ascending aortic (n = 9), and combined operations (n = 23). Groups were as follows: standard, roller pump, membrane oxygenator, methylprednisolone (n = 112); aprotinin, standard plus aprotinin (n = 109); leukocyte depletion, standard plus a leukocyte filtration strategy (n = 112); and heparin-bonded circuitry, centrifugal pumping with surface modification (n = 67). RESULTS: Analysis of variance, linear and logistic regression, and Pearson correlation were applied. Actual mortality (2.3%) was less than half the risk stratification predicted mortality (5.7%). The treatment strategies effectively attenuated markers of the inflammatory response to extracorporeal circulation. Compared with the other groups the heparin-bonded circuit had highly significantly decreased complement activation (p = 0.00001), leukocyte filtration blunted postpump leukocytosis (p = 0.043), and the aprotinin group had less fibrinolysis (p = 0.011). Primary end points, length of stay, and hospital charges, were positively correlated with operation type, age, pump time, body surface area, stroke, pulmonary sequelae, predicted risk for stroke, predicted risk for mortality, and risk strata/treatment group interaction (p = 0.0001). In low-risk patients, leukocyte filtration reduced length of stay by 1 day (p = 0.02) and mean charges by $2,000 to $6,000 (p = 0.05). For high-risk patients, aprotinin reduced mean length of stay up to 10 fewer days (p = 0.02) and mean charges by $6,000 to $48,000 (p = 0.0007). CONCLUSIONS: These pharmacologic and mechanical strategies significantly attenuated the inflammatory response to extracorporeal circulation. This translated variably into improved patient outcomes. The increased cost of treatment was offset for selected strategies through the added value of significantly reduced risk.