Pulmonary thromboendarterectomy combined with other cardiac operations: indications, surgical approach, and outcome.

BACKGROUND: Patients with pulmonary hypertension due to chronic thromboembolic disease benefit from pulmonary thromboendarterectomy. A subset of these patients present with concomitant coronary or valvular disease. METHODS: From July 1990 to July 2000, 90 patients (68 males, 22 females, mean age 68 years) with pulmonary vascular resistance (PVR) ranging from 297 to 2261 dynes x sec x cm(-5) underwent pulmonary thromboendarterectomy in conjunction with coronary bypass grafting (59 patients), coronary artery bypass grafting/foramen ovale closure (24 patients), tricuspid annuloplasty (3 patients), mitral valve repair (2 patients), and aortic valve replacement (2 patients). The perioperative and hemodynamic outcomes of these patients were compared with the cohort of 1,100 isolated pulmonary thromboendarterectomies performed at our institution during this time. RESULTS: Overall perioperative survival (93.3%; 84 of 90 patients) and mean diminution in PVR (521 dynes x sec x cm(-5)) for patients undergoing combined operations were similar to those undergoing pulmonary thromboendarterectomy alone (94.2% survival; 1034 of 1100 patients; 547 dynes x sec x cm(-5) mean PVR reduction). Although patients undergoing combined operations were older (mean age 68 vs 50 years, p < 0.0001), had longer hospital stays (median 14 vs 9 days), and had worse left ventricular function (mean preoperative cardiac output 3.1 vs 4.4, p < 0.0001), there was no difference in cross-clamp time, resolution of tricuspid regurgitation, or postoperative systolic function between these two groups. CONCLUSIONS: Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension may be performed safely in conjunction with other cardiac operations. Older patients evaluated for pulmonary thromboendarterectomy should be screened for concomitant coronary and valvular disease.

The use of cylexin (CY-1503) in prevention of reperfusion lung injury in patients undergoing pulmonary thromboendarterectomy.

Pulmonary thromboendartectomy (PTE) for chronic thromboembolic pulmonary hypertension may be complicated by reperfusion lung injury. This has previously been demonstrated to be neutrophil-mediated. We postulated that blocking selectin-mediated adhesion of neutrophils to the endothelium with Cylexin (CY-1503) would prevent reperfusion lung injury in this patient population. In this double-blind, randomized, placebo-controlled, parallel study, 26 patients received Cylexin the day of surgery and 25 received placebo. Significantly fewer patients in the treated group (31%) compared with the placebo group (60%) developed lung injury (p = 0.036). However, the average number of days of mechanical ventilation, days in the intensive care unit (ICU) and hospital, as well as mortality were not significantly different between the treatment groups. Those with reperfusion lung injury had significantly elevated percent neutrophils, total protein, and soluble P-selectin in bronchoalveolar lavage fluid compared with those without lung injury. We conclude that reperfusion lung injury after PTE is a high-permeability lung injury and its incidence can be reduced by the administration of Cylexin on the day of surgery.

Successful pulmonary thromboendarterectomy in a patient with Klippel-Trenaunay syndrome.

Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by a triad of cutaneous vascular nevi, soft tissue or bony hypertrophy, and varicose veins or venous malformations involving one or more extremities. An incidence of venous thromboembolism of up to 22% has been reported in this disorder. Also reported is the development of chronic thromboembolic pulmonary hypertension (CTEPH) and subsequent death from right ventricular failure. We report the first patient with KTS to undergo a successful pulmonary thromboendarterectomy for CTEPH.

Chronic thromboembolic pulmonary hypertension.

Under most circumstances, chronic thromboembolic pulmonary hypertension represents a correctable form of pulmonary hypertension. Approximately 1500 thromboendarterectomy procedures have now been performed worldwide. Mortality rates reported by established programs with experience in the management of patients with this disease process have fallen to a range of 6 to 8%. This reduction in mortality has been contributed to by several factors: improved methods of preoperative evaluation and more selective surgical referral, increased surgical experience and refined techniques, and an increased understanding of the unique postoperative problems that occur following pulmonary thromboendarterectomy. Despite these advances, a great deal more needs to be accomplished. The early natural history and pathophysiologic mechanisms of the disease remain uncertain; improved diagnostic techniques are required; and the most feared complication of the procedure, reperfusion pulmonary edema, remains enigmatic in terms of its pathogenesis, prevention, and therapy.

A pilot study of expiratory flow limitation and lung volume reduction surgery.

STUDY OBJECTIVES: To examine the relationships between changes in expiratory flow limitation (FL) during anesthesia and postoperative responses to lung volume reduction surgery (LVRS). DESIGN: Prospective consecutive case comparison. SETTING: University medical center. PATIENTS: Eight patients with severe emphysema. INTERVENTIONS: General anesthesia with muscle paralysis and thoracic epidural analgesia were provided for LVRS via median sternotomy. MEASUREMENTS: FEV(1), functional residual capacity (FRC), and total lung capacity (TLC) were measured preoperatively and 3 months postoperatively. Tidal volume (VT) flow/volume (F/V) curves were obtained with a Pitot-type spirometer. VT, expiratory flow rate at 0. 25 x VT (V'VT,25% ), and peak expiratory flow rate (V'VT,MAX) were obtained from VT F/V curves to derive V'VT,25%/V'VT,MAX ratio as a measure of FL. RESULTS: Closed chest VT F/V curves during anesthesia pre-LVRS showed four patients with FL (group A) whose V'VT,25%/V'VT, MAX ratio was 0.38 +/- 0.06 (mean +/- SD) and four patients without FL (group B) whose V'VT,25%/V'VT,MAX ratio was 0.82 +/- 0.06 (p = 0. 0001). Closed chest post-LVRS V'VT,25%/V'VT,MAX ratio during anesthesia increased by 0.48 +/- 0.08 in group A, compared with a 0. 19 +/- 0.16 reduction in group B (p = 0.0001). Preoperative FEV(1) was 0.57 +/- 0.10 L for group A vs 0.82 +/- 0.13 L for group B (p = 0.02). Postoperative FEV(1) increased by 67 +/- 40% for group A (p = 0.03) vs 29 +/- 21% for group B (not significant). FRC decreased by 33 +/- 3% for group A vs 17 +/- 5% for group B (p = 0.0007), and FRC/TLC decreased by 0.14 +/- 0.05 for group A vs 0.01 +/- 0.07 for group B (p = 0.026). Post-LVRS V'VT,25%/V'VT,MAX ratio change during anesthesia correlated with postoperative reduction in FRC (r(2) = 0. 89, p = 0.0004) and FRC/TLC (r(2) = 0.52, p = 0.045). CONCLUSION: Post-LVRS change in V'VT,25%/V'VT,MAX ratio during anesthesia showed a linear relationship with 3-month postoperative improvement in dynamic hyperinflation. Thus, V'VT,25%/V'VT,MAX ratio may help provide valuable insights into the interactions between chest wall recoil, dynamic hyperinflation, and VT flow rates in patients with severe COPD and LVRS.

Reoperative pulmonary thromboendarterectomy.

BACKGROUND: Recurrent symptomatic pulmonary hypertension is uncommon after primary pulmonary thromboendarterectomy (PTE). We reviewed our experience with patients undergoing repeat PTE to determine the risk factors for recurrent disease, and the selection criteria, relative risks, and functional outcomes of reoperative PTE. METHODS: Since 1990, 13 of 870 (1.5%) patients underwent reoperative PTE at our institution. These 7 men and 6 women (mean age 38.6 years) were contrasted with the most recent 225 patients (111 men, 114 women, mean age 52.7 years) who underwent primary PTE for whom complete hemodynamic data are available. The preoperative evaluation of all patients was similar. Pulmonary hemodynamic data and outcome measures were compared between groups. RESULTS: Of 13 reoperated patients: 69% (9/13) had their primary operation at another institution, 54% (7/13) initially underwent unilateral PTE, 38% (5/13) had identifiable coagulation disorders, 38% (5/13) had ineffective caval filtration, 31% (4/13) had suboptimal anticoagulation management, and 31% (4/13) had complete unilateral pulmonary artery obstruction. The mean interval to reoperation was 5.2 years (range 0.7 to 10.9 years). All control patients underwent bilateral PTE using hypothermic circulatory arrest. Operative mortality was 7.7% (1/13) with reoperation vs 8.4% (19/225) in controls. No difference (p = NS) was observed between groups in the preoperative pulmonary artery pressure (PAP) or pulmonary vascular resistance; however, the control group had a significantly (p < 0.05) greater reduction in the postoperative PAP (46/19, mean 28 mm Hg vs 59/23, mean 35 mm Hg) and PVR (271 +/- 172 vs 399 +/- 154 dynes/s/cm(-5)) compared with the redo group. No substantial difference in morbidity or functional outcomes was observed between groups. CONCLUSIONS: Reoperative PTE can be performed with a perioperative risk comparable with primary PTE, although the improvement in pulmonary hemodynamics is not as favorable. Bilateral primary operation, effective caval filtration, and vigilant anticoagulant management would prevent the need for most reoperative PTEs.

Long-term outcome after pulmonary thromboendarterectomy.

This study evaluated long-term outcome of pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Survival, functional status, quality of life, health care utilization, and relationships between these parameters and postoperative pulmonary hemodynamics were assessed. Questionnaires were mailed to 420 patients who were more than 1 yr post-PTE; 308 responded (mean age, 56 yr [range, 19-89 yr]; mean years since PTE, 3.3 [range, 1- 16]). Survival after PTE was 75% at > 6 yr. After surgery, symptoms were markedly reduced. Median distance walked was 5,280 ft; 56 patients could walk "indefinitely." Of the working population, 62% of patients unemployed before PTE returned to work. Post-PTE patients scored several quality of life components of the Rand SF-36 slightly lower than reported normals but significantly higher than did pre-PTE patients. Ten percent of patients used oxygen. Ninety-three percent were in NYHA Class I or II. Disease-related hospitalizations/ER visits were minimal. A relationship was shown between 48 h postoperative pulmonary vascular resistance (PVR) and walking and stair-climbing ability, NYHA class, dyspnea scores, and the physical function and general health quality of life components. These data indicate that PTE offers most CTEPH patients substantial improvement in survival, function, and quality of life, with minimal disease-related health care utilization.

Successful pulmonary thromboendarterectomy in two patients with sickle cell disease.

Patients with sickle cell disease have been reported to have an increased risk of thromboembolism and pulmonary hypertension. Some of these patients may benefit from pulmonary thromboendarterectomy (PTE), a procedure that requires profound hypothermia, cardiopulmonary bypass, and periods of circulatory arrest, factors that may potentially increase the risk of sickling. Two patients with sickle cell disease (sickle-thalassemia [Hb S/beta+] and Hb SS) presented to the Pulmonary Vascular Center of UCSD Medical Center with significant shortness of breath and limitation of daily activities. Both of these patients were found to have surgically accessible chronic thromboembolic disease with pulmonary hypertension. PTE was performed in both patients using exchange transfusion, with avoidance of anemia, hypoxia, and acidosis. A successful outcome with resolution of pulmonary hypertension was achieved in both cases. To our knowledge this is the first report of patients with sickle cell disease who successfully underwent PTE for chronic thromboembolic pulmonary hypertension.

Chronic thromboembolism: diagnosis with helical CT and MR imaging with angiographic and surgical correlation.

PURPOSE: To evaluate the accuracy of identification of central and segmental chronic thromboembolic disease on helical computed tomographic (CT) scans and on magnetic resonance (MR) images. MATERIALS AND METHODS: Radiologic findings in 55 patients suspected of having chronic thromboembolic pulmonary hypertension were analyzed; these included findings from angiography (n = 55), helical CT (n = 47), and MR imaging (n = 26). Forty patients underwent thromboendarterectomy. CT and MR images were independently interpreted by two readers for the presence of thromboembolic material in central and segmental vessels. Surgical findings and angiographic findings were the reference standards for disease in central and segmental vessels, respectively. RESULTS: Central vessel disease was determined more accurately with helical CT scans (accuracy of 0.79 for each of the two readers) than with angiograms (accuracy of 0.74) or with MR images (accuracy of 0.39 and 0.46 for two readers). Segmental vessel disease was also more accurately determined with CT scans (accuracy of 0.75 and 0.76 for two readers) than with MR images (accuracy of 0.61 and 0.57 for two readers). CONCLUSION: Helical CT is a useful alternative to conventional angiography for diagnosis of chronic thromboembolism but may not be sufficient for selecting candidates for surgery in all cases.

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.

Inhaled nitric oxide (40 ppm) during one-lung ventilation, in the lateral decubitus position, does not decrease pulmonary vascular resistance or improve oxygenation in normal patients.

OBJECTIVES: To determine the effects of inhaled nitric oxide (NO) on venous admixture (Qs/Qt), mean pulmonary artery pressure (MPAP), and pulmonary vascular resistance (PVR) in patients undergoing one-lung ventilation (1LV) in the lateral decubitus position. DESIGN: Prospective, blinded, crossover. SETTING: University hospital. PARTICIPANTS: Six adult patients scheduled for thoracotomy. INTERVENTIONS: Patients were anesthetized with thoracic epidural lidocaine, intravenous fentanyl, and inhaled isoflurane and were monitored with a systemic and pulmonary artery catheter (PAC). In the lateral decubitus position, the dependent lung was ventilated with 70% oxygen (O2) and 30% nitrogen (N2) for the control 1LV condition. For the experimental 1LV condition, the dependent lung was ventilated with the same gas concentration + NO at 40 ppm. Patients were alternated between the control and the experimental NO (40 ppm) conditions every 15 minutes for as long as the case would allow. MEASUREMENTS AND MAIN RESULTS: During all conditions, oxygenation, Qs/Qt, and pulmonary and systemic hemodynamics were measured in a double-blinded fashion. The mean PVR during 1LV was 128 +/- 39 (SD) dyne.s.cm(-5). Inhaled NO at 40 ppm did not affect MPAP, PVR, or Qs/Qt. CONCLUSIONS: Inhaled NO at 40 ppm, during 1LV in the lateral decubitus position, did not significantly decrease MPAP in patients with normal baseline PVR. Oxygenation and Qs/Qt did not change in this setting because MPAP was not altered. At present, interventions other than administration of inhaled NO should be applied to patients with normal PVR who experience hypoxia during one-lung ventilation.

A comparison of thoracoscopic talc insufflation, slurry, and mechanical abrasion pleurodesis.

The purpose of this study was to compare the anatomic and histopathologic results of four different methods of pleurodesis in 10 dogs. Each animal was randomly assigned to receive two of the following methods of pleurodesis: thoracoscopic talc insufflation (poudrage), talc slurry administration, focal gauze abrasion by limited thoracotomy, and mechanical abrasion by thoracoscopy using a commercially available pleural abrader. Animals were killed 30 days after pleurodesis. At autopsy, the efficacy of pleurodesis was graded by evaluating the gross appearance of each pleural cavity and lung (pleurodesis score), and by determining the extent of adhesion formation (obliteration grade). Pleural and lung biopsy specimens were obtained from the areas most representative of adhesion formation for histopathologic evaluation. Pleurodesis scores (on a scale of 0 to 4) were 3.0 +/- 0.7 for talc poudrage (p < 0.05 when compared with talc slurry), 2.2 +/- 1.7 for thoracotomy, and 1.6 +/- 1.1 for talc slurry. Adhesions produced by gauze abrasion during thoracotomy were mostly peri-incisional. Thoracoscopic pleural abrasion using the pleural abrader was uniformly unsatisfactory. Granulation tissue formation was greatest in both talc models. The degree of parietal pleural thickening was greatest in the talc slurry model, but fibrosis and inflammation occurred mostly in gravity-dependent areas within the pleural cavity. Although differences were not statistically significant, thoracoscopic talc insufflation consistently produced the most widespread, firm fibrotic adhesions as evidenced by higher obliteration grades.

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.

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.

Survival in lung reperfusion injury is improved by an antibody that binds and inhibits L- and E-selectin.

The selectins are a three-member family of leukocyte, platelet, and endothelial cell adhesion proteins that mediate leukocyte traffic into normal and inflamed tissues. P-selectin is expressed by endothelial cells and platelets, E-selectin by endothelial cells, and L-selectin by circulating leukocytes. To determine if selectin-mediated leukocyte adhesion influences the development of lung reperfusion injury, we studied hemodynamics and respiratory and inert gas exchange in sheep subjected to 3-hour in situ left lung ischemia followed by 6-hour left lung reperfusion with the right lung excluded. Ten minutes before reperfusion, eight animals received EL-246 (1 mg/kg intravenously), a novel antihuman selectin antibody that recognizes and blocks both L- and E-selectin and cross-reacts in sheep. Eight control animals with ischemia received no treatment, whereas three received an isotype-matched antihuman L-selectin antibody that does not cross-react in sheep (DREG-56, 1 mg/kg intravenously). Eight sham control sheep underwent an identical operative procedure but were never subjected to ischemia. Volume-cycled, pressure-limited (20 cm H2O) mechanical ventilation was consistent in all animals throughout the experiment. Six-hour survival in EL-246 recipients (100%) was significantly higher than in either ischemic control sheep (37.5%) or DREG-56 recipients (33.3%), but gravimetric lung water was equivalent in EL-246 recipients (5.9 +/- 1.7 ml/kg), ischemic control sheep (8.3 +/- 3.0 ml/kg), and DREG-56 recipients (9.1 +/- 2.6 ml/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of severe cardiac allograft rejection with extracorporeal photochemotherapy.

Two patients were treated with photopheresis for marked cardiac allograft rejection with hemodynamic compromise that had become unresponsive to standard therapy. Multiple episodes of rejection had occurred, and initial response to standard therapy was favorable. However, progressive deterioration was documented by serial endomyocardial biopsies, fever, congestive heart failure, and abnormal cardiac catheterization findings. In the absence of retransplantation, death seemed imminent. Photopheresis was begun. Both patients received oral 8-methoxypsoralen and > or = 5 x 10(9) mononuclear cells were collected, treated with ultraviolet light A for 1.5 hours, and were reinfused. One procedure was performed weekly x4 and then monthly x5. Responses were striking with rapid loss of fever, improvement in exercise tolerance, normalization of cardiac hemodynamics, and improvement in endomyocardial biopsies. Although our experience with these two patients is anecdotal, photopheresis merits further study as treatment for severe cardiac allograft rejection.

Cytokine and complement levels in patients undergoing cardiopulmonary bypass.

Patients undergoing cardiopulmonary bypass are known to develop whole body inflammation that often results in a characteristic syndrome early postoperatively. This phenomenon has been attributed to complement activation caused by exposure of blood to the foreign surfaces of the cardiopulmonary bypass circuit. It has been unknown if cytokines are involved. Plasma levels of complement activation products (C3a, C4a, C5a, and C5b-9), interleukins (IL-1 beta, IL-2, IL-4, and IL-6), and tumor necrosis factor-alpha were measured at multiple time points before, during, and after cardiopulmonary bypass in 29 patients. No significant increase over preinduction levels was seen in the cytokines except for IL-6, which was significantly increased during cardiopulmonary bypass (p < 0.001), reaching a maximum 3 hours after cardiopulmonary bypass. C3a, C4a, and C5b-9 levels were significantly elevated during cardiopulmonary bypass (p < 0.001), with maximum C5b-9 levels preceding the IL-6 elevation. Heparin coating of the cardiopulmonary bypass circuit was not demonstrated to have an effect on activation of complement or cytokine production. There was no statistically significant correlation among hemodynamic variables or pulmonary function and complement, interleukin, or tumor necrosis factor-alpha levels. These results confirm the presence of complement activation and demonstrate the production of IL-6 after the generation of C5b-9 in patients undergoing cardiopulmonary bypass. IL-6 may contribute to adverse systemic reactions associated with cardiopulmonary bypass.