Monitoring of mononuclear cells from arterial and central venous blood in lung transplant patients.
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Graft Rejection↗
Biomedical subjects
G Laufer
Publications and source records attributed to G Laufer.
Long-term intrinsic pacemaker function in patients paced for sinus node deficiency after cardiac transplantation.
Fifteen cardiac transplant recipients requiring permanent pacing (AAI, n = 9; VVI, n = 6; rate responsive devices, n = 11) for postoperative sinus node (SN) insufficiency underwent evaluation of long-term SN function 240 to 1,461 days after transplantation. The intrinsic rhythm at the time of discharge was sinus in 7 patients; junctional escape in 6 patients; and pacemaker dependent in 2 patients. At follow-up, 5 patients had regained regular sinus rhythm, accounting for a total of 11 patients in sinus rhythm while 4 patients were in junctional bradycardia. The SN recovery time as determined by the permanent pacemaker was normal (< 1,500 msec) in only 1/8 patients in whom it was determined, although 4 of these 8 patients were temporarily overriding the pacemaker during ambulatory monitoring. Patients with pathological SN recovery times included 3 patients with late return of sinus rhythm and 4 patients who had recovered normal sinus rhythm before their discharge from the hospital. Three patients developed late symptoms despite apparent early normalization and underwent delayed pacemaker implantations on postoperative days 35, 52, and 225, respectively. We conclude that, in patients requiring pacemaker implantation after cardiac transplantation, normalization of SN function cannot be inferred from just return of sinus rhythm, regardless of whether it occurs early or late. These findings may have implications when a pacemaker exchange or explantation is being considered.
Electrocardiography↗
Sinus node dysfunction after orthotopic cardiac transplantation: postoperative incidence and long-term implications.
We investigated incidence, normalization rates, and clinical significance of sinus node (SN) dysfunction after cardiac transplantation. Thirty-nine of 90 patients systematically evaluated presented with impaired SN function in the postoperative period. Of these, 22 normalized their SN function during follow-up while 17 remained impaired after 3 months. The proportion normalized was higher in patients with prolonged SN recovery time (11/16, 68.8%) and those reverting from escape rhythm to sinus rhythm until discharge (5/8, 62.5%) when compared to patients in escape rhythm throughout the postoperative period (5/11, 45.5%) or pacemaker dependence (1/4, 25%). There was no reliable postoperative predictor of normalization and necessity of long-term pacing. A postoperative heart rate consistently less than 70 beats/min (irrespective of the native rhythm) was significantly related to outcome (P = 0.01), but revealed unacceptable sensitivity (61.5%) and specificity (81%). After all, both patients with severe symptoms (near syncopes and syncope), were derived from this group. These two patients, who had been discharged in sinus rhythm, had late pacemakers implanted. An additional 17 patients had early pacemaker placement, only seven of which were constantly paced during follow-up. Given the low normalization rates, patients with postoperative escape rhythm are those most likely to benefit from pacemaker therapy over the long term. Even those in, or reverting back to, sinus rhythm until discharge may experience severe symptoms, particularly in the setting of a postoperative rate consistently less than 70 beats/min since this indicates a relatively lower probability of recovery.
Algorithms↗
One and one-half year experience with unilateral and bilateral lung transplantation.
Lung transplantation has now become an established form of treatment for end-stage pulmonary parenchymal and vascular diseases. Despite its wide acceptance, technical aspects are still in discussion. We report on the initiation of our own lung transplant program and the technical changes we have performed during our first 1 1/2-year experience. During that period of time, we have performed 26 lung transplantations (16 single lung [SLTX] and 10 bilateral lung transplantations [BLTX]). Three-month survival for the whole group was 74% (69% for the SLTX group and 77% for the BLTX group). No instance of bronchial dehiscence was observed; however, there were eight cases of bronchial stenosis: six were managed by silicone stent insertion, one by bronchoplastic correction, and one by retransplantation. Changes in the technique of the bronchial anastomosis together with the addition of prednisone to the immediate postoperative immunosuppressive regime resulted in almost complete avoidance of these problems.
Adult↗
Postoperative sinus node dysfunction in the transplanted heart. Impaired automaticity but normal refractoriness.
We describe the use of the extrastimulus technique to define the range of sinus node (SN) effective refractoriness (SNERP) in the denervated transplanted human heart. SNERP could be successfully determined in 18 of 28 patients corresponding to 25 of 43 SN studies and ranged from 210 to 360 ms at a basic pacing cycle length of 500 ms (95 percent confidence limits: 252.5 to 296.2 ms), which is shorter than reported in the innervated native heart. Sixteen data sets in 12 patients showed normal SN function and nine sets of measurements in seven patients showed abnormal SN function (corrected SN recovery time greater than 520 ms). While recovery time was profoundly abnormal (279.7 +/- 94 vs 7,284.8 +/- 10,454, p less than 0.001), the SNERP did not differ significantly between the groups (274.3 +/- 40 vs 286 +/- 42 ms at 500 ms, p = 0.5) and was normal at a range of 220 to 340 ms even in those patients with grossly impaired SN recovery (SNERP in patients with normal SN function: 210 to 360 ms at 500 ms). This study demonstrates that SN refractoriness in the transplanted human heart is shorter than previously reported in innervated controls and suggests that posttransplantation SN dysfunction is characterized by impaired automaticity rather than impaired refractoriness.
Adult↗
[The coronary sinus as a source of activated T-lymphocytes in patients after orthotopic heart transplantation].
Mononuclear cells are the component of blood responsible for allograft recognition, rejection and acceptance. Shifts in the patterns of various mononuclear cell subpopulations were often used as a diagnostic tool in detection of heart rejection. The specificity of mononuclear cell monitoring has remained a controversial point until today, because infections led to similar changes as organ rejection. In this study we investigated whether mononuclear cells taken from coronary sinus blood give more information about the immunological status of the transplanted heart than those taken from central verous blood. After endomyocardial biopsy, coronary sinus blood was sampled by catheterization under X-ray control. Blood from the right atrium was taken for control measurement. Mononuclear cells obtained by density gradient cytocentrifugation were stained with monoclonal fluorescein conjugated antibodies detecting CD4- (T helper)-, CD8- (T suppressor)-, CD25- (Interleukin-2 receptor), and the CD71- (Transferrin receptor) antigens. Endomyocardial biopsies were graded according to the Billingham scheme. In the absence of rejection, the phenotypes of mononuclear cells from the coronary sinus did not differ from those of right atrial cells. Mild rejection led to a statistically insignificant increase of CD4- CD25- and CD7-antigen bearing cells in the coronary sinus blood, whereas the CD8 positive cells remained stable as compared to mononuclear cells from the right atrium. However, patients with moderate rejection showed a significant elevation of CD4 positive cells and activated T-cells (CD15-, CD71-positive cells) in the coronary sinus as compared with cells from the right atrium. The T helper/suppressor ratio (Th/s-ratio) shifted towards the T-helper population.(ABSTRACT TRUNCATED AT 250 WORDS)
CD4-CD8 Ratio↗
The determinants of elevated total plasma cholesterol levels in cardiac transplant recipients administered low dose cyclosporine for immunosuppression.
Elevated total plasma cholesterol level is a frequent finding after cardiac transplantation. To identify risk factors for the development of hypercholesterolemic states, we applied multivariate statistics in a logistic and linear manner. Six-month posttransplantation levels of total plasma cholesterol in 57 adult heart recipients were available for analysis. Maintenance immunosuppression was carried out with either cyclosporine and azathioprine or both agents plus low-dose steroids. Total plasma cholesterol levels were dichotomized for the logistic analysis (1) by the age- and sex-matched 75th and 90th percentiles of a reference population according to National Institutes of Health treatment guidelines and (2) by the cut point 250 mg/dl. Twelve potential risk factors were evaluated as covariates: recipient age, body weight after 6 months, body weight gain over 6 months, body mass index after 6 months, body mass index gain over 6 months, current cyclosporine dosage, trough level of cyclosporine in whole blood according to high-performance liquid chromatography after 6 months, cumulative cyclosporine dosage over 6 months, serum bilirubin, type of original cardiac disease, maintenance steroids, and steroid bolus treatment. Multivariate logistic regression yielded the type of original cardiac disease as a significant predictor of posttransplantation hypercholesterolemia exceeding the 90th percentile (p = 0.019) and of hypercholesterolemia exceeding 250 mg/dl (p = 0.032). Maintenance steroids were identified as a second significant cofactor (p = 0.069) for total plasma cholesterol levels exceeding 250 mg/dl. Multiple linear regression again revealed the type of original cardiac disease and maintenance steroids as significant predictors by p values of 0.005 and 0.013, respectively. Patients with coronary artery disease as the original cardiac pathology and low-dose maintenance steroids had the greatest risk for the development of elevated total plasma cholesterol levels after cardiac transplantation. However, the overall predictive quality of the linear model was limited (multiple r value 0.43), which indicates that other variables besides the tested ones attributed to elevated total plasma cholesterol levels. These results confirm the adverse role of maintenance steroids on posttransplantation hypercholesterolemia and demonstrate the type of original cardiac disease as the most important risk factor. They suggest that abnormalities of lipoprotein metabolism and dietary factors continue to affect total plasma cholesterol levels after cardiac transplantation.
Adult↗
Mechanical bridge to transplantation with the Vienna heart in TAH and LVAD configuration.
The Vienna heart uses a vacuum formed, pellethane pulsatile ventricle and is available in left ventricular assist (LVAD) and total artificial heart (TAH) configurations. This device was used as mechanical support of the failing heart in nine patients intended for heart transplantation. In two patients with cardiomyopathy an orthotopic TAH was implanted; one survived despite severe preoperative ischemic liver damage, and the other died of sepsis. In seven patients an atrio-aortic LVAD was implanted; six had suffered an acute myocardial infarction with cardiogenic shock, and one could not be weaned off bypass. Three patients survived. These included one 65-year-old with incipient ARDS at operation, and a 40-year-old with preoperative liver and kidney insufficiency who was transplanted in septicemia. In this patient the septic focus, natural and artificial heart, were removed at transplantation. Four patients died. In one we were unable to establish satisfactory circulation, one died after failure of the transplanted heart, one suffered a lethal cerebral embolism and one developed multi-organ failure after repeated attacks of ventricular fibrillation. With the Vienna heart sufficient circulatory support could be established with cardiac outputs between 6 and 8 l/min for the TAH and 3.5 to 4.5 l/min for the LVAD. With this type of support an overall survival rate of 44% could be achieved. Mechanical hemolysis was not a clinical problem and no device failure occurred.
Cardiomyopathies↗
Fluorescence guided excimer laser ablation of intervertebral discs in vitro.
Laser induced fluorescence of intervertebral discs was investigated in this study for the first time in order to develop a fluorescence guided percutaneous excimer laser discectomy. For this purpose 35 human cadaveric intervetebral discs from level L1 to L5 were irradiated with a 308 nm XeCl excimer laser with a 60 nsec pulse width at 10, 20 and 30 mj/mm2. Laser light was transmitted over a 1000 microns core optical fiber. Fluorescence emitted from the irradiated tissue was transmitted back over the same fiber over a semireflective mirror to another optical fiber, coupled into a spectrograph and O-SMA optical simultaneous multichannel spectral analyzer system. The spectral lineshape of both the annulus fibrosus and the nucleus pulposus was characterized by a broadband emission between 320 nm and 616 nm with 3 peak emissions at 358, 423 and 457 nm. Relative intensities were calculated by forming two ratios of the peak intensities of the three peaks (R1 = I 423/I 358; R2 = I 423/I 457). Statistical analysis of both ratios revealed a highly significant discrimination between annulus fibrosus and nucleus pulposus (P less than 0.001). Under penetrating conditions multiple recorded spectra showed the spectral profile of subsequently ablated nucleus and annulus. The results of this study demonstrate that discrimination between annulus fibrosus and nucleus pulposus by excimer laser-induced fluorescence is feasible under laboratory conditions. Fluorescence spectroscopy could possibly be developed into a valuable guiding system for percutaneous laser discectomy.
Humans↗
A beat-by-beat analysis of electrocardiograms from cardiac transplant recipients.
A software system is described for producing a beat-by-beat analysis of the electrocardiograms from patients after heart transplantation. Pacemaker spikes are automatically detected and eliminated from the signals. R waves are located by a robust and accurate two-step algorithm. Based on the variable length of single heart beats, the Fourier coefficients of three orthogonal surface leads and of two intracardiac leads are calculated beat-by-beat. Power spectra are then obtained by combining contributions from the variable fundamental frequency and its multiples (harmonics) into fixed frequency classes of 1 Hz width and averaging over 60-120 cardiac cycles. Additionally, averaged beat-by-beat power spectra are calculated for windowed QRS complexes and T waves. As by-products, single beat quantities, such as R-R and R-T intervals, averaged signals for all leads, and the orientational autocorrelation function of the electrical vector of the heart, are obtained. Following beat-by-beat evaluation, mean values and standard deviations are obtained for all quantities.
Algorithms↗
The progression of mild acute cardiac rejection evaluated by risk factor analysis. The impact of maintenance steroids and serum creatinine.
The natural course of mild acute cardiac allograft rejection (MAR) under cyclosporine-based therapy is generally considered benign, and usually antirejection therapy is not instituted. The present study was undertaken to determine the frequency of and the risk factors for progression of MAR into a clinically significant (moderate or severe) rejection on subsequent endomyocardial biopsy (EMB). Among 167 cardiac recipients, transplanted from 3/1984 to 4/1990, MAR under cyclosporine-based therapy was diagnosed on 220 EMBs. Depending upon the outcome on the subsequent EMB, MAR was categorized as progressive or nonprogressive. This served as the dependent variable for a stepwise logistic regression analysis evaluating 11 covariates as potential risk factors: perioperative antibody prophylaxis (ATG vs. OKT3), maintenance therapy, underlying disease, HLA-mismatches for A- and B + DR-loci, serum creatinine (mg/dl) and cyclosporine HPLC blood level (ng/ml) at diagnosis of MAR and at subsequent biopsy, recipient age, donor age. 40 (18.2%) of 220 MARs became progressive as opposed to 37 (7.3%) of a control cohort of 507 negative EMBs (P less than 0.0001). Stepwise logistic regression yielded the type of maintenance therapy (P = 0.0019) and serum creatinine level at diagnosis of MAR (P = 0.0615) as independent predictors of progression of MAR. After adjustment for influence of maintenance therapy and serum creatinine none of the cyclosporine variables provided any additional information. MARs without maintenance steroids and low serum creatinine levels had the highest risk (37.2% observed incidence) to develop moderate or severe rejection on subsequent EMB. This analysis supports evidence that diagnosis of MAR on EMB is associated with a considerable high progression rate into clinically significant rejection when compared to negative EMBs. Progression particularly occurs in MAR under steroid-free maintenance therapy and suggests early augmentation of immunosuppression. In terms of progression of MAR serum creatinine values, obviously indicating cyclosporine nephrotoxicity, appear to reflect the extent of cyclosporine-mediated immunosuppressive activity more properly than parameters of its bioavailability by measuring cyclosporine HPLC blood levels.
Adrenal Cortex Hormones↗
Demographic and perioperative factors associated with initial and prolonged sinus node dysfunction after orthotopic heart transplantation. The impact of ischemic time.
The etiology of sinus node (SN) dysfunction after orthotopic heart transplantation as assessed by the origin of rhythm, heart rate (HR), and, provided the origin of rhythm was sinus, by corrected sinus node recovery time (CSNRT) was studied in 50 patients. The possible influences on postoperative donor SN function of donor age, recipient age, underlying pretransplant heart disease, pretransplant amiodarone (AMIO) treatment, date of surgery, ischemic time, surgical technique of atrial incision, the use of different cardioplegic solutions during the study period, and rejection were evaluated. The results thus obtained indicate that SN dysfunction is common after cardiac transplantation and pinpoint to a different etiology of transient (restoration of normal SN function within 4 postoperative weeks) and persistent (SN function still impaired at 3 months) SN dysfunction. Of the several demographic and perioperative variables evaluated, only ischemic time had an influence on postoperative SN function in that ischemic times were significantly longer in patients with impaired SN function when compared with patients exhibiting normal SN function (148 +/- 39 min vs. 110.5 +/- 36 min, respectively, P = 0.001). Further stratification according to the duration of SN dysfunction revealed significantly longer ischemic times in patients with transiently impaired SN function only (156.3 +/- 35 min vs. 110.5 +/- 36 min, P = 0.0026). No relation to persistent SN dysfunction of ischemic time (130.5 +/- 36 min vs. 110.5 +/- 36 min, P = ns) or any other factor investigated was found.
Amiodarone↗
[Uni- and bilateral lung transplantation: surgical results and experiences of the 1st year. Vienna Lung Transplant Group].
Transplantation of the lung has gained increasing importance during the last years and is now an established therapy for end stage lung disease. After a 3 years period of preparation the first single lung transplantation (SLTX) was performed at the Second Surgical Department of the University of Vienna in November 1989, followed by the first double lung transplantation (DLTX) in April 1990. Until the end of 1990 11 patients underwent SLTX and 6 DLTX. 7 of the 11 SLTX patients and 4 of the 6 DLTX patients are at present alive with significantly improved lung function and therefore markedly improved quality of life.
Adult↗
[Unilateral lung transplantation as an effective therapy in primary lung emphysema].
Unilateral lung transplantation is the treatment of choice for terminal restrictive lung disease. We report about three patients with end-stage pulmonary emphysema treated by single lung transplantation. All patients are alive 3, 6 and 7 months after the operation with good quality of life. Blood gases have normalized and lung function parameters have markedly improved. We conclude, that single lung transplantation can be an effective treatment for selected patients with end-stage obstructive lung diseases in the absence of chronic infections.
Adult↗
Timing for implantation and transplantation in mechanical bridge to transplantation.
The implantation of a mechanical blood pump in a deteriorating candidate for heart transplantation is indicated in general if the cardiac index is less than 1.9 L/min/m2 despite maximal inotropic support. Deterioration of end organ function may be taken as a second factor indicating the need for mechanical support as patients with acute onset of shock may react differently from patients with chronic deterioration. Preoperative need for dialysis largely reduces the chances of long-term survival. The time on support should be long enough to normalize or at least improve secondarily damaged organ systems, but with time infectious and thromboembolic complications will increase. So optimal periods for artificial heart support range between two days and four weeks. Age less than 40 years is a positive predictor for outcome in TAH bridging. The general guidelines, however, do not preclude a favourable outcome in complicated cases, as we show in our own series.
Adult↗
Monitoring of mononuclear cell subsets isolated from the coronary sinus and the right atrium in patients after heart allograft transplantation.
The rejection of a transplanted heart leads to an accumulation of mononuclear cells in the cardiac tissue and to reactions of the antigen-recognizing cells with the foreign tissue. Consequently, during rejections immunologic changes, such as the number of mononuclear cells and the patterns of mononuclear cell subpopulations, should be detectable by analysis of mononuclear cells from the coronary sinus of transplanted hearts. Seventy-nine endomyocardial biopsies were performed in 37 patients. Severity of graft rejection was classified by the Billingham scheme. Thirty-two biopsy specimens showed no rejection, 33 mild, and 14 moderate rejection. After endomyocardial biopsy the coronary sinus was catheterized under x-ray guidance. Heparinized blood samples were obtained from the coronary sinus and the right atrium, and mononuclear cell counts and subpopulation pattern were compared. Patients without rejection and patients with mild rejection showed no significant differences in the patterns of mononuclear cell subpopulation identified in right atrium blood. However, a significant (1.56-fold) increase of mononuclear cells was assessed in the CS blood (p less than 0.01). Moderate rejections showed a 4.2-fold augmentation of mononuclear cells in the coronary sinus (p less than 0.005) compared with nonrejections. In addition, the T-helper/inducer (CD4) percentage increased from 27.1% in the right atrium to 41.2% in the coronary sinus (p less than 0.005), natural killer cells (CD16) from 17.7% to 31.8% (p less than 0.005), and the interleukin 2 receptor-bearing cells from 6.6% to 15.3% (p less than 0.005). Percentage of pan-T cells (CD3), T-cytotoxic/suppressor cells (CD8), and monocytes (CD14) showed no statistically significant changes. These findings correlated with grading according to endomyocardial biopsy. Using the ratio of values obtained from cells of the coronary sinus and the right atrium rendered the coronary sinus immunologic monitoring independent of changes in the administered immunosuppressive regimen. The specificity of the described method was as good as that of endomyocardial biopsy. It is concluded that the discrimination of the patterns of mononuclear cell subpopulations from right atrium versus coronary sinus blood samples is highly sensitive and allows the correct diagnosis of graft rejection within 1 to 2 hours.
Antigens, CD↗
Analysis of heart rate changes in cardiac transplant recipients related to graft rejection.
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Adult↗
Clinical and electrophysiologic correlates of sinus node dysfunction after orthotopic heart transplantation. Observations in 42 patients.
We assessed incidence and course of postoperative SN dysfunction in 42 cardiac transplant recipients. RHY, HR and CSNRT were compared in distinguishing between persistent (9 of 42 patients) and transient (11 of 42) SN dysfunction. Persistent SN dysfunction was distinguished by a significantly lower HR (day 14: 46.2 +/- 12 vs 67 +/- 19 bpm; day 21: 40.3 +/- 21 vs 70.8 +/- 16 bpm; p less than 0.05, respectively) and by RHY: postoperative AS (3 of 42) was found only in patients whose SN dysfunction persisted while patients with SR but prolonged CSNRT more often had transient impairment (6 of 42 vs 2 of 42); CSNRT, in contrast, is unlikely to be useful in distinguishing between transient and persistent SN dysfunction since exceptionally long CSNRTs (11,340 ms. 12,080 ms) occurred in patients with both types. Ischemic times were significantly longer in patients with transient impairment when compared with the group with normal SN function (155.1 +/- 36 vs 109.2 +/- 36 min, p less than 0.05) but did not differ significantly in patients with persistent SN dysfunction (124.8 +/- 32 min). Thus, (1) SN dysfunction after cardiac transplantation is common but most often transient; (2) RHY and HR are adequate follow-up parameters and best predictors of long-term SN function; (3) SN dysfunction after transplantation has important clinical implications given the unreliability of lower pacemakers to take over in 3 patients; (4) transient SN dysfunction is related to duration of ischemia during hypothermic preservation whereas pathogenesis of persistent SN dysfunction remains to be elucidated.
Adult↗