Robotic mitral valve surgery: a United States multicenter trial.

OBJECTIVE: In a prospective phase II Food and Drug Administration trial, robotic mitral valve repairs were performed in 112 patients at 10 centers by using the da Vinci surgical system. The safety of performing valve repairs with computerized telemanipulation was studied. METHODS: After institutional review board approval, informed consent was obtained. Patients had moderate to severe mitral regurgitation. Operative technique included peripheral cardiopulmonary bypass, a 4- to 5-cm right minithoracotomy, a transthoracic aortic crossclamp, and antegrade cardioplegia. The successful study end point was grade 0 or 1 mitral regurgitation by transthoracic echocardiography at 1 month after surgery. RESULTS: Valve repairs included quadrangular resections, sliding plasties, edge-to-edge approximations, and both chordal transfers and replacements. The average age was 56.4 +/- 0.09 years (mean +/- SEM). There were 77 (68.8%) men and 35 (31.2%) women. Valve pathology was myxomatous degeneration in 105 (91.1%), and 103 (92.0%) had type II leaflet prolapse. Leaflet repair times averaged 36.7 +/- 0.2 minutes, with annuloplasty times of 39.6 +/- 0.1 minutes. Total robot, aortic crossclamp, and cardiopulmonary bypass times were 77.9 +/- 0.3 minutes, 2.1 +/- 0.1 hours, and 2.8 +/- 0.1 hours, respectively. On 1-month transthoracic echocardiography, 9 (8.0%) had grade 2 mitral regurgitation, and 6 (5.4%) of these had reoperations (5 replacements and 1 repair). There were no deaths, strokes, or device-related complications. CONCLUSIONS: Multiple surgical teams performed robotic mitral valve repairs safely early in development of this procedure, with a reoperation rate of 5.4%. Advancements in robotic design and adjunctive technologies may help in the evolution of this minimally invasive technique by decreasing operative times.

Synchronous cardiac myxoma and colorectal cancer: a case report.

The occurrence of synchronous but unrelated cardiac and colorectal tumors is extremely rare. We present the case of a 56-year-old man who had a left atrial cardiac myxoma that nearly obstructed the mitral valve outflow tract and an unrelated, synchronous colorectal-vesicle carcinoma that nearly obstructed the lumen of the intestine. The patient underwent emergency resection of the cardiac mass under cardiopulmonary bypass and underwent successful resection of the colorectal mass 2 weeks later Two years after these operations, the patient is well with no recurrence of either tumor Synchronous tumors, particularly when one of them involves the heart, require aggressive surgical treatment at multiple sites in order for the patient to survive.

Regional topical hypothermia of the beating heart: preservation of function and tissue.

BACKGROUND: Protection of the myocardium during beating heart operations is paramount. The goal of this study is to determine if regional topical hypothermia (RTH) preserves myocardial viability and function during periods of temporary coronary artery occlusion. METHODS: Sixteen pigs were divided into two groups (RTH and control). Each group received 40 minutes of midleft anterior descending coronary occlusion followed by 3 hours of reperfusion. The RTH group (n = 10) received RTH and the control group (n = 6) received no cooling. Myocardial and core temperatures were measured with thermistors. Sonomicrometers and micromonameters were used to determine load independent indices of myocardial function. These indices were measured at base line, during coronary occlusion, and at 3 hours of reperfusion. The myocardium at risk and the infarct area were determined with monastral blue dye and triphenyl tetrazolium chloride staining. RESULTS: The mean myocardial temperature in the risk zone during coronary occlusion was significantly less in the RTH group (29.4 degrees C +/- 5.6 degrees C versus 35.7 degrees C +/- 1.1 degrees C, p < 0.05). After 40 minutes of coronary occlusion, both the RTH group and control had a significant reduction in regional elastance (9.38 +/- 3.54 and 11.05 +/- 1.67 mm Hg/mm) compared with base line measurements (14.70 +/- 2.42 and 16.80 +/- 4.79 mm Hg/mm), p < 0.05. However, after 3 hours of reperfusion, the elastance returned to base line levels in the RTH group (15.83 +/- 3.06 mm Hg/mm) but remained significantly depressed in the control group (9.97 +/- 3.63 mm Hg/mm, p < 0.04). Myocardial necrosis as a percentage of the risk zone was significantly less in the hypothermia group (25% +/- 2% versus 62% +/- 5%, p < 0.001). CONCLUSIONS: Regional topical hypothermia during isolated temporary coronary occlusion provides regional myocardial protection expressed as a return of function and decreased necrosis. Regional topical hypothermia may be clinically applicable to myocardial preservation during beating heart operations.

Dual cell seeding and the use of zymogen tissue plasminogen activator to improve cell retention on polytetrafluoroethylene grafts.

OBJECTIVE: The purpose of this study was to enhance the retention of seeded endothelial cells (EC) on prosthetic vascular grafts. Dual-layer EC and smooth muscle cell (SMC) seeding and gene transfer of a zymogen tissue plasminogen activator gene (tPA) into seeded EC were studied. METHODS: Polytetrafluoroethylene (PTFE) grafts were precoated with fibronectin, seeded with SMC followed by EC a day later, and then, 24 hours later, exposed to an in vitro flow system for 1 hour. Cell retention rates were determined for grafts seeded with EC only, a dual layer of EC on top of SMC, EC transduced with wild-type tPA, and EC transduced with zymogen tPA. RESULTS: Seeding efficiency of PTFE pretreated with fibronectin was 260 +/- 8 cell/mm(2). After exposure to flow, only 39% +/- 14% of the EC were retained when EC were seeded alone, whereas 73% +/- 22% of EC remained on grafts when EC were seeded on top of SMC (P <.001, n = 10). The enzyme activity of a mutant zymogen tPA in absence of fibrin was 14 +/- 1 IU/mL, which is 3.6-fold lower than that in the presence of fibrin (50 +/- 19 IU/mL), whereas fibrin has no effect on the wild-type tPA activity. EC expressing a high level of wild-type tPA had a lower retention rate (37%) when compared with normal EC (45%). EC expressing the mutant zymogen tPA had an improved retention rate (54%, P =.001, n = 10) in absence of fibrin, whereas its retention rate was reduced to 43% when the cells were exposed to fibrin. CONCLUSION: SMC seeded between EC and PTFE improves EC retention in vitro. Transduction of zymogen tPA increases thrombolytic ability of seeded cells with less adverse impact on cell retention than wild-type tPA.

Midterm results of the Ross procedure.

BACKGROUND: The optimal hemodynamic performance and potential growth of the pulmonary autograft has led to expanded indications for the Ross procedure. We reviewed our institutional experience to assess midterm results with the Ross operation. METHODS: In a 7-year period (1992 to 1999), 111 patients with a median age of 15.7 years (range 2 days to 67 years), underwent the Ross procedure. Ninety-five patients had isolated aortic valve disease and 16 pediatric patients had a more complex left ventricular outflow tract obstruction. RESULTS: There were 3 early (2.7%) and 3 late deaths over a median follow-up of 3.6 years (range 6 months to 7.6 years). Actuarial survival at 5 years was 94%+/-2%. In pediatric patients, the pulmonary autograft annulus enlarged from 14.7+/-6.2 mm to 22+/-6.3 mm. This growth followed the expected increase in pulmonary valve diameter based on body surface area. Eight reoperations were necessary for autograft insufficiency at a median interval of 14 months (range 2 days to 31 months). Freedom from replacement of the pulmonary autograft was 91%+/-3% at 5 years. Three patients developed important obstruction of the pulmonary homograft requiring reoperation at a median of 29 months (range 9 to 31 months). CONCLUSIONS: The Ross procedure can be performed with good midterm results. In pediatric patients, autograft growth has been appropriate. The potential for development of important autograft insufficiency suggests close follow-up through the intermediate and late term.

Living donor lung transplantation.

Since 1993 a total of 101 living-donor bilateral lung transplants have been performed with acceptable results when compared with those utilizing cadaveric lung grafts. Though most recipients were patients with cystic fibrosis who were rapidly deteriorating, the indications for live-donor lung transplantation have been expanded to include some cystic fibrosis patients in a more elective setting, as well as select patients with other end-stage pulmonary diseases. One-year Kaplan-Meler recipient survival is 72%. Seventy-six percent of deaths occur within the first 2 months after transplantation. The most common cause of death is infection, which accounts for 62% of the 1-year mortality rate. The incidence of rejection is 0.8 episodes per patient. Thirty percent of rejection episodes are unilateral, and most tend to be mild. Altogether, 203 patients have undergone donor lobectomy, with a mean age of 37 +/- 12 years (range 18-56 years). Operations included left lower lobectomy (102 patents), right lower lobectomy (97 patients), and right middle and lower lobectomy (4 patients). There has been no donor mortality. Postoperative Rand 36 Question Quality of Life scores, rating physical function, social functioning, and role limitation due to physical and emotional health, are well over 92 (of a possible score of 100). Eighty-five percent of donors said that their health was no different or improved since donation.

Bronchiolitis obliterans is not the primary cause of death in pediatric living donor lobar lung transplant recipients.

BACKGROUND: Obliterative bronchiolitis (OB) is the chief cause of mortality in cadaveric lung transplant patients (CL). But, is OB the primary cause of mortality for living donor lobar recipients? To answer this question, we reviewed the causes of mortality in our pediatric patients who underwent living donor lobar lung transplantation (LD) and compared them with our pediatric patients who received whole cadaveric lungs (CL). METHODS: Data collected included demographics, transplant type, hospital days, immunosuppression regimen, and cause of death. Statistical analysis was done using Fisher's Exact test and Student's t-test (mean +/- SD). RESULTS: From May 1993 to December 1999, 53 patients underwent lung transplantation (21 males, 32 females; mean age 12.4 +/- 5.4 years). Twenty-nine patients had LD procedures (12 males, 17 females; mean age 14.4 +/- 3.6 years) and 24 patients had CL surgery (9 males, 15 females; p = .78 [not significant]; mean age 9.8 +/- 6.3 years; p =.001). All patients received triple immunosuppression without induction. During the study period, 9 LD (6 males, 3 females; mean age 15.7 +/- 5.0 years) and 14 CL (3 males, 11 females; mean age 11.3 +/- 6.9 years) patients died. There was no significant difference between patients in the LD and CL groups who died with regard to gender (p = .08), age at the time of death (p = .12), mortality rate (p = .06), number of hospital days (p = .09), immunosuppressive medications (p > .08), incidence of non-specific graft failure (p = .26), or incidence of infection (p = .18). However, there was a significant difference in the incidence of OB between LD and CL recipients (p = .002). CONCLUSIONS: OB was not found to be the chief cause of mortality in pediatric LD recipients. We speculate that prevention of infections, possibly by a modest reduction in immunosuppressive therapy and aggressive antimicrobial therapy, may improve long-term survival in pediatric living donor lobar lung transplant recipients.

Psychosocial responses of adolescent cystic fibrosis patients to lung transplantation.

What psychosocial issues do adolescent cystic fibrosis (CF) patients experience after undergoing lung transplantation (Tx)? The aim of this study was to determine, using an ethnographic study design, the common themes and emotional responses in post-lung transplant adolescent CF patients of the Cardiothoracic Transplant Clinic at the Childrens Hospital Los Angeles. Nineteen CF lung transplant recipients were studied (eight males, 11 females: mean age at time of transplant, 15.7 +/- 2.7 yr). The mean time interval from Tx to interview was 25.4 months (range 1-58 months). Sixteen patients had living donor lobar lung Tx while three patients received cadaveric lungs. A series of 25 questions was used to assess the psychosocial impact of Tx, and a semi-structured interview focused on the following five domains: lifestyle, family functioning, social functioning, body image, and psychological functioning. The major themes identified by patients included: a strong desire to set and attain meaningful long-range goals, the need to control as many aspects of their lives as possible while dealing with parental over-protectiveness, and the adjustment to a new lifestyle. Common emotional responses included manageable fear/anxiety of lung rejection and uncertainty of the future, impatience with disruptions of daily routines caused by post-transplant medical management and its effect on the attainment of set goals, and frustration with parental over-protectiveness. In general, patients reported a positive outlook on life, with greater emphasis on sought-after goals as well as inter-personal relationships. This study demonstrates that adolescent CF transplant recipients develop long-term goals and plans for independence. By identifying and anticipating the emotional needs of this population, health care providers can assist patients in improving the quality of their lives from a physiological, as well as a psychological, viewpoint.

Building a clinical cardiothoracic surgical program: a multi-institutional model.

Building a multi-institutional cardiothoracic surgical program has the same guiding principles and values as a traditional single institutional program: ensuring high-quality patient care, training and fostering residents, recruiting and retaining quality faculty, and contributing to basic and clinical research. With a well-designed infrastructure and support system, this more complicated type of organization may permit academic cardiothoracic surgical programs to compete effectively and grow in a constantly changing economic and political environment.

The effect of pleural adhesions on pediatric cystic fibrosis patients undergoing lung transplantation.

The degree of pleural scarring complicating cystic fibrosis (CF) lung disease is thought to impact on the outcome of adult lung transplantation. This has not been previously studied in the pediatric population. We studied all patients undergoing lung transplantation at Children's Hospital Los Angeles from 1993 through 2000. Operative times, grade of pleural scarring, blood product transfusion requirements, and perioperative mortality were compared for patients with cystic fibrosis (35) versus those without this diagnosis (11). Patients with CF were slightly older (14.7+/-3.8 vs 10.6+/-5.6 years; P = 0.01) but had similar weights (34.8+/-8.7 vs 34.4+/-12.3 kg). The degree of pleural scarring was greater in the CF group but was only severe in four patients. Scarring did not impact on operative times (237+/-46 vs 219+/-39 minutes; P = 0.22) or cardiopulmonary bypass times (127+/-40 vs 133+/-49 minutes). Total perioperative blood requirements for the two groups were similar (35.6+/-14.9 vs 42.8+/-76.7 cm3/kg; P = 0.82). Pleural scarring in the pediatric CF patients undergoing lung transplantation is only severe in a minority of patients. It does not increase duration of operation nor blood transfusion requirements. CT scanning is consequently unnecessary in the preoperative workup of CF patients being evaluated for transplantation. CF patients undergoing transplantation have perioperative outcomes similar to those of noncystic patients.

Modulation of pulmonary NA+ pump gene expression during cold storage and reperfusion.

BACKGROUND: Reperfusion injury with pulmonary edema continues to be a major complication after lung transplantation. Alveolar fluid homeostasis is regulated by Na+/K+-ATPase activity on the basolateral surface of alveolar epithelial cells. Intact Na+/K+-ATPase is essential to the resolution of pulmonary edema. We characterized the effects of cold ischemia and reperfusion on expression of Na+/K+-ATPase mRNA and protein. METHODS: Baseline values for Na+/K+-ATPase mRNA and protein were determined from freshly harvested lungs with no cold storage time or reperfusion (group I). Group II lungs were analyzed after cold storage times of 12 or 24 hr without subsequent reperfusion. Group III lungs were analyzed after cold storage times of 12 or 24 hr with subsequent reperfusion. Lungs were flushed with either Euro-Collins (EC) or University of Wisconsin (UW) solution in each group. All samples were quantified for Na+/K+-ATPase mRNA and Na+/K+-ATPase protein. Physiological parameters including oxygenation and compliance were also measured. RESULTS: There were no significant differences in the level of mRNA and protein for samples that were cold stored without reperfusion (group II). With reperfusion (group III) there was a significant increase in the level of the Na+/K+-ATPase mRNA after 12 hr of storage for both EC and UW. After 24 hr of storage and subsequent reperfusion, lungs flushed with EC had significantly decreased Na+/K+-ATPase protein and mRNA, although lungs preserved with UW maintained their increased levels of Na+/K+-ATPase protein and mRNA. CONCLUSIONS: Our data suggest that ischemia-reperfusion injury results in an initial up-regulation of Na+/K+-ATPase mRNA. With prolonged injury in lungs preserved with EC, the level of the mRNA decreased with a corresponding decrease in the Na+/K+-ATPase protein. The different response seen in EC versus UW may be explained by better preservation of pump function with UW than EC and correlates with improved physiological function in lungs preserved with UW solution.

Platelet activating factor acetylhydrolase decreases lung reperfusion injury.

BACKGROUND: Ischemia-reperfusion injury involves free radical production, polymorphonuclear neutrophil chemotaxis/degranulation, and production of proteolytic enzymes, complement components, coagulation factors, and cytokines. Activated polymorphonuclear neutrophils, endothelial cells, and macrophages produce platelet activating factor, which further promotes these inflammatory reactions. The recently cloned plasma form of platelet activating factor-acetylhydrolase (PAF-AH) demonstrates antiinflammatory effects by degrading platelet activating factor. We evaluated the effects of PAF-AH in an isolated perfused rat lung model by adding it to the flush solutions or to the reperfusion blood. METHODS: Rat lungs were isolated, flushed with EuroCollins (EC) or University of Wisconsin (UW) solution, stored at 4 degrees C for 6 or 12 hours, and reperfused using a cross-circulating syngeneic support rat. During reperfusion, oxygenation, compliance, and capillary filtration coefficient were calculated. There were four groups in the study; group I (control) had no PAF-AH added, group II had PAF-AH added to the flush solution, group III had PAF-AH added to reperfusion blood, and group IV had PAF-AH added to both flush solution and reperfusion blood. RESULTS: After 6 hours of storage, oxygenation, compliance, and capillary filtration coefficient significantly improved for EC in group IV. For UW, oxygenation improved in group IV whereas compliance improved in groups II, III, and IV. After 12 hours of storage, compliance improved for EC in group IV and capillary filtration coefficient improved in groups III and IV. For UW, oxygenation and compliance improved in groups II and IV, whereas capillary filtration coefficient improved in group IV. CONCLUSIONS: Addition of PAF-AH to intracellular organ preservation solutions and to the blood reperfusate significantly improves postreperfusion oxygenation and compliance, and reduces lung capillary permeability.

Isolated right ventricular outflow tract mass presenting as hemoptysis.

Infective endocarditis presenting as an isolated right ventricular outflow tract mass is rare. We report a 34-year-old man with no history of congenital heart defect or intravenous drug abuse who presented with hemoptysis and fevers. Diagnostic workup revealed isolated right ventricular outflow tract vegetation. Despite aggressive antibiotic treatment for endocarditis, he developed septic emboli and acute respiratory distress. He was taken to the operating room for successful resection of the ventricular mass.

Indwelling catheter-induced right ventricular rupture.

We describe a case of a 68-year-old man who, because of postoperative mediastinitis, underwent a multiple muscle flap closure of the mediastinum. A chronic indwelling catheter led to erosion and rupture of the anterior wall of the right ventricle. The near exsanguinating hemorrhage was corrected under circulatory arrest. A pericardial patch repair was performed with good results.

Impact of respiratory syncytial virus infection on surgery for congenital heart disease: postoperative course and outcome.

OBJECTIVES: a) To describe the postoperative course and outcome of cardiac surgery in children with recent respiratory syncytial virus (RSV) infection; and b) to evaluate whether timing of surgery has any impact on the outcome. DESIGN: Retrospective case series. SETTING: Intensive care unit and medical and surgical wards of a teaching pediatric hospital. PATIENTS: Twenty-five children (aged 25 days to 3.5 yrs; median, 4 months) with congenital heart disease who had cardiac surgery within 6 months after RSV infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We reviewed the clinical course and outcome of all patients. The cardiac diagnoses included ventricular septal defect (n = 11), tetralogy of Fallot (n = 3), atrioventricular canal (n = 3), and others (n = 8). Thirteen patients had surgery during the same admission as RSV infection (group I), and 12 patients had surgery electively after being discharged to home after RSV infection (group II). Two patients in group I died; both of these patients had undergone total repair of tetralogy of Fallot within 2 wks after admission for RSV infection. Postoperative complications in group I patients included pulmonary hypertension (n = 5), adult respiratory distress syndrome (n = 1), tracheal stenosis (n = 1), left ventricular dysfunction (n = 1), pericardial effusion (n = 1), secondary bacterial or fungal infection (n = 7), and deep venous thrombosis (n = 1). Of all group I patients, the ones who were operated on early appeared to be at higher risk for complications, especially for postoperative pulmonary hypertension. No patient in group II died, and only two patients had minor complications (one had reactive airway disease, and the other had a transient superior vena cava syndrome after a bidirectional Glenn operation). CONCLUSIONS: Cardiac surgery performed during the symptomatic period of RSV infection is associated with a high risk of postoperative complications, especially postoperative pulmonary hypertension. These complications appeared to be more frequent and of greater severity in patients who had earlier surgery compared with those who had later surgery. More studies are needed regarding the proper timing of cardiac surgery in patients with congenital heart disease and RSV infection.

Addition of a water-soluble alpha-tocopherol analogue to University of Wisconsin solution improves endothelial viability and decreases lung reperfusion injury.

BACKGROUND: Reperfusion injury following lung preservation has been associated with free radical formation and subsequent endothelial cell damage. Trolox is a water-soluble analogue of the free radical scavenger alpha-tocopherol. We hypothesized that addition of this form of vitamin E to University of Wisconsin (UW) solution would decrease reperfusion injury and improve lung function after cold ischemic preservation. MATERIALS AND METHODS: Bovine aortic endothelial cells were cultured and stored at 4 degrees C for 12, 24, and 48 h in UW or UW + Trolox (UWT). Endothelial cell viability after storage was assessed by dimethylthiazole tetrazolium cytotoxicity assay. An isolated rat perfused lung (IPL) model was used and lungs were flushed with the respective solutions with cold storage times of 6 and 12 h. Following storage, the lungs were reperfused with fresh blood and lung function was assessed by blood gas analysis, alveolar-arterial gradient, and compliance. RESULTS: There was no difference in endothelial cell viability between UW and UWT after 12 or 24 h; however, UWT had higher endothelial cell viability than UW with 48 h of cold ischemic storage. Using the IPL model, the pO2 was higher with UWT than UW after 6 and 12 h of cold ischemia. The alveolar-arterial oxygen difference was significantly lower for UWT versus UW at 6 h. UWT provided increased compliance at 6 and 12 h of ischemia. CONCLUSIONS: The addition of a water-soluble vitamin E analogue to UW solution resulted in increased endothelial cell viability after prolonged storage and improved whole lung preservation in the postreperfusion period as evidenced by higher oxygenation and increased compliance. These results are clinically relevant as the lung is extremely sensitive to reperfusion injury and UW solution is being increasingly used in lung transplantation and remains the predominant solution in abdominal organ transplantation.

Sirolimus (rapamycin) potentiates cyclosporine in prevention of acute lung rejection.

BACKGROUND: Cyclosporine-based immunosuppressive regimens (INN: ciclosporin) in human lung transplantation continue to result in a high incidence of acute cellular rejection. We investigated the use of sirolimus, a macrolide with structural similarity to tacrolimus, as monotherapy and in combination with cyclosporine in a rodent lung transplant model. METHODS: Orthotopic left lung transplantation was performed in Lewis recipients from Brown-Norway donor rats with syngeneic Lewis-to-Lewis controls. Open biopsies were performed on postoperative day 7, and the severity of acute lung rejection was graded by a pathologist blinded to the protocol. RESULTS: All recipients survived despite the amount of acute rejection seen on examination of the biopsy tissue. Lewis-to-Lewis isografts demonstrated near normal pulmonary architecture. Allogeneic recipients receiving high-dose cyclosporine (25 mg/kg) monotherapy showed mild to moderate acute rejection with some perivascular focal interstitial infiltrates. Recipients receiving low-dose cyclosporine (5 mg/kg) monotherapy or low- or high-dose sirolimus (0.5 or 2.0 mg/kg, respectively) monotherapy demonstrated massive cellular infiltration leading to necrosis and infarction and could not be graded. However, the addition of low-dose sirolimus (0.5 mg/kg) to low-dose cyclosporine (5 mg/kg) demonstrated a significant potentiating immunosuppressive effect, and the addition of high-dose sirolimus (2.0 mg/kg) to low-dose cyclosporine (5.0 mg/kg) demonstrated an even greater effect, with rejection scores better than those obtained with high-dose cyclosporine monotherapy and similar to those obtained with isografts. CONCLUSIONS: This study demonstrates that low-dose sirolimus has a cyclosporine-sparing effect and that a higher dose of sirolimus in combination with cyclosporine strongly protects lung allografts from acute cellular rejection. These results suggest that sirolimus may be indicated as an adjunct to current cyclosporine-based immunosuppressive regimens in clinical lung transplantation.

RNA antisense abrogation of MAT1 induces G1 phase arrest and triggers apoptosis in aortic smooth muscle cells.

The human MAT1 gene (ménage à trois 1) is an assembly factor and a targeting subunit of cyclin-dependent kinase (CDK)-activating kinase. The novel mechanisms by which MAT1 forms an active CDK-activating kinase and determines substrate specificity of CDK7-cyclin H are involved in the cell cycle, DNA repair, and transcription. Hyperplasia of vascular smooth muscle cells (SMC) is a fundamental pathologic feature of luminal narrowing in vascular occlusive diseases, and nothing is yet known regarding the cell cycle phase specificity of the MAT1 gene in its involvement in SMC proliferation. To investigate such novel regulatory pathways, MAT1 expression was abrogated by retrovirus-mediated gene transfer of antisense MAT1 RNA in cultured rat aortic SMCs. We show that abrogation of MAT1 expression retards SMC proliferation and inhibits cell activation from a nonproliferative state. Furthermore, we have demonstrated that these effects are due to G1 phase arrest and apoptotic cell death. Our studies indicate a link between cell cycle control and apoptosis and reveal a potential mechanism for coupling the regulation of MAT1 with G1 exit and prevention of apoptosis.

A comparison of the new preservation solution Celsior to Euro-Collins and University of Wisconsin solutions in lung reperfusion injury.

BACKGROUND: The lung is particularly susceptible to reperfusion injury, both experimentally and clinically after transplantation. The extracellular-type preservation solution Celsior, which has been predominantly studied in cardiac preservation, has components designed to prevent cell swelling, free radical injury, energy depletion, and calcium overload. Using an isolated blood-perfused rat lung model, we investigated whether Celsior would decrease preservation injury and improve lung function after cold ischemic storage and reperfusion compared to Euro-Collins (EC) and University of Wisconsin (UW) solutions. METHODS: Lewis rat lungs were isolated, flushed with the respective cold preservation solution, and then stored at 4 degrees C for 6 or 12 hr. After ischemic storage, the lung block was suspended from a force transducer, ventilated with 100% O2, and reperfused for 90 min with fresh blood via a cannula in the pulmonary artery. Lung compliance, alveolar-arterial oxygen difference, and outflow oxygen tension were all measured. The capillary filtration coefficient (Kf), a sensitive measure of changes in microvascular permeability, was determined. RESULTS: For 6 hr of cold storage, lungs stored in Celsior had lower Kf values than those stored in EC, indicating decreased microvascular permeability. No other significant differences were noted between Celsior and EC or UW. For 12 hr of cold storage, Celsior provided increased oxygenation, decreased alveolar-arterial O2 differences, increased compliance, and decreased Kf values as compared to both EC and UW. CONCLUSIONS: Celsior provides better lung preservation than EC or UW as demonstrated by increased oxygenation, decreased capillary permeability, and improved lung compliance, particularly at 12-hr storage times. These results are highly relevant, inasmuch as EC and UW are the most common clinically used lung preservation solutions. Further studies of Celsior in experimental and clinical lung transplantation, as well as in other solid organs, are indicated.