Images in cardiovascular medicine. Left main coronary artery compression by the pulmonary trunk in pulmonary hypertension.
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Coronary Angiography↗
Biomedical subjects
Walter Klepetko
Publications and source records attributed to Walter Klepetko.
Bilateral lung transplantation with intra- and postoperatively prolonged ECMO support in patients with pulmonary hypertension.
OBJECTIVE: Lung transplantation for pulmonary hypertension (PH) is usually performed on cardiopulmonary bypass, with the disadvantage of full systemic anticoagulation, uncontrolled allograft reperfusion and aggressive ventilation. These factors can be avoided with intra- and postoperatively prolonged extracorporeal membrane oxygenator (ECMO) support. PATIENTS AND METHODS: Between February 1999 and March 2001, 17 consecutive patients with PH (systolic pulmonary artery pressure >70 mmHg) of different etiologies underwent bilateral lung transplantation (BLTX). There were 11 females and six males in the age range from 7 to 50 years (mean age, 28.4+/-12.9 years). Six patients were preoperatively hospitalized, four in the intensive care unit (ICU), one was on ECMO for 3 weeks pretransplantation, and one was resuscitated and bridged with ECMO for 1 week until transplantation. Femoral venoarterial ECMO support with heparin-coated circuits was set up after induction of anesthesia and discontinued at the end of surgery (n=3) or extended for 12 h median into the postoperative period (n=14). Postoperative ventilation pressure was kept below 25 mmHg. Allograft function at 2 h after discontinuation of ECMO, outcome and adverse events were monitored in all patients. Mean follow up time was 18+/-11.4 months. RESULTS: The perioperative mortality was 5.9% (n=1). Arterial oxygen pressure measured 2 h after weaning from ECMO, and under standard mechanical ventilation with a peak pressure of 25 mmHg and inspired oxygen fraction of 0.4, was 157+/-28 mmHg. The mean pulmonary artery pressures were reduced to 29+/-3,4 from 66+/-15 mmHg before transplantation. Postoperative complications included rethoracotomy due to bleeding (n=4) and temporary left ventricular failure (n=4). Median ICU stay was 12 days. Incidence of rejection within the first 100 days was 0.4 per patient. CONCLUSION: BLTX with intraoperative and postoperatively prolonged ECMO support provides excellent initial organ function due to optimal controlled reperfusion and non-aggressive ventilation. This results in improved outcome even in advanced forms of PH.
Adolescent↗
Successful lung volume reduction surgery brings patients into better condition for later lung transplantation.
OBJECTIVES: Lung volume reduction surgery (LVRS) is accepted as a potential alternative therapy to lung transplantation (LTX) for selected patients. However, the possible impact of LVRS on a subsequent LTX has not been clearly elucidated so far. We therefore analyzed the course of 27 patients who underwent LVRS followed by LTX in our institution. METHODS: Twenty-seven patients (11 male, 16 female, mean age 51.9+/-2.2 years) out of 119 patients who underwent LVRS between 1994 and 1999 underwent LTX 29.7+/-3.2 months (range 2-57 months) after LVRS. Based on the postoperative course of FeV1 after LVRS (best value within the first 6 months postoperatively compared with the preoperative value) patients were divided into two groups: Group A (n=11) without any improvement (FeV1 <20% increase), and Group B (n=16) with FeV1 increase > or = 20% after successful LVRS which declined to preoperative values after 8-42 months. Subsequent LTX was performed 22.9+/-5.6 months after LVRS in Group A and 34.3+/-4.9 months after LVRS in Group B (P<0.05). Patients were analyzed according to the course of their functional improvement and of their body mass index (BMI) after LVRS and to survival after LTX, respectively. Values are given as the mean+/-SEM and significance was calculated by the chi(2)-test whereas continuous values were estimated by Student's t-test. RESULTS: Patients in Group A without improvement in FeV1 after LVRS had no increase in BMI as well and this resulted in a high perioperative mortality of 27.3% after LTX. On the contrary, patients in Group B, who had a clear increase of FeV1 after LVRS, experienced a significant increase of BMI of 23.2+/-4.5% as well (P<0.05). This improvement in BMI remained stable despite a later deterioration of FeV1 prior to LTX. After LTX, these patients had a significantly lower perioperative mortality of 6.3% as compared to Group A (P=0.03). CONCLUSIONS: Successful LVRS delays the need for transplantation, improves nutritional status and brings patients into a better pretransplant condition, which results in decreased perioperative mortality at LTX. Patients after failed LVRS, however, should be considered as poor candidates for later transplantation.
Body Mass Index↗
Co-expression of endothelin-1 and vascular endothelial growth factor mediates increased vascular permeability in lung grafts before reperfusion.
Endothelin-1 (ET-1) protein levels increase in lung transplant recipients, although the source of ET-1 remains uncertain. Evidence is accumulating that ET-1 coregulates the expression of vascular endothelial growth/permeability factor (VEGF-A). By using real-time polymerase chain reaction and Western blotting, we describe upregulated ET-1 mRNA and VEGF-A protein levels as well as increased fluid content in donor lung-tissue biopsies before reperfusion. Hypoxia and ET-1 co-upregulate VEGF-A overexpression, therefore temporary VEGF-A antagonism during graft preservation might be of benefit in lung transplantation.
Adult↗
Detection of novel CD antigens on the surface of human mast cells and basophils.
BACKGROUND: Mast cells (MC) and basophils are effector cells of allergic reactions. Growth and function of these cells are regulated by a network of cytokines, other ligands, and respective cell surface membrane receptors. METHODS: In the present study, we examined the expression of novel CD antigens on human lung MC, skin MC, blood basophils, the MC line HMC-1, and the basophil cell line KU-812. Expression of surface antigens was analyzed by monoclonal antibodies (mAbs) and indirect immunofluorescence staining techniques. RESULTS: Primary MC were found to react with mAbs against KIT (CD117), the signal regulatory protein SIRP-alpha (CD172a), and the ectoenzyme E-NPP3 (CD203c). Human basophils were found to express large amounts of E-NPP3 and lower levels of Siglec-5 (CD170), CXCR4 (CD184) and SIRP-alpha. The HMC-1 cell line was recognized by mAbs against SIRP-alpha, CXCR4, endothelial protein C receptor (CD201) and E-NPP3. KU-812 cells were found to react with mAbs against E-NPP3, CXCR4 and glycophorin C (CD236R), but did not react with mAb against endothelial protein C receptor. Most of the other CD antigens tested disclosed negative results. CONCLUSIONS: In summary, our data provide further evidence that MC and basophils express a unique composition of surface antigens. The use of novel CD antibodies may help to isolate MC and basophils and to study their functional properties.
Antibodies, Monoclonal↗
Unilateral chronic thromboembolic pulmonary disease associated with combined inherited thrombophilia.
Chronic thromboembolic pulmonary hypertension (CTEPH) is considered to be an extreme variant of pulmonary thromboembolism. The underlying mechanisms for the failure of thrombus resolution are still unclear. In looking for inherited thrombophilia, an association with a lupus anticoagulant has been described repeatedly, and single cases of anticoagulant deficiencies (ie, antithrombin [AT], protein C, and protein S) have been reported. We describe a young patient with type I AT deficiency, the heterozygous prothrombin G20210A mutation, and unilateral chronic thromboembolic pulmonary disease presenting after a single thrombotic event. Pulmonary vascular patency was restored successfully by surgical pulmonary thromboendarterectomy. This case is unique because unilateral CTEPH is extremely uncommon, and it illustrates the severe clinical sequelae of the cosegregation of inherited thrombophilic defects.
Adult↗
DNA transfer into human lung cells is improved with Tat-RGD peptide by caveoli-mediated endocytosis.
Cell lines and primary cells exhibit varying degrees of resistance to DNA transfection strategies. In this study, we employed the synthetic peptide Tat-RGD (TR), composed of the HIV-1 derived translocation peptide Tat fused to the integrin binding RGD motif, as a tool for improving DNA transfer into pulmonary cells. Binding experiments between DNA and TR and cytotoxicity measurements of TR treated cells were undertaken to optimize DNA and TR concentrations for transfection. Addition of a complex of TR and DNA (TRD) to A549 cells yielded significant transgene expression. When TRD was combined with Lipofectamine (TRDL), the expression was increased by 5-fold over Lipofectamine (DL) and by approximately 30-fold over TRD-mediated transfections. Also, in primary smooth muscle cells (SMC) and fibroblasts (FB) derived from pulmonary arteries, an increase in TRDL-mediated transfection efficiency was observed by a factor of approximately 2 and approximately 3 over that of DL. Laser scanning confocal microscopy for visualizing TR-dependent DNA uptake demonstrated that the internalization of TRDL complexes is linked to caveoli in the plasma membrane. Interfering with caveoli formation by methyl-b-cyclo-dextrin drastically decreased the transfection efficiency by TR. In conclusion, the Tat-RGD peptide mediates efficient gene delivery in human pulmonary cells, in particular when combined with a standard cationic lipid based transfection reagent. The enhancement of DNA uptake by Tat-RGD is suggested to be mediated by caveoli-dependent endocytosis.
Animals↗