Outpatient inhaled nitric oxide in a patient with idiopathic pulmonary fibrosis: a bridge to lung transplantation.

Inhaled nitric oxide (INO) has been shown to improve oxygenation and decrease intrapulmonary shunt and pulmonary hypertension in various lung diseases. In this study we report a patient with end-stage idiopathic pulmonary fibrosis and pulmonary hypertension who received INO after coronary artery bypass surgery, with significant improvement in arterial oxygenation and pulmonary arterial pressure. Using a pulsing delivery system, the patient continued to receive outpatient INO for 30 months while waiting for lung transplantation. Exercise study and two-dimensional echocardiogram, after 3 months of inhaled NO, demonstrated continued benefits of INO for improvement of arterial oxygenation, pulmonary arterial pressure and exercise tolerance.

Surgical management of congenital obstruction of the left main coronary artery with supravalvular aortic stenosis.

OBJECTIVE: Stenosis of the left main coronary artery is a recognized complicating feature of supravalvular aortic stenosis. We have retrospectively identified three anatomic subtypes of left main coronary obstruction in patients with supravalvular aortic stenosis, each necessitating a distinct surgical approach. METHODS: From 1991 to 1998, 9 patients underwent surgical repair of supravalvular aortic stenosis and left main coronary stenosis. Five patients (group 1) had obstruction from near-circumferential thickening of the left main ostium, 2 patients (group 2) had restricted coronary flow due to fusion of an aortic valve leaflet to the supravalvular ridge, and 2 patients (group 3) had diffuse narrowing of the left main coronary artery. Group 1 patients were treated with patch aortoplasty encompassing the left main ostium and supravalvular aortic stenosis. Group 2 patients were treated with excision of the fused leaflet from the aortic wall and patch aortoplasty. Group 3 patients were treated with bypass grafting and aortoplasty. RESULTS: Surgical strategy was determined by coronary angiography and intraoperative assessment of coronary anatomy. There was 1 early death. All surviving patients underwent echocardiography with or without postoperative catheterization. The mean postoperative supravalvular gradient for 7 patients was 8 mm Hg (range 2-15 mm Hg). One patient required reoperation for a residual aortic gradient as a result of aortic arch involvement. No evidence of left main coronary artery stenosis was seen in groups 1 and 2; bypass grafts were patent in group 3 patients at a mean follow-up of 54.8 months. CONCLUSION: Three subtypes of left main coronary stenosis with supravalvular aortic stenosis are described. Each anatomic type mandates an individual surgical approach. Favorable surgical outcomes are achievable with each category.

Surgical repair of an atrial septal defect in a juvenile Sumatran orangutan (Pongo pygmaeus sumatraensis).

A systolic heart murmur was auscultated in a 2-yr-old female Sumatran orangutan (Pongo pygmaeus sumatraensis) with a slower than expected growth rate. Cardiac ultrasound revealed an 11-mm atrial septal defect. Cardiac catheterization confirmed the diagnosis. Surgical repair was performed during cardiopulmonary bypass using a pericardial patch. The bypass pump was primed with human albumin and donor orangutan whole blood of a compatible type. Hematuria occurred shortly after the initiation of cardiopulmonary bypass. Successful repair was immediately confirmed with transesophageal ultrasonography. The animal was extubated shortly after returning to spontaneous ventilation but had to be reintubated 4 hr later due to tachypnea and decreased SpO2. Additional extubation attempts failed, necessitating continuous positive pressure ventilation, monitoring, and intensive care environment. Thoracic radiographs suggested adult respiratory distress syndrome. The animal required 14 days of intensive care before extubation of the trachea was successful. After 4 wk of isolation, the orangutan was successfully reintroduced to its family group.

Atrial septostomy as a bridge to lung transplantation in patients with severe pulmonary hypertension.

Long waiting times for lung transplantation have limited the survival of patients with advanced pulmonary hypertension. Atrial septostomy has been used in this group of patients in an attempt to prolong survival. We evaluated the results of atrial septostomy in 12 patients using the static graded balloon dilation technique. Between December 1990 and May 1998, 10 women and 2 men (ages 13 to 56 years, mean 37 years) underwent atrial septostomy. Nine patients had primary and 3 patents had secondary pulmonary hypertension. Five patients deteriorated despite long-term intravenous prostacyclin infusions. The atrial septum was crossed with a Brockenbrough needle, followed by an 0.035-J exchange wire and progressively larger catheter balloons for atrial septal dilation, until systemic oxygen saturation decreased 5% to 10%. An atrial septal defect was successfully created in each patient. The mean right atrial pressure decreased from 23 to 18 mm Hg and the mean systemic oxygen saturation decreased from 93% to 85%. The mean cardiac index increased from 1.7 to 2.1 L/min/m2 and the mean systemic oxygen transport increased from 268 to 317 ml/min/m2. Complications occurred in 3 patients: transient hypotension during transesophageal echocardiography, a femoral pseudoaneurysm, and a femoral arteriovenous fistula. After septostomy, 6 patients had clinical improvement (resolution of ascites, edema, and no further episodes of syncope); 5 of these 6 patients underwent lung transplantation a mean of 6.1 months after septostomy. Six patients did not have clinical improvement after septostomy. Atrial septostomy improves the hemodynamic status and may be useful as a bridge to lung transplantation in selected patients with pulmonary hypertension.

Volume reduction surgery in the native lung after single lung transplantation for emphysema.

The natural history of emphysema suggests that progression of disease in the native lung may contribute to late deterioration in respiratory function after single lung transplantation. In this report, we describe our experience with unilateral volume reduction surgery in three single lung transplant recipients with emphysema. Each patient had had a late decline in lung function with a recurrence of symptoms. Chest radiographs demonstrated hyperinflation of the native lungs with encroachment on the grafts. Serial pulmonary function testing documented progressive reduction in expiratory flows with increases in residual volumes. Exercise testing confirmed severe intolerance to maximal exercise. Unilateral volume reduction surgery was undertaken at 36, 39, and 55 months after transplantation without incident. Radiographs obtained after the procedures demonstrated restoration of normal diaphragmatic contour, decreased aeration of the native lungs, and improved inflation of the allografts. Exercise testing at 3 months documented a mean improvement in maximal oxygen consumption of 35%. Expiratory flows improved by a mean of 60%. Quantitative ventilation and perfusion scans, however, were essentially unchanged. This experience suggests that unilateral volume reduction surgery may be considered as an alternative strategy in single lung transplant recipients with emphysema who exhibit clinically significant functional deterioration. Differentiation of the adverse effects of hyperinflation of the native lung from other potential causes of late deterioration might not be necessary but may be predictive of the degree of functional improvement after volume reduction. The relief of thoracic overdistention seems to play a primary role in the improvement pulmonary function.

Surgical management of ventricular tachycardia.

BACKGROUND: Ventricular tachyarrhythmias are the leading cause of death from coronary artery disease. A small percentage of these arrhythmias originate in chronically ischemic myocardium, rather than acutely ischemic myocardium, and can be refractory to medical management. Epicardial mapping and focal cryoablation of foci demonstrating early activation may provide definitive therapy when pharmacologic management fails. We report a series of 42 consecutive patients with refractory ventricular tachycardia (VT) who were treated with open epicardial mapping and focal cryoablation after pharmacologic management failed. METHODS: We retrospectively reviewed the records of patients who underwent surgical treatment of malignant VT. For patients not recently seen in the clinic, we conducted telephone interviews. At the time of operation, epicardial mapping was performed to locate foci of early electrical activation. These foci were then cryoablated, using 2-minute applications of liquid nitrogen-cooled probes. All patients underwent postoperative electrophysiologic studies to test for inducible VT. RESULTS: Of these 42 patients, 34 (81%) were male, 8 (19%) female. Average age was 62.9 +/- 10.6 years; ejection fraction, 0.20 (range, 0.04 to 0.50); and number of foci ablated, 2.1 +/- 1.1 (range, 1 to 6). At the time of cryoablation, all patients underwent additional procedures, including aneurysmectomy, coronary artery bypass, or valve replacement. The 30-day operative mortality was 9.5% (4 of 42). Of the 38 survivors, 36 (94.7%) were clinically free of VT; the remaining 2 had spontaneous or inducible VT. CONCLUSIONS: Open cryoablation of foci propagating VT appears to be safe and effective. It may be the most definitive treatment for malignant VT.

Prevalence of retrograde accessory pathway conduction during atrial fibrillation.

INTRODUCTION: Although atrial fibrillation occurs frequently in patients with the preexcitation syndrome, its pathogenesis remains controversial. The purpose of this study was to test the hypothesis that retrograde conduction over the accessory pathway occurs during atrial fibrillation and can serve as an important source of new wavefronts in atrial fibrillation. METHODS AND RESULTS: Eight patients undergoing surgical division of their accessory pathway(s) were studied. A plaque electrode array containing 56 (7 x 8) bipolar electrodes (5-mm resolution) was placed epicardially at the AV junction over the accessory pathway and atrial fibrillation was electrically induced. Excluding one patient who had only preexcited QRS complexes during atrial fibrillation and another whose accessory pathway was outside the mapped region, 4 of the 6 patients studied showed retrograde conduction over the accessory pathway during atrial fibrillation (mean atrial cycle length 157 +/- 59 msec). In these patients, 186 atrial wavefronts near the accessory pathway were analyzed. Among 67 wavefronts immediately following nonpreexcited QRS complexes, 17 originated from retrograde conduction. This constituted 9% (17/186) of total atrial wavefronts near the accessory pathway. Estimated atrial refractory period during atrial fibrillation ranged from 81 to 165 msec. CONCLUSIONS: (1) In patients with the preexcitation syndrome and atrial fibrillation, retrograde conduction over the accessory pathway contributed up to 9% of total atrial wavefronts near the accessory pathway. (2) The presence of an excitable gap in human atrial fibrillation was suggested by atrial preexcitation during retrograde conduction.

Prothrombotic activation of pulmonary arterial endothelial cells in a patient with tuberculosis.

Activation of endothelial cells occurs in response to numerous physiological stimuli and results in the concerted expression of endothelial cell proteins that change the nonthrombogenic intimal surface of a vessel into a thrombogenic surface, with the subsequent development of local thrombosis. For example, both type 1 plasminogen activator inhibitor and tissue factor expression are mediated by endothelial cell stimulation in vitro; however, in contrast to type 1 plasminogen activator inhibitor, it has been difficult to detect tissue factor associated with endothelial cells in vivo. This case study describes the presence of both type 1 plasminogen activator inhibitor and tissue factor antigen associated with pulmonary arterial endothelial cells of a patient exhibiting a mycobacterial infection. The disease was associated with chronic hemoptysis and characterized by extensive tissue destruction and local thrombosis within the pulmonary artery. The data show that conditions occur in vivo in which local thrombosis is associated with increased levels of type 1 plasminogen activator inhibitor and tissue factor.

Quality of well-being predicts survival in lung transplantation candidates.

Predictors of survival were evaluated among 74 patients selected for a lung transplantation program. Each patient received the quality of well-being scale, a utility-based outcome measure that gives a score on a continuum ranging from 0 (for dead) to 1.0 (for optimum function), and a measure of depressive symptoms (Beck depression inventory). Over the course of follow-up, 24 patients died (ranging from listing date, 3 to 1, 110 d). Of the 49 patients who received lung transplantation, 13 died. In a multivariate analysis, the most significant predictor of survival was quality of well-being (relative risk = 0.454, p < 0.05). Lung transplant status, when entered as a time-dependent covariate (a function of how long the patient waited for surgery) was not a significant predictor of survival (relative risk = 0.942, p > 0.05). Depression was not a significant predictor of survival (relative risk = 0.961, p > 0.05). We conclude that health-related quality of life is a significant predictor of survival for patients with serious lung diseases.

Techniques for bronchial anastomosis.

BACKGROUND: Many techniques have been described to optimize the construction of the bronchial anastomosis in lung transplantation. Over the past 60 months we have performed 86 bronchial anastomoses in 70 patients receiving single lung or bilateral single lung transplants. METHODS: No anastomosis was wrapped and no attempt was made at revascularization of bronchial arteries. A continuous nonabsorbable suturing technique was used in all cases. Standard triple-drug immunotherapy with cyclosporine, azathioprine, and prednisone (starting at day 7) was used for each patient. RESULTS: There were no anastomotic leaks, and seven stenoses were identified in five patients (7%). All complications were managed conservatively with stenting, and there were no related deaths. Mean time to stent placement was 109 days. One patient had bilateral stents placed prophylactically during an episode of severe infection for questionable anastomotic viability but without evidence of airway necrosis or obstruction. This patient died of infection at 16 days. Another patient died with stents in place at 71 days. In the four remaining patients, all stents have been removed after a mean of 310 days. These patients were followed up with serial bronchoscopy and were without evidence of recurrent obstruction at 2, 34, 35, and 36 months. Six of seven stenoses occurred in patients with cystic fibrosis. In each patient where stenosis developed the anastomosis was telescoped. Since abandoning the telescoping technique in the remaining 50 anastomoses (14 in patients with cystic fibrosis), no dehiscence or stenosis was encountered. CONCLUSIONS: These data suggest that elaborate techniques aimed at construction of the bronchial anastomosis are not necessary. Moreover, attempts at telescoping may be detrimental. Patients with cystic fibrosis may be a population at higher risk for anastomotic complications. Airway complications can be managed conservatively with good results and little risk to the patient.

The relation between atrial fibrillation wavefront characteristics and accessory pathway conduction.

Although the source-sink relationship for impulse propagation in cardiac tissues has been demonstrated in vitro, there has been no verification of this hypothesis in humans. Accordingly, eight patients undergoing surgical division of their accessory pathways were studied. A 56-channel (7 x 8) bipolar plaque electrode array was placed over the atrioventricular groove on the accessory pathway and atrial fibrillation electrically induced. 10 episodes of QRS transition from consecutively preexcited to nonpreexcited complexes were analyzed. This showed that consecutively preexcited QRS complexes were always associated with uniform large atrial wavefronts. Immediately prior to QRS transition, four general types of changes were observed: (a) premature invasion by secondary wavefronts creating local conduction block (n = 5); (b) wavefront collision leading to wavefront curvature (n = 2); (c) transition from a uniform large atrial wavefront to multiple fractionated small wavefronts (n = 1); and (d) uniform atrial wavefronts "marching" into the accessory pathway refractory period (n = 2). We conclude that local atrial wavefront characteristics are important factors influencing impulse propagation through the accessory pathway. The findings that local wavefront collision, curvature, or fractionation often precede loss of accessory pathway conduction support the notion that source-sink relationship is an important determinant of the safety factor for impulse propagation in the human heart.

Primary pulmonary artery sarcoma: a report of six cases.

Pulmonary artery tumors are rare and a frequently overlooked cause of pulmonary artery occlusion. The presentation is one of progressive pulmonary dysfunction and right ventricular failure. The diagnosis seldom is made preoperatively. We report 6 cases of primary sarcoma of the pulmonary artery identified at operation, which were treated surgically. Resection with or without adjuvant therapy currently offers the only chance for survival. Emphasis must be placed on earlier identification of these tumors.

Lung transplantation without the use of antilymphocyte antibody preparations.

Survival, infection, and rejection rates and functional data are reported in 35 lung recipients treated with triple-drug immunosuppression without antilymphocytic antibody therapy. Early mortality (less than 60 days) was 6%. Thirty recipients (86%) are alive, with a mean follow-up period of 16 months (range, 1 to 36 months). Actuarial survival was 91% at 1 year and 83% at 2 years. Thirty-seven infections occurred in 24 patients. Actuarial freedom from infection was 61% at 3 months and 27% at 1 year. Only one patient died of infection (aspergillosis). Thirty-six episodes of acute rejection were treated in 23 patients. Time to first rejection was 14 +/- 7.8 days. Actuarial freedom from acute rejection was 36% at 2 months. Significant functional improvement was evident in all operative survivors. Pulmonary function and exercise performance data in patients without bronchiolitis obliterans remain stable 1 year after transplantation. We conclude that the use of triple-drug immunosuppression without antilymphocytic antibody preparations in lung transplantation provides effective immunosuppression with a low risk of serious infectious complications.

Experience and results with 150 pulmonary thromboendarterectomy operations over a 29-month period.

A program to alleviate chronic, major vessel thromboembolic pulmonary hypertension by pulmonary thromboendarterectomy was initiated at this institution in 1970. Multiple evolutionary changes in the diagnostic evaluation, surgical approach, and postoperative management have been implemented over the series of 323 thromboendarterectomies performed through March 1992. A sequence of five surgeons at the University of California at San Diego have performed these procedures, with the last 150 having been performed by one surgeon. We report here the changes in surgical approach developed over the last 150 cases and the results obtained. The operation involves a median sternotomy incision, the institution of cardiopulmonary bypass, and deep hypothermia with circulatory arrest periods. Incisions are made in both pulmonary arteries into the lower lobe branches. Pulmonary thromboendarterectomy is always bilateral, with removal of both organized thrombus and an endarterectomy plane from all involved vessels. The right atrium is routinely explored for atrial septal defects. Current techniques appear to allow more thorough revascularization and shorter circulatory arrest times. The surgical mortality of 8.7% over this span is below that previously reported from this and other institutions. Among survivors, the hemodynamic and functional results have been excellent. Surgically correctable chronic thromboembolic pulmonary hypertension likely remains underdiagnosed. The diagnostic, surgical, and postoperative management evolution provided by the coordinated team involved at this institution has established that pulmonary thromboendarterectomy can be performed with an acceptable risk and good hemodynamic and symptomatic results.

Relation between upper limit of vulnerability and defibrillation threshold in humans.

BACKGROUND: In the canine model, an upper limit of shock strength exists that can induce ventricular fibrillation during the vulnerable period of the cardiac cycle. This shock strength (the upper limit of vulnerability) closely correlates with the defibrillation threshold and supports the "upper limit of vulnerability" hypothesis of defibrillation. It is not known whether an upper limit of vulnerability exists in humans or whether this limit correlates with the defibrillation threshold. METHODS AND RESULTS: In 13 patients undergoing implantable cardioverter-defibrillator implantation, the shock strengths associated with a 50% probability of reaching the upper limit of vulnerability (ULV50) and a 50% probability of reaching the defibrillation threshold (DFT50) were determined by the up-down algorithm. The ULV50 was determined only for the mid-upslope of the positive T waves and for the mid-downslope of the negative T waves. No major complications occurred during surgery. An upper limit of vulnerability was demonstrated in each patient. The ULV50 was 300 +/- 138 V or 6.8 +/- 5.8 J, which was significantly lower than the DFT50 of 347 +/- 167 V (p = 0.038) or 9.1 +/- 7.3 J (p = 0.013). The correlation between the ULV50 and the DFT50 was significant (r = 0.90, p < 0.001 for voltage; r = 0.93, p < 0.001 for energy). CONCLUSIONS: An upper limit of vulnerability is present in humans. There is a significant correlation between the ULV50 and the DFT50, and the ULV50 is significantly lower than the DFT50.

Potentiation of cyclosporine nephrotoxicity by nafcillin in lung transplant recipients.

The interaction between nafcillin and cyclosporine was examined in lung transplant recipients receiving cyclosporine-based immunosuppression. Nine recipients received nafcillin for one week posttransplant and 10 recipients did not receive nafcillin. Age, sex, pretransplant renal function, type of transplant procedure, use of cardiopulmonary bypass, and initial cyclosporine dose were not significantly different between groups. The degree of renal dysfunction during the early postoperative period was significantly greater in the lung recipients receiving nafcillin. Although cyclosporine doses were significantly higher in the nafcillin group, this was not reflected by differences in cyclosporine levels. No difference in survival or incidence of allograft rejection was seen--however, the incidence of viral infection was significantly higher in the patients who received nafcillin. Based on our findings the use of an alternative antibiotic for antistaphylococcal prophylaxis in transplant recipients receiving cyclosporine is recommended.

Primary diagnosis predicts prognosis of lung transplant candidates.

Optimal timing for consideration of lung transplantation remains unknown. This study examined survival in patients with end-stage lung disease awaiting transplantation. Primary disease group and relevant indicators were evaluated. Ninety-three patients who met selection criteria for lung transplantation were included in this retrospective review. Of this total, 31% underwent transplantation, 38% remain waiting, and 31% died. Results demonstrate that the six-month actuarial survival rate was 89% for Eisenmenger's syndrome, 81% for emphysema, 74% for cystic fibrosis, 60% for primary pulmonary hypertension, and 38% for interstitial lung disease. Parameters found to be significant included a higher mean right atrial pressure in primary pulmonary hypertension patients who died awaiting transplantation, and lower forced expiratory volume in one second and forced vital capacity measurements in cystic fibrosis patients who died awaiting transplantation. We conclude that primary disease significantly affects survival in candidates awaiting transplantation. Reliable indicators predictive of survival are not available. Earlier referral for consideration of lung transplantation is recommended.