201 The antiproliferative effects of MMF are believed to be the mechanism of its immunosuppressive action. To further investigate its mechanism we used several novel whole blood assays of lymphocyte function (PD) in MMF-treated transplant recipients to investigate the suppression of activation antigen expression and to determine the relationships among MMF dose, PD and histology. Methods: 18 LW recipients of BN hearts were treated once daily with 5, 10 or 20 mg/kg of MMF (n = 6 rats/group). On day 7 rats blood was obtained before dosing (0 hr) and 6, 12 and 24 hrs after dosing. Blood was stimulated with Con A (signal 1 and 2) and PMA+anti-CD28 (signal 2). Using flow cytometry, suppression of lymphocyte activation was measured by changes in the expression of CD25 (IL-2 R), CD71 (transferrin R), CD11a (LFA-1) and CD54 (ICAM) and calculated as mean inhibition of lympho-cyte activation over 24 hrs (area under the effect curve, AUE0-24h). All grafts were removed on day 8. Results: There was a clear dose-dependent inhibition of signal 1- and signal 2-stimula-ted proliferation (data not shown) and expression of cell surface receptors (Fig). The median graft histology scores (scale 0 - 3) in the 5, 10 and 20 mg/kg groups were 2.6, 1.7 and 1.0, respectively (p < 0.05, ANOVA on ranks). The correlation of AUE for all antigens with graft histology scores was higher in the Con A stimulated assay (r2=0.70) compared with the PMA+anti-CD28 stimulated assay (r2 = 0.53). Conclusion: We show for the first time a new mechanism of action of MMF: suppression of signal 1- and 2-stimulated expression of important lymphocyte function receptors. We also show high correlations between histologic grade of rejection and PD. These studies show that MMF suppresses many lymphocyte functions in addition to its antiproliferative effects and suggest that PD may be a useful means of monitoring MMF to optimize treatment.Figure
: Bilateral anterior transsternal thoracotomy incision (clamshell technique) is the standard approach used for bilateral sequential lung transplantation (LTX). The morbidity and wound complications of this large incision can be considerable and costly. Muscle sparing anterior thoracotomies without division of the sternum may lead to decreasing the sequelae of wound complications. The objective of this study was to determine the rate of wound complications in the nonsternal incising lung transplant patients.: We used the single-institution-based transplant data bank, phone questionnaire, and ambulatory care unit follow-up data to investigate retrospectively the incidence of wound healing complications following muscle and sternum sparing and mammary artery protecting limited access small submammary anterior thoracotomy incisions (AT) for LTX surgery. In the need for cardiopulmonary bypass, the femoral artery and vein were cannulated.: After exclusion of seven clamshell operations for LTX combined with cardiac surgery, 91 recipients (65% male), aged 19 to 68 years (mean, 54 ± 8 years), underwent 84 AT and 48 lateral thoracotomies (LT) for idiopathic pulmonary fibrosis (IPF) (48%), obstructive disease (40%), cystic fibrosis (CF) (5%), and pulmonary arterial hypertension (PAH) (7%). AT ranged from 5.5 to 26 cm (mean, 20.3 ± 4.8 cm) and LT from 12 to 25 cm (mean, 19.8 ± 2.4 cm) and was not significantly different (P = 0.37). Warm ischemic times ranged from 30 to 92 minutes (mean, 56 ± 11 minutes). Four patients required rethoracotomy for bleeding/hematoma formation. Cardiopulmonary bypass/intraop extracorporeal membrane oxygenation (ECMO) was used in 64%. Superficial wound infection and subsequent drainage/care was needed in four LTX incisions. Reoperation for lung herniation using patch repair technique for thoracic wall stabilization was required in two AT and three LT.: Sternum sparing and mammary artery protecting limited access submammary anterior and lateral thoracotomy incisions for LTX surgery are safe and effective. This approach avoids complications related to sternal transaction and may minimize the development of severe wound complications following LTX surgery.
Implantation of implantable cardioverter defibrillators (ICD) reduces the risk of all-cause mortality in symptomatic heart failure (HF) patients with severe left ventricular (LV) dysfunction. Nevertheless, the prognostic impact of ICD therapy in continuous flow left ventricular assist device (LVAD) recipients remains controversial. 162 consecutive HF patients, who underwent LVAD implantation at our institution between 2010 and 2019, were categorized according to the presence (n = 94, ICD-group) or absence (n = 68, Control-group) of ICDs. Apart from clinical baseline and follow-up parameters, adverse events (AEs) related to ICD therapy and overall survival rates were retrospectively analyzed. Out of 162 consecutive LVAD recipients 79 patients (48.8%) were preoperatively categorized as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile ≤2. The prevalence of severe HF symptoms and preoperative use of short-term circulatory support devices (54.4% vs. 13.8%, p < 0.001) was higher within the Control-group, although baseline severity of LV and RV dysfunction was similar. Apart from an increased prevalence of perioperative right heart failure (RHF) within the Control-group (45.6% vs. 17.0%; p < 0.001), procedural characteristics and perioperative outcome were similar. Overall-survival during a median follow-up of 14 (3.0-36.5) months was similar within both groups (p = 0.46). During the first 2 years after LVAD implantation 53 ICD-related AEs occurred within the ICD-group. Thereof, lead-dysfunction occurred in 19 patients and unplanned ICD-reintervention in 11 patients. Furthermore, in 18 patients appropriate shocks without loss of consciousness occurred, whereas inappropriate shocks occurred in 5 patients. ICD therapy in LVAD recipients was not associated with a survival benefit or reduced morbidity after LVAD implantation. Conservative ICD-programming seems to be justified to avoid ICD-related complications and "awake shocks" after LVAD implantation.
Objective: Extracorporeal life support (ECLS) is an established and recommended treatment modality in patients with acute carcinogenic shock. Safety and feasibility of this technique increased this treatment to out of hospital implantation and transportation. However, in this very sick patient cohort further treatment remains challenging and complicated. We here present our treatment algorithms and describe the need of secondary interventions after arterial-venous ECLS implantation outside our own center.
There is a regenerative potential of bone marrow-derived stem cells (BMCs) in ischemic cardiomyopathy, but little is known of their effects in nonischemic cardiomyopathy. This study evaluates the effects of BMC transplantation on contractility and remote capillary density of doxorubicin-induced failing hearts.Heart failure was induced in rabbits by doxorubicin (3 mg/kg; 6 weeks), followed by BMC transplantation (BMC group, 1.5-2.0 x 10(6) cells, n = 15), sham treatment (Medium group, n = 10), or no therapy (Dox group, n = 6). Healthy rabbits were used as controls (n = 10). Cells were transplanted locally into the left ventricle (LV). Four weeks later, contractility was assessed. Cross-sections of hearts were investigated by H&E, Picrosirius red stain, and immunohistologically (Troponin I, alpha-Actinin, Connexin43). Capillary density (CD31-antigen) was examined in the LV, septum, and right ventricle (RV).Global contractility was significantly higher in the BMC group versus Medium group (ejection fraction: 39.0 +/- 1.4% vs. 30.0 +/- 1.9%, p = 0.002, and fractional shortening: 22 +/- 0.8 vs. 19 +/- 0.6, p < 0.01). Hemodynamic measurements by Millar catheter (Millar Instruments, Houston, TX, USA) were also significantly improved. Capillary density increased in cell-treated hearts (LV: 55 +/- 2.2 vs. 42 +/- 2.0, p < 0.001, RV: 40 +/- 2.1 vs. 35 +/- 1.7, p = 0.065, and septum: 46 +/- 1.5 vs. 39 +/- 1.7, p = 0.005), when compared to the Medium group. The transplanted cells failed to express cardiac markers. The collagen content was reduced in BMC-treated rabbits.Despite local cell transplantation, autologous BMCs improve global contractility and enhance remote capillary density and collagen content in doxorubicin-induced cardiomyopathy. However, BMCs failed to transdifferentiate into new cardiomyocytes.
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