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Biomedical subjects

H Reichenspurner

Publications and source records attributed to H Reichenspurner.

At least 73 records · Page 4Linked to original sources
PubMed1999

Economic evaluation of different minimally invasive procedures for the treatment of coronary artery disease.

OBJECTIVE: Several different techniques exist within the field of minimally invasive coronary artery surgery. In this study the impact of all these techniques on the total costs and economics has been evaluated. METHODS: Since May 1997, 121 minimally invasive direct coronary artery bypass (MIDCAB) procedures, 125 off-pump coronary artery bypass (OPCAB), ten Port-Access coronary artery bypass (PA-CABG) and 10 endoscopic coronary artery bypass grafting (ENDO-CABG) procedures were performed at our institution. A relative cost analysis of the different procedures was carried out in addition to a thorough evaluation done in five patients of each group dividing the costs into staff-related costs, material-related costs and general hospital costs. The costs were set in relation to regular CABG procedures. RESULTS: Specific less invasive coronary artery surgical techniques, such as the MIDCAB or OPCAB technique already are able to reduce the total costs when compared to regular CABG procedures. Within the Port-Access group as well as the ENDO-CABG group, increased material- and general costs are present when compared to regular CABG leading to increased total hospital costs for PA-CABG and Endo-CABG in Germany. CONCLUSION: At present, MIDCAB and OPCAB procedures are able to reduce total hospital charges, when compared to regular CABG procedures. Increased costs for Port-Access, as well as Endo-CABG surgeries may be compensated in the future by decreased costs due to a shorter phase of rehabilitation and faster return to regular professional activities.

Angioscopy↗
PubMed1999

Continuous transesophageal echocardiographic (TEE) monitoring during port-access cardiac surgery.

BACKGROUND: Since the introduction of the closed-chest minimally invasive heart surgery using the Port-Access system a variety of monitoring techniques including fluoroscopy, transesophageal echocardiography (TEE) and invasive pressure measurements have been described. We investigated whether or not single TEE is feasible for perioperative monitoring of the placement, localization and proper function of the endovascular cardiopulmonary bypass (CPB) devices. METHODS: Fifty-one patients (35 mitral valve repair or replacement [MVR], 8 coronary artery bypass grafting [CABG], 5 atrial septal defects [ASD] and 3 left atrial myxoma) were subjected to Port-Access surgery (PAS). Intraoperative Omniplane-TEE (2D- and color-flow Doppler techniques) was used as the leading monitoring device for correct positioning of the endopulmonary vent catheter and the venous cannula, and for the visualization of the guide wire and the endoaortic occlusion catheter (Endoclamp). After balloon inflation, its proper positioning and function during endo-aortic occlusion, sufficient delivery of cardioplegia into the coronary ostia, absence of leakage flow and adequate venting were controlled. Left and right radial artery catheters as well as aortic root pressure measurements served as controls. Additional fluoroscopy was used as standby device. RESULTS: In 46 patients (90.1%) sufficient perioperative monitoring was provided by single TEE. In five cases additional intermittent fluoroscopy was necessary for correct positioning of the guide wire (CABG) and the Endoclamp (three MVR and one ASD). Dislocation of the Endoclamp into the left ventricle was observed once but was successfully corrected by TEE guidance. Weaning from CPB and de-airing were easily guided with TEE. We did not observe balloon-mediated aortic injury or aortic valve dysfunction, and myocardial recovery from CPB was uneventful. All cases of MVRs showed sufficient results (68% without evidence of regurgitation, 32% showed residual mitral valve incompetence of less than grade II). Neither perivalvular leakage (MV-replacement) nor shunt- (residual ASD) flow were detectable. CONCLUSIONS: We recommend single TEE as a safe and effective on-line imaging device for monitoring the endovascular CPB system during PAS. Fluoroscopy with its potential risk for the patients and the staff due to x-ray exposure should only be used in the presence of peripheral vascular disease or when echocardiographic imaging is insufficient.

Cardiopulmonary Bypass↗
PubMed1999

Contrast-enhanced magnetic resonance angiography for control of minimally invasive coronary artery bypass conduits (MIDCAB/OPCAB).

OBJECTIVE: The purpose of this study was to delineate the course and determine the patency of venous and arterial conduits in the early postoperative period following minimally invasive bypass grafting. A less invasive magnetic resonance angiogram was evaluated as alternative to standard contrast angiography and cardiac catheterization. METHODS: Twelve patients (8 males and 4 females) with a mean age of 65.3 (+/- 7.4 ) years were evaluated four to seven days following minimally invasive direct coronary artery bypass surgery (MIDCAB) or off-pump multivessel revascularization with the Octopus stabilizer on the beating heart. Altogether 17 coronary bypass grafts were investigated: 12 left-sided mammary artery grafts to the LAD and five aortocoronary venous bypass grafts. The examination was performed with a 1.5 Tesla Magnetom Vision (Siemens AG, Erlangen) with phased array coil technology. Data acquisition was done with an ultrafast 3D gradient-echosequence in single breathhold and sagittal and coronal views. Contrast enhancement of the vessels was performed with automatic intravenous bolus injection of Gadolinium-DTPA after determination of the individual contrast transit time. Traditional contrast angiography was obtained in all patients during the same time period as a comparison to assess the sensitivity and specificity of the magnetic resonance imaging. RESULTS: All five venous grafts and 11 of the 12 IMA grafts were detected and shown to be patent with the MRA technique. Contrast angiography demonstrated complete patency for all 17 bypass grafts with adequate anastomoses and no evidence of stenosis. The calculated sensitivity for the visualization with MRA was therefore 92% for IMA grafts and 100% for venous grafts. CONCLUSION: The contrast-enhanced ultrafast MRA in single breathhold technique is a reliable, noninvasive method for visualization and determination of the patency of arterial and venous coronary grafts.

Aged↗
PubMed1999

3D-visualization improves the dry-lab coronary anastomoses using the Zeus robotic system.

BACKGROUND: Robotic surgical instruments enable quick and precise movements and may allow complete endoscopic coronary artery bypass grafting. However, cardiac surgeons will have to become familiar with this technology and endoscopic viewing. We present our training program with special focus on 2D- and 3D-visualization. METHODS: A thoracic skeleton, covered with a neoprene suit, served as model for the chest wall. Either a glove, fixed on a metal plate, or a pig heart were placed inside for training. On the glove, a suture line consisting of two lines of 16 points each, with a distance of 2 mm between each point, was stamped. On the pig heart, the LAD was prepared and incised; subsequently an anastomosis was done using the dissected right coronary artery as a graft. The time required was measured for both models. For suturing, the Zeus System (Computer Motion, Goleta, CA) was used and the third robotic arm positioned the endoscopic camera. The scopes were connected to a 3D-camera and the picture was displayed on a headset with two integrated monitors. Visualization was set to either 2D or 3D. Three surgeons were involved in the study. Each one did at least 12 anastomoses on 2D and 3D. RESULTS: The three surgeons involved showed a clear and rapid learning curve. The times required for the suture line decreased from 12.5 +/- 1.6 to 8.5 +/- 0.5 minutes with 2D and from 11.9 +/- 5.4 to 7.8 +/- 0.5 minutes for 3D respectively. This decrease did reach statistical significance (p = 0.03). In the pig heart model, the anastomosis times decreased from 33.2 +/- 8.4 to 15.7 +/- 0.3 minutes with 3D-visualization, and from 36.2 +/- 2.2 to 29.5 +/- 3.3 minutes with 2D. The decrease in anastomosis time did again reach significance (p = 0.025). At the end of the study, the times achieved with 2D-visualization were significantly longer than those with 3D (p = 0.01). CONCLUSIONS: A surgical training program is mandatory to become familiar with these new technologies. Both models showed learning curves over an acceptable time course. 3D-visualization facilitated quick and precise movements, thus resulting in shorter anastomosis times.

Anastomosis, Surgical↗
PubMed1998

Assessment of troponin-T for detection of clinical cardiac rejection.

Non-invasive detection of cardiac rejection still remains a challenge after heart transplantation. We assessed troponin-T as a new serum marker to diagnose cardiac rejection. Twenty-five heart transplant patients (Berne) were monitored prospectively for up to 2 years, and compared to 89 retrospectively assessed patients (Stanford). Blood samples (392 Berne and 320 Stanford) were analyzed (creatine kinase, isoenzymes MB activity and MB mass, troponin-T and troponin-I). Regression analysis between the results of these blood samples and cardiac rejection grading from simultaneously performed endomyocardial biopsies was carried out. Troponin-T tests done in two different laboratories showed a good correlation (r = 0.91; P < 0.0001), whereas troponin-T versus troponin-I showed a lower correlation (r = 0.53; P < 0.0001). Troponin-T and -I in contrast to other enzymes were elevated for a longer period (up to 4 weeks before returning to baseline) after transplantation than during conventional cardiac surgery. Beyond 3 months the following correlations were found between troponin-T (new or old test) and the other enzymes (creatine kinase: r = 0.26, MB activity: r = 0.4, and MB mass: r = 0.68). The correlation between the degree of rejection and the enzyme release is poor, however, the best results were obtained for troponin-T (r = 0.22; P < 0.001). We found a low correlation between troponin-T and the degree of rejection beyond 3 months after heart transplantation. Despite a troponin-T elevation in some patients with rejection, the new test is not sensitive enough to be used alone for the non-invasive diagnosis of cardiac rejection.

Biomarkers↗
PubMed1998

Endothelium-dependent microvascular vasomotion and its correlation with vasoactive mediators early after cardiac transplantation in humans.

Endothelial dysfunction precedes and predicts transplant vasculopathy. We investigated the relationship between endothelial dysfunction and the vasoactive mediators nitric oxide and endothelin, 33.7 +/- 2.0 days after heart transplantation. Coronary flow was measured in 18 patients to determine the endothelial microvascular vasomotor response to acetylcholine. Endomyocardial biopsies were taken to determine the levels of gene expression of isozymes of endothelin and nitric oxide synthases (NOS). Blood samples from the coronary sinus and aorta were withdrawn for measurement of endothelin, nitrite and cytokines. Five patients (30%) showed an impaired coronary flow reserve response to acetylcholine, significantly higher inducible NOS gene expression and significant transcardiac nitrite production. Plasma nitrite correlated with tumour necrosis factor-alpha levels in coronary sinus and a transcardiac net extraction of endothelin was noted in all patients. In conclusion, 30% of patients develop endothelial dysfunction early after heart transplantation; this correlates with the expression and activation of vasoactive and immunomodulatory mediators, which may predict the development of transplant vasculopathy.

Endothelin-1↗
PubMed1998

[Minimally invasive heart surgery--a fad or a clinically recognized therapy method?].

Within the last 5 years new less invasive surgical techniques have been developed in the field of cardiac surgery. This new field named "minimally invasive cardiac surgery" can be subdivided into techniques which do not require cardiopulmonary bypass and are used mainly for coronary artery surgery (called minimally invasive direct coronary artery surgery, MIDCAB technique). This MIDCAB procedure can be done through a small left anterior thoracotomy or a sternotomy. In addition there are other methods which allow the performance of complex cardiac surgery through small accesses in combination with the use of an endovascular CPB system and internal aortic clamping to achieve cardioplegic arrest (so-called Port-Access method). Also for valvular surgery, new surgical techniques were developed allowing access to mitral and aortic valves through limited incisions. In addition, new less invasive techniques were developed for congenital heart surgery. This article will describe the various surgical techniques and define the indications for minimally invasive cardiac surgery.

Endoscopes↗
PubMed1998

Port-Access coronary artery bypass grafting with the use of cardiopulmonary bypass and cardioplegic arrest.

BACKGROUND: To reduce surgical trauma, we performed minimally invasive Port-Access (Heartport Inc, Redwood City, CA) coronary artery bypass grafting with cardiopulmonary bypass and cardioplegic arrest. METHODS: Thirty-six men and 6 women with a median age of 59 years (range, 31 to 75 years) and isolated lesions of the left anterior descending branch of the coronary artery underwent Port-Access coronary artery bypass grafting. A small (6- to 9-cm) incision was made parasternally on top of the fourth rib. The left internal thoracic (mammary) artery was dissected and taken down through the minithoracotomy either alone or using an additional thoracoscopic approach. Cardiopulmonary bypass was instituted through femoral cannulation, and an additional endoarterial balloon catheter (Heartport Inc) was introduced into the ascending aorta for aortic occlusion, aortic root venting, and the delivery of cold antegrade crystalloid cardioplegia. After cardioplegic arrest, the left internal mammary artery was anastomosed to the left anterior descending artery under direct vision. RESULTS: The median left internal mammary artery takedown time was 49.5 +/- 21.9 minutes, the duration of cardiopulmonary bypass was 59.5 +/- 32.8 minutes, the aortic occlusion time was 28.5 +/- 7.9 minutes, the intensive care unit stay was 1.0 +/- 3.2 days, and the total hospital stay was 5.0 +/- 2.5 days. Intraoperative angiograms were done in the first 10 patients and showed patent left internal mammary artery grafts without anastomotic complications in all cases. Two arterial dissections, including one aortic dissection, were observed in patients with preexisting peripheral vascular disease. The other complications were minor. All but 1 patient recovered well, with no major limitations in their daily activities. CONCLUSIONS: Using this minimally invasive method, sternotomy-related complications can be avoided, the hospital stay can be reduced, and a safe coronary artery bypass grafting procedure can be performed with the advantage of cardiopulmonary bypass and cardioplegic arrest as are used routinely in conventional coronary artery operations.

Adult↗
PubMed1998

Minimally invasive coronary artery bypass grafting: port-access approach versus off-pump techniques.

BACKGROUND: Within the past 5 years several surgical techniques have been developed for less invasive surgical treatment of coronary artery disease. The aim of this study was to define specific indications for the various minimally invasive coronary artery surgical procedures. METHODS: Minimally invasive direct coronary artery bypass grafting through a minithoracotomy was performed in 67 patients. The left internal mammary artery was anastomosed on the beating heart with the use of a pressure or suction stabilizer without the use of extracorporeal circulation. In 58 other patients with multivessel disease, the off-pump coronary artery bypass grafting technique through a sternotomy was applied with a left internal mammary artery to left anterior descending artery and additional vein grafts without extracorporeal circulation. In a third group, Port-Access (Heartport Inc, Redwood City, CA) coronary artery bypass grafting was performed through a left minithoracotomy with the use of an endovascular extracorporeal circulation system and cardioplegic arrest. Angiographic follow-up was complete in 64% of the patients. RESULTS: There was minimal perioperative or postoperative mortality (0.5%). The medium surgical procedure time for all minimally invasive and off-pump procedures was 2.5 hours; it was 4.5 hours for Port-Access procedures. The median postoperative intensive care unit stay was 1.0 days, and the median hospitalization was 5.0 days. Overall graft patency was 97.3%; in 8 patients (4.1%) a stenosis either at or distal to the graft anastomosis was dilated with coronary angioplasty. CONCLUSIONS: For single-vessel disease of the left anterior descending artery, the minimally invasive coronary artery bypass grafting procedure can be performed safely without the use of extracorporeal circulation. In case of hemodynamic instability or anatomic variation, the Port-Access procedure can be applied without additional necessity for sternotomy. For multivessel disease, the off-pump bypass grafting procedure with sternotomy can be recommended depending on the coronary arteries involved. In case of necessary grafts to the lateral marginal or circumflex branches, Port-Access grafting can be recommended and may play an important role in the future for the development of fully endoscopic robot-assisted coronary artery bypass grafting.

Adult↗
PubMed1998

Microhemodynamics and leukocyte sequestration after pulmonary ischemia and reperfusion in rabbits.

OBJECTIVE: Investigation of leukocyte sequestration in alveolar capillaries and of microhemodynamic changes after pulmonary ischemia/reperfusion injury. METHODS: The kinetics of leukocyte passage and the hemodynamics in pulmonary microcirculation were investigated in 16 rabbits by intravital microscopy. Mean red blood cell velocity and the number of sticking leukocytes were measured in pulmonary arterioles, venules, and capillaries after 1 hour of tourniquet ischemia and 10 minutes and 1 hour after reperfusion. RESULTS: The decrease of red blood cell velocity after reperfusion was associated with a largely increased heterogeneity of blood flow. Immediately after the onset of blood flow, sequestered leukocytes were found in all microvascular segments. An increased number of leukocytes was present in arterioles, venules, and alveolar capillaries 10 minutes and 1 hour after reperfusion. Concomitantly, width of alveolar septa was increased while arterial oxygen tension was reduced, indicating the development of interstitial pulmonary edema. CONCLUSION: Leukocytes are sequestered after pulmonary ischemia and reperfusion not only in alveolar capillaries but also in arterioles and venules, and they may contribute to the development of reperfusion edema.

Animals↗
PubMed1998

Minimally invasive mitral valve surgery--clinical experiences with a PortAccess system.

OBJECTIVE: This is the initial experience with a new minimally invasive surgical technique for the treatment of mitral valve disease using a PortAccess system. METHODS: Between May 1996 and May 1997, 21 patients (nine male, 12 female, aged 30-75 years, median 64 years) underwent minimally invasive mitral valve surgery. The underlying diseases were: mitral valve insufficiency (n = 11), mitral valve stenosis (n = 5) and combined mitral valve disease (n = 5). Through a small right thoracotomy (6-8 cm) access to the pericardium and the heart was gained. Cardiopulmonary bypass was instituted through femoral cannulation and an intraaortic balloon-catheter (Heartport Inc., Redwood City, CA) was introduced for aortic occlusion, aortic root venting and delivery of cold crystalloid cardioplegia. Mitral valve repair (four patients) or replacement (15 patients) was performed. RESULTS: There was no death during the whole follow-up period. There was no perivalvular leak and only minor residual mitral valve regurgitation was observed on intraoperative or postoperative (3 months) transesophageal echocardiography. There was no postoperative study-related complication. Time of ventilation, intensive care unit and hospital-stay were comparable with the data of patients undergoing conventional mitral valve surgery. CONCLUSIONS: This technique of PortAccess mitral valve surgery combines the advantage of less invasive operative trauma with the safety of conventional mitral valve surgery.

Female↗
PubMed1998

Port-Access cardiac surgery using endovascular cardiopulmonary bypass: theory, practice, and results.

BACKGROUND: Reduction of surgical trauma is the aim of minimally invasive cardiac surgery. This can be achieved by reducing the size of the incision or by eliminating or changing the cardiopulmonary bypass system. However, certain cardiac surgical procedures, such as valvular surgery and complex multivessel coronary artery surgery, are not feasible without the use of cardiopulmonary bypass. Therefore endovascular cardiopulmonary bypass may allow reduction of surgical trauma for these patients. METHODS: Since its first application in April 1995, more than 1100 procedures have been performed worldwide using the EndoCPB endovascular cardiopulmonary bypass system. The authors' experience consists of 60 Port-Access coronary artery bypass grafting procedures, 34 Port-Access mitral valve procedures (18 replacements, 16 repairs), 5 atrial septal defect closures, and 3 atrial myxoma removals. RESULTS: The patient survival rate was 99%, the incidence of perioperative stroke was 1%, and the incidence of aortic dissection was 1%. In the Port-Access mitral valve and atrial septal defect patients, the survival rate was 100% with no peri- or postoperative complications. Peri- and postoperative transesophageal echocardiography revealed no perivalvular leak or remaining mitral insufficiency after valve repair. CONCLUSIONS: The EndoCPB endovascular cardiopulmonary bypass system allows the application of true Port-Access minimally invasive cardiac surgery in procedures that require the use of cardiopulmonary bypass and cardioplegic arrest. Sternotomy and its potential complications can be avoided, and the surgical procedures can be performed safely on an empty, arrested heart with adequate myocardial protection.

Adult↗
PubMed1998

3D-video- and robot-assisted minimally invasive ASD closure using the Port-Access techniques.

BACKGROUND: Video-assisted minimally invasive surgical methods with endovascular-based femoral cardiopulmonary bypass (CPB) and balloon occlusion of the aorta (Port-Access technique) were used to close an ostium-secundum atrial septal defect (ASD) in 7 patients. METHODS: Minor modifications were made to the system to provide drainage of the superior vena cava. The surgery was performed through a small (3.5-5cm) right anterolateral thoracotomy with 3D video and robotic arm assistance. RESULTS: The operative procedures were completely uneventful and the patients were discharged four days postoperatively in good condition and with excellent cosmesis. CONCLUSION: Using the modifications described, the Port-Access surgical method can be recommended for minimally invasive closure of an ASD.

Adolescent↗
PubMed1998

Preoperative 3D-reconstructions of ultrafast-CT images for the planning of minimally invasive direct coronary artery bypass operation (MIDCAB).

BACKGROUND: The direct left internal mammary artery (LIMA) bypass to the left anterior descending (LAD) without the use of extracorporal circulation through a small anterolateral thoracotomy has become established among the minimally invasive techniques in cardiac surgery. Technical difficulties may occur in patients with an enlarged left ventricle and subsequent lateral positioning of the LAD, a small LAD, or a small LIMA. We used electron beam tomography (EBT) for preoperative visualization of the topographical structures to seek out patients with potential technical difficulties. METHODS: Eighteen patients, mean age 62 +/- 13 years, were entered in this study; in all cases the indication for revascularization was a significant stenosis of the LAD. Preoperatively an ECG-triggered EBT was performed. Following the image acquisition, a three-dimensional reconstruction of the data was performed. The LIMA, LAD, first diagonal branch, and chest wall were stained different colors for better visualization. Surgery was performed using a left anterolateral mini-thoracotomy and through this access, the LIMA was dissected and anastomosed using a stabilizer without the use of extracorporal circulation. RESULTS: In all but one of the 18 patients who had a preoperative EBT, the minimally invasive direct coronary artery bypass (MIDCAB) procedure was successfully performed using an anterolateral mini-thoracotomy. Based on the results of the EBT, the 5 centimeter incision was done parasternally in six patients, and more laterally (2-4 cm parasternally) in the other eleven cases. In 13 patients the access penetrated the fourth intercostal space; in four cases the fifth intercostal space was used. In one patient EBT revealed a very laterally positioned and diffusely arteriosclerotic LAD so the patient was operated using a median sternotomy, but without the use of extracorporal circulation. In all 18 patients the preoperatively acquired information of the anatomical topography was confirmed intraoperatively. One case without a preoperative EBT had to be converted to a conventional procedure due to a small, intramyocardial LAD and a very small LIMA. Postoperative angiography revealed patent LIMA grafts and uneventful anastomoses. CONCLUSIONS: For minimally invasive direct coronary artery bypass (MIDCAB) the topography of the LIMA, LAD and intercostal spaces is of major importance. Using the ECG-triggered EBT with subsequent three-dimensional reconstruction these relationships can be visualized. This enables an individual planning of the operation and a minimalization of the skin incision.

Aged↗
PubMed1998

Enhancement of obliterative airway disease in rat tracheal allografts infected with recombinant rat cytomegalovirus.

BACKGROUND: Cytomegalovirus infection has been identified as a significant risk factor for the development of obliterative bronchiolitis in human lung transplant recipients. This study was designed to assess the influence of rat cytomegalovirus (RCMV) on the pathogenesis and development of obliterative bronchiolitis in an experimental model of obliterative airway disease, which occurs after allogenic heterotopic tracheal transplantation in rodents. METHODS: Sixty Lewis rats were infected intraperitoneally with 10(7) plaque-forming units of recombinant lac-Z-tagged RCMV expressing the gene for beta-galactosidase. Rats were either infected at the time of surgery (acute infection, n = 30) or 56 days before surgery (chronic infection, n = 30). Tracheae from Brown Norway (allograft) or Lewis (isograft) rats were implanted and wrapped in the greater omentum of infected Lewis rats. RCMV infection was verified in different recipient tissues by in vitro plaque-assays and by direct in situ staining for beta-galactosidase activity. The tracheal grafts were harvested on days 7, 14, and 21 after transplantation and stained with hematoxylin-eosin and Masson's trichrome. The peritracheal cellular inflammation was scored visually. The cellular density of the infiltrating cells and the extent of airway obliteration were analyzed by use of computer-digitized morphometry and compared with uninfected allografts as control. RESULTS: Both acute and chronic cytomegalovirus infection produced significantly higher mononuclear cell density values on days 7 and 14 compared with noninfected controls, indicating a more intense immune response in the infected allografts. Tracheal allograft obliteration was also more extensive after acute and, in particular, after chronic cytomegalovirus infection (64% narrowing after 21 days compared with 36% in grafts from noninfected control animals). CONCLUSIONS: Our experimental results provide direct evidence that the tracheal grafts were infected with RCMV and that the development of obliterative airway disease was enhanced in the acutely and chronically infected allografts compared with grafts from noninfected control animals.

Animals↗
PubMed1998

Single-center randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of acute myocardial rejection.

BACKGROUND: To compare the efficacy and safety of tacrolimus and cyclosporine in heart transplantation, this single-center, prospective, randomized, open-label clinical trial was undertaken. METHODS: Seventy-three adult patients were randomly assigned at the time of transplantation to receive either tacrolimus (n=43) or cyclosporine (n=30) as the primary immunosuppressant. Ten of the 43 patients in the tacrolimus group received the drug intravenously in the perioperative period; all other patients received only oral tacrolimus. RESULTS: With a mean follow-up of 27 months, patient survival rates (tacrolimus 83%, cyclosporine 81%) were similar. Fewer patients experienced acute rejection in the tacrolimus group (79%) than in the cyclosporine group (100%), but the difference was not statistically significant. The number of infections and dialysis and insulin requirements were similar for the 2 treatment groups, but the proportion of patients requiring multidrug antihypertensive regimens was lower in the tacrolimus group (12.5% vs 50.0% at month 6; p=.025). The interpatient variance in pharmacokinetic parameters in a subset of 10 patients was much higher after the first oral dose of tacrolimus than at steady-state (eg, first-dose time at which maximal concentration is reached (t(max)): 3.5+/-2.5h, steady-state t(max): 2.0+/-0.7h), and patients treated with intravenous tacrolimus (n=13) rather than oral tacrolimus (n=30) reached target concentrations faster and with less interpatient variability (eg, at day 0: 9.72+/-10.9 ng/mL intravenously vs 3.31+/-8.1 orally). CONCLUSIONS: Tacrolimus was associated with similar efficacy and safety profiles compared with cyclosporine. The higher interpatient variance in absorption associated with oral tacrolimus during the first few days after transplantation would suggest that intravenous tacrolimus should be used during the perioperative period.

Administration, Oral↗
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↗