Genome sequence of the plant pathogen and biotechnology agent Agrobacterium tumefaciens C58.

Agrobacterium tumefaciens is a plant pathogen capable of transferring a defined segment of DNA to a host plant, generating a gall tumor. Replacing the transferred tumor-inducing genes with exogenous DNA allows the introduction of any desired gene into the plant. Thus, A. tumefaciens has been critical for the development of modern plant genetics and agricultural biotechnology. Here we describe the genome of A. tumefaciens strain C58, which has an unusual structure consisting of one circular and one linear chromosome. We discuss genome architecture and evolution and additional genes potentially involved in virulence and metabolic parasitism of host plants.

Clinical outcomes after aortic valve replacement with the Toronto stentless porcine valve.

BACKGROUND: Hemodynamic benefits of the Toronto stentless porcine valve have been documented. Clinical well-being and freedom from major valve-related events have been less well defined. METHODS: A total of 447 patients were prospectively followed for up to 8 years (1,745.2 valve years total, 3.9 valve years/patient). The patient demographics included 66% men, mean age 65 years, New York Heart Association functional class III-IV 55%, concomitant coronary artery bypass grafting 41%. RESULTS: We found that 83.7% of patients were in New York Heart Association functional class I and 80.8% had 0 to 1+ aortic insufficiency. Mean gradient at 6 years (n = 75) was 4.4 mm Hg and mean effective orifice area (EOA) 2.4 cm2. Late adverse event rates per patient per year were: embolism 1.0%, endocarditis 0.4%, thrombosis 0%, structural deterioration 0.2%, explant 0.3%, and valve-related death 0.6%. Freedom from valve-related death at 6 years was 95.8%; from cardiac death 96.3%. Freedom from endocarditis was 98.4%, from embolism 93.9%, from structural deterioration 97.4%, and freedom from explant 98.1%. For patients older than 60 years, freedom from structural deterioration was 100%. CONCLUSIONS: These results confirm satisfactory clinical outcomes after aortic valve replacement with the Toronto stentless porcine valve, with a low incidence of valve-related adverse events as long as 96 months after valve replacement.

The radial artery versus the saphenous vein graft in contemporary CABG: a case-matched study.

BACKGROUND: Although use of the internal thoracic artery has been shown to improve outcomes after coronary artery bypass grafting, the same cannot be said of alternative arterial conduits. To determine the benefit of radial artery (RA) grafting, a case-matched review was undertaken. METHODS: Between March 1994 and March 1999, 2,847 patients underwent isolated coronary artery bypass grafting with a left internal thoracic artery graft, plus saphenous vein grafts (SVGs). Of these patients, 478 also received an RA graft (RA group). The RA patients were matched at a ratio of 1:2 with patients receiving only SVGs and a left internal thoracic artery graft (SVG group; n = 956) using six prognostic risk factors: age, sex, Canadian Cardiovascular Society class, left ventricular grade, number of diseased vessels, and timing of operation. Target vessels were graded according to quality and graftability and were similar between groups. Outcomes were evaluated by univariate and multivariate analyses. RESULTS: There was a significantly higher prevalence of diabetes, hypertension, and peripheral vascular disease in the RA group (p < 0.05). Although stay in the intensive care unit was shorter in the RA group (RA, 30 +/- 2 hours, and SVG, 37 +/- 2 hours; p = 0.0002), total hospital stay was similar between groups. The incidence of perioperative myocardial infarction was higher in the SVG group (SVG, 31 of 956 or 3.2%, and RA, 6 of 478 or 1.3%; p = 0.02). Multivariate analysis revealed RA grafting to be protective against early mortality and morbidity (odds ratio = 0.58; 95% confidence interval, 0.37 to 0.90; p = 0.015) and late mortality and morbidity including late reintervention (risk ratio = 0.60; 95% confidence interval, 0.37 to 0.93; p = 0.02). Actuarial freedom from events at 36 months postoperatively was greater in the RA group (RA, 95% +/- 2%, and SVG, 86% +/- 4%; p = 0.01). CONCLUSIONS: Despite a higher prevalence of preoperative comorbidity, patients in the RA group demonstrated improved outcomes after coronary artery bypass grafting. The RA is a viable and beneficial conduit for this operation.

Midterm survival of stented versus stentless valves: does concomitant coronary artery bypass grafting impact survival?

The purpose of this study was to examine the impact of concomitant coronary artery bypass grafting (CABG) and valve design on survival following aortic valve replacement (AVR) with stentless and stented bioprostheses. Survival data for 1798 patients undergoing AVR between 1991 and 1997 with either a stentless (Medtronic Freestyle = 700, Toronto SPV = 447; N = 1147) or stented (Hancock II = 224, Carpentier-Edwards SAV = 427; N = 651) valve were analyzed. Bivariable analyses using Kaplan-Meier survival curves and log-rank test were performed to compare survival probabilities by valve type. Multivariable stepwise Cox's proportional hazard models were used to control for potentially confounding variables. Concomitant CABG was performed in 41% of stentless and 46% of stented patients (P =.04). Survival probability at 5 years was 0.84 (95% CI = 0.81, 0.87) for stentless versus 0.79 (95% CI = 0.75, 0.83) for stented patients (P =.004). In the absence of concomitant CABG, survival was superior in stentless (0.84) over stented (0.80) patients, but these differences were not statistically significant (P =.053). In patients that underwent AVR with concomitant CABG, survival was significantly better in stentless patients (0.82) than in stented individuals (0.77, P =.049). The unadjusted hazard ratio for stented versus stentless was 1.44 (95% CI = 1.12, 1.86, P =.005). In the final Cox's proportional hazard model the variables that effected survival were valve type and age in decades. New York Heart Association class at the time of surgery had a marginal effect on survival. The data demonstrate improved midterm survival with stentless versus stented valves. Subgroup analysis suggests survival benefits of stentless valves may be greater in patients who undergo concomitant CABG surgery.

Late results of the Warm Heart Trial: the influence of nonfatal cardiac events on late survival.

BACKGROUND: The Warm Heart Trial randomized 1732 CABG patients to receive warm or cold blood cardioplegia. In the warm cardioplegia patients, nonfatal perioperative cardiac events were significantly decreased and the mortality rate was nonsignificantly decreased (1. 4% versus 2.5%, P:=0.12). The purpose of the present study was to evaluate the late results of these trial patients. METHODS AND RESULTS: Randomization was stratified according to surgeon and urgency of the operation. Seven hundred sixty-two patients recruited from 1 of the centers were followed through the hospital clinic for late events. Late survival (including perioperative deaths) at 72 months was nonsignificantly greater in the warm cardioplegia patients (94.5+/-1.7%, mean+/-SEM) than in the cold cardioplegia patients (90.9+/-2.6%). Independent predictors of mortality by Cox proportional hazards model were redo CABG, diabetes mellitus, renal insufficiency, and increasing age. The influence of nonfatal perioperative events (perioperative myocardial infarction according to computerized ECG readings or low output syndrome as determined by an outcome committee) on late survival was also analyzed. Late survival at 84 months was significantly reduced in the group who experienced nonfatal perioperative outcomes (94.5+/-1.7% versus 84. 9+/-4.5%, P:<0.001) and remained a significant predictor after adjustment for other important variables (risk ratio 6.4, 95% CI 1. 87 to 8.73, P:<0.0001). CONCLUSIONS: Effective myocardial protection through either cold or warm blood cardioplegia is essential, because late survival is significantly reduced in patients with nonfatal perioperative cardiac outcomes.

The influence of gender on the outcome of coronary artery bypass surgery.

BACKGROUND: To assess the impact of gender as an independent risk factor for early and late morbidity and mortality following coronary artery bypass surgery. METHODS: Perioperative and long-term data on all 4,823 patients undergoing isolated coronary bypass operations from November 1989 to July 1998 were analyzed. Of these patients, 932 (19.3%) were females. RESULTS: During the years 1989 to 1998 there was a progressive increase in the percentage of women undergoing coronary artery bypass surgery. The following preoperative risk factors were more prevalent among women than men: age above 70, angina class 3 or 4, urgent operation, preoperative intraaortic balloon pump usage, congestive heart failure, previous percutaneous transluminal coronary angioplasty, diabetes, hypertension, and peripheral vascular disease (all p < 0.05). Men were more likely to have an ejection fraction less than 35%, three-vessel disease, repeat operations, and a recent history of smoking. Women had a statistically significant smaller mean body surface area than men (1.72+/-0.18 versus 1.96%+/-0.26% m2). On average, women had fewer bypass grafts constructed than men (2.9%+/-0.8% versus 3.2%+/-0.9%) and were less likely to have internal mammary artery grafting (76.2% versus 86.1%), multiple arterial conduits (10.1% versus 19.8%), or coronary endarterectomy performed (4.9% versus 8.6%). The early mortality rate in women was 2.7% versus 1.8% in men (p = 0.09). Women were more prone to perioperative myocardial infarction (4.5% versus 3.1% p < 0.05). After adjustment for other risk variables, female gender was not an independent predictor of early mortality but was a weak independent predictor for the prespecified composite endpoint of death, perioperative myocardial infarction, intraaortic balloon counterpulsation pump insertion, or stroke (8.55 versus 5.9%; odds ratio, 1.30; 95% confidence interval, 0.99 to 1.68; p = 0.05) Recurrent angina class 3 or 4 was more frequent in female patients (15.2%+/-4.0% versus 8.5%+/-2.0% at 60 months, p = 0.001) but not repeat revascularization procedures (percutaneous transluminal coronary angioplasty, redo) (0.6%+/-0.3% versus 4.1%+/-0.8% at 60 months). Actuarial survival at 60 months was greater in women then men (93.1%+/-1.7% versus 90.0%+/-1.0%), and after adjustment for other risk variables, female gender was protective for late survival (risk ratio, 0.40; 95% confidence interval, 0.16-0.74; p < 0.005). CONCLUSIONS: Perioperative complications were increased and recurrent angina more frequent in women. Despite this, late survival was increased in women compared with men after adjustment for other risk variables

Oxidation-reduction properties of disulfide-containing proteins of the Rhodobacter capsulatus cytochrome c biogenesis system.

Oxidation-reduction titrations for the active-site disulfide/dithiol couples of the helX- and ccl2-encoded proteins involved in cytochrome c biogenesis in the purple non-sulfur bacterium Rhodobacter capsulatus have been carried out. The R. capsulatus HelX and Ccl2 proteins are predicted to function as part of a dithiol/disulfide cascade that reduces a disulfide on the apocytochromes c so that two cysteine thiols are available to form thioether linkages between the heme prosthetic group and the protein. Oxidation-reduction midpoint potential (E(m)) values, at pH 7.0, of -300 +/- 10 and -210 +/- 10 mV were measured for the HelX and Ccl2 (a soluble, truncated form of Ccl2) R. capsulatus proteins, respectively. Titrations of the disulfide/dithiol couple of a peptide designed to serve as a model for R. capsulatus apocytochrome c(2) have also been carried out, and an E(m) value of -170 +/- 10 mV was measured for the model peptide at pH 7.0. E(m) versus pH plots for HelX, Ccl2, and the apocytochrome c(2) model peptide were all linear over the pH range from 5.0 to 8.0, with the -59 mV/pH unit slope expected for a reaction in which two protons are taken up for each disulfide that is reduced. These results provide thermodynamic support for the proposal that HelX reduces Ccl2 and that reduced Ccl2, in turn, serves as the reductant for the production of the two thiols of the CysXxxYyyCysHis heme-binding motif of the apocytochromes.

Trends in coronary artery bypass surgery results: a recent, 9-year study.

BACKGROUND: The demographics of patients undergoing coronary artery bypass grafting (CABG) have changed over time and may contribute to differing operative mortality and the combination of mortality and morbidity (M + M). In this study, the trends in results are analyzed and causes are suggested. METHODS: Prospectively collected data concerning 4,839 CABG operations was divided into three time cohorts (1990 to 1992, 1993 to 1995, 1996 to 1998) and analyzed by univariate and multivariate techniques. RESULTS: Mean age and female gender frequency increased in the later time cohorts (60.7 +/- 9.0 to 63.4 +/- 9.9 years and 16.5% to 21.4%, respectively). The following comorbidities were more prevalent in the later time cohorts: diabetes (26.7% versus 18.6%), renal failure (8.5% versus 2.2%), peripheral vascular disease (20.7% versus 11.0%), previous cerebrovascular accident (6.7% versus 5.0%), urgent procedures (41.5% versus 26.9%), unstable angina (47.8% versus 31.7%), urgent CABG following myocardial infarction (17.1% versus 7.3%), previous percutaneous transluminal coronary angioplasty (8.0% versus 4.5%), ejection fraction less than 35% (20.5% versus 10.4%), (all p < 0.05). Procedurally, increased utilization of the left internal mammary artery, multiple arterial conduits, and warm blood cardioplegia occurred in the later cohorts (91.2%, 22.2%, and 80.4% versus 78.7%, 3.4%, and 38.0%, respectively). The mortality rate was 2.0% and the M + M rate was 15.6% in all 4,839 patients. The mortality and M + M for the three cohorts were 1.6%, 2.0%, and 2.3% and 18.4%, 17.2% and 12.5%, respectively. The risk-adjusted mortality and M + M decreased from 2.4% and 15.9%, respectively, in 1990 to 1992 to 1.8% and 8.4% in 1996 to 1998 (p < 0.001). The difference in adjusted event rates was minimized when the surgical factors were entered into the model. CONCLUSIONS: Over time, there has been a trend toward operating on older patients with more comorbidities. Though hospital mortality has been stable, risk-adjusted M + M has been in a constant decline. This decline was associated with an increased use of left internal mammary artery grafts, multiple arterial conduits, and warm blood cardioplegia during the later years of the study.

Aprotinin and tranexamic acid for high transfusion risk cardiac surgery.

BACKGROUND: Studies have shown that aprotinin and tranexamic acid can reduce postoperative blood loss after cardiac operation. However, which drug is more efficacious in a higher risk surgical group of patients, has yet to be defined in a randomized study. METHODS: With informed consent, 80 patients undergoing elective high transfusion risk cardiac procedures (repeat sternotomy, multiple valve, combined procedures, or aortic arch operation) were randomized in a double-blind fashion, to receive either high dose aprotinin or tranexamic acid. Patient and operative characteristics, chest tube drainage and transfusion requirements were recorded. RESULTS: There was no significant difference between the 2 treatment groups with respect to age, cardiopulmonary bypass time, complications (myocardial infarction, stroke, death), chest tube drainage (6, 12, or 24 hours), blood transfusions up to 24 hours postoperatively, total allogeneic blood transfusions for entire hospital stay, or induction/postoperative hemoglobin levels. However, multiple regression analysis revealed a positive relationship between cardiopulmonary bypass time and 24 hour blood loss in the tranexamic acid group (p = 0.001), unlike the aprotinin group where 24 hour blood loss is independent of cardiopulmonary bypass time (p = 0.423). CONCLUSIONS: Overall, there was no significant difference in blood loss, or transfusion requirements, when patients received either aprotinin or tranexamic acid for high transfusion risk cardiac operation. Aprotinin, when given as an infusion in a high-dose regimen, was able to negate the usual positive effect of cardiopulmonary bypass time on chest tube blood loss.

Echocardiography and excision of lipomatous hypertrophy of the interatrial septum.

We present a case of massive lipomatous hypertrophy of the interatrial septum, in which transesophageal echocardiography was used to guide surgical resection. Tissue removal was undertaken without entering either the left or right atrium, thereby obviating the need for atrial septal reconstruction.

Current status of transmyocardial laser revascularization: review of the literature.

BACKGROUND: Transmyocardial laser revascularization (TMLR) is a new procedure for the treatment of angina pectoris in which high power laser energy is used to create channels in ischemic myocardium. OBJECTIVE: To describe in detail the historical, experimental and state-of-the-art studies regarding TMLR. DATA SOURCES: The English-language literature published from 1966 to 1998 was thorougly searched in MEDLINE. Further information regarding unpublished data was obtained on request. STUDY SELECTION: The most important experimental studies and randomized prospective clinical trials were examined. Additional papers were selected to provide a historical perspective and future prospects of TMLR. DATA SYNTHESIS: Although the results of TMLR in terms of angina relief are impressive, the procedure is associated with significant mortality and morbidity, and the results of objective cardiac perfusion measurements such as radionucleic perfusion scans and positron emission tomography are not conclusive. Furthermore, little information is available concerning the effect of this procedure on life expectancy. This article reviews the historical background of TMLR and possible mechanisms by which it may work, and discusses existing evidence for and against the procedure and how it may be applied in the future. CONCLUSIONS: At present, TMLR is potentially indicated for patients with severe angina that is refractory to medical therapy and who have contraindications for the more traditional therapies (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty and transplantation). More data are needed to evaluate fully the indications for this procedure.

A novel comparison of stentless versus stented valves in the small aortic root.

BACKGROUND: Previous studies have compared prosthetic valves on the basis of industry-labeled valve sizes. Unfortunately, the relationship between the labeled size and the true measured external or internal diameter differs between valve manufacturers. Therefore hemodynamic comparisons between prosthetic valves are inaccurate if based solely on industry-labeled valve sizes. METHODS: We have previously demonstrated that the internal diameter of a 21-mm Carpentier-Edwards pericardial stented valve is similar to that of a 25-mm Toronto stentless porcine valve. Therefore we chose to compare postoperative hemodynamics in patients who received 19-, 21-, or 23-mm Carpentier-Edwards pericardial stented valves (inner diameter 18-22 mm, n = 69) with those in patients who received 23- or 25-mm stentless porcine valves (internal diameter 19-21 mm, n = 41). RESULTS: Patients in the Carpentier-Edwards group were more likely to be elderly and more likely to require concomitant revascularization. Operative mortality was lower in the stentless porcine valve group (0% vs 9%, P =.06). Hospital stay and ventilation requirements were shorter in the stentless porcine valve group. Postoperative hemodynamics were similar in the two groups. CONCLUSIONS: These data provide evidence that stentless and stented valves have similar hemodynamic profiles in the small aortic root when matched on true measured internal diameters. The clinical benefit of the stentless porcine valve may be due to patient selection or the lack of a rigid stent in the small aortic root, but it is not due to hemodynamic superiority over stented aortic valves of similar sizes.

Multiple arterial grafts. Radial versus right internal thoracic arteries.

BACKGROUND: Left internal thoracic artery (LITA) grafts to the left anterior descending coronary artery (LAD) during coronary bypass surgery (CABG) have greater patency rates than saphenous vein grafts and reduce long-term cardiac morbidity and mortality rates. The benefits of multiple versus single arterial grafts and the role of different arterial conduits with respect to short- and medium-term outcome remains controversial. The purpose of this study was to compare the perioperative and intermediate-term results of: (1) patients receiving 2 arterial grafts versus 1 arterial graft and (2) patients receiving a right internal thoracic artery (RITA) versus a radial artery (RA) as the second arterial graft. METHODS AND RESULTS: Retrospective analysis of prospectively gathered data on consecutive patients undergoing isolated CABG at our institution between 1989 and 1996 was conducted. The first section of the study compared outcomes for 1 arterial graft (LITA to LAD, n = 2333) versus 2 arterial grafts (LITA + RA or LITA + RITA, n = 378). The second section of the study compared outcomes for the RITA (n = 132) versus the RA (n = 171) as second arterial grafts since 1992, when the radial series was initiated. Part I: By multivariable stepwise logistic regression, the use of 1 arterial graft was associated with an increased incidence of perioperative cardiac morbidity and mortality (odds ratio 2.2, 95% confidence interval 1.4 to 3.3), with the use of our current patient selection criteria. Double-arterial graft patients had a nonsignificant trend toward increased intermediate-term actuarial survival (P = 0.12) and cardiac event-free survival (P = 0.09). Part II: Comparison of preoperative demographics revealed a higher incidence of diabetes (27% vs 11%, P < 0.001), peripheral vascular disease (16% vs 8%, P = 0.03), and elderly age (13% vs 2%, P = 0.001) in patients receiving an RA versus those receiving a RITA as the second arterial graft. Perioperative outcome analysis revealed a decreased intensive care unit stay in the RA versus RITA group (median 30.4 vs 36.2 hours, respectively, P = 0.005) but no significant difference in hospital length of stay. There was no significant difference in perioperative mortality or cardiac morbidity rates. RITA patients had a higher incidence of sternal wound infection (5.3% vs 0.6%, P = 0.01), however, and tended to have increased blood product transfusion rates (51% vs 40%, P = 0.06). CONCLUSIONS: The use of 2 arterial grafts is safe, with a reduction in perioperative cardiac morbidity or mortality rates compared with 1 arterial graft after adjustment for other risk variables. When comparing RITA to RA as second arterial grafts, patients receiving an RA have a lower incidence of sternal wound infection and decreased transfusion requirements, with no difference in perioperative or intermediate-term cardiac morbidity or mortality rates.

Phase 2 studies of adenosine cardioplegia.

BACKGROUND: Laboratory evidence supports the use of adenosine-supplemented cardioplegia. An initial phase 1 dose-ranging clinical evaluation demonstrated that an adenosine concentration of 15 mumol/L could be safely administered with warm blood cardioplegia and suggested that phase 2 studies were warranted. METHODS AND RESULTS: Two separate double-blind, randomized, placebo-controlled trials were performed in patients undergoing primary, isolated, nonemergent coronary artery bypass graft surgery. Patients were randomized to receive adenosine 15 mumol/L versus placebo in the first study (n = 200) and adenosine 50 or 100 mumol/L versus placebo in the second study (n = 128). Adenosine was infused with both initial and final doses of warm antegrade blood cardioplegia. The data from the 2 trials were combined using the methods of Mantel and Haenszel, and the results of the meta-analysis are presented as the relative risk with their associated 95% confidence intervals (CI). The different study groups were comparable with respect to all preoperative clinical characteristics, angiographic findings, and intraoperative variables. In both trials 1 and 2, no differences were found between groups in the incidence of the individual primary or secondary outcomes. Similarly, when both studies were combined, there was no significant evidence of any consistent treatment benefit (primary: death: relative risk [RR] = 1.02, 95% CI = 0.06, 16.6; myocardial infarction by CK-MB: RR = 0.84, CI = 0.54, 1.31; low output syndrome: RR = 1.38, CI = 0.29, 6.42; any of the above: RR = 0.98, CI = 0.78, 1.25; secondary: Q-wave myocardial infarction: RR = 1.30, CI = 0.41, 4.13; myocardial infarction by troponin T: RR = 0.7, CI = 0.40, 1.21; inotrope requirement: RR = 0.9, CI = 0.46, 1.79; intra-aortic balloon pump requirement: RR = 0.6, CI = 0.07, 4.81; P > 0.20). CONCLUSIONS: Despite promising experimental data, adenosine supplementation of warm blood cardioplegia did not demonstrate any statistically significant benefit in patients undergoing elective coronary artery bypass graft surgery. Although sample sizes were relatively small, based on our interim analyses, it is unlikely that increased patient enrollment would reveal any substantive clinical differences between groups.

Inaccurate and misleading valve sizing: a proposed standard for valve size nomenclature.

BACKGROUND: The sizes with which manufacturers label valves are nonuniform and haphazard. This has led to confusion and inappropriate comparisons of hemodynamics between valves with the same labeled size. Hemodynamic performance of valves is primarily determined by the internal diameter (ID) of their orifice. METHODS: The purpose of this study was to determine the ID and external diameter of aortic valves used at our institution and compare the measurements to manufacturers' labeled sizes. We also evaluated valve size (ID, manufacturers' labeled size) in 527 patients undergoing isolated aortic valve replacement between 1990 and 1996. RESULTS: We demonstrated that no two manufacturers' tissue or mechanical valves have the same ID or external diameter for a given labeled size. The labeled size of tissue valves was 1 to 4 mm larger than the measured ID. The labeled size of mechanical valves was 3 to 5 mm larger than the measured ID. The St. Jude HP mechanical valve has a greater ID than all other mechanical valves for each labeled size. Among 403 patients operated on for predominant aortic stenosis, those patients receiving the Toronto Stented Porcine Valve (n = 98) had a larger mean ID (22.3+/-1.9 mm) than 204 patients receiving stented tissue valves (ID = 20.9+/-1.9 mm) and the 101 patients receiving mechanical valves (ID = 19.3+/-1.9 mm, p < 0.0001). However, when the manufacturers' labeled size was used as a measure of the size, the results were greatly exaggerated in favor of the Toronto Stented Porcine Valve (ID = 26.3+/-1.9 mm) compared with stented tissue valves (ID = 23.1+/-2.1) or mechanical valves (ID = 23.6+/-1.9) (p < 0.0001). CONCLUSIONS: Manufacturers' labeling of valves is nonuniform and may lead to erroneous comparisons and conclusions of hemodynamic differences between valves. We therefore recommend a standardized nomenclature for the size of all valves based on the ID measurement.

Transmembrane heme delivery systems.

Heme proteins play pivotal roles in a wealth of biological processes. Despite this, the molecular mechanisms by which heme traverses bilayer membranes for use in biosynthetic reactions are unknown. The biosynthesis of c-type cytochromes requires that heme is transported to the bacterial periplasm or mitochondrial intermembrane space where it is covalently ligated to two reduced cysteinyl residues of the apocytochrome. Results herein suggest that a family of integral membrane proteins in prokaryotes, protozoans, and plants act as transmembrane heme delivery systems for the biogenesis of c-type cytochromes. The complete topology of a representative from each of the three subfamilies was experimentally determined. Key histidinyl residues and a conserved tryptophan-rich region (designated the WWD domain) are positioned at the site of cytochrome c assembly for all three subfamilies. These histidinyl residues were shown to be essential for function in one of the subfamilies, an ABC transporter encoded by helABCD. We believe that a directed heme delivery pathway is vital for the synthesis of cytochromes c, whereby heme iron is protected from oxidation via ligation to histidinyl residues within the delivery proteins.

Coronary bypass with arterial conduits.

To assess the efficacy of arterial revascularization 368 patients were studied who underwent myocardial revascularization with two or more arterial conduits (group M) and compared with 2092 patients in whom a single internal mammary artery +/- veins (group S), and to a third group in which only saphenous vein conduits (group V, n = 602) were used. Group M patients were younger (aged 54.0(9.5) years; 4.1% aged > 70 years) than either group V (67.6(8.9) years, 40.7% > 70 years, P < 0.0001) or group S patients (62.0(8.5) years, 15.7% > 70 years, P < 0.0001). Furthermore, this cohort group had the lowest percentage of females (8.4%), of urgent cases (21.7%), of preoperative myocardial infarction (6.0%), and of redo surgery (0.8%). In contrast, patients who received only saphenous vein conduits had the highest proportion of female patients (29.2%), of urgent cases (47.4%), of preoperative myocardial infarction (16.5%), and of redo surgery (5.5%). By multivariate logistic regression analysis (odds ratio in parentheses), redo surgery (6.06, P = 0.0001), preoperative intra-aortic balloon pump assist (6.11, P = 0.0001), diabetes (1.97, P = 0.03), urgent surgery (1.80, P = 0.05), and advanced age (2.14, P = 0.01) were all predictors of operative mortality. In contrast, while choice of conduit appeared to influence outcome by univariate analysis (4.2% mortality in group V, P < 0.001), it was not found to be a predictor of either mortality or morbidity by regression analysis. The present results indicate that, in carefully selected patients, despite increased technical demands with longer periods of aortic occlusion and longer pump times, multi-arterial grafting (compared with conventional revascularization) is a safe and efficacious procedure. Whether or not this approach to revascularization will increase long-term survival and freedom from reoperation will require further study.

Early results using an ePTFE membrane for pericardial closure following coronary bypass grafting.

A prospective randomized trial was conducted to evaluate the early efficacy and safety of the Gortex surgical membrane. Three hundred two patients (265 males, 37 females) undergoing isolated coronary bypass surgery were randomized to receive a Gortex membrane (GM = 138) or have the pericardium left open (complication [C] = 164). The groups did not differ in age, gender, urgency of procedure, length of procedure, or use of arterial grafts. Two deaths occurred in each group giving an overall mortality of 1.3%. Fifty-three (17%) patients experienced some complication (C = 34, 21%), GM = 19 (14%). Although the combined complication rate was higher in the control group, this was not statistically significant (chi2 = 2.51, p = 0.11). Postoperative ischemic events (C = 8, GM = 4) observed between the groups were not significant (chi2 = 0.05, p = 0.8), and no statistically significant difference was observed between the incidences of infections (C = 7, GM = 5) or mediastinal complications (C = 3, GM = 3). The Gortex surgical membrane can be used safely without increasing the risk of infection or mediastinal complications. The incidence of recurrent myocardial ischemia, a possible indicator of graft compression, was not higher following membrane implantation. Efficacy at injury prevention will need to be determined by a longitudinal follow-up study presently underway.

Preferred method for insertion of the Toronto Stentless Porcine Valve.

The Toronto Stentless Porcine Valve has been extensively used for aortic valve replacement. A standardized, detailed description of a preferred operative technique has been absent from the literature. A method is described that stresses (a) proper position and orientation of the aortotomy, (b) debridement of the diseased native valve, (C) proper sizing of the aortic root and choice of prosthesis and (d) implantation of the valve. Using this technique, the prosthesis can be reproducibly implanted with relative ease, without valvular insufficiency or coronary obstruction.

Coronary artery bypass grafting in patients with non-dialysis-dependent renal insufficiency.

BACKGROUND: Preoperative renal failure increases the morbidity and mortality of coronary artery bypass graft (CABG) surgery. The results of CABG in patients with non-dialysis-dependent, mild renal insufficiency are unknown. METHODS: From a population of 2978 consecutive patients undergoing isolated CABG from 1990 to 1996, 38 patients with preoperative renal insufficiency (Renal group; serum creatinine >150 micromol/L) were identified and matched on six prognostic variables to a cohort of 152 control patients (Control group). Two patients with preoperative dialysis-dependent renal failure were excluded from analysis. RESULTS: Compared to the overall population, the Renal group were more likely to be over age 70, diabetic, hypertensive, and suffer from peripheral vascular disease and left ventricular dysfunction. Compared to the Control group, the Renal group were more likely to require perioperative blood transfusions (P<.001) and had a greater requirement for postoperative dialysis (P<.01). The Renal group had longer ventilation times, intensive care unit stay, and postoperative hospital stay. Mild renal insufficiency was found to be an independent predictor of postoperative low output syndrome (odds ratio=3.6). CONCLUSIONS: Mild renal insufficiency, even in the absence of dialysis, increases the risk of blood transfusion, low output syndrome and prolonged the length of intensive care unit and postoperative stay for patients undergoing CABG.