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.

Living donor lobar lung transplantation: current status and future directions.

Living lobar lung transplantation was developed as a procedure for adult and pediatric patients considered too ill to await cadaveric transplantation. One hundred thirty-eight living lobar transplants have been performed in 133 patients at our institution between January 1993 and September 2004. Actuarial 1-, 3-, and 5-year survival are similar to ISHLT registry data. There has been no donor mortality, and morbidity has been relatively low. Long-term postoperative pulmonary function studies demonstrate the relatively smaller-sized lobes can provide similar pulmonary function and exercise capacity to bilateral cadaveric lung transplants. Living lobar lung transplantation should be considered a viable option in patients with end-stage lung disease deemed unable to await a cadaveric organ and in those patients in which further deterioration would make cadaveric transplantation inappropriate.

Infectious complications in heart-lung transplantation. Analysis of 200 episodes.

BACKGROUND: Infection remains an important cause of morbidity and mortality in heart-lung transplant recipients. This study was designed to assess the frequency, type, and timing of infection in heart-lung transplant recipients. METHODS: A retrospective analysis of 200 episodes of serious infections occurring in 73 heart-lung recipients at Stanford (Calif) University Medical Center between 1981 and 1990. RESULTS: Bacterial infections accounted for half of all infections, with the highest incidence in the first month after transplantation. Fungal infections (14%) were also common in the first month. Cytomegalovirus was the most common viral agent (15%), occurring primarily in the second month after transplantation. Other viruses (herpes simplex, adenovirus, and respiratory syncytial virus) accounted for a further 15% of total infections. Pneumocystis carinii infections were common 4 to 6 months after transplantation, and Nocardia typically infected recipients later than 1 year after transplantation. There was no significant difference in incidence of infections between patients receiving triple (cyclosporine, prednisone, immuran) or double (cyclosporine and prednisone) immunosuppression therapy. Mortality due to infection accounted for 40% of all deaths. CONCLUSIONS: Knowledge of the incidence and timing of infection should help in the prevention, early detection, and initiation of therapy in these patients.

Targeting retroviral vectors to vascular lesions by genetic engineering of the MoMLV gp70 envelope protein.

Targeted gene delivery to vascular lesions is a major challenge in the development of gene therapy protocols for cardiovascular diseases. One approach would be to enable retroviral vectors to accumulate at sites of vascular injury and enhance local vector concentration. An early step in wound repair is the adhesion of platelets to collagen exposed from damaged vasculature. Hence, the Moloney murine leukemia virus (MoMLV) envelope (env) protein was engineered to incorporate a high-affinity collagen-binding domain derived from von Willebrand clotting factor, and expressed in Escherichia coli and in mammalian cells. The chimeric env protein bound tightly to collagen, and virions bearing this collagen-binding env protein exhibited viral titers approaching those of virions expressing wild-type (WT) env protein. The chimeric virions were concentrated on collagen matrices, and they retained their infectivity under conditions in which virions bearing WT env protein were washed away. Targeted delivery of the chimeric env protein to injured mouse aorta and selective binding of the collagen-targeted virions to injured rabbit artery were observed. In comparative studies, vascular smooth muscle cell transduction was demonstrated in catheter-injured carotid arteries following infusion of collagen-targeted virions but not of virions bearing WT env protein. Taken together, these observations demonstrate the ability of collagen-targeted virions to localize gene delivery to sites of vascular injury.

Cellular mechanisms underlying differential rejection of sequential heart and lung allografts in rats.

As the simultaneous transplantation of two or more organs into a single recipient has become increasingly common, asynchronous allograft rejection has become an important clinical problem. To investigate the cellular and molecular mechanisms underlying differential organ rejection, we developed a rat model in which heart and lung allografts were transplanted sequentially. Heterotopic heart allografts transplanted into DA recipients from PVG donors survived indefinitely if the recipients were given a short course of rabbit antirat thymocyte globulin or cyclosporine at the time of transplantation. In contrast, orthotopic left lungs transplanted under the same conditions were rejected in ATG-treated recipients and accepted in most CsA-treated recipients. These animals were then given a second organ allograft from the same strain or a third party to assess whether they exhibited donor specific tolerance and whether the acceptance or rejection of the first allograft would influence the survival of the second transplant. Animals tolerized to a heart allograft with ATG rejected an orthotopic lung transplant from the same strain as the original allograft, whereas recipients treated with CsA at the time of their heart transplant accepted a subsequent lung graft. Surprisingly, animals treated with either ATG or CsA that had rejected a lung allograft accepted a subsequent heart transplant. Using limiting dilution analysis and adoptive transfer studies, we found that some recipients had developed suppressor cells while others demonstrated anergy. We conclude that major histocompatibility complex antigens as well as other antigens are involved in the differential rejection of heart and lung allografts.

Trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii infections in heart-lung and lung transplantation--how effective and for how long?

Pneumocystis carinii pneumonia (PCP) is a common clinical problem in the setting of organ transplantation, particularly in heart-lung and lung allograft recipients. Without prophylactic measurements, the incidence of P carinii pneumonia can reach up to 88% of heart-lung transplant recipients. We conducted a retrospective analysis of the Stanford heart-lung and lung transplant experience in order to assess the efficacy of the prophylactic therapy and to try to define the duration of therapy necessary for prevention. During a 9-year period 82 heart-lung and 13 single-lung transplants were performed. Of the patients not on prophylaxis therapy 27% (13 patients) developed P carinii infection as compared with 0% of patients on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. The incidence of PCP infection peaked between 3 and 6 months posttransplantation. No case of infection was observed before the 7th week posttransplant. PCP was more common following induction immunosuppression with OKT3 as compared with RATG (P less than 0.05). All cases of infections later than one year posttransplant were associated with recent increase in the immunosuppression regimen with high-dose corticosteroids for treatment of acute or chronic (obliterative bronchiolitis) rejection. Although our study is retrospective and based on various immunosuppressive and diagnostic technique periods, it seems that TMP-SMX is highly effective in preventing PCP infections in heart-lung and lung transplant recipients. Twelve months of therapy is probably a sufficient length of therapy if immunosuppressive therapy is stable. However, whenever augmentation in the immunosuppression regimen is indicated, prophylactic therapy should promptly be restarted.

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.

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.

A novel paracorporeal method for isolated rodent lung reperfusion.

BACKGROUND: The isolated perfused lung model is commonly used in small animals to study lung function after preservation and cold storage. Measurements of oxygenation, compliance, and capillary filtration coefficient (Kf) permit analysis of preservation solutions or modifications of these solutions. However, inter-investigator variability using different perfusates makes comparisons difficult. Whole blood perfusion more closely mimics the in vivo situation, but extracorporeal circulation may alter the physiologic integrity of the model. Paracorporeal support has been used, but this technique required mechanical ventilation of the support rodent and did not incorporate a method for determining Kf. We evaluated a less-invasive technique, of providing cross-circulatory syngeneic support, maintaining the ability to compute Kf. METHODS: Angiocatheters were inserted into both femoral arteries and one femoral vein of the support rat. The venous cannula was connected to the pulmonary artery of the ex vivo lung block to provide inflow. Pulmonary effluent blood from the lung block was collected via a left atrial cannula and returned to the support rat via the femoral artery. A separate, height-adjustable column was included in the circuit for measurement of Kf. RESULTS: Each support rat was used to sequentially perfuse three double-lung blocks. The inflow sample to each lung block was analyzed for pH, pO2, pCO2, and hematocrit to follow alterations in support rat physiology. There were no statistical differences in the pH, PO2, or hematocrit. No significant differences were noted in the pO2 of the pulmonary effluent blood or the Kf; analyzed to determine whether the sequence of reperfusion affected the pulmonary function assessment. CONCLUSIONS: The syngeneic support rat delivers constant pressure systemic venous blood at stable physiologic parameters to the ex vivo lung block. Recirculation of the perfusate through the support rat diminishes the need to pool blood from donors, detoxifies and deoxygenates pulmonary effluent blood, and permits examination of sequential lung blocks. This technique represents a hybrid model between isolated perfused and orthotopic transplant models, maintaining Kf determination, a sensitive indicator of reperfusion injury. This technique could be applicable to reperfusion injury models of other organs (using arterial inflow instead) and may permit increased standardization among investigators.

Cytokine gene expression in human lung transplant recipients.

The polymerase chain reaction was used to evaluate cytokine gene expression in bronchoalveolar lavage (BAL) cells and peripheral blood leukocytes in 31 human lung transplant recipients. All patients were maintained on a triple immunosuppression regimen consisting of CsA, AZA, and prednisone. Posttransplant survival ranged from 0.5 to 100.5 months (mean = 16.3 months). Cytokines IL-1 alpha, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, TNF-beta, and IFN-gamma were studied. In BAL, transcripts for IL-1 alpha, IL-7, IL-8, and TNF-beta were found in over 60% of samples and those for IL-5, IL-6, and IFN-gamma in 40-50%, while IL-2 and IL-4 mRNA were rarely found (< 20%). Considerable variation in the frequency of cytokine gene expression between BAL and peripheral blood was observed. When analyzed for the presence of acute pulmonary allograft rejection (without infection), transcripts for IL-4 and IL-6 in BAL demonstrated the greatest increase in frequency compared with nil rejection (P = 0.07 and P = 0.17, respectively). Pulmonary infection (without rejection) was associated with a modest increase in the expression of genes for IL-1 alpha and IFN-gamma (> 10%). Transcripts for IL-4 were not found in association with pulmonary infection, suggesting that this cytokine may be useful as a discriminatory rejection marker.

Cytokine gene expression in rejecting cardiac allografts.

Heart transplantation is now a viable therapeutic option for patients with certain end-stage cardiac diseases. However, episodes of rejection, opportunistic infection, and life-threatening side effects of generalized immunosuppression remain very real problems for these patients. A better understanding of the molecular mechanisms underlying rejection may provide the basis for the development of more specific, less toxic immunosuppressive therapies. While cytokines have long been implicated in the pathogenesis of rejection, the precise role of each cytokine in this process has yet to be defined. We report here the application of the polymerase chain reaction (PCR) to the detection of cytokine mRNA in biopsies obtained from heterotopic abdominal cardiac allografts in cynomolgus monkeys. With the exception of IL-6 and IL-8, cytokine transcripts were undetectable in samples obtained from the donor heart pretransplant. In contrast, IFN-gamma transcripts were detected in all transplants two days after surgery before evidence of rejection was demonstrable by histopathologic analysis. IL-1 beta, IL-2, and IL-6 transcripts were detected when minimal rejection was noted. At later times, IL-1 alpha, IL-1 beta, IL-2, IL-6, IL-8, TNF-beta, and IFN-gamma transcripts were detectable. Further characterization of the spectrum of cytokines expressed at various stages of rejection may lead to insights into the biology of transplant rejection and to the development of more specific and potent reagents to diagnose and/or treat rejection.

The use of granzyme A as a marker of heart transplant rejection in cyclosporine or anti-CD4 monoclonal antibody-treated rats.

Granzyme A is a serine protease expressed by populations of human and mouse natural killer cells and activated CD4+ and CD8+ cytotoxic lymphocytes; its expression marks a subset of inflammatory cells in allografts, autoimmune diabetes, and a number of other inflammatory lesions. In order to describe more completely the correlation between granzyme A expression and the presence of in vivo cytolytic effects, we grafted allogeneic rat hearts with vascular anastomoses in a heterotopic location, and treated the hosts with either cyclosporine, anti-CD4 monoclonal antibody (MRC OX38), or no therapy. The grafts were evaluated by palpation for cardiac functions, by immunohistochemistry for CD4/CD8 expression, by hematoxylin-and-eosin staining for inflammatory infiltration, and by in situ hybridization for granzyme A expression. The appearance of granzyme A+ cells in untreated allografts preceded both functional and standard histopathological and immunohistochemical evidence of graft rejection by two days. In donor-recipient combinations where cyclosporine and anti-CD4 treatments allowed indefinite allograft survival, the allografts showed minimal numbers of granzyme A+ cells, whether cellular infiltrates developed or not. The number of granzyme A+ cells present in the cardiac allografts in treated and untreated animals correlated with either current or impending episodes of rejection. The early time course of granzyme A expression suggests that it can be used as an early and reliable marker of graft rejection.

Characteristics of immunoglobulin gene usage of the xenoantibody binding to gal-alpha(1,3)gal target antigens in the gal knockout mouse.

BACKGROUND: Natural antibodies that react with galactose-alpha(1,3)galactose [galalpha(1,3)gal] carbohydrate epitopes exist in humans and Old World primates because of the inactivation of the alpha1,3-galactosyltransferase (alpha1,3GT) gene in these species and the subsequent production of antibodies to environmental microbes that express the galalpha(1,3)gal antigen. The Gal knockout (Gal o/o) mouse, produced by homologous disruption of the alpha1,3GT gene, spontaneously makes anti-galalpha(1,3)gal antibodies and can be used to study the genetic control of humoral immune responses to this carbohydrate epitope. METHODS: Six hybridomas that produce monoclonal antibodies (mAbs) to galalpha(1,3)gal were generated in Gal o/o mice. The mAbs were tested to characterize the binding activity with flow cytometry using pig aortic endothelial cells and ELISA with galalpha(1,3)gal carbohydrates. The VH and VK genes of these hybridomas were cloned, sequenced, and analyzed. RESULTS: The mAbs showed distinct patterns of antibody binding to galalpha(1,3)gal antigens. The VH genes that encode the mAb binding activity were restricted to a small number of genes expressed in their germline configuration. Four of six clones used closely related progeny of the same VH germline gene (VH441). Comparison of the mouse gene VH441 to the human gene IGHV3-11, a gene that encodes antibody activity to galalpha(1,3)gal in humans, demonstrates that these two genes share a nonrandom distribution of amino acids used at canonical binding sites within the variable regions (complimentary determining regions 1 and 2) of their immunoglobulin VH genes. CONCLUSIONS: These results demonstrate the similarity of the Gal o/o mice and humans in their immune response to galalpha(1,3)gal epitopes. Gal o/o mouse can serve as a useful model for examining the genetic control of antibody/antigen interactions associated with the humoral response to pig xenografts in humans.

Induction of donor-specific unresponsiveness to cardiac allografts in rats by pretransplant anti-CD4 monoclonal antibody therapy.

In the present report a monoclonal antibody designated OX-38 directed against the rat CD4 molecule was tested for its ability to prolong the survival of heterotopic vascularized rat heart allografts transplanted across major histocompatibility barriers. Fluorescence-activated cell-sorter analysis showed that administration of OX-38 selectively depleted 80-95% of CD4+ cells from peripheral blood of treated rats. The immunosuppressive effects of OX-38 in vivo were verified by suppression of an antibody response against OX-38 itself as a heterologous protein immunogen. Recipient rats received OX-38 antibody as a single agent given in pretransplant regimens. Nine of 12 treated rats have maintained heterotopic abdominal heart allografts for greater than 175 days. Control rats that did not receive antibody therapy rejected their grafts within 14 days. Rats that maintained heart allografts for greater than 100 days accepted second donor strain hearts but rejected third-party heart grafts transplanted into the femoral space. Anti-CD4-induced allograft unresponsiveness persisted for at least 90 days following surgical removal of donor tissue and retransplantation of a second donor-matched heart. These results indicated that transient, pretransplant therapy with monoclonal antibodies directed against the CD4+ lymphocyte induced specific, long-lasting unresponsiveness to fully MHC-mismatched cardiac allografts in rats without additional immunosuppression.

Pediatric heart transplantation at Stanford: results of a 15-year experience.

The long-term results of pediatric heart transplantation were evaluated in 53 patients, aged 0.25 to 18.94 years, who received transplants at Stanford University Medical Center between 1974 and 1989. Indications for transplantation were idiopathic cardiomyopathy (68%), congenital heart disease (21%), endocardial fibroelastosis (8%), and doxorubicin cardiomyopathy (3%). Immunosuppression was achieved with combinations of cyclosporine, prednisone, and azathioprine. Thirty-seven of 42 recipients leaving the hospital after transplantation were alive and in New York Heart Association class I at study's end. Cumulative survival was 79% at 1 year, 76% at 3 years, and 69% at 5 years. Fourteen recipients have survived more than 5 years (5.1 to 12.4 years). Hospital readmission for illness has been infrequent, decreasing from 6.8 days to 0.9 days per year over 5 years. Eleven patients have required no rehospitalization. Posttransplant deaths were due to infection (19%), rejection (4%), pulmonary hypertension (4%), coronary artery disease (2%), and lymphoproliferative disease (2%). Retransplantation was required for intractable rejection in 4 patients and advanced coronary artery disease in 2. Hypertension and elevated blood urea nitrogen and creatinine levels were common in individuals receiving cyclosporine. Growth was often impaired in prepubertal children receiving daily prednisone. Based on this 15-year experience, it is concluded that heart transplantation represents a reasonable alternative for selected young patients with end-stage cardiac disease.

Recovery of the right ventricle after single-lung transplantation in pulmonary hypertension.

Single-lung transplantation has been successfully performed in patients with pulmonary fibrosis and emphysema. In contrast, patients with end-stage pulmonary hypertension (either primary or secondary to Eisenmenger's syndrome) have conventionally been offered heart-lung transplantation. The rationale underlying this approach is that chronic pulmonary hypertension results in irreversible right ventricular dilatation and failure. Recovery of the right ventricle has previously been reported after thromboendarterectomy for chronic large-vessel pulmonary embolism, correction of atrial septal defect or mitral valve replacement. The evolution of right ventricular morphology and function after lung transplantation has not been previously described. This study examines the reversibility of right ventricle dysfunction following normalization of pulmonary artery pressure after single-lung transplantation in 4 patients with pulmonary hypertension. Cardiac function was assessed using electrocardiography, echocardiography and radionuclide angiography. Pulmonary hemodynamic measurements, including pulmonary artery pressure and pulmonary vascular resistance, decreased in all patients after single-lung transplantation. Electrocardiographic changes observed were leftward shift in the QRS axis, and a decrease in P-wave amplitude and in right ventricular force. Echocardiographic examination revealed decreased right atrial, right ventricular and tricuspid valve annular dimensions, normalization of septal motion, and decreased tricuspid regurgitation. Thus, improved pulmonary hemodynamics after single-lung transplantation for pulmonary vascular disease results in reversal of right heart dilatation and dysfunction, and improved myocardial performance. The extent of right ventricular dysfunction beyond which recovery is unlikely to occur has yet to be determined.

Cardiac function after domino-donor heart transplantation.

A major limitation in cardiac transplantation is donor availability. A possible way to increase the supply of donor hearts is to use explanted hearts from patients undergoing heart-lung transplantation for primary lung disease. One potential advantage of this approach, termed domino-donor transplantation, is the existence of a donor right ventricle already adapted to pulmonary hypertension, which would therefore theoretically decrease the likelihood of acute donor right heart failure in recipients with preexisting elevation of pulmonary vascular resistance. Potential disadvantages include graft failure secondary to chronic effects of pulmonary hypertension on the right ventricle, arrhythmia and infections. Seven domino-donor transplants were performed at Stanford University Hospital; graft and patient survival to date are 100% at a mean follow-up of 20 months (range 1 to 26). Infection and rejection rates have been comparable to those of the current Stanford experience for conventional orthotopic transplantation. Right ventricular function and size have either improved or remained unchanged in all patients after transplantation. Transient early postoperative donor right ventricular dilation, a characteristic adaptive response seen in nondomino transplants, occurred in 4 patients with pulmonary hypertension before surgery. These data indicate that, with adequate assessment before surgery, domino-donor cardiac transplantation is an appropriate means of augmenting the donor pool.

Predictors of left ventricular outflow obstruction following single-stage repair of interrupted aortic arch and ventricular septal defect.

This study looked at echocardiographic predictors of left ventricular outflow obstruction after primary neonatal repair of interrupted aortic arch and ventricular septal defect. Results of this study indicate that the only significant independent predictor of left ventricular outflow obstruction is aortic valve diameter; all patients with an aortic valve diameter <4.5 mm (Z score <-5) subsequently developed obstruction, whereas patients with annuli >4.5 mm (Z score >-5) remained free from obstruction.

Lobar transplantation. Indications, technique, and outcome.

Lobar transplantation represents a therapeutic option for children and some adults with severe end-stage pulmonary disease. Six patients including two neonates, three children, and one adult underwent lobar transplantation. Ages ranged from 17 days to 21 years. Transplant procedures were unilateral in the neonates and two of the children and bilateral in the child and adult who had cystic fibrosis. The donor lobes were from cadavers in the two neonates and living related donors in the children and the adult. Unilateral grafts involved use of the right upper lobe in the 12-year-old patient with bronchopulmonary dysplasia; right middle lobe with a ventricular septal defect repair in the 4-year-old patient with Eisenmenger's syndrome, left upper lobe in the 28-day-old patient with primary pulmonary hypertension, and the right upper and middle lobes in the 17-day-old patient with diaphragmatic hernia. Bilateral lobar transplantations were performed with the right lower and left lower lobes in the two patients with cystic fibrosis (aged 13 and 21 years). The two neonates underwent emergency transplantation with the use of extracorporeal membrane oxygenation as a bridge. Perioperative survival was 83%, with only the 4-year-old patient with ventricular septal defect/Eisenmenger's syndrome dying early. No airway complications were observed. The unilateral grafts received most of the blood flow as shown by perfusion scanning (range 74% to 99%). Living related donor complications included prolonged air leaks (> 6 days) in two patients. In urgent situations, such as an infant requiring extracorporeal membrane oxygenation, and in the existing milieu of donor shortage, lobar transplantation (living related or cadaveric) is a surgically feasible procedure and can provide a donor source in the limited time frame of these clinical situations. Bilateral lobe transplantation may be a viable option for patients with cystic fibrosis and life-threatening respiratory decompensation.

The clamshell incision for bilateral pulmonary artery reconstruction in tetralogy of Fallot with pulmonary atresia.

BACKGROUND: Patients with tetralogy of Fallot/pulmonary atresia often have bilateral pulmonary artery lesions, including diminutive central and peripheral vessels, major aortopulmonary collaterals, and distortion from previous operations. Staged procedures through lateral thoracotomies and median sternotomies have traditionally been used for repair. METHODS: Between October 1993 and December 1995, 10 patients 3 months to 15 years old with complex tetralogy of Fallot/pulmonary atresia underwent repair via a clamshell approach. Nine had undergone a mean of 2.8 +/- 0.8 previous operations (range 1 to 4). Indications for operation were repair of pulmonary artery arborization anomalies in 10 (4 unilateral, 6 bilateral), with unifocalization in 6 (2 unilateral, 4 bilateral). RESULTS: Eight of 10 patients had concomitant complete repair. There were no deaths at a mean follow-up of 17.1 +/- 4.0 months (range 12 to 26). Mean ventilation time was 3.7 +/- 2.1 days (range 1 to 14) and hospital stay 8.7 +/- 4.6 days (range 4 to 19). At follow-up, the peak right ventricular/left ventricular pressure ratio in patients who received complete repair was 0.44 +/- 0.13 (0.30 to 0.67). One patient (10%) required reoperation because of pseudoaneurysm of the main pulmonary artery 14 months after repair, and one had successful stent placement because of recurrent left and right pulmonary artery stenosis 8 months after repair. Two infants who underwent complete unifocalization and central pulmonary artery reconstruction are awaiting completion of repair. CONCLUSIONS: The clamshell approach to complex tetralogy of Fallot/ pulmonary atresia provides simultaneous exposure of bilateral central and peripheral pulmonary artery lesions and intracardiac pathologic conditions. This procedure appears safe and may decrease the number of operations required to complete repair of tetralogy of Fallot/pulmonary atresia in selected patients.