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Biomedical subjects

B A Reitz

Publications and source records attributed to B A Reitz.

At least 37 records · Page 2Linked to original sources
PubMed1997

Obliterative airway disease after heterotopic tracheal xenotransplantation: pathogenesis and prevention using new immunosuppressive agents.

BACKGROUND: The purpose of this study was to investigate whether obliterative bronchiolitis might occur after xenogenic pulmonary transplantation. A model for obliterative airway disease (OAD) after tracheal allograft transplantation in the rat undergoes tracheal obliteration with histologic features characteristic of obliterative bronchiolitis in human lung transplant recipients. Using this model, the pathogenesis of OAD and its prevention with immunosuppressive drugs was studied in rat recipients of hamster tracheal grafts. METHODS: Tracheae from 30 hamsters (xenografts) or 23 Brown-Norway rats (allografts) were implanted and wrapped in the greater omentum of untreated Lewis rats. The grafts were removed on day 1, 3, 7, 14, 21, or 28 after transplantation and stained with hematoxylin and eosin and Masson's trichrome and by immunohistochemistry and immunofluorescence (IFL) techniques. In addition, 25 recipients were treated with cyclosporine (CsA, 10 mg/kg p.o.), leflunomide (LFM, 20 mg/kg p.o.), or rapamycin (RPM, 6 mg/kg i.p.) for 14 or 21 days (5 animals per treatment group). Visual and morphometric analyses were used to evaluate the extent of airway obliteration, luminal coverage by respiratory or flattened cuboidal epithelium, and extent and density of peritracheal cellular inflammation. RESULTS: In all xenografts, a neutrophilic infiltration of the mucosa and submucosa was observed from day 1 until day 14 and was associated with complete loss of tracheal epithelium by day 14. A marked peritracheal mononuclear cellular infiltrate mixed with plasma cells and eosinophils was seen on days 7 and 14. Both the extent of peritracheal inflammation and the density of the mononuclear cell infiltrate were significantly increased in xenograft tracheae when compared with the allografts. Tracheal obliteration began on day 14 and reached a maximum of 43% on day 21 with evidence of intraluminal fibrosis. In contrast to IFL of allografts, IFL of xenografts demonstrated marked deposition of rat immunoglobulin in the peritracheal tissue on days 7 and 14. The effects of treatment with immunosuppressive drugs on tracheal graft narrowing and protection of respiratory epithelium were as follows: After 14 days of treatment, the percentage of tracheal graft narrowing was 12%, 23%, and 19% in the no treatment, CsA, and LFM groups, respectively; the percentage of respiratory epithelium at 14 days was 0%, 21%, and 95%. After 21 days of treatment, the percentage of tracheal graft narrowing was 43%, 49%, 12%, and 5% for the no treatment, CsA, LFM, and RPM groups, respectively; the percentage of respiratory epithelium at 21 days was 0%, 39%, 86%, and 0%. Using computerized morphometry, the extent and densities of the peritracheal cellular infiltrates were significantly reduced in LFM- and CsA-treated groups when compared with untreated xenograft controls. LFM and RPM, but not CsA, significantly reduced the degree of luminal obliteration compared with no treatment (P<0.05). LFM and, to a lesser extent, CsA were able to prevent the loss of normal respiratory epithelium. Analysis by IFL revealed a marked decrease in rat immunoglobulin deposition in xenografts from LFM- and RPM-treated groups compared with xenografts from CsA-treated or untreated rats. CONCLUSIONS: (1) OAD occurs not only after tracheal allotransplantation but also after xenotransplantation. (2) Subepithelial infiltration of neutrophils and the appearance of plasma cells and eosinophils in the peritracheal infiltrates distinguished the histology of rejected xenografts from allografts. (3) Antibody deposition was detected by IFL only in xenografts. (4) Treatment with LFM or RPM significantly decreased the severity of luminal obliteration. Importantly, LFM also prevented the loss of respiratory epithelium.

Airway Obstruction↗
PubMed1997

Monitoring considerations for port-access cardiac surgery.

BACKGROUND: A method for monitoring patients was evaluated in a clinical trial of minimally invasive port-access cardiac surgery with closed chest endovascular cardiopulmonary bypass. METHODS AND RESULTS: Cardiopulmonary bypass was conducted in 25 patients through femoral cannulas. An endovascular pulmonary artery vent was placed in the main pulmonary artery through a jugular vein. For mitral valve surgery, a catheter was placed in the coronary sinus for delivery of cardioplegia. A balloon catheter ("endoaortic clamp," EAC) used for occlusion of the ascending aorta, delivery of cardioplegia, aortic root venting, and pressure measurement was inserted through a femoral artery and initially positioned by use of fluoroscopy and transesophageal echocardiography (TEE). Potential migration of the EAC was monitored by (1) TEE of the ascending aorta, (2) pulsed-wave Doppler of the right carotid artery, (3) balloon pressure, (4) comparison of aortic root pressure and right radial artery pressure, and (5) fluoroscopy. TEE, fluoroscopy, and pressure measurement were effective in monitoring catheter insertion and position. With inadequate balloon inflation, migration of the EAC toward the aortic valve could be detected with TEE. During administration of cardioplegia, TEE showed movement of the balloon away from the aortic valve, and migration into the aortic arch was detectable with loss of carotid Doppler flow. Stability of EAC position was demonstrated with appropriate balloon volume. Cardioplegic solution was visualized in the aortic root, and aortic root pressure changed appropriately during administration of cardioplegia. Venous cannula position was optimized with TEE and endopulmonary vent flow measurement. CONCLUSIONS: An effective method has been developed for monitoring patients and the catheter system during port-access cardiac surgery.

Cardiopulmonary Bypass↗
PubMed1997

Port-access cardiac operations with cardioplegic arrest.

BACKGROUND: A less invasive approach to cardiac surgery has been propelled by recent advances in video-assisted surgery. Previous obstacles to minimally invasive cardiac operations with cardioplegic arrest included limitations in operative exposure, inadequate perfusion technology, and inability to provide myocardial protection. METHODS: Port-access technology allows endovascular aortic occlusion, cardioplegia delivery, and left ventricular decompression. The endoaortic clamp is a triple-lumen catheter with an inflatable balloon at its distal end. Antegrade cardioplegia is delivered through a central lumen, which also acts as an aortic root vent, a second lumen is used as an aortic root pressure monitor, and a third lumen is used for balloon inflation to provide aortic occlusion. RESULTS: Experimental and clinical studies have demonstrated the feasibility of port-access coronary artery bypass grafting and port-access mitral valve procedures. Endovascular cardiopulmonary bypass using the endoaortic clamp was effective in achieving cardiac arrest and myocardial protection to allow internal mammary artery to coronary artery anastomosis in a still and bloodless field. Intracardiac procedures, such as mitral valve replacement or repair, have been successfully performed clinically. CONCLUSION: The port-access system effectively achieves cardiopulmonary bypass and cardioplegic arrest, thereby enabling the surgeon to perform cardiac procedures in a minimally invasive fashion. This system provides for endovascular aortic occlusion, cardioplegia delivery, and left ventricular decompression.

Cardiac Surgical Procedures↗
PubMed1997

Cardiac operations in children with Marfan's syndrome: indications and results.

BACKGROUND: The development of new screening techniques for the early detection of Marfan's syndrome has prompted evaluation of the results of cardiac operations in children with this syndrome. The purpose of this study was to determine the surgical indications, operative results, and need for reoperation in children with Marfan's syndrome. METHODS: From 1980 to 1996, 245 patients underwent cardiac operations for complications of Marfan's syndrome; 26 (11%) were less than 18 years of age. The mean age at the time of operation was 10.3 +/- 1 years (range, 8 months to 17 years); 18 of the patients were male. Indications for operation were aortic root dilatation (15 patients), mitral regurgitation (4 patients), aortic root dilatation and mitral regurgitation (6 patients), and aortic arch aneurysm (1 patient). Operations included aortic root replacement (15 patients), aortic root replacement and mitral repair (5 patients), aortic root replacement and mitral replacement (1 patient), mitral repair (3 patients), mitral replacement (1 patient), and arch aneurysm repair (1 patient). The mean aortic root diameter in patients undergoing aortic root replacement was 6.2 +/- 0.2 cm. Only 1 patient underwent ascending aortic dissection. RESULTS. There were no operative deaths. At a mean follow-up of 67.1 +/- 10.2 months, 8 patients required a second cardiac procedure (41% +/- 17% 10-year freedom from reoperation). Indications for further operations were distal aortic pathology (3 patients), aortic root dilatation after initial mitral operation (3 patients), failed mitral repair (1 patient), and homograft degeneration (1 patient). Risk factors for a second cardiac procedure were age less than 10 years at the time of the first operation (p < 0.003) and mitral regurgitation (p < 0.04). Overall, 25 (96%) of 26 patients have undergone aortic root replacement and 11 (42%) patients have undergone a mitral procedure. There have been 4 late deaths, all of presumed cardiac origin. The 10-year survival rate is 79% +/- 10%. All surviving patients are in New York Heart Association functional class I or II. CONCLUSIONS: We conclude that (1) aortic root dilatation is the most common surgical indication in children with Marfan's syndrome, (2) mitral regurgitation is the second most common indication, (3) aortic dissection is unusual in children with Marfan's syndrome, and (4) careful follow-up is necessary, particularly in younger children, because more than half of all children with Marfan's syndrome require repeated cardiac operations within 10 years.

Adolescent↗
PubMed1997

Long-term survivors of pediatric heart transplantation: a multicenter report of sixty-eight children who have survived longer than five years.

OBJECTIVE: Short-term survival after pediatric heart transplantation is now excellent, but ultimately the efficacy of this procedure will depend on duration and quality of survival. We sought to evaluate the clinical course of long-term survivors of heart transplantation in childhood. METHODS: Patients who had undergone heart transplantation at the university hospitals of Stanford, Columbia, and Pittsburgh between 1975 and 1989 and survived longer than 5 years from transplantation were identified and their clinical courses retrospectively reviewed. RESULTS: Sixty eight children have survived more than 5 years from transplantation, and 60 (88%) are currently alive with a median follow-up of 6.8 years (5 to 17.9 years). Thirteen have survived more than 10 years from transplantation. Renal dysfunction caused by immunosuppressive agents was common, and two patients required late renal transplantation. Lymphoproliferative disease or other neoplasm occurred in 12 patients, but none resulted in death. Coronary artery disease was diagnosed in 13 patients (19%), leading to retransplantation in eight. Death after 5 years was related to acute or chronic rejection in 5 of 8 cases. Two of the deaths were directly related to noncompliance with immunosuppressive medication. All survivors are in New York Heart Association class 1. CONCLUSIONS: Long-term survival with good quality of life can be achieved after heart transplantation in childhood, though complications of immunosuppression remain common. Posttransplantation coronary artery disease is emerging as the main factor limiting long term graft and patient survival.

Adolescent↗
PubMed1997

Perinatal induction of immunotolerance to cardiac and pulmonary allografts.

OBJECTIVES: Tolerance appears to be more easily induced in the fetus before full immunocompetence is established, but elucidation of this process is needed. A model of perinatal tolerance induction to neonatal skin allografts followed by cardiac and pulmonary allografts is described. METHODS: Sixty Lewis (RT11) rat fetuses were inoculated intraperitoneally at 18 days gestation with 1 x 10(7) ACI (RT1a) rat fetal liver cells (group I); 20 Lewis fetuses were inoculated with 2 x 10(7) ACI fetal liver cells (Group II). control groups consisted of Lewis fetuses inoculated with saline solution (n = 25, group III) and fetuses that were not inoculated (n = 25, group IV). Twenty-five of the 50 surviving group I rats received ACI skin (< 24 hours old) and heart (8 to 10 weeks old) allografts (group IA); the remaining 25 rats received only ACI heart grafts (group IB). Groups II, III, and IV received ACI skin and cardiac allografts. Recipients tolerant to both skin and cardiac grafts received orthotopic ACI lung grafts and third-party skin grafts. Tolerance was indicated by graft survival for more than 100 days. Limiting dilution and flow cytometric analyses were performed. RESULTS: Abortion rates in groups I, II, III, and IV were 17% (10/60), 65% (13/20), 8% (2/25), and 4% (1/25), respectively. Specific tolerance to skin, cardiac, and lung allografts was observed in seven of 25 group IA recipients (28%) and seven of seven group II recipients (100%) compared with no tolerance in any group IB, III, or IV recipients (p = 0.03, chi 2 test). A 100-fold reduction of precursor cytotoxic T lymphocytes and significant splenocyte and bone marrow chimerism in tolerant versus nontolerant rats were noted (p = 0.0001, Student's t test). CONCLUSIONS: Using donor-strain fetal liver cells and neonatal skin grafts, we achieved higher frequencies of tolerance to solid organ grafts in adulthood with lower cell inocula and abortion rates than previously described. Chimerism and depressed precursor cytotoxic T lymphocyte frequencies in tolerant recipients suggest that hematopoietic stem cell engraftment and clonal deletion/anergy are involved in induction of perinatal tolerance.

Animals↗
PubMed1997

Perfusion during coronary and mitral valve surgery utilizing minimally invasive Port-Access technology.

Minimally invasive surgery has been used in the treatment of some cardiovascular diseases. Port-Access surgery is a new minimally invasive technique that utilizes cardiopulmonary by-pass and a specialized catheter system that provides cardiopulmonary support and myocardial preservation. Extrathoracic cardiopulmonary support is established with femero-femoral bypass with kinetic assisted venous drainage. An endovascular catheter system allows for all the benefits of mechanical support as well as myocardial preservation. This catheter system includes an endoaortic balloon catheter which functions as an aortic cross clamp and antegrade cardioplegia delivery catheter, endopulmonary vent, and endocoronary sinus catheter used for administration of retrograde cardioplegia. An initial cohort of 20 patients was treated by the Port-Access surgical approach with cardiopulmonary bypass. Ten patients had coronary artery surgery and 10 patients had mitral valve surgery. The average bypass times were 94.4 min (coronary artery) and 152.8 min (mitral valve). The mean aortic occlusion times were 49.7 min (coronary artery) and 112.6 min (mitral valve). All patients were weaned from bypass. This initial patient series demonstrated that Port-Access surgery was feasible in selected patients.

Adult↗
PubMed1997

A rodent model of in utero chimeric tolerance induction.

BACKGROUND: In utero tolerance induction has potential application in pediatric heart transplantation. Immunotolerance appears to be more easily induced in the fetus before full immunocompetence is established; however, the mechanisms behind this phenomenon are still undefined. METHODS: One hundred thirty Lewis (RT1l) rat fetuses from 10 litters were inoculated intraperitoneally at 18 days gestation with 1 x 10(7) ACI (RT1a) rat fetal liver cells. Fifty of the 100 viable neonates successfully brought to term were grafted with neonatal ACI skin within 24 hours of birth and heterotopic ACI hearts at 8 to 10 weeks of age (group 1A); the remaining 50 neonates only received heterotopic ACI heart grafts at 8 to 10 weeks (group 1B). Control groups consisted of 50 Lewis fetuses (five litters) inoculated in utero with phosphate-buffered saline solution (group 2) and 50 Lewis fetuses (five litters) that received no inoculum (group 3); all of these surviving progeny received both neonatal ACI skin and adult ACI cardiac allografts. Skin and cardiac grafts were monitored by daily visual inspection and palpation, respectively. Limiting dilution analysis was performed among all groups to assess precursor cytotoxic lymphocyte frequencies. Likewise, peripheral blood lymphocyte and splenocyte populations were analyzed with flow cytometry to detect allogeneic chimerism. RESULTS: Abortion rates among groups 1, 2, and 3 were 23% (30/130 abortions), 10% (5/50 abortions), and 6% (3/50 abortions), respectively. Tolerance to both ACI skin and cardiac allografts was induced in 14 of the 50 group 1A Lewis recipients (28%). Tolerance was not achieved in any of the recipients in groups 1B, 2, or 3. Limiting dilution analysis among all groups revealed a marked reduction of precursor cytotoxic T-lymphocytes in tolerant allograft recipients compared with recipients in the other groups. Flow cytometry detected significant splenocyte chimerism among tolerant rats; significant peripheral blood chimerism was not noted. CONCLUSIONS: We describe allogeneic tolerance induction in utero to both rat skin and heart tissue by use of donor-strain fetal liver cells. Compared with previous studies with adult splenocytes as the tolerogen, we achieved a higher frequency of tolerance with a markedly lower cell inoculum and lower abortion rate. Allogeneic chimerism was noted in the tolerant recipients, suggesting hematopoietic stem cell engraftment. Cytotoxic T-lymphocyte precursor frequencies were markedly depressed in tolerant animals. Interestingly, both donor-strain fetal liver cells and neonatal skin grafts were required to induce tolerance. These data suggest a period of hematopoietic "education" during and shortly after hematopoietic stem cell engraftment.

Animals↗
PubMed1997

Minimally invasive coronary artery bypass grafting.

Minimally invasive cardiac surgery has generated a tremendous amount of enthusiasm in the cardiology and cardiac surgical communities. Coronary revascularization without cardiopulmonary bypass through a small anterior thoracotomy or mediastinotomy has been introduced as an alternative to the conventional approach. An endovascular or port-access technique for cardiopulmonary bypass and cardioplegic arrest has been developed for use in cardiac surgery. This peripherally based system achieves aortic occlusion, cardioplegia delivery, and left ventricular decompression; thus, coronary revascularization and various cardiac procedures can be effectively performed in a less invasive fashion than conventional median sternotomy. Continued technical advances in minimally invasive cardiac surgery will facilitate these procedures, increase patient safety, and contribute to acceptable long-term results.

Coronary Artery Bypass↗
PubMed1997

Minimally invasive mitral valve surgery.

Because of advances in video-assisted general and thoracic surgery, minimally invasive cardiac surgery has been successfully performed experimentally and clinically. Recently described techniques of less invasive mitral valve surgery include limited right thoracotomy, parasternal incision, and partial sternotomy. These methods have been coupled to video-assisted thoracoscopy to further decrease the incision size. Cardiopulmonary bypass (central or peripheral) and either hypothermic fibrillatory arrest or cardioplegic arrest are used. The Port-Access approach is a catheter-based system that provides effective cardiopulmonary bypass, cardioplegic arrest, and ventricular decompression. At Stanford University, 10 Port-Access mitral valve procedures were performed between May 1996 and January 1997. The mean age of the patients (eight men and two women) was 54 +/- 7 (SD) years. Nine patients had severe mitral regurgitation from myxomatous degeneration, and one suffered from severe mitral regurgitation and moderate mitral stenosis from a rheumatic etiology. Five patients underwent mitral valve replacement, and five underwent mitral valve repair. There was no operative mortality. The mean incision length was 8.1 +/- 2.5 cm. The aortic "cross-clamp" time was 99 +/- 22 minutes, and the cardiopulmonary bypass time was 151 +/- 52 minutes. The total hospitalization averaged 4.3 +/- 1.4 days. One patient developed third-degree atrioventricular block, requiring a prolonged stay in the intensive care unit and pacemaker placement; the same patient was found to have a perivalvular leak on follow-up, requiring reoperation at 3 months. Port-Access mitral valve procedures can be performed safely with satisfactory outcome. Greater clinical experience and long-term follow-up are necessary to fully assess these less invasive techniques of mitral valve surgery.

Adult↗
PubMed1996

Tolerance to cardiac allografts induced in utero with fetal liver cells.

BACKGROUND: Induction of immunological tolerance in utero has potential application in pediatric cardiac transplantation. We describe an inexpensive, reproducible, and well-characterized model of allogeneic tolerance induction in utero using donorstrain fetal liver cells. METHODS AND RESULTS: Each of 9 Lewis (LEW, RTl1) rat fetuses in one litter (group 1) and 10 LEW fetuses in another litter (group 2) were inoculated intraperitoneally at 17 to 18 days of gestation with 1 x 10(6) ACI (RTla) rat fetal liver cells. Ten LEW fetuses in a third litter inoculated with PBS (group 3) and 10 LEW noninoculated fetuses in a fourth litter (group 4) served as controls. The LEW rats were brought to term, and groups 1, 3, and 4 were grafted with neonatal ACI skin within 24 hours of birth and with heterotopic ACI hearts at 8 to 10 weeks of age; group 2 rats received only an ACI heart graft at 8 to 10 weeks. Skin and cardiac grafts were monitored by daily visual inspection and palpation, respectively. Peripheral blood lymphocyte (PBL) populations in all LEW recipients were analyzed with flow cytometry. All LEW fetuses survived to term and developed normally. The ACI skin and cardiac allografts on 3 of the 9 LEW rats in group 1 are viable to date (skin, > 170 days; cardiac, > 100 days). The remaining 6 recipients of this group and all animals in groups 2, 3, and 4 rejected their skin and cardiac grafts by postgrafting day 7. Significant PBL chimerism (1.57%) was observed in only 1 tolerant rat. CONCLUSIONS: We describe allogeneic tolerance induction in utero to both rat skin and cardiac tissue with donor-strain fetal liver cells. Compared with previous studies using adult splenocytes as the tolerogen, we achieved a higher frequency of tolerance with a markedly lower cell inoculum and no abortions. Interestingly, both donor-strain fetal liver cells and neonatal skin grafts were required to maintain tolerance into adulthood. Immunocompetence sufficient to reject allografts was noted in neonates, and PBL chimerism was not prominent in tolerant recipients.

Animals↗
PubMed1996

Twenty-year clinical experience with porcine bioprostheses.

BACKGROUND: For the past 25 years, porcine valves have been the most widely implanted bioprosthesis, thereby becoming the standard for comparison with newer bioprosthetic valves. METHODS: We retrospectively analyzed 2,879 patients who underwent aortic (AVR; n = 1,594) or mitral (MVR; n = 1,285) valve replacement between 1971 and 1990. Follow-up was 97% complete and extended to 20 years (total, 17,976 patient-years). Patient age ranged from 16 to 94 years; mean age in patients who underwent AVR was 60 +/- 15 (+/- standard deviation) years; that for patients who underwent MVR was 58 +/- 13 years. RESULTS: The operative mortality rates were 7% +/- 1% (70% confidence limits) for AVR and 10% +/- 1% for MVR. Actuarial estimates of freedom from structural valve deterioration at 10 and 15 years were 78% +/- 2% (SE) and 49% +/- 4%, respectively, for the AVR subgroup; and 69% +/- 2% and 32% +/- 4%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from reoperation at 10 and 15 years were 76% +/- 2% and 53% +/- 4%, respectively, for the AVR subgroup and 70% +/- 2% and 33% +/- 4%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from thromboembolism at 10 and 15 years were 92% +/- 1% and 87% +/- 2%, respectively, for the AVR subgroup and 86% +/- 1% and 77% +/- 3%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from anticoagulant-related hemorrhage at 10 and 15 years were both 96% +/- 1% for the AVR subgroup and 93% +/- 1% and 90% +/- 2%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from valve-related mortality at 10 and 15 years were 86% +/- 1% and 78% +/- 3%, respectively, for the AVR subgroup and 84% +/- 2% and 70% +/- 4%, respectively, for the MVR subgroup (p = not significant). Multivariate analysis (Cox model) showed younger age, later year of operation, and valve site (MVR > AVR) to be significant risk factors for structural valve deterioration. Younger age, later year of operation, valve site (MVR > AVR), and renal insufficiency were the significant, independent risk factors for reoperation. Multivariate analysis revealed that higher New York Heart Association functional class, longer cardiopulmonary bypass time, congestive heart failure, renal insufficiency, and longer cross-clamp time were significant risk factors for valve-related mortality. Valve manufacturer did not emerge as a factor in any analysis. CONCLUSIONS: These long-term results with porcine bioprostheses were satisfactory, particularly in older patients and those undergoing AVR. As expected, younger age was a significant risk factor for structural valve deterioration and reoperation in both groups. Surprisingly, the durability of porcine bioprosthetic valves has not improved over time, which possibly can be attributed to more enhanced postoperative surveillance and earlier reintervention. These first-generation Hancock and Carpentier-Edwards porcine bioprostheses achieved similar long-term performance.

Actuarial Analysis↗
PubMed1996

Stanford experience with obliterative bronchiolitis after lung and heart-lung transplantation.

BACKGROUND: Obliterative bronchiolitis (OB) is the main chronic complication after heart-lung (HLTx) and lung transplantation (LTx), limiting the long-term success of both transplant procedures. METHODS: Since 1981, 135 HLTxs and 61 isolated LTxs were performed in 184 patients at Stanford University. RESULTS: The overall prevalence of OB in patients surviving longer than 3 months postoperatively was 64% after HLTx and 68% after LTx. The actuarial freedom from OB was 72%, 51%, 44%, and 29% at 1, 2, 3, and 5 years, respectively, after HLTx and LTx. An analysis of potential risk factors revealed that the frequency and severity of acute rejection episodes (p < 0.001) and the appearance of lymphocytic bronchiolitis on biopsy (p < 0.05) were significantly associated with the development of OB. With regard to diagnosis of OB, pulmonary function tests show early reductions of the forced expiratory flow between 25% and 75% of the forced vital capacity with subsequent decreases in the forced expiratory volume in 1 second. The sensitivity of transbronchial biopsies has increased to 71% since 1993. Current treatment consists of augmented immunosuppression. Concurrent acute rejection episodes or active OB on biopsy have been treated aggressively with high-dose steroid pulses. Analysis of data from 73 patients with OB after HLTx and LTx revealed actuarial 1-, 3-, 5-, and 10-year survival of 89%, 71%, 44%, and 17% versus 86%, 77%, 63% and 56% in patients without OB (p < 0.05 by log-rank analysis). The main complication and cause of death in patients with OB was superimposed respiratory tract infection, which was treated aggressively. CONCLUSIONS: Early diagnosis of OB using pulmonary function tests or transbronchial biopsy is possible and important, because immediate treatment initiation has led to acceptable survival rates, with nearly 50% of affected patients still alive 5 years after transplantation. Current experimental research on OB suggests that immune injury is the main pathogenetic event of airway obliteration in animal models; rapamycin and leflunomide are new immunosuppressive agents that may have the potential to prevent and treat airway obliteration.

Actuarial Analysis↗
PubMed1996

Port-access mitral valve replacement in dogs.

OBJECTIVE: The objective was to assess mitral valve replacement in a minimally invasive fashion by means of port-access technology. METHODS: Fifteen dogs, 28 +/- 3 kg (mean +/- standard deviation), were studied with the port-access mitral valve replacement system (Heartport, Inc., Redwood City, Calif.). Eleven dogs underwent acute studies and were sacrificed immediately after the procedure. Four dogs were allowed to recover and then were sacrificed 4 weeks after operation. Cardiopulmonary bypass was conducted by femoral cannulation with an endovascular balloon catheter for aortic occlusion, root venting, and antegrade delivery of cardioplegic solution. Catheters were inserted in the jugular vein for pulmonary artery venting and retrograde delivery of cardioplegic solution. Through the oval port, a prosthesis (St. Jude Medical, Inc., St. Paul, Minn., or CarboMedics, Inc., Austin, Texas) was inserted through the left atrial appendage and secured to the anulus with sutures. Deairing was performed. RESULTS: Cardiopulmonary bypass duration was 114 +/- 24 minutes and aortic crossclamp time was 68 +/- 14 minutes. All animals were weaned from cardiopulmonary bypass in sinus rhythm. Cardiac output and pulmonary artery occlusion pressure were unchanged (2.8 +/- 0.7 L/min and 7 +/- 3 mm Hg before operation vs 2.6 +/- 0.6 L/min and 9 +/- 4 mm Hg after operation). There was no mitral regurgitation according to left ventriculography in 13 of 15 dogs. In two dogs there was interference with prosthetic valve closure by residual native anterior leaflet tissue. Pathologic examination otherwise showed normal healing without perivalvular discontinuity. Microscopic studies showed no damage to the valve surfaces. Transthoracic echocardiography of the four dogs in the long-term study showed normal ventricular and prosthetic valve function 4 weeks after the operation. CONCLUSION: Mitral valve replacement with a minimally invasive method has been demonstrated in dogs. A clinical trial is in progress.

Animals↗
PubMed1996

Port-access coronary artery bypass grafting: a proposed surgical method.

Minimally invasive surgical methods have been developed to provide patients the benefits of open operations with decreased pain and suffering. We have developed a system that allows the performance of cardiopulmonary bypass and myocardial protection with cardioplegic arrest without sternotomy or thoracotomy. In a canine model, we successfully used this system to anastomose the internal thoracic artery to the left anterior descending coronary artery in nine of 10 animals. The left internal thoracic artery was dissected from the chest wall, and the pericardium was opened with the use of thoracoscopic techniques and single lung ventilation. The heart was arrested with a cold blood cardioplegic solution delivered through the central lumen of a balloon occlusion catheter (Endoaortic Clamp; Heartport, Inc., Redwood City, Calif.) in the ascending aorta, and cardiopulmonary bypass was maintained with femorofemoral bypass. An operating microscope modified to allow introduction of the 3.5x magnification objective into the chest was positioned through a 10 mm port over the site of the anastomosis. The anastomosis was performed with modified surgical instruments introduced through additional 5 mm ports. In the cadaver model (n = 7) the internal thoracic artery was harvested and the pericardium opened by means of similar techniques. A precise arteriotomy was made with microvascular thoracoscopic instruments under the modified microscope on four cadavers. In three other cadavers we assessed the exposure provided by a small anterior incision (4 to 6 cm) over the fourth intercostal space. This anterior port can assist in dissection of the distal internal thoracic artery and provides direct access to the left anterior descending, circumflex, and posterior descending arteries. We have demonstrated the potential feasibility of grafting the internal thoracic artery to coronary arteries with the heart arrested and protected, without a major thoracotomy or sternotomy.

Anastomosis, Surgical↗
PubMed1996

Port-access coronary artery bypass with cardioplegic arrest: acute and chronic canine studies.

BACKGROUND: Our goal is to perform minimally invasive coronary artery bypass grafting without sacrificing the benefits of myocardial protection with cardioplegia. METHODS: Twenty-three dogs underwent acute studies and 4 dogs underwent survival studies. The left internal mammary artery was taken down using a thoracoscope. Cardiopulmonary bypass was conducted via femoral cannulas and using an endovascular balloon catheter for ascending aortic occlusion, root venting, and delivery of antegrade blood cardioplegia. Pulmonary artery venting was achieved with a jugular vein catheter. An internal mammary artery-to-coronary artery anastomosis was performed using a microscope through a 10 mm port. RESULTS: All animals were weaned from cardiopulmonary bypass in sinus rhythm without inotropes. Cardiopulmonary bypass duration was 104 +/- 28 minutes and aortic clamp duration was 61 +/- 22 minutes. Cardiac output and pulmonary artery occlusion pressure were unchanged. The internal mammary artery was anastomosed to the left anterior descending artery (25) or the first diagonal (2) with patency shown in 25 of 27. One dog in the survival study had a very short internal mammary artery pedicle under tension and was euthanized for excessive postoperative hemorrhage. Three weeks postoperatively the remaining dogs had angiographically patent anastomoses, normal transthoracic echocardiograms, and histologically normal healing and patent grafts. CONCLUSIONS: Endovascular cardiopulmonary bypass using a balloon catheter is effective in arresting and protecting the heart to allow thoracoscopic internal mammary artery-to-coronary artery anastomosis.

Animals↗
PubMed1996

Actuarial survival of heart-lung and bilateral sequential lung transplant recipients with obliterative bronchiolitis.

BACKGROUND: Obliterative bronchiolitis is a progressive form of obstructive airway disease that threatens long-term survival in lung transplant recipients. Its incidence and the long-term survival of lung transplant recipients with obliterative bronchiolitis are unknown. METHODS: The results of 89 heart-lung and 13 bilateral sequential lung transplant survivors beyond 90 days of their operation were analyzed. The date of diagnosis for obliterative bronchiolitis was established histologically (presence of submucosal fibrosis) or physiologically by a persistent reduction in the forced vital capacity to less than 0.7 for greater than 6 weeks. There were 43 patients without obliterative bronchiolitis and 59 patients with obliterative bronchiolitis. RESULTS: No differences were found in the mean age and gender ratios between the two groups. The actuarial 1-, 5-, and 10-year percentage freedom from obliterative bronchiolitis was 72 +/- 4.6, 30 +/- 5.6, and 15 +/- 7.4, respectively, with a median onset of 689 days (range 55 to 3404 days). About half the patients with biopsy-proven obliterative bronchiolitis had a fall in their forced expiratory flow at 50% of forced vital capacity/forced vital capacity nearly 4 months before fulfilling the forced expiratory volume in 1 second criteria established by the Working Group on chronic lung dysfunction. The actuarial 1-, 5-, and 10-year percentage survival of obliterative bronchiolitis negative patients was 90 +/- 4.5, 74 +/- 8.4, and 66 +/- 10.6, respectively, versus 90 +/- 3.9, 49 +/- 6.9, and 27 +/- 10.0, respectively, for obliterative bronchiolitis positive patients (p = 0.38). The actuarial 1-, 3-, 5-, 8-, and 10-year percentage survival of lung transplant recipients after the diagnosis of obliterative bronchiolitis was 74 +/- 5.8, 50 +/- 7.5, 43 +/- 7.8, 23 +/- 8.7, and 11 +/- 9.1, respectively, with a median survival of 1084 days (range 0 to 3442 days). CONCLUSIONS: The forced expiratory flow at 50% of forced vital capacity/forced vital capacity is a more sensitive indicator for the early detection of obliterative bronchiolitis than the forced expiratory volume in 1 second after heart-lung or bilateral sequential lung transplantation. The obliterative bronchiolitis negative group survival tends to be better than the obliterative bronchiolitis positive group. The obliterative bronchiolitis positive lung transplant recipients have reasonable outcomes with a median survival time of nearly 3 years after the diagnosis of obliterative bronchiolitis. Earlier detection of obliterative bronchiolitis and refinements in management may further improve these results.

Actuarial Analysis↗