Evaluation of Leuconostoc mesenteroides YML003 as a probiotic against low-pathogenic avian influenza (H9N2) virus in chickens.

AIM: The aims of the study were to isolate anti-H9N2 bacteria from Korean Kimchi isolates and to evaluate its performance in cell line, egg and in specific pathogen-free (SPF) chickens. METHODS AND RESULTS: Using Madin-Darby canine kidney (MDCK) cell line, 220 bacterial isolates were screened and the isolate YML003 was selected having pronounced antiviral activity against H9N2 virus. This isolate was identified as Leuconostoc mesenteroides by 16S rRNA gene sequencing. Anti-H9N2 activity of the strain was also evaluated by hemagglutination assay. Leuconostoc mesenteroides YML003 was assessed for its survival in gastric juice and 5% bile acid and the antibiotic susceptibility. Both live and heat-killed cells were selected for in vivo chicken feeding experiment. Body weight, immune index, serobiochemical parameters and splenic IFN-γ production were assessed during selected intervals. Viral population in the trachea and cloacae were calculated by quantitative real-time reverse transcriptase PCR (qRT-PCR). CONCLUSIONS: Leuconostoc mesenteroides YML003 exhibited anti-H9N2 activity both in in vitro cell line as well as in vivo SPF chickens. SIGNIFICANCE AND IMPACT OF THE STUDY: This is a primary report on the anti-H9N2 activity by a Leuconostoc strain. Amid the increasing reports of avian influenza virus occurrence resulting in severe losses to the poultry industry, prophylactic administration of such probiotic strains are highly significant.

Clinical course and predictors of pericardial effusion following cardiac transplantation.

OBJECTIVE: Pericardial effusions occur frequently after orthotopic heart transplantation. There have been conflicting reports describing etiology, prognosis, and outcomes associated with these early postoperative effusions. METHODS: A retrospective review of 91 patients transplanted between January 2001 and September 2004 was performed. Pericardial effusion was defined by serial echocardiography and graded as none, small, moderate, or large. A total of 1088 echocardiograms were evaluated during the first posttransplant year. Perioperative variables were evaluated by logistic regression analysis to define predictors for occurrence of effusions. RESULTS: Echocardiographic data were available for 88 patients. Thirty-one patients (35%) developed moderate to large effusion in the immediate postoperative period. Three patients developed hemodynamic compromise that required immediate intervention. All other effusions resolved within 3 months of heart transplantation without any specific intervention. Only prolonged donor ischemic time was associated with higher risk of occurrence of moderate to large pericardial effusions (odds ratio 1.012, 95% confidence interval 1.001 to 1.019, P = .033). There was no difference in morbidity or early mortality between patients with and without pericardial effusions. CONCLUSION: Moderate to large pericardial effusions occur frequently after heart transplantation. In a vast majority, these effusions are not associated with any adverse clinical outcomes and resolve within 3 months postoperatively. Early postoperative close monitoring is still required to evaluate for tamponade.

Cardiac surgery in nonagenarians.

AIM: To evaluate outcomes following cardiac surgery in nonagenarians. METHODS: A retrospective analysis of patients > or = 90 years of age undergoing cardiac surgery at Barnes-Jewish Hospital from 1996-2006 was performed. The Social Security Death Index was used to determine late survival. RESULTS: Twenty-two subjects were identified. The mean age was 91 years (range 90-94) and 64% were women. The most common comorbidities included hypertension in 91% and heart failure (HF) in 65%. Mean New York Heart Association class was 3.5, mean left ventricular ejection fraction was 50% (range 27-80%), and mean creatinine clearance was 34 +/- 11 cc/min. No patients had prior cardiac surgery. Nine patients underwent coronary bypass grafting only, 11 had valve replacement only, and 2 had both. Concurrent operations included 1 ventricular septal defect repair, 2 carotid endarterectomies, and 1 ascending aortic patch angioplasty. Two cases were urgent, 2 were emergent, and the remainder were elective. There was one intraoperative death (5%), during urgent mitral valve replacement. The most common postoperative complications included atrial fibrillation and need for vasopressors for >48 hrs. Mean length of intensive care and total hospital stay were 3.4 +/- 4.5 and 12.2 +/- 8.5 days, respectively. Independent predictors of increased hospital stay were higher serum creatinine (P=0.028) and the presence of HF (P=0.050). Survival to 30, 90 and 365 days were, respectively: 86%, 77%, and 64%. At study conclusion, 7 patients (32%) were alive at a mean follow-up of 4.1 years. CONCLUSION: Despite higher morbidity and mortality, in carefully selected nonagenarians referred for cardiac surgery, short-term complication rates and long-term outcomes appear to be acceptable.

Potential renal protective benefits of intra-operative BNP infusion during cardiac transplantation.

BACKGROUND: Recombinant BNP (nesiritide) is known to reduce endothelin levels, cause afferent arteriole vasodilation, and increase natriuresis and diuresis. We hypothesized that intraoperative infusion of BNP may benefit renal function in cardiac transplant patients. METHODS: From June 2003 to September 2005, 22 consecutive heart transplant patients received BNP at a dose of 0.01 microg/kg/min before initiation of cardiopulmonary bypass (group A). BNP infusion was continued for a mean of 3.3 +/- 1.9 days. Hemodynamics, urine output, and serum creatinine levels were prospectively collected and compared with 22 consecutive patients who underwent heart transplantation between May 2002 and June 2003 following the identical transplant protocol, but without BNP infusion (group B). RESULTS: At 24 hours postoperatively, mean blood pressure was comparable between groups (87 +/- 11 mm Hg vs 89 +/- 17 mm Hg, P = .7), but pulmonary artery pressure (18 +/- 5 mm Hg vs 24 +/- 5 mm Hg, P = .001) and central venous pressure (12 +/- 5 mm Hg vs 16 +/- 4 mm Hg, P = .01) were lower with BNP infusion, whereas cardiac index was augmented (2.8 +/- 0.5 vs 2.4 +/- 0.6, P = .03). Requirement of low-dose inotropic and vasopressor support was equally distributed between groups (P > or = .72). Postoperative urine output for the initial 24 hours was higher in group A (84 +/- 15 vs 55 +/- 36 mL/h, P = .01). None of the patients with BNP infusion required additional diuretics or renal replacement therapy during the first week after transplantation. Mean postoperative serum creatinine levels as compared with preoperative values remained unchanged within group A (P = .12), but increased significantly in group B (P < .001). CONCLUSIONS: Intraoperative BNP infusion in heart transplant recipients was associated with favorable postoperative hemodynamics, significantly improved urine output, and stable serum creatinine levels. A prospective, randomized, multicenter trial is warranted to evaluate the potential renal protective benefits of intraoperative BNP infusion in this patient population.

Surgical treatment of atrial fibrillation with bipolar radiofrequency ablation: mid-term results in one hundred consecutive patients.

AIM: The Cox-Maze procedure was introduced nearly two decades ago for the surgical treatment of atrial fibrillation (AF). Recently, our group has replaced most of the incisions of the Cox-Maze procedure with bipolar radiofrequency (RF) ablations (Cox-Maze IV procedure). The purpose of this study was to examine our midterm results with the Cox-Maze procedure using bipolar RF ablation. METHODS: From January 2002 to October 2005, 100 consecutive patients underwent a modified Cox-Maze procedure with bipolar RF ablation for AF; 32 were lone operations, and 68 were concomitant procedures. Follow-up was performed at 1, 3, 6, and 12 months, and then annually thereafter. Heart rhythm was confirmed by electrocardiography. RESULTS: The mean age of patients was 62+/-13 years; 57% were male. Duration of AF was 6.3+/-7.6 years (0.1 to 40 years), 59% had paroxysmal AF, and 34% had permanent AF. Follow-up was complete for all patients with a mean follow-up of 13+/-10 months. At 12-month follow-up, 91% (49/54) of patients were free of AF. Cross-clamp time in the lone Cox-Maze IV procedure patients was 42+/-15 minutes, while it was 101+/-29 minutes for the Cox-Maze IV with a concomitant procedure (compared to 93+/-34 minutes and 122+/-37 minutes for the traditional procedure, P<0.05). There were four operative deaths. CONCLUSIONS: The Cox-Maze IV procedure had good mid-term efficacy. The use of bipolar RF energy significantly decreased operative time and simplified the procedure compared to the traditional Cox-Maze procedure, potentially increasing utilization of the procedure among cardiac surgeons.

Quality of life after aortic valve replacement at the age of >80 years.

BACKGROUND: The optimal management of aortic valve disease in patients >80 years old depends on functional outcome as well as operative risks and late survival. METHODS AND RESULTS: We retrospectively identified 133 patients (62 men, 71 women) aged 80 to 91 years (mean 84+/-3 years) who underwent aortic valve replacement alone or in combination with another procedure between January 1, 1993, and April 31, 1998. Demographics included hypertension 68%, diabetes mellitus 17%, and history of stroke 11%. Operative (30 day) mortality rate was 11%. Urgent or emergent surgery, aortic insufficiency, and perioperative stroke or renal dysfunction were risk factors for operative death by multivariable analysis. Intensive care unit and total hospital length of stay were prolonged at 6.2 and 14.7 days, respectively. Late follow-up between July 1, 1998, and November 1, 1999, was 98% complete. Actuarial survival at 1 and 5 years was 80% and 55%, respectively. Predictors of late mortality were preoperative or perioperative stroke, chronic obstructive pulmonary disease, aortic stenosis, and postoperative renal dysfunction. The mean New York Heart Association functional class for 65 long-term survivors improved from 3.1 to 1.7. Quality of life assessed with the Medical Outcomes Study Short Form-36 was comparable to that predicted for the general population >75 years old. CONCLUSIONS: Functional outcome after aortic valve replacement in patients >80 years old is excellent, the operative risk is acceptable, and the late survival rate is good. Surgery should not be withheld from the elderly on the basis of age alone.

Activation of NF-kappaB varies in different regions of the gastrointestinal tract during endotoxemia.

The transcription nuclear factor-kappaB (NF-kappaB) regulates a large number of genes involved in the inflammatory response to sepsis and endotoxemia. We recently found that NF-kappaB is activated in the jejunal mucosa during endotoxemia, but the response of NF-kappaB in other parts of the gastrointestinal tract is not known. We hypothesized that NF-kappaB is differentially activated in different regions of the gastrointestinal tract during endotoxemia. NF-kappaB DNA binding activity was determined by electrophoretic mobility shift assay in mucosa of the stomach, jejunum, ileum, and colon from endotoxemic and saline-injected mice. Cytoplasmic levels of the NF-kappaB inhibitory proteins IkappaB-alpha and IkappaB-beta were determined by Western blot analysis. Endotoxemia increased NF-kappaB activity in mucosa of stomach, jejunum, and ileum, with jejunum responding to smaller doses of endotoxin than the other parts of the gastrointestinal tract. NF-kappaB DNA binding activity was not induced in colonic mucosa, even following administration of high doses of endotoxin. IkappaB-alpha and IkappaB-beta levels decreased in jejunal mucosa of endotoxin injected mice, concomitant with activation of NF-kappaB. The results suggest that during endotoxemia, NF-kappaB is activated in mucosa of stomach and small intestine, but not in colon, and that the jejunum is particularly sensitive to endotoxin.

Interleukin-1beta induces complement component C3 and IL-6 production at the basolateral and apical membranes in a human intestinal epithelial cell line.

In previous studies, stimulation of cultured enterocytes with IL-1beta resulted in production of IL-6 and complement component C3. The cellular mechanisms of these responses in the enterocyte are not fully understood. We tested the hypothesis that IL-1beta-induced C3 and IL-6 production is differentially regulated at the apical and basolateral membranes of the enterocyte. Caco-2 cells (a transformed human colonic carcinoma cell line) were grown in a 2-chamber system to full differentiation. The cells were treated with IL-1beta either at the apical or basolateral membrane, and C3 and IL-6 mRNA levels and release of C3 and IL-6 into the apical and basal chambers were determined. The release of C3 was greatest into the basal chamber regardless of whether the cells were stimulated at the apical or basolateral membrane. In contrast, the production of IL-6 was greatest at the cell membrane that was stimulated with IL-1beta. Stimulation of the Caco-2 cells with IL-1beta resulted in increased mRNA levels for C3 and IL-6 with no major differences noted when the cells were treated at the apical or basolateral membrane. The results suggest that enterocyte production and release of at least some acute phase proteins and cytokines are differentially regulated at the apical and basolateral membrane of the enterocyte after stimulation with IL-1beta.

IL-1beta induction of NF-kappaB activation in human intestinal epithelial cells is independent of oxyradical signaling.

IL-1beta stimulation of cultured epithelial cells induces the degradation of IkappaBalpha and the consequent nuclear translocation of NF-lambdaB, a critical proinflammatory transcription factor in the mucosal host immune response. The role of reactive oxygen intermediates, serine protease activity, and tyrosine kinase activity in the activation of NF-kappaB is weakly conserved across various cell lineages and has not been defined in human enterocytes, a major target of oxidant stress in sepsis, thermal injury, and hemorrhagic shock. We report here that in Caco-2BBe cells, a transformed human colon cancer cell line with features of small intestinal epithelial cells in culture, exposure to oxidant stress (hydrogen peroxide 1-10 mM) did not induce NF-kappaB activation. Similarly, scavenging of free radicals and oxidants by pyrrolidine dithiocarbamate and dimethyl sulfoxide did not block IL-1beta-induced IkappaBalpha degradation and NF-kappaB activation. Genistein, a nonspecific tyrosine kinase inhibitor, also had no effect on IL-1beta-mediated effects on NF-kappaB. Serine protease inhibition by tosyl-lysine-chloromethylketone and tosyl-phenylalanine-chloromethylketone inhibited IkappaBalpha degradation and NF-kappaB activation stimulated by IL-1beta. Our data highlight the strong divergence between epithelial and mononuclear cells in the signal transduction pathways relating IL-1beta stimulation and NF-kappaB nuclear translocation.

Heart-lung versus double-lung transplantation for suppurative lung disease.

OBJECTIVE: The purpose of this study was to compare outcomes after heart-lung or double-lung transplantation in patients undergoing transplantation because of end-stage suppurative lung disease. METHODS: We reviewed our experience in patients with cystic fibrosis or bronchiectasis who had heart-lung or double-lung transplantation between January 1988 and September 1997. Twenty-three patients (14 male, 21 cystic fibrosis) had heart-lung transplantation and 24 patients (8 male, 19 cystic fibrosis) had double-lung transplantation. There were no statistically significant differences between the groups in age, weight, preoperative creatinine level, cytomegalovirus status, maintenance immunosuppression, or donor demographics. Patients received induction therapy with monoclonal (OKT3) or polyclonal (rabbit anti-thymocyte globulin) antibody. RESULTS: Sixteen of 24 patients had double-lung transplantation after 1994 whereas 13 of 22 patients had heart-lung transplantation before 1991, allowing longer follow-up for the heart-lung group. Mean waiting times for transplantation were 270 +/- 245 days (heart-lung) and 361 +/- 229 days (double-lung; P =.20). The 1-, 3-, and 5-year actuarial survival figures were respectively 86%, 82%, and 65% (heart-lung) and 96%, 75%, and unavailable (double-lung; P = no significant difference). The 1-, 3-, and 5-year rates of freedom from obliterative bronchiolitis were respectively 77%, 61%, and 45% (heart-lung) and 86%, 78%, and unavailable (double-lung; P = no significant difference). Linearized overall infection rates (events/100 patient-days) were 2.05 +/- 0.33 (heart-lung) and 2.34 +/- 0.34 (double-lung; P = NS) at 3 months. Thirty-day survival was 100% (heart-lung) and 96% (double-lung). There were 7 late deaths among heart-lung recipients (3 obliterative bronchiolitis, 2 infection, 0 graft coronary artery disease, 2 other) whereas 2 late deaths related to obliterative bronchiolitis occurred in double-lung recipients. Graft coronary artery disease (all stenoses < 50%) affected 15% of heart-lung survivors, whereas 3 double-lung recipients (12.5%) required either bronchial dilatation or stenting. CONCLUSION: Heart-lung and double-lung transplantation provide similar palliation for patients with end-stage suppurative lung disease. Therefore double-lung transplantation should be the preferred operation for most patients with end-stage suppurative lung disease.

Annuloplasty with flexible or rigid ring does not alter left ventricular systolic performance, energetics, or ventricular-arterial coupling in conscious, closed-chest dogs.

Eighteen dogs were randomly chosen to undergo mitral annuloplasty with either a Carpentier-Edwards rigid ring (n = 6 in each group) or a Duran-Medtronic flexible ring or to undergo a sham procedure with an operation, but no ring. Tantalum markers were inserted to measure left ventricular volume and geometry. After 1 and 6 weeks, biplane videofluoroscopic images were obtained during steady-state conditions and during vena caval occlusion. Global and regional systolic function was assessed with load-insensitive indexes. Comparison of all three groups and both times (1 and 6 weeks) showed no significant differences among the three groups in global or regional (basal, equatorial, and apical) left ventricular systolic performance. Furthermore, neither type of annuloplasty ring significantly affected left ventricular pump efficiency, ventricular-arterial coupling ratio, or systolic circumferential contraction and rotation of the basal left ventricular sites.

Effects of mechanical left ventricular support on right ventricular diastolic function.

BACKGROUND: Previous studies have shown that left ventricular (LV) unloading alters right ventricular (RV) systolic mechanics, but the effects of LV assist device (LVAD) support on RV diastolic function have not been examined in intact subjects. METHODS: Seven closed-chest, sedated dogs were studied after placement of a LVAD and 27 myocardial markers; in four animals, a right coronary artery occluder was placed to induce acute RV free wall ischemia. Data were recorded with the LVAD off and LVAD on before (control) and during RV ischemia. Assessment of RV diastolic function included RV myocardial relaxation (time constant of isovolumic pressure decay [tau]), RV chamber stiffness (slope of the end-diastolic pressure-volume relation), and RV filling dynamics (peak filling rate and mean filling rate during early diastole). RESULTS: During control, full LVAD support did not alter RV tau (104 +/- 67 msec LVAD off versus 109 +/- 49 msec LVAD on, p > 0.50), RV diastolic stiffness (0.56 +/- 0.31 versus 0.51 +/- 0.25 mm Hg/ml, p > 0.20), peak filling rate (107 +/- 51 versus 119 +/- 82 ml/sec, p > 0.35) or mean filling rate during early diastole (32 +/- 28 versus 27 +/- 18 ml/sec, p > 0.40). With right coronary artery occlusion, RV tau rose to 136 +/- 33 msec (p < 0.001), and RV diastolic stiffness fell to 0.29 +/- 0.13 mm Hg/ml (p < 0.005), but there was no change in RV filling rates (p > 0.20). With mechanical LV support during acute RV ischemia, there was no additional change in RV tau, diastolic stiffness, or filling dynamics (p > 0.20). CONCLUSIONS: In intact animals, RV ischemia impaired RV relaxation and decreased chamber stiffness, but there was no change in RV filling rates. Mechanical LV support, during the control state and with RV ischemia, did not affect RV diastolic performance.

Effect of the duration of symptoms, transport time, and length of emergency room stay on morbidity and mortality in patients with ruptured abdominal aortic aneurysms.

BACKGROUND: Despite improvements in emergency medical services, surgical technology, and postoperative critical care, ruptured abdominal aortic aneurysm (AAA) is associated with constantly high morbidity and mortality. To determine the effect of the duration of symptoms, transport time to hospital, and length of emergency department assessment on outcome, we evaluated 124 consecutive patients with ruptured AAA treated during the past decade. METHODS: The medical records for 122 patients were abstracted for preoperative hypotension, cardiopulmonary resuscitation (CPR), blood loss, and three time intervals: symptom onset to operation, transport time to hospital, and emergency department assessment. RESULTS: Intraoperative mortality was 26% (n = 32), 30-day mortality was 51% (n = 63), and cumulative hospital mortality was 56% (n = 69). Death occurred in 52 (64%) of 81 patients with hypotension compared with 14 (35%) of 40 patients without hypotension (p < or = 0.01). Hypotension was present in 37 (82%) of 45 patients who arrived in the operating room in 2 hours or less compared with 26 (60%) of the 43 patients who arrived later than 2 hours (p < or = 0.05). Death followed in 21 (91%) of 23 patients who received CPR compared with 46 (46%) of 99 patients who did not receive CPR (p < or = 0.01). Bowel ischemia was observed in 18 (30%) of 60 patients who received more than 10 units of blood compared with 3 (5%) of 61 patients who received 10 units or less (p < or = 0.01). CONCLUSIONS: For patients with ruptured AAA, prolonged presurgical time was associated with a more hemodynamically stable patient and a lower mortality. Progressive bleeding in those hemodynamically stable patients was reflected by a larger blood transfusion requirement. Such patients exhibited an increased incidence of ischemic bowel complications, perhaps caused by splanchnic arterial ischemia augmented by preexisting atherosclerosis, as well as extrinsic compression by mesenteric hematomas.

Transhiatal and transthoracic esophagectomy for adenocarcinoma of the esophagus.

Adenocarcinoma of the esophagus is no longer rare and is treated by resection. To determine whether the approach used for resection influences outcome, we studied 88 patients who underwent resection; 14 had stage I or II disease, 74 had stage III, and 40 had stage IV. One third of those with Barrett's esophagus were noted on screening endoscopy to have potentially curable disease; the others were diagnosed with stage III or IV disease. Transhiatal esophagectomy was performed in 63 patients; 24 patients underwent transthoracic esophagectomy. We found no difference in survival or morbidity between transhiatal and transthoracic esophagectomy. Overall 5-year survival for stage I and II disease was 86%. For stage III and IV disease, 5-year survival was 14.5%. Aggressive surveillance of Barrett's esophagus facilitates the discovery of early disease. Esophagectomy for adenocarcinoma can result in cure of early cancers and improved palliation of more advanced disease.

Induction of the stress response in vivo decreases nuclear factor-kappa B activity in jejunal mucosa of endotoxemic mice.

BACKGROUND: Results of previous studies suggest that the stress response protects cells and tissues by regulating proinflammatory mediators. The transcription factor nuclear factor-kappa B (NF-kappa B), normally sequestered in the cytoplasm by its inhibitory protein, I kappa B, regulates many genes involved in inflammatory responses to critical illness. Endotoxemia is associated with increased NF-kappa B activity in intestinal mucosa, but the effect of the stress response on endotoxin-induced NF-kappa B activation in intestinal mucosa is not known. HYPOTHESIS: Induction of the stress response inhibits NF-kappa B DNA binding activity in jejunal mucosa during endotoxemia. METHODS: The stress response was induced in mice by hyperthermia (42 degrees C) or injection with sodium arsenite (10 mg/kg). After 2 to 5 hours, mice were injected with endotoxin (lipopolysaccharide, 12.5 mg/kg) or a corresponding volume of sterile saline. One hour later, jejunal mucosa was harvested for preparation of nuclear and cytoplasmic extracts. RESULTS: Mucosal levels of heat shock protein-72 increased after hyperthermia or treatment with sodium arsenite, consistent with induction of the stress response. The increase in NF-kappa B DNA binding activity and decrease in I kappa B-alpha levels seen after endotoxin injection were inhibited by previous induction of the stress response. CONCLUSION: The protective effects of the stress response in vivo might, at least in part, be due to inhibited NF-kappa B activation.

Oxygenator support for partial left-heart bypass.

Partial left-heart bypass provides circulatory support and distal perfusion for repair of thoracic and thoracoabdominal aortic disease without requiring full anticoagulation. Unfortunately some patients, such as those with significant lung contusion in the setting of trauma or those with severe chronic obstructive pulmonary disease and degenerative aneurysms, do not tolerate single-lung ventilation. We have recently modified our left-heart bypass circuit in selected cases to provide supplementary oxygenation, making this technique more broadly applicable.

Experimental evaluation of different chordal preservation methods during mitral valve replacement.

During chordal-sparing mitral valve replacement (MVR), some recommend anatomic reattachment of the anterior leaflet chordae to the anterior annulus; others advocate shifting the chordae to the posterior annulus. To compare the results of these techniques with those of conventional MVR (total chordal excision), 21 dogs were studied 5 to 12 days after implantation of tantalum markers to measure left ventricular volume and geometry. One to 3 weeks later, animals underwent conventional MVR (n = 7) or chordal-sparing MVR with either anterior chordal reattachment (n = 7) or posterior transposition (n = 7). Contractility was assessed using physiologic volume intercepts for end-systolic elastance, preload recruitable stroke work, and the relationship of the maximum rate of change of left ventricular pressure to the end-diastolic volume. The physiologic intercept for end-systolic elastance did not change after anterior or posterior MVR, but increased from 60 +/- 14 mL before MVR to 72 +/- 17 mL with conventional MVR (p < 0.002), indicating impaired left ventricular contractility. Similarly, the physiologic intercept for preload recruitable stroke work and the relationship of the maximum rate of change of left ventricular pressure to the end-diastolic volume increased 22% +/- 13% and 28% +/- 13%, respectively, after conventional MVR, but neither changed after anterior or posterior MVR. Although the end-diastolic pressure-volume relationship did not change with either chordal-sparing technique, its slope increased 98% +/- 73% after conventional MVR (p < 0.008). Thus, although chordal preservation maintained better systolic and diastolic function, there was no substantial difference between the results of the anterior and posterior chordal-sparing techniques in this model.

Effects of mitral valve replacement on regional left ventricular systolic strain.

BACKGROUND: Mitral valve replacement (MVR) with chordal excision impairs left ventricular (LV) systolic function, but the responsible mechanisms remain incompletely characterized. Loss of normal annular-papillary continuity also adversely affects LV torsional deformation, possibly due to changes in myocardial fiber contraction pattern. METHODS: Twenty-seven dogs underwent insertion of LV myocardial markers and a sham procedure (cardiopulmonary bypass, no MVR, n = 6), conventional MVR with chordae tendineae excision (n = 7), or chordal-sparing MVR with reattachment of the anterior leaflet chordae to the anterior annulus (n = 7) or to the posterior annulus (n = 7). In the anterior, lateral, posterior, and septal LV regions, linear chords were constructed from each region's central marker to its surrounding markers. Percent systolic shortening (regional LV strain) was calculated for each chord, and the chords were assigned to one of four angular groups: I, left-handed oblique (subepicardial fiber direction); II, circumferential (midwall); III, right-handed oblique (subendocardial); or IV, longitudinal. Regional LV strain data were compared before and after MVR. RESULTS: Sham and anterior chordal-sparing MVR had minimal effects on regional LV strain. With posterior chordal-sparing MVR: anteriorly, left-oblique (I) strain fell (31%, p<0.05), as did circumferential (II) and right-oblique (III) strains (by 49% and 51%, respectively; p<0.01). Laterally, left-oblique (I) strain fell by 36% (p<0.05), as did longitudinal (IV) strain (54% decline, p<0.01). Conventional MVR with chordal excision disrupted regional fiber shortening diffusely, affecting oblique fibers (I and III) in the anterior and septal regions and impairing longitudinal (IV) strain in all regions (45% to 68% fall, p<0.05). CONCLUSIONS: Sham and anterior chordal-sparing MVR did not substantially alter regional LV strain; however, loss of normal anatomic valvular-ventricular integrity (conventional MVR) or posterior chordal-sparing MVR resulted in pronounced alterations in LV strain, most notably in the longitudinal and oblique fiber directions. These findings demonstrate that the deleterious effects of chordal excision are associated with perturbed internal myocardial systolic deformation, which suggests that chordal disruption distorts myofiber architecture or regional systolic loading.

Options for repair of a bicuspid aortic valve and ascending aortic aneurysm.

BACKGROUND: Intrinsic abnormality of the aortic wall may explain the association of bicuspid aortic valves with ascending aortic aneurysms. Separate valve and graft repair of such lesions, rather than composite valve graft replacement, is more straightforward but leaves potentially abnormal sinuses behind. METHODS: Between January 1985 and January 1998, 45 patients underwent separate valve and graft (n = 27) or composite valve graft (n = 18) for an ascending aortic aneurysm and bicuspid aortic valve. Perioperative events and late results were compared. RESULTS: Patients undergoing separate valve and graft were older (mean age, 60 +/- 13 vs 42 +/- 12 years, p < 0.001) and were more likely to have purely stenotic (48% vs 6%, p = 0.003) than purely regurgitant (11% vs 72%, p < 0.001) disease. They were also more likely to require concomitant coronary artery bypass grafting (56% vs 6%, p = 0.001). There were no significant differences in operative risk and no known late complications related to recurrent aneurysms. CONCLUSIONS: Root replacement with a composite valve graft can be accomplished with low operative risk and is the first choice for repair of this lesion. Separate valve and graft repair, however, yields satisfactory early and late results and remains an acceptable option, especially when the coronary ostea are not displaced or when concomitant procedures must be performed.

Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass.

Heparin is normally used for anticoagulation during cardiopulmonary bypass (CPB), but its use is contraindicated in patients with a history of heparin-induced thrombocytopenia, heparin-provoked thrombosis, or both. Heparin therapy can also be ineffective due to heparin resistance. A short-acting, oligonucleotide-based thrombin inhibitor (thrombin aptamer) may potentially serve as a substitute for heparin in these and other clinical situations. We tested a novel thrombin aptamer in a canine CPB pilot study to determine its anticoagulant efficacy, the resultant changes in coagulation variables, and the aptamer's clearance mechanisms and pharmacokinetics. Seven dogs were studied initially: Four received varied doses of the aptamer (to establish the pharmacokinetic profile) and 3 received heparin. Subsequently, 4 other dogs underwent CPB, receiving a constant infusion of the aptamer before CPB (to characterize the baseline coagulation status), with partial CPB and hemodilution, during 60 minutes of total CPB, and, finally, after a 2-hour recovery period. At a 0.5 mg.kg-1.min-1 dose, the activated clotting time rose with aptamer infusion from 106 +/- 12 seconds to 187 +/- 8 seconds (+/- 1 standard deviation) (p = 0.014), increased further with hemodilution (to 259 +/- 41 seconds; p = 0.017), and was even more prolonged during total CPB (> 1,500 seconds; p < 0.001). This later increase in the activated clotting time paralleled a rise in the plasma concentration of the thrombin aptamer during total CPB, as determined by high-performance liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)