Technique of immunoapheresis in heterotopic and orthotopic xenotransplantation of pig hearts into cynomolgus and rhesus monkeys.
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Animals↗
Biomedical subjects
B Reichart
Publications and source records attributed to B Reichart.
Incomplete sympathic reinnervation of the orthotopically transplanted human heart: observation up to 13 years after heart transplantation.
OBJECTIVE: Heart transplantation (HTx) is associated with autonomic denervation of the donor heart. Sympathetic reinnervation (RI) as defined by the presence of functional nerve terminals occurs only if sympathetic ganglia outside the heart are connected with nerve terminals in the transplanted heart. The purpose of this study was to define the incidence and functional consequences of RI over time after HTx. The activity and distribution of norepinephrine (NE) uptake sites were assessed by positron emission tomography (PET) imaging. Symptom limited exercise testing was performed by bicycle-ergometer. METHODS: Forty-seven patients (m:f=42:5, 47.6+/-8. 2 years, age range 27-65 years) were investigated between 2 months and 13.6 years after HTx using PET and the NE analogue C-11-hydroxyephedrine (HED). Tracer uptake was quantified using dynamic imaging protocols yielding regional HED retention fraction. A regional value above 7%/min (+/-2.5 SD above the mean value of denervated hearts) was considered evidence for RI. The functional significance of RI was investigated in 34 patients (m:f=30:4, 49. 3+/-8.4 age range 27-62 years) by symptom limited exercise testing. Cardiac catheterization was performed at the time of PET imaging. RESULTS: RI could not be assessed in the first year after HTx, in 11% in the second year and in 80% of the patients from the third year on. Retention values plateaued then. In all time intervals, beyond the third year, not reinnervated patients were found. RI remained incomplete and was always restricted to the anterior wall of the left ventricle. Extent of retention of the left ventricle revealed a large individual range up to 66%, averaging of 20%. Recipient age at the time of HTx, reinnervated patients were 5.5 years younger than not reinnervated ones, proved as the only significant influencing factor for RI (P<0.05). Dividing patients into scintigraphically reinnervated (n=20) and not reinnervated (n=14), reinnervated patients displayed during exercise a higher maximal heart rate (137+/-14 vs. 123+/-20/min, P<0.05), heart rate increase (40+/-15 vs. 28+/-13/min, P<0.05), max. oxygen consumption (1674+/-424 vs. 1279+/-308 ml/min, P<0.01) and anaerobic threshold (887+/-170 vs. 717+/-183 mlO(2)/min, P<0.01) than not reinnervated ones. A correlation between transplant vasculopathy and RI could not be demonstrated. CONCLUSION: ++: RI assessed by PET and the NE analogue HED is time dependent, incomplete, displays a typical pattern and demonstrates a broad individual spread. Furthermore, RI enhances functional parameters of exercise testing.
Carbon Radioisotopes↗
Sympathetic reinnervation of sinus node and left ventricle after heart transplantation in humans: regional differences assessed by heart rate variability and positron emission tomography.
BACKGROUND: Orthotopic heart transplantation (HTx) results in complete cardiac denervation. Reestablished partial sympathetic nerve function has been found in patients some years after HTx. However, the atrial and ventricular regional patterns of reinnervation have not been established. METHODS: Two parallel methods were used to evaluate the regional restoration of sympathetic nerves in the myocardium. Patients were investigated with respect to ventricular reinnervation (VI) using positron emission tomography (PET) and the norepinephrine analogue C-11-hydroxyephedrine (HED). Tracer uptake was quantified using dynamic imaging protocols, yielding regional HED retention fraction. A regional value above 7%/minute ( +/- 2.5 SD above the mean value of denervated hearts) was considered evidence of sympathetic reinnervation. Spectral analysis of heart rate variability (HRV) served as a quantitative marker for reinnervation at the sinus node (SI). Spectra of HRV during positive head-up tilt were calculated. The low frequency (LF) power spectral density (0.05 to 0.18 Hz) was evaluated. RESULTS: After HTx (4. 6 +/- 3.9 years; range, 0.2 to 13.6 years), 38 patients (aged 50.9 +/- 7.6 years; range, 37 to 65 years) were investigated by PET imaging and HRV. Twenty-two patients with a mean HED retention of 10. 7 +/- 2.6%/minute were classified as left ventricular reinnervated. Sixteen patients with a mean HED retention of 4.8 +/- 0.8%/minute did not reach the threshold. The time difference after HTx was significant for these 2 groups, 5.3 +/- 3.0 years vs 3.8 +/- 4.7 years ( p < 0.05 ). The LF power spectral density of the ventricular reinnervated patients was 5.9 +/- 8.6 ms(2), and 1.8 +/- 4.4 ms(2) (p <0.005 ) for those not reinnervated. Low frequency showed small values and narrow distribution for the patients not reinnervated, assuming sinus node denervation, and showed extended distribution for the reinnervated, suggesting a heterogeneous reinnervation pattern. CONCLUSIONS: Two non-invasive parallel methods were used to investigate regional reestablishment of cardiac nerves in the myocardium in HTx patients. Left VI assessed by PET imaging and SI by HRV was congruent in 60% of HTx patients. Lack of SI paralleled absence of VI. Our results suggest that partial VI occurs prior to SI.
Adult↗
Vagal reinnervation in the long term after orthotopic heart transplantation.
BACKGROUND: Sympathetic reinnervation after orthotopic heart transplantation (HTx) has become an accepted phenomenon, particularly in long-term transplanted patients. Parasympathetic reinnervation, however, still remains questionable. METHODS: In 38 HTx recipients, mean age of 51.6 +/- 9.7 years (range, 29 to 70 years), with a time span after HTx of 4.6 +/- 2.8 years (0.5 to 10.5 years), we stimulated carotid baroreceptors using periodic neck suction at low (0.1 Hz) and high (0.2 Hz) frequencies to test sympathetic and vagal responses, respectively. Respiratory rate was fixed at 0.25 Hz. We simultaneously recorded surface electrocardiogram, finger blood pressure, respiration and neck pressure signals while patients rested in the supine position. Time series of RR intervals, respiration, and neck and blood pressures were generated and subjected to spectral analysis. RESULTS: All patients demonstrated a 0.25-Hz peak in RR-interval spectrum, caused by non-autonomic respiratory sinus arrhythmia. Thirteen patients (5. 2 +/- 3.5 years after HTx; range, 0.9 to 10.2 years) showed a baroreflex-induced sharp peak at 0.1 Hz in RR-interval power spectrum during 0.1-Hz neck suction, indicating sympathetic reinnervation. However at 0.2-Hz neck suction, 4 of the 13 sympathetically reinnervated patients displayed a baroreflex-induced 0.2-Hz peak, which could be suppressed with atropine administration-strong evidence for vagal reinnervation. CONCLUSIONS: Non-invasive carotid baroreflex stimulation is an appropriate tool to prove restoration of autonomic control after orthotopic HTx. Sympathetic reinnervation parallels parasympathetic reinnervation in long-term transplanted patients.
Adult↗
Optimizing cerebral oxygenation during cardiac surgery: a review of experimental and clinical investigations with near infrared spectrophotometry.
OBJECTIVES: Near-infrared spectrophotometry (NIRS) is a promising method for non-invasive monitoring of cerebral oxygenation and hemodynamics. This paper reviews studies in which we aimed to validate NIRS in an experimental model of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) (validation study), use the method in experimental settings to optimize cerebral oxygenation during CPB (oxygenation study), and test its utility during routine cardiac surgery (clinical study). METHODS: Validation study: Forty 8-10 kg piglets underwent 60 min of DHCA at 15 degrees C, were extubated on the first postoperative day, and sacrificed on the 4th postoperative day for histologic investigations. During CPB and DHCA, the animals were investigated by NIRS (monitoring of cerebral oxygenated hemoglobin (HbO2) and oxidized cytochrome aa3 (Cytox)) and magnetic resonance spectroscopy (MRS) (monitoring of cerebral adenosine triphosphate (ATP) and phosphocreatine (PCr). Oxygenation study: A normoxic (n = 5) and a hyperoxic group (n = 5) of piglets underwent 120 min of DHCA and 6 h of reperfusion with NIRS monitoring. Neuronal damage was evaluated by histology. Clinical study: Patients (n = 41) undergoing routine cardiac surgery were investigated by NIRS and neuropsychological testings. RESULTS: Validation study: Reductions of CytOx and HbO2 values were closely correlated with decreases in ATP, PCr, and pHi. The changes in CytOx and PCr showed the strongest correlation (r = 0.623). Maximal CytOx reduction during DHCA predicted brain damage. Oxygenation study: Histology revealed a significant increase in brain damage in the normoxic group. Cytox and HbO2 tended to be lower during DHCA (p = 0.16). Clinical study: During CPB, arterial PCO2, pH and temperature were closely related to CytOx and HbO2. Patients who suffered from neuropsychological deficits had a lower CytOx minimum compared to those without these. CONCLUSIONS: NIRS measurements, especially the CytOx signal, correlate well with high energy phosphates and have a high sensitivity to predict histologic brain damage. NIRS is an important and useful tool in studies investigating cerebral oxygenation during CPB. The CytOx signal predicted impaired neuropsychological outcome in patients. Therefore, the CytOx signal holds much interest for future studies.
Animals↗
Clinical use of a computer-enhanced surgical robotic system for endoscopic coronary artery bypass grafting on the beating heart.
The aim of the study was to perform endoscopic coronary artery bypass grafting on the beating heart using a surgical robotic system. In the study, the surgical system ZEUS was used in combination with 3D visualization for endoscopic coronary artery bypass grafting in 25 patients. In a total of 10 cases, the coronary artery anastomosis was done on the beating heart using endoscopic stabilizers without cardiopulmonary bypass. In all cases, total OR time ranged from 4.0 to 8.0 hours (median 5.5 h); the times for endoscopic coronary artery anastomoses ranged from 14 to 50 minutes (median 25 minutes) with no difference between arrested-heart or beating-heart procedures. All patients had an uneventful angiographic control result. An endoscopic coronary artery anastomosis is possible on the arrested as well as on the beating heart.
Cardiopulmonary Bypass↗
Replacement of the valves of a Novacor LVAS without cardiopulmonary bypass.
We report the case of a 54-year old man with end-stage heart disease in whom the malfunctioning valves of a Novacor LVAS needed to be replaced after 490 days of circulatory support. This procedure could be performed without cardiopulmonary bypass.
Equipment Failure↗
Reduced expression of systemic proinflammatory cytokines after off-pump versus conventional coronary artery bypass grafting.
BACKGROUND: Both cardiopulmonary bypass (CPB) and operative trauma are associated with increased expression of proinflammatory cytokines. We assessed the relative contribution of CPB on activation of various proinflammatory cytokines in patients undergoing coronary revascularization by comparing them with patients receiving coronary artery bypass grafts using off-pump (OPCAB) techniques. METHODS: Twenty-six patients were assigned to either the OPCAB procedure using a suction device and regular sternotomy (n = 13) or were treated conventionally using extracorporeal circulation, blood cardioplegia and hypothermic arrest (29-31 degrees C; n = 13). C-reactive protein and systemic levels of TNF-alpha, TNF specific receptors Rp1 and Rp2, Interleukin-6 (IL-6) and soluble IL-2 receptors (sIL-2r) were assayed by ELISA or EIA. To account for systemic nitric oxide production, total nitrate/nitrite (NOx) was measured using the Griess reaction. RESULTS: Coronary revascularization with CPB was associated with a significant expression increase in the TNF-system and sIL-2r when compared to the OPCAB patients. Although IL-6 expression did not differ between both groups, C-reactive protein levels were significantly lower in the OPCAB group. Moreover, systemic NOx levels as the stable end-product of nitric oxide were lower in the OPCAB group. CONCLUSIONS: The data of the present study indicate that, despite comparable surgical trauma, the OPCAB revascularization procedure without the use of CPB and cardioplegic arrest significantly reduces the systemic inflammatory response syndrome and early catecholamine requirement. This may contribute to improved organ function, subsequently resulting in improved postoperative recovery from surgical revascularization procedures, particularly in critically ill patients.
Aged↗
Standards and concepts in valve surgery. A report of the task force of european heart institute (EHI) of the european academy of sciences and arts and the international society of cardiothoracic surgeons (ISCTS).
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Aortic Valve Insufficiency↗
Health-related quality of life and post-traumatic stress disorder in patients after cardiac surgery and intensive care treatment.
OBJECTIVES: Health-related quality of life and patient satisfaction have become important end points in cardiac surgery. Post-traumatic stress disorder has been described in patients with life-threatening heart disease. In this study, we investigated the occurrence of post-traumatic stress disorder in a sample of patients after cardiac surgery and compared health-related quality of life and patient satisfaction between patients with and without evidence of post-traumatic stress disorder. METHODS: We studied 80 patients serially admitted to the intensive care unit after cardiac surgery (bypass grafting, n = 51; aortic valve replacement, n = 29). Health-related quality of life was assessed with the use of the SF-36 Health Status Questionnaire. Post-traumatic stress disorder was measured with a previously validated instrument (the Post-Traumatic Stress Syndrome 10-Questions Inventory), and 20 different aspects of life satisfaction were quantified on a scale ranging from 0 to 10. For measurements of health-related quality of life and post-traumatic stress disorder, age- and gender-comparable healthy individuals, as well as patients with cardiovascular diseases, served as control groups. RESULTS: Patients who had cardiac surgery described high life satisfaction summary scores (156 of a maximum of 200 points) and only small impairments in physical and mental SF-36 summary scores when compared with healthy control groups (median reduction 7.15, P <.05). Patients with evidence of post-traumatic stress disorder (n = 15) reported the lowest SF-36 mental health summary scores when compared with patients without stress disorder (38.3 vs 48.4, P =.004) and rated their life satisfaction lower (121.5 vs 162.0, P =.002). CONCLUSIONS: Patients who have had cardiac surgery demonstrate a high life satisfaction with an acceptable degree of physical and mental health-related quality of life. Impairments in psychosocial function and life satisfaction were found in a subgroup of patients with evidence of post-traumatic stress disorder.
Aged↗
Hemodynamic monitoring by double-indicator dilution technique in patients after orthotopic heart transplantation.
STUDY OBJECTIVES: A transpulmonary thermal-dye dilution (TDD) technique using cold indocyanine green dye was utilized to monitor cardiac index (CI) and preload in patients after heart transplantation. Preload, determined by intrathoracic blood volume index (ITBVI) and global end-diastolic volume index (GEDVI), was compared to central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP) and was correlated with stroke volume index (SVI). DESIGN: Prospective study. SETTING: Cardiac surgery ICU at a university hospital. PATIENTS: Forty patients (34 men, 6 women) with a mean (+/- SD) age of 54.4+/-8.5 years after orthotopic heart transplantation. MEASUREMENTS AND RESULTS: CI and preload measurements were performed with TDD and pulmonary artery catheters in the ICU at 3, 6, 12, 24, 36, 48, and 72 h postoperatively. The femoral artery CI was compared with the pulmonary artery CI. Changes in the ITBVI, GEDVI, CVP, and PAOP were correlated with changes in the SVI. No difference was found between the femoral and pulmonary arterial CIs (r = 0.98 [bias, 0.35 L/min/m(2)]; p<0.01). There was no statistically significant correlation between changes in the SVI and changes in CVP (r = -0.23,) and PAOP (r = -0.06). However, the ITBVI (r = 0.65; p<0.01) and the GEDVI (r = 0.73; p<0.01) were significantly correlated to changes in the SVI. Changes in the same direction occurred between the SVI and the GEDVI as well as between the SVI and the ITBVI in 76.3% and 71.9% of patients, respectively, while CVP and PAOP also changed in the same direction as SVI in only 35.1% and 36.9% of patients, respectively. CONCLUSION: ITBVI and GEDVI are more reliable preload parameters than CVP and PAOP. Even in denervated hearts, ITBVI and GEDVI show significant correlations with SVI. The transpulmonary indicator dilution technique is promising and should be investigated further.
Adult↗
Mitral valve surgery utilizing homografts: early results.
BACKGROUND AND AIM OF THE STUDY: Mitral valve repair is superior to prosthetic valve replacement due to preservation of the subvalvular apparatus. We used cryopreserved homografts for mitral valve replacement in selected cases, in whom valve repair would not have been successful. METHODS: Cryopreserved homografts were used in 10 patients (four males, six females; mean age 47 +/- 8 years; range: 27-65 years), for either complete (n = 7) or partial (n = 3) mitral valve replacement. Surgery was indicated due to acute endocarditis (n = 3), stenosis (n = 4) or combined mitral valve disease (n = 3). Transesophageal echocardiography (TEE) was performed to determine correct homograft size; these values were compared with intraoperative measurements of valvular dimensions. The function of the implanted grafts was examined intraoperatively by TEE. Follow up included clinical examination, electrocardiography and echocardiography. RESULTS: All patients survived surgery. Intraoperative TEE revealed mild insufficiency (grade I) in six cases and no insufficiency in four. The papillary muscle-mitral annulus distance was the most reliable preoperative echocardiographic parameter to determine the required homograft. Mean pressure gradients were 3.2 +/- 0.7 mmHg for complete and 2.4 +/- 0.5 mmHg for partial homograft replacement. Sinus rhythm was present in all cases at discharge. Mean follow up was 24 months (range: 6-36 months). At six-month and one-year follow up, the pressure gradients had risen slightly to 3.4 +/- 0.6 mmHg (complete) and 2.8 +/- 0.6 mmHg (partial). To date, four patients had competent grafts, and six presented with an insufficiency (grade I). All patients had normal left ventricular function (EF 65 +/- 6%) at their last follow up; there were no signs of endocarditis during the follow up period. CONCLUSION: Mitral homografts for valve replacement or repair are recommended in selected cases in whom conservative reconstruction techniques are not possible. The avoidance of long-term anticoagulation therapy and preservation of left ventricular geometry are clear advantages to other mitral valve prostheses.
Adult↗
Standards and concepts in valve surgery.
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Aortic Valve Insufficiency↗
Predictors of reduced coronary flow reserve in heart transplant recipients without angiographically significant coronary artery disease.
BACKGROUND: Determination of coronary flow reserve (CFR) is increasingly used to assess the functional significance of cardiac allograft vasculopathy. Although the relation between CFR and angiographically defined vasculopathy has been studied extensively, little is known about other factors determining CFR in heart transplant recipients without significant lesions by coronary angiography. METHODS: Sixty consecutive patients were studied 0.5 to 148 months after heart transplantation with intracoronary Doppler and intravascular ultrasound. An endothelium-independent CFR< or =2.5 was defined as abnormal. Stepwise logistic regression analysis was used to identify factors (demographic data of donor and recipient, lipid profile, epicardial vessel morphology by intravascular ultrasound, left ventricular hypertrophy, acute rejection episodes, and hemodynamics) potentially associated with a reduced CFR. RESULTS: Only the presence of left ventricular hypertrophy (48% vs. 14%, P=0.007 and P=0.023, bivariate and multivariate analysis, respectively) and higher donor ages (41+/-12 vs. 29+/-11 years, P=0.002 and P=0.013, bivariate and multivariate analysis, respectively) showed an independent association with an abnormal flow reserve. CFR in patients with left ventricular hypertrophy was reduced due to higher baseline flow velocities (27+/-11 vs. 20+/-6 cm/sec, P=0.004). Furthermore, resting flow velocity increased as a function of donor age (r=0.264, P=0.047), while hyperemic flow velocity was not different. Other patient characteristics and hemodynamics did not affect CFR. CONCLUSION: The presence of left ventricular hypertrophy and higher donor ages independently contribute to a reduced CFR in patients after heart transplantation. This reduction in CFR is due to elevated baseline flow velocities rather than to a change in hyperemic flow velocities. These findings should be taken into account for the interpretation of reduced CFR values obtained by intracoronary Doppler in heart transplant recipients without angiographically overt coronary lesions.
Adult↗
Lung procurement by low-potassium dextran and the effect on preservation injury. Munich Lung Transplant Group.
BACKGROUND: This clinical study was performed to evaluate the effect of low-potassium dextran (LPD) solution on organ function in human lung transplantation. METHODS: A total of 80 patients were included in this study. Donor lungs were flushed with Euro-Collins (EC) solution in 48 cases or LPD (Perfadex) in 32 cases. Subsequently, single- (EC: n = 31; LPD: n = 15) or double-lung transplantations (EC: n = 17; LPD: n = 17) were performed. The evaluation parameters of transplant function were the reperfusion injury score (grade I to V); the alveolar/arterial oxygen ratio; the duration of respirator therapy; and the length of intensive care treatment and survival. RESULTS: Incidence and severity of reperfusion injury score were more severe in the EC group (31 of 48: grade I: n = 13; II: n = 8; III: n = 5; IV: n = 2; V: n = 3; LPD group: 17 of 32 patients; grade I: n = 12; II: n = 1; III: n = 3; IV: n = 0 grade V: n = 0), leading to death in three patients. In the LPD group, despite of the use of cardiopulmonary bypass, alveolar/arterial oxygen ratio values were significantly (P = 0.009) better during the early postoperative phase. Thirty-day mortality was 12% in the EC group and 6% in the LPD group. The one-year survival rate was 79% after the use of LPD (vs. EC: 62%). CONCLUSIONS: Graft preservation using LPD leads to better immediate and intermediate graft function after pulmonary transplantation and also results in better long-term survival.
Adult↗
Inducible nitric oxide synthase activation after ischemia/reperfusion contributes to myocardial dysfunction and extent of infarct size in rabbits: evidence for a late phase of nitric oxide-mediated reperfusion injury.
BACKGROUND: Ischemia/reperfusion (I/R) leads to the induction of inducible nitric oxide synthase. The present study investigated the effects of selective and continuous inhibition of iNOS on myocardial performance, infarct size and histomorphological changes after I/R in rabbits. METHODS AND RESULTS: Ischemia/reperfusion (I/R) was induced by occlusion of the circumflex coronary artery for 30 min followed by 48 h of reperfusion. Sham animals (group A) served as control. Three groups were subjected to I/R: (B) placebo; (C) aminoguanidine (AMG; 10 mg/kg bolus) given prior to and 48 h after I/R to test its acute effects; (D) AMG (300 mg/kg/day s.c.) to test effects of continuous treatment. Hemodynamics, myocardial blood flow, infarct size, iNOS activity, cGMP levels, immunohistochemical analysis of iNOS expression and AMG tissue levels were determined. Continuous AMG treatment improved myocardial performance (hemodynamics and blood flow) compared to placebo group. iNOS was highest in placebo-treated animals. AMG tissue levels were highest in tissues affected by I/R. Infarct size (% of the circumflex region) was significantly smaller in group D when compared to group B. CONCLUSIONS: This is the first study showing that activation of myocardial iNOS isozyme during 48 h of reperfusion contributes to a late phase of I/R-induced injury in rabbits. Selective and continuous modulation of iNOS by AMG over this time period exerts protective effects with respect to myocardial performance, coronary blood flow, cellular infiltration and reduction of infarct size; this may be a novel therapeutic approach in the clinical situation to limit irreversible myocardial injury associated with ischemia and reperfusion.
Adrenergic beta-Agonists↗
Diagnostic and prognostic value of serial dobutamine stress echocardiography for noninvasive assessment of cardiac allograft vasculopathy: a comparison with coronary angiography and intravascular ultrasound.
BACKGROUND: Routine methods for surveillance of cardiac allograft vasculopathy (CAV) are coronary angiography and intravascular ultrasound (IVUS). This study analyzed the diagnostic and prognostic value of dobutamine stress echocardiography (DSE) for noninvasive assessment of CAV. METHODS AND RESULTS: In 109 heart transplant recipients, 333 DSEs were compared with 285 coronary angiograms and 199 IVUS analyses. Studies were repeated after 1, 2, 3, 4, and >/=5 years in 88, 74, 37, 18, and 7 patients, respectively. Resting 2D echocardiography detected CAV defined by IVUS and angiography with a sensitivity of 57% (specificity 88%). DSE increased the sensitivity to 72% (P=0.002). M-mode analysis increased the sensitivity of 2D rest and stress analysis (P=0.001, 0.004). Cardiac events occurred after 1.9% of normal stress tests by 2D analysis (combined 2D and M-mode: 0%), compared with 6.3% (3.8%) of normal resting studies. Worsening of serial DSE indicated an increased risk of events compared with no deterioration (relative risk 7.26, P=0.0014). Serial deterioration detected by stress only was associated with a higher risk of events than changes evident from resting studies (relative risk 3.06, P=0.0374). CONCLUSIONS: DSE identifies patients at risk for events and facilitates monitoring of CAV. A normal DSE predicts an uneventful clinical course and justifies postponement of invasive studies. The prognostic value of DSE is comparable to that of IVUS and angiography.
Adrenergic beta-Agonists↗
Optimization of the immunosuppressive protocol after lung transplantation.
BACKGROUND: The successful use of tacrolimus (Tac)-based immunosuppressive therapy in organ transplantation and our own positive experience in heart transplantation led us to investigate regimens including this agent at our center for lung transplantation. METHODS: From 1991 to 1998, 86 patients underwent lung transplants at our center and 78 of them were included in this analysis. The first 34 patients were treated with cyclosporin (CsA), azathioprine (Aza), and rabbit antilymphocyte globulin; the subsequent 30 patients received Tac with Aza, and the most recent 12 patients Tac with mycophenolate mofetil (MMF). In addition, all patients received prednisone. RESULTS: The number of acute rejection episodes per 100 patient days was 1.5, 0.6, and 0.3 for three treatment groups, respectively. Similarly, the incidence of refractory acute rejection per 100 patient days was lower in both Tac groups (0.20, 0.03, and 0, respectively). Freedom from acute rejection was highest in the Tac-MMF group (P=0.0037 vs. Tac/Aza, P=0.0007 vs. CsA/Aza). Freedom from recurrent acute rejection was significantly higher in both Tac groups (P=0.027 Tac/ Aza vs. CsA/Aza and P=0.025 Tac/MMF vs. CsA/Aza). The incidence of infections per 100 patient days was similar (0.8, 0.5, and 0.8) in all three treatment groups, with a similar distribution of fungal, bacterial, and viral infections. Freedom from infection also showed no difference. The survival rate was significantly higher for the Tac population, with actuarial 1- and 3-year survival rates of 93% and 71%, compared with the CsA group (71% and 51%, respectively, P=0.04). Prevalence of renal dysfunction (creatinine >2.0 mg/ dL) was 18%, 13%, and 0% in the 3 treatment groups, respectively. The development of glucose metabolism disorders was lower in the CsA group than in the Tac-Aza group (15% vs. 27%, P<0.05). CONCLUSIONS: Tac-based immunosuppressive therapy results in a lower rate of acute rejection after pulmonary transplantation, with similar infection rates and a slightly higher incidence of new onset diabetes mellitus compared with CsA-based therapy.
Acute Disease↗