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Biomedical subjects

K Kallenbach

Publications and source records attributed to K Kallenbach.

16 recordsLinked to original sources

Outcome following single vs bilateral lung transplantation in recipients 60 years of age and older.

AIMS: The significant shortage of donor organs in lung transplantation necessitates a careful selection of lung transplant recipients. The outcome of lung transplant recipients aged 60 years and older has not been analyzed systematically. METHODS: We retrospectively reviewed our experience with older recipients. Between January 1999 and July 2003, 248 patients underwent lung transplantation at our institution, of which 18 were aged 60 years and older (7.3%, range 60-66, mean 62 +/- 1.1). RESULTS: Eleven (61%) of the recipients 60 years and older received a single (SLTx) and seven (39%), a bilateral lung transplant. Donor age in the single transplant cohort was 30 +/- 4 years. It was 33 +/- 3 years in bilateral patients. Posttransplant ventilation time was significantly different among groups, with 282 +/- 32 hours after bilateral and 56 +/- 13 hours after transplant (P < .05). Also significantly longer was the length of the ICU stay in the bilateral group. First PaO2 in the ICU was not different among the two groups. The 1-year survival in the single transplant group was significantly better compared to the bilateral group with 73% versus 43%, respectively. CONCLUSIONS: The 1-year survival following lung transplantation in patients older than 60 years is markedly reduced compared to recipients under 60 years of age. If a lung transplant is considered in a recipient above the age of 60 years, a single transplant should be favoured. If that is not indicated, patients over 60 should be very carefully selected for bilateral transplant.

Aged↗

Acute aortic dissection versus aortic root aneurysm: comparison of indications for valve sparing aortic root reconstruction.

OBJECTIVES: To prove whether different indications for valve sparing aortic root reconstruction may have an impact on the outcome and longevity of the repair. METHODS: From July 1993 to March 2003, the reimplantation technique for valve sparing aortic root reconstruction was applied to 232 patients. In 44 patients, indication for operation was acute aortic dissection type A (AADA). These patients were compared with 44 randomised patients operated for aortic root aneurysm (root) by matched pair analysis with respect to age, gender, time point of operation and presence of Marfan's syndrome. Peri- and post-operative courses with focus on survival and valvular stability were analysed. RESULTS: Pre-operative grade of aortic insufficiency was 2.4+/-1 in root vs. 1.5+/-1.7 in AADA (P = 0.004) Mean CPB-time (214+/-60 vs. 171+/-42 min;P < 0.001), aortic cross clamp time (158+/-40 vs. 129+/-39 min; P = 0.001) and stay on ICU (5.2+/-9 vs. 1.7+/-1 days; P = 0.034) were longer for AADA, while hospitalisation was comparable (14+/-10 vs. 14+/-7 days; P = 0.88). Five patients (11.4%) from AADA died peri-operatively compared to no patient from root (P = 0.055). None of the early deaths were valve-related. Re-thoracotomy rate was 6.8% for both groups. Mean follow-up was 19+/-21 months for AADA vs. 28+/-21 months for root (P = 0.038) Survival at 3 years was 88+/-5% for AADA and 100% for root (P = 0.028). Freedom from valvular reoperation was 97+/-2.7% for root and 97+/-3% for AADA at 3 years (P = 0.44). At last investigation, mean grade of aortic insufficiency for AADA was 0.2+/-0.3 compared to 0.3+/-0.3 for root (P = 0.34) CONCLUSIONS: Regardless of the underlying indication, the aortic valve preserving reimplantation technique can be performed with favourable functional results.

Acute Disease↗

Impact of preoperative aortic root diameter on long-term aortic valve function after valve sparing aortic root reimplantation.

BACKGROUND: Valve sparing aortic root reimplantation technique in patients with aortic root aneurysm have shown excellent mid-term results. In conjunction with the diameter of the aortic root the mechanical leaflet stress increase, which might have an impact on long-term aortic valve function after valve sparing aortic root reimplantation. METHODS AND RESULTS: From July 1993 to October 2001, 168 patients with aortic root aneurysm underwent valve sparing aortic root reimplantation. Patients with type A aortic dissection were excluded. Thus, 123 patients were analyzed. We identified 47 patients with an preoperative aortic root diameter exceeding 60 mm (group A), 58 patients with an diameter between 50 and 60 mm (group B), and 18 patients with a diameter less than 50 mm (group C). The groups were compared regarding mortality, long-term survival, freedom from reoperation, freedom from severe and moderate aortic valve insufficiency (AI), and postoperative morbidity. Mean follow-up (group A 43+/-26 months, group B 40+/-25 months, group C 23+/-19 months; group C versus group A, P=0.005; group C versus group B, P=0.011) was shorter in group C. Perioperative mortality (group A 2.2%, group B 1.9%, group C 5.2%; P=ns) was comparable between the groups with each one patient. The 3-year survival for group A was 98+/-2%, for group B 96+/-3%, and for group C 100+/-0% (P=ns). Freedom from reoperation for group A was 98+/-2%, for group B 96+/-3%, and for group C 88+/-8% (P=ns). Four patients developed severe or moderate AI, thus freedom from severe and moderate AI for group A was 100+/-0%, for group B 88+/-8%, and for group C 94+/-5% (P=ns). During follow-up no thromboembolic or bleeding events were noticed. CONCLUSIONS: Our data show that the preoperative diameter of the aortic root has no impact on the longevity of the repair. Thus, the reimplantation technique can be recommended for all patients presenting with an aortic root aneurysm and normal leaflets regardless of the aortic root diameter.

Adult↗

Acellularized porcine heart valve scaffolds for heart valve tissue engineering and the risk of cross-species transmission of porcine endogenous retrovirus.

OBJECTIVE: Acellularized porcine heart valve scaffolds have been successfully used for heart valve tissue engineering, creating living functioning heart valve tissue. However, there is concern about the possibility of porcine endogenous retrovirus transmission. In this study we investigated whether acellularized porcine heart valve scaffold causes cross-species transmission of porcine endogenous retrovirus in a sheep model. METHODS: Acellularized porcine pulmonary valve conduits (n = 3) and in vitro autologous repopulated porcine pulmonary valve conduits (n = 5) were implanted into sheep in the pulmonary valve position. Surgery was carried out with cardiopulmonary bypass support. The animals were killed 6 months after the operation. Blood samples were collected regularly up to 6 months after the operation and tested for porcine endogenous retrovirus by means of polymerase chain reaction and reverse transcriptase-polymerase chain reaction. In addition, explanted tissue-engineered heart valves were tested for porcine endogenous retrovirus after 6 month in vivo. RESULTS: Porcine endogenous retrovirus DNA was detectable in acellularized porcine heart valve tissue. However, 6 months after implantation of in vitro and in vivo repopulated acellularized porcine heart valve scaffolds, no porcine endogenous retrovirus sequences were detectable in heart valve tissue and peripheral blood. CONCLUSION: Acellularized porcine matrix scaffolds used for creation of tissue-engineered heart valves do not transmit porcine endogenous retrovirus.

Animals↗

Acute dissection of the ascending aorta: first results of emergency valve sparing aortic root reconstruction.

OBJECTIVE: Acute dissection of the ascending aorta requires immediate surgical intervention. In this study, we report our first results with valve sparing aortic root reconstruction removing all the diseased tissues. METHODS: From August 1995 to December 2000, 22 patients with acute aortic dissection of the ascending aorta (Stanford type A) underwent valve sparing aortic root reconstruction. Their ages ranged from 20 to 76 years (52+/-15, 68% males). Dissection was found in the ascending aorta (3 patients) or both in the ascending aorta and aortic arch (19 patients; 86%). Course and length of hospitalization, echocardiographic and clinical follow-up, complications and mortality were analysed. RESULTS: Mean cardiopulmonary bypass time was 212+/-56 min (134-352 min), mean aortic cross clamp time was 157+/-24 min (114-205 min). In patients undergoing additional arch replacement (n=19), circulatory arrest was 35+/-18 min (11-75 min). After reconstruction, intraoperative echocardiography showed aortic insufficiency (AI) grade 0 in 16 patients (84%) and grade 1 in three patients (16%). Stay in intensive care unit was 2.1+/-0.7 days, and postoperative hospitalization was 21+/-14.4 days. There were three perioperative deaths (14%). Mean post-operative follow-up was 18.4+/-18 months (0.4-65.4 month). One patient died 10 months postoperatively. At follow-up, no patient suffered AI grade 2 or higher, and no reoperation for aortic valve failure was necessary. All patients presented with a favorable exercise tolerance being in New York Heart Association functional class I or II. CONCLUSION: Valve sparing aortic root reconstruction in patients with type A dissection can be performed with acceptable intraoperative mortality and morbidity and excellent results during follow-up. The complete resection of the diseased aorta is particularly appealing.

Acute Disease↗

[Modified endothelial cells in graft vasculopathy].

Occlusion of venous bypass grafts after coronary revascularization grafting represents the main reason for re-do operations. Arterial pressure as well as mechanical injury of the venous wall lead to endothelial dysfunction, causing intimal hyperplasia with luminal stenosis and eventually occlusion. In the transplanted heart, coronary artery disease limits the long-term success of cardiac transplantation. The disease is characterized by the interaction of activated immunologic cells and donor epicardical and microvascular endothelium. The ex vivo modification of endothelial cells may offer a therapeutic option to overcome both kinds of graft vasculopathy. Seeding of human endothelial cells on artificial and bioartificial acellularized vessel matrices has proven possible. The use of xenogenic matrices initially acellularized and recellularized with autologic endothelial cells and myofibroblasts may help to overcome the lack of vascular and valvular grafts with long durability. In addition, gene therapeutic methods to modify the function of such endothelial cells may offer a new therapeutic strategy, such as over-expression of nitric monoxide or inhibition of matrix metalloprotinases. First results of large animal studies show promising results and may lead to the first clinical trials in the near future.

Animals↗

Valve sparing aortic root reconstruction versus composite replacement -- perioperative course and early complications.

OBJECTIVE: In patients with aneurysm of the ascending aorta, dilatation of the sinotubular junction is the major cause of aortic valve regurgitation. Valve sparing aortic root replacement in patients without valvular structural defects offers a new form of treatment. The aim of this study was the assessment of the perioperative course and early complications of this method compared to composite replacement in a large single center cohort. METHODS: From 1992 to 1999, valve sparing replacement of the ascending aorta (recon) has been performed in 78 patients, while 269 patients underwent replacement by a composite graft (comp). A comparison of matched pairs (n=52) with respect to age, gender, presence of Marfan's syndrome, aortic dissection as well as date of surgery, was chosen. Aortic insufficiency was 2.8+/-0.7 for recon vs. 2.2+/-1.1 for comp preoperatively. Course and length of hospitalization, echocardiographic follow-up, complications, and mortality were compared at 1-year follow-up. RESULTS: There were no operative deaths. During follow-up, one patient (2%) died 5 months postoperatively (recon) vs. two patients (3.9%) in the comp group. Bypass-time (123+/-31 vs. 153+/-31 min, P<0.0001) and cross-clamp-time (82+/-22 vs. 120+/-23 min, P<0.0001) were significantly shorter in comp. Stay in ICU (1.9+/-1.6 for recon vs. 2.3+/-2.1 days for comp) and post-op hospitalization (18.3+/-5.7 vs. 21.2+/-11.1 days) were comparable. Improvement of NYHA-class was significant after both operations (recon 2.6+/-0.8 vs. 1.3+/-0.5 and for comp 2.4+/-0.6 vs. 1.5+/-0.7, both P<0.0001). One patient (1.9%) in the recon group had to be reoperated for valve failure. Thrombembolic or bleeding complications were observed in 6 patients (12%) in comp, zero in recon (P=0.027). CONCLUSION: Valve sparing aortic root reconstruction is feasible with low perioperative morbidity and mortality and good early results. Major advantages of recon are significant reduction of thrombembolic and anticoagulation related complications as opposed to longer cross-clamp and bypass times as well as a valve failure in one patient. Further follow-up is needed to confirm our data in a long-term perspective.

Aorta↗

[Replacement of the ascending aorta with aortic valve reimplantation: indications, technique and results].

The main cause of aortic valve insufficiency is a dilatation of the sinotubular junction in patients with an ascending aortic aneurysm. Morphologically preserved aortic valve cusps represent an ideal condition for preservation and reconstruction of the aortic valve with an simultaneous replacement of the ascending aorta with a Dacron graft. This report presents the results of 140 patients, who underwent such surgery since 1993 in our institution. Indications for surgery, operative technique and different outcome parameters are discussed. Intra- and perioperative morbidity and mortality are low and quality of life excellent. Reoperation due to progressive aortic valve insufficiency was necessary in 2.1% of patients during follow-up. When compared with the standard operation (composite replacement utilizing a mechanical valve), patients with aortic valve reconstruction demonstrate similar results with regard to hospital stay and functional improvement. However, bleeding complications and thromboembolic events are significantly reduced in patients undergoing valve reconstruction. Due to these long-term results combined with excellent stress hemodynamics and improvement in LV function, aortic valve reconstruction currently represents our standard operative strategy in this patient group.

Adolescent↗

Impact of heparin bonding on pediatric cardiopulmonary bypass: a prospective randomized study.

BACKGROUND: Heparin-coated circuits reduce the inflammatory response to cardiopulmonary bypass in adult patients; however, little is known about its effects in the pediatric population. Two studies were performed to assess this technology's impact on inflammation and clinical outcomes. METHODS: In a pilot study, complement and interleukins were measured in 19 patients who had either uncoated cardiopulmonary bypass circuits or heparin-bonded circuits. Subsequently, 23 additional patients were studied in a randomized fashion. Respiratory function and blood product utilization were recorded. RESULTS: In the pilot study, heparin-bonded circuit patients had less complement 3a (p < 0.001) and interleukin-8 (p < 0.05) compared with uncoated cardiopulmonary bypass circuit patients. The randomized study revealed that the heparin-bonded circuit was associated with reduced complement 3a (p = 0.02). Multiple variable analysis revealed that the following postoperative variables were increased with bypass time (p = 0.01) and diminished with heparin-bonded circuits: interleukins (p = 0.01), peak airway pressures (p = 0.05), and prothrombin time (p = 0.03). CONCLUSIONS: Heparin-bonded circuits significantly reduce cytokines and complement during cardiopulmonary bypass and lower interleukin levels postbypass; they were also associated with improved pulmonary and coagulation function. Heparin-bonded circuits ameliorate the systemic inflammatory response in pediatric patients from cardiopulmonary bypass.

Cardiopulmonary Bypass↗

Inhibition of endothelial cell migration by gene transfer of tissue inhibitor of metalloproteinases-1.

BACKGROUND: Angiogenesis requires degradation of the vessel's basal lamina and endothelial cell migration into the tissue stroma. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play important roles in this process. MMP activity is tightly regulated during vessel growth. This work was designed to characterize the effect of TIMP-1 upregulation on endothelial cell invasion of the extracellular matrix. METHODS: We constructed replication-deficient recombinant adenoviruses that encode either TIMP-1 (Ad.TIMP-1) or Escherichia coli lac Z (Ad.beta gal) cDNA. Bovine aortic endothelial (BAE) cells were infected with 100 infectious particles/cell. Gene expression was assessed by Northern and Western blotting. TIMP-1 activity in cell-conditioned media was measured by a resorufin-labeled casein protease assay. BAE cell migration was measured by Boyden chamber assays with 0.2% gelatin-coated, 8. 0-mcm polycarbonate membranes. RESULTS: TIMP-1 was overexpressed by Ad.TIMP-1-infected BAE cells relative to control, Ad. beta gal-infected or uninfected cells. TIMP-1 activity in Ad.TIMP-1 cell-conditioned medium was 2.8-fold higher than in control cells. By Boyden chamber assays with gelatin-coated membranes, Ad. TIMP-1-infected BAE cells showed 89.97 +/-1.64% (mean +/- SEM) reduction in migration relative to Ad.beta gal-infected cells (P < 0. 02) and 90.53 +/- 1.12% relative to uninfected cells (P < 0.02). Without gelatin coating, migration was equivalent in all groups. CONCLUSION: The replication-deficient recombinant adenovirus we constructed affords rapid and efficient upregulation of functional TIMP-1 in endothelial cells. Infection results in a dramatic decrease in cell migration and invasion of extracellular matrix. Thus, such a recombinant vector may provide a useful tool for the gene therapy of vascular remodeling and inhibition of angiogenesis.

Animals↗

Comparison of post-operative pain, stress response, and quality of life in port access vs. standard sternotomy coronary bypass patients.

OBJECTIVE: Although it has been postulated that minimally invasive cardiac surgery using the port access method would reduce operative stress and postoperative pain and accelerate postoperative recovery to a good quality of life, few data are currently available to document this intuitively appealing claim. Therefore, this study was designed to examine differences in stress response, postoperative pain, rapidity of recovery, and quality of life after port access (PA) isolated coronary artery bypass surgery compared with standard sternotomy (STD) isolated coronary bypass surgery. METHODS: Fourteen PA and 15 STD coronary bypass patients were studied postoperatively for pain score, FEV, catecholamine and cortisol levels, resumption of activity, and Duke Activity Scale ratings. The surgical approach was based on the surgeon's preference. Although the PA patients were younger, there were no other differences between the groups in gender or preoperative risk factors. RESULTS: There were no operative deaths and no differences between the groups in perioperative complications. Repeated measures analysis of variance showed lower pain scale ratings over the first 4 postoperative weeks in the PA group (P < 0.001). The PA patients also had less muscle soreness, shortness of breath, fatigue, and poor appetite at 1, 2, 4, and 8 weeks (P < 0.05), better FEV at 1 day (1.59 vs. 0.97 l/s; P < 0.02) and 3 days (2.20 vs. 1.49 l/s; P < 0.03), and lower norepinephrine levels at days 1, 2, and 3 (P = 0.005). The Duke Activity Scale questionnaire results demonstrated that more PA patients were able to walk 1-2 blocks at 1 week, climb stairs at 1 and 2 weeks, perform light or moderate housework at 1 and 2 weeks, and engage in moderate recreational activities and perform heavy housework at 4 and 8 weeks (P < 0.05). CONCLUSIONS: These results show that compared with STD coronary bypass patients PA patients enjoyed significant postoperative physiologic and quality of life advantages with less pain, less early stress response, better pulmonary function, and superior Duke Activity scores during the first 2 postoperative months.

Aged↗

Early results of posterior leaflet folding plasty for mitral valve reconstruction.

BACKGROUND: Standard reconstruction for posterior mitral leaflet (PML) disease is quadrangular resection and annular plication; when the PML is excessively high, a sliding plasty is used. We have developed an alternative technique, a posterior leaflet folding plasty. It is performed by folding down the cut vertical edges of the PML. The central height of the PML is reduced, leaflet coaptation is moved posteriorly, and annular plication is unnecessary. METHODS: From March 1995 to August 1996, 26 (17.9%) of 145 patients undergoing mitral reconstruction had a posterior leaflet folding plasty. Concomitant procedures included anterior leaflet resection or resuspension and myotomy and myectomy. In 3 patients, the PML resection extended to a commissure. RESULTS: There was one death and no reoperations. The mean New York Heart Association class was improved from 2.4 preoperatively to 1.4. There was no major postoperative mitral insufficiency in the 26 patients. Systolic anterior motion was transiently seen in 1 patient in whom left ventricular outflow tract obstruction was present preoperatively. CONCLUSIONS: The data demonstrate the safety and short-term efficacy of posterior leaflet folding plasty. This technique may help avoid systolic anterior motion after reconstruction of the PML.

Adult↗

Modulation of matrix metalloproteinase activity in human saphenous vein grafts using adenovirus-mediated gene transfer.

BACKGROUND: Neointima formation after human saphenous vein grafting (hSVG) involves several matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). This study assessed the feasibility of modulating MMP activity in hSVGs by adenovirus-mediated gene transfer. METHODS: First, 1 x 10(9) plaque-forming units (pfu) of replication-deficient recombinant adenoviruses encoding either beta-galactosidase (ad beta gal), MMP-3 (AdMMP-3), or TIMP-1 (AdTIMP-1) were added into the lumen of hSVGs for 1 hour. After incubation at 37 degrees C for 24 hours, specimens were analyzed by immunohistochemistry, in situ zymography, and X-gal staining. RESULTS: By X-gal staining ad beta gal-infected hSVGs stained positively in the intima and occasionally in the media. Immunohistochemistry of AdMMP-3- and AdTIMP-1-infected hSVGs localized these proteins to the intima. In situ zymography showed increased MMP activity in the intima of AdMMP-3-infected hSVGs relative to AdTIMP-1- or Ad beta gal-infected vessels. CONCLUSIONS: MMP-3 and TIMP activity can be regulated in hSVGs by replication-deficient recombinant adenoviruses. We have previously demonstrated that MMP-3 or TIMP-1 transduction, or both, inhibit SMC migration in an in vitro reconstituted vessel wall. Modulation of MMP activity may thus afford high patency rates in genetically engineered hSVGs. However, adenovirus-mediated gene delivery is limited to the vessel's intima; strategies to infect medial smooth muscle cells need to be developed.

Adenoviridae↗

Structurally modified anthracyclines retain activity in a cell line with simultaneous typical and atypical multidrug resistance.

Resistance to the classical anthracyclines may be due to one or several mechanisms, most notably p-glycoprotein (pGP) associated multidrug resistance (mdr1, "typical mdr") and altered activity of topoisomerase II (topo II) ("atypical mdr"). Modulators of mdr1 will be of limited value in case of combined forms of resistance. A Friend murine erythroleukemia cell line (F4-6R) carrying both mdrl and topo II mediated anthracycline resistance was used to determine the efficacy of structurally altered anthracyclines against such extended multidrug resistance. Proliferation assays showed that 3'N-morpholinyl substituted anthracyclines were able to retain much of their activity even in this setting. MX2 (KRN8602; 3'-deamino-3'-[4-morpholinyl]-13-deoxo-10-hydroxycarminomycin+ ++), which is 9-alkylated in addition to carrying a 3'N-morpholinyl group, was the most promising agent tested.

Animals↗