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T Doenst

Publications and source records attributed to T Doenst.

At least 19 recordsLinked to original sources
PubMed2006

Differential gene expression in response to ventricular unloading in rat and human myocardium.

UNLABELLED: Left ventricular unloading by mechanical assist devices induces myocardial atrophy. We aimed to systematically identify differentially expressed genes in a model of physiological atrophy (unloading of healthy rat myocardium) and compare these changes to those in a unloaded, failing human heart. METHODS: Atrophy in rat hearts was induced by heterotopic transplantation of a donor heart into the abdomen of an isogenic recipient. After one week, donor and recipient RNA was isolated. Differential gene expression was assessed by subtractive hybridization. Two screens with radioactive probes were performed to verify differentially expressed clones. Positive clones were sequenced and cDNA of genes of known homology were used as probes for hybridization with RNA from separate atrophied rat hearts and human tissue from a normal, failing or failing and unloaded left ventricle. RESULTS: We picked 1880 clones from the subtractive hybridization procedure (940/940: forward/reverse runs assessing up- or down-regulation, respectively). The first screen verified 465/140 and the second screen verified 67/30 clones. 24/23 clones were sequenced and 14/10 homologies to known genes were found. In the atrophied heart, respiratory chain and metabolic genes were down-regulated (NADH-DH, cytochrome c oxidase, acetyl-CoA synthetase, myoglobin) and cellular recognition and stress genes were up-regulated (MHC1 and 2, HSP70). In the human heart, cytochrome c oxidase, acetyl-CoA synthetase, and myoglobin expression was increased in the failing heart and returned to normal with unloading. Unloading also resulted in up-regulation of HSP70. CONCLUSIONS: The genetic responses of failing human and healthy rat myocardium to mechanical unloading show similarities that appear to be independent of species differences and/or underlying disease. Thus, heterotopic heart transplantation is a relevant model for investigating the mechanisms of mechanical unloading.

Animals↗
PubMed2004

Long-term results of bioprosthetic mitral valve replacement: the pericardial perspective.

Pericardial valve bioprostheses were introduced in early 1970s and were widely used in the 1980s. The longterm results with the Ionescu-Shiley valve, the first commercially available pericardial valve, were disappointing because of high rate cusp tears during the first decade after implantation. The enthusiasm for this type of bioprosthetic valve was further hampered by the premature failure of the Hancock pericardial valve. The long-term results of aortic valve replacement with the Carpentier-Edwards pericardial valve, which was introduced in 1981, indicated that that valve was durable and the issue of cusp tears had been resolved by an appropriate design. This knowledge prompted surgeons to revisit the merits of pericardial valves for mitral valve replacement and several other pericardial valves are now commercially available. The largest data on long-term results are with the Carpentier-Edwards pericardial mitral valve. The reported freedom from structure valve failure ranged from 69% to 85% at 10 years in patient population with mean age of 60 to 70 years. Young age is a major determinant of valve failure, which is largely due to calcification. There are also long-term data, albeit more limited on the Sorin Pericarbon and Mitroflow valves used for mitral valve replacement. This paper review the published experience with various pericardial bioprosthetic valves used for mitral valve replacement during the past 3 decades.

Adult↗
PubMed2003

The Jarvik 2000 is associated with less infections than the HeartMate left ventricular assist device.

OBJECTIVES: Device-related infections remain a considerable problem of left-ventricular support. We compared the device-related-infections between the HeartMate left ventricular assist device (LVAD) and the Jarvik 2000 permanent LVAD, a device with a novel retroauricular power-supply. METHODS: Between December 2000 and September 2002 we implanted the HeartMate-vented, electrical-system in 11 patients and the permanent Jarvik 2000 in six patients. Total support time was 1626 patient-days (HeartMate, 26-271 days) versus 1246 patient-days (Jarvik 2000, 8-411 days). As potential risk factors for infection we analyzed age, preoperative hospital-days, total protein, cardiac index, maximal oxygen uptake, use of inotropes, LVAD risk-score-index and Aaronson-Mancini-score, intubation time, and intensive care unit stay. We used the Center of Disease Control definitions for surgical site infections. RESULTS: HeartMate-patients were younger than Jarvik 2000 patients (46+/-13 versus 58+/-6 years, P=0.056), there were no other differences in the risk factors. Four HeartMate-patients needed late (>or=48 h) surgical revisions for bleeding/hematomas versus no revisions in the Jarvik 2000 patients. In the HeartMate-patients, there were seven (64%) driveline-infections, five (45%) device-pocket infections, and three (27%) bloodstream-infections, or 0.43 device-related infections/100 patient-days. Infections occurred early (34+/-31 days). Three patients required urgent transplantation due to bloodstream infection. There were no adverse outcomes in the HeartMate-group due to infection. In the Jarvik 2000 patients, there was one driveline-infection (16%) after 270 days of support (0.08 device-related infections/100 patient-days), significantly less than in the HeartMate-group (P=0.044). Driveline infections resolved with antibiotics and local wound care in the Jarvik 2000 patient, but only in one of seven HeartMate-patients. CONCLUSIONS: Implantation of the Jarvik 2000 is associated with less device-related infections than the HeartMate-LVAD. The power-supply of the permanent Jarvik 2000 is suitable for long-term mechanical support.

Anti-Bacterial Agents↗
PubMed2003

Experimental model for heart failure in rats--induction and diagnosis.

BACKGROUND: Clinical heart failure is generally preceded by hypertrophy. Many animal models (e. g. toxic heart failure models) do not consider this hypertrophy. We set out to develop a heart failure model in rats by inducing pressure-overload hypertrophy. METHODS: We induced coarctation of the aortic arch with a tantalum clip (0.35 mm internal diameter) In 3-week-old rats (n=17). Starting at seven weeks postoperatively, we measured ejection fraction (EF), fractional shortening (FS), end-systolic (LVESD) and end-diastolic (LVEDD) left ventricular dimensions by echocardiography each week. Heart, lung, and liver specimens were analyzed histopathologically at least eleven weeks after the operation. RESULTS: Contractile function was significantly decreased in hearts from animals with aortic banding (EF: 45+/-5% vs. 73+/-5%, p<0.01; FS: 20+/-3% vs. 35+/-5%, p<0.01). At the same time, left ventricles were dilated (LVEDD: 9.1+/-0.6 mm vs. 7.4+/-0.5 mm; LVESD: 7.3+/-0.6 mm vs. 4.8+/-0.4 mm, p<0.01). These observations were associated with clinical and histopathological changes characteristic for chronic left heart failure. CONCLUSION: Placing a tantalum clip around the aortic arch in 3-week-old rats consistently induces left ventricular decrease in contractile function and dilatation after eleven weeks.

Animals↗
PubMed2001

[Endoventricular patch plasty in patients with idiopathic dilated cardiomyopathy: an alternative to heart transplantation?].

BACKGROUND: Although the concept of reducing wall tension as a treatment for advanced heart failure is convincing, clinical data from the Batista operation are conflicting. Despite a number of publications, it is not clear whether left ventricular reduction surgery is truly of benefit for patients with idiopathic, dilated cardiomyopathy (DCM). Surgery may reduce wall tension but the reason for dilation and contractile dysfunction remains. Thus, the potential benefit of the operation may be overshadowed by the natural course of the underlying disease. CASES: We report a series of five cases where left ventricular reduction was performed and physiological geometry was restored in patients with DCM by a modification of Dor's endoventricular patch plasty. All patients demonstrated an improvement in cardiac function immediately after the operation. This improvement was sustained in one of the patients at 18 months follow-up. Another patient developed severe heart failure due to therapy resistant ventricular arrhythmia (Lown IVb), and underwent successful transplantation 4 months after ventricular reduction surgery. Left ventricular dilation reoccurred in two patients 9 and 12 months after reduction surgery, and they were listed for transplant. One patient died after 9 weeks due to sepsis and respiratory dysfunction. CONCLUSIONS: Although the endoventricular patch plasty as used in this study is well tolerated by most patients with dilated cardiomyopathy and results in immediate improvement of contractile function, the long-term benefits of this technique for DCM are uncertain. Thus, the technique is currently not an alternative for heart transplantation. However, the procedure may be an option in patients with contraindications for transplantation.

Adolescent↗
PubMed2001

Bronchial artery perfusion during cardiopulmonary bypass does not prevent ischemia of the lung in piglets: assessment of bronchial artery blood flow with fluorescent microspheres.

OBJECTIVE: Blood supply of the lungs during total cardiopulmonary bypass (CPB) is limited to flow through the bronchial arteries. This study was undertaken to assess the bronchial artery blood flow during CPB with fluorescent microspheres in a piglet model. METHODS: We subjected ten piglets (mean weight 5.0+/-0.5 kg) to 120 min of normothermic, total CPB without aortic cross-clamping, followed by 60 min of post-bypass perfusion. Fluorescent microspheres were injected into the left atrium or the aortic cannula or distal to the cannula to assess bronchial artery blood flow before, during and after CPB. The reference samples were taken from the descending aorta. We compared the different sites of injection. Tissue samples of the lungs were taken before and 60 min after CPB. RESULTS: Before CPB, total bronchial artery perfusion was 43.6+/-14.1 ml/min (4.8+/-1.3% of cardiac output) as by injection distal to the aortic cannula. These values were not different when microspheres were injected into the left atrium or the aortic cannula. There was no difference in scatter or in the amount of microspheres in the reference samples among the three injections sites. During CPB, bronchial artery perfusion was significantly decreased (4.4+/-2.4 ml/min vs. 40.0+/-5.0 ml/min before CPB) and returned to baseline values 60 min after CPB. Light microscopy of the tissue samples revealed alveolar septal thickening and a decrease in alveolar surface area after 60 min of reperfusion which was associated with a decreased capacity to oxygenate blood. CONCLUSIONS: (1) Bronchial artery blood flow can quantitatively be assessed during CPB when microspheres are injected into the ascending aorta and the reference samples are taken from the descending aorta. (2) Despite adequate perfusion pressure bronchial artery blood flow is decreased substantially during CPB. (3) The decrease in blood flow and the ultrastructural changes present at the end of CPB suggest the presence of low-flow ischemia of the lung during total CPB.

Analysis of Variance↗
PubMed2001

A technique of heterotopic, infrarenal heart transplantation with double anastomosis in mice.

Mouse heart transplantation is frequently used to investigate mechanisms of rejection and immune response. A fully vascularized technique is presented in which the graft ascending aorta is anastomosed end-to-side to the recipient's aorta and the pulmonary aorta is anastomosed end-to-side to the inferior vena cava using 11-0 Ethilon suture. We suggest that this double anastomosis technique is a valuable tool to investigate immune mechanisms in mice.

Anastomosis, Surgical↗
PubMed2001

Load-induced changes in vivo alter substrate fluxes and insulin responsiveness of rat heart in vitro.

It has been observed that opposite changes in cardiac workload result in similar changes in cardiac gene expression. In the current study, the hypothesis that altered gene expression in vivo results in altered substrate fluxes in vitro was tested. Hearts were perfused for 60 minutes with Krebs-Henseleit buffer containing glucose (5 mmol/L) and oleate (0.4 mmol/L). At 30 minutes, either insulin (1 mU/mL) or epinephrine (1 micromol/L) was added. Hearts weighed 35% less after unloading and 25% more after aortic banding. Contractile function in vitro was decreased in transplanted and unchanged in banded hearts. Epinephrine, but not insulin, increased cardiac power. Basal glucose oxidation was initially decreased and then increased by aortic banding. The stimulatory effects of insulin or epinephrine on glucose oxidation were reduced or abolished by unloading, and transiently reduced by banding. Oleate oxidation correlated with cardiac power both before and after stimulation with epinephrine, whereas glucose oxidation correlated only after stimulation. Malonyl-coenzyme A levels did not correlate with rates of fatty acid oxidation. Pyruvate dehydrogenase was not affected by banding or unloading. It was concluded that atrophy and hypertrophy both decrease insulin responsiveness and shift myocardial substrate preference to glucose, consistent with a shift to a fetal pattern of energy consumption; and that the isoform-specific changes that develop in vivo do not change the regulation of key metabolic enzymes when assayed in vitro.

Animals↗
PubMed2001

The beating open heart for rebuilding ventricular geometry during surgical anterior restoration.

Heart failure is an increasing problem because of successful therapies in younger age groups and an overall increase in age in the general population. Ischemic cardiomyopathy secondary to myocardial infarction is the most prevalent entity among the several causes for cardiac failure. Among the surgical options for these patients, neither transplantation nor current ventricular assist devices are able to treat a sufficient number of patients. Ventricular restoration, however, may evolve as a surgical option to treat myocardial failure secondary to postinfarction ventricular dilatation. This procedure must be undertaken in high-risk coronary artery bypass graft (CABG) patients in heart failure. We describe the techniques for both the conventional procedure (CABG +/- mitral valve [MV] repair) using cardioplegic methods, and the beating open heart for surgical anterior ventricular restoration (SAVR) for dyskinetic and akinetic areas in ischemic cardiomyopathies. This combined approach allows safe restoration of the ventricular geometry with minimal use of mechanical support (ie, intra-aortic balloon pump [IABP]) in 195 consecutive patients undergoing this procedure by members of an international team called the RESTORE group.

Cardiac Surgical Procedures↗
PubMed2001

Left ventricular reduction for idiopathic dilated cardiomyopathy as alternative to transplant--truth or dare?

BACKGROUND: Although the concept of reducing wall tension a treatment for advanced heart failure is convincing, clinical data from the Batista operation are conflicting. Despite a number of publications, it is not clear whether left ventricular reduction surgery truly benefits patients with idiopathic, dilated cardiomyopathy (DCM). Surgery may reduce wall tension, but the reason for dilation and contractile dysfunction remains. Thus, the potential benefit of the operation may be overshadowed by the natural course of the underlying disease. CASES: We report a series of five cases where left ventricular reduction was performed and physiological geometry was restored in patients with DCM by a modification of Dor's endoventricular patch plasty. All patients demonstrated an improvement in cardiac function immediately after the operation. This improvement was sustained in one of the patients after 18 months of follow-up. Another patient developed severe heart failure due to therapy-resistant ventricular arrhythmia (Lown IV b), and underwent successful transplantation 4 months after ventricular reduction surgery. Left ventricular dilation reoccurred in two patients 9 and 12 months after reduction surgery, and they were listed for transplant. One patient died after 9 weeks due to sepsis and respiratory dysfunction. CONCLUSIONS: Although the endoventricular patch plasty, as used in this study, is well tolerated by most patients with dilated cardiomyopathy, and results in immediate improvement of contractile function, the long-term benefits of this technique for DCM are uncertain. Thus, the technique is currently not an alternative for heart transplantation. However, the procedure may be an option in patients with contraindications for transplantation.

Adolescent↗
PubMed2001

[Explantation of aortic stent-grafts].

BACKGROUND: Endoluminal stent graft placement for the treatment of infrarenal aortic aneurysms (AAA) has gained widespread acceptance because it is associated with lower perinterventional morbidity than conventional transabdominal surgery. In this study the long-term morbidity of the procedure was evaluated. METHODS AND RESULTS: Between 9/94 and 12/98, 150 patients (age = 69.6 +/- 8.5 y; m = 142, f = 8) with AAA were treated by placing an intravascular nitinol stent graft (Stentor, n = 55; Vanguard-System, n = 95; 8 tubular grafts, 142 bifurcated grafts). Initial placement of the stent graft was successful in 144 patients. In 12 % of stent graft placements we encountered one of the following complications (n, days after stent placement): migration or dislocation of the prosthesis (4, 914 +/- 220 d), rupture of the aorta (2, 452 d/802 d), recurrent thrombosis of the stent graft (3, 478 +/- 359 d), endoleak (3, 955 +/- 472 d), infection of the prosthesis (5, 798 +/- 495 d). There was no correlation between the complications and the type of stent used. All of these patients were treated by surgical replacement of the prosthesis with a dacron graft. CONCLUSIONS: 1. The results suggest that most complications are due to a continuation of the disease process leading to loosening of the prosthesis. 2. Explantation of the prosthesis and surgical repair is feasible but bears additional risks. 3. Since the onset of reperfusion of the excluded aneurysm can not be predicted, all patients with infrarenal aortic stent grafts require frequent computer tomographic follow up. 4. Lastly, the results call for further improvements in the design of the stent graft.

Aged↗
PubMed2001

Serious complications that require surgical interventions after endoluminal stent-graft placement for the treatment of infrarenal aortic aneurysms.

BACKGROUND: Endoluminal stent-graft placement for the treatment of infrarenal abdominal aortic aneurysms has gained widespread acceptance because it is associated with lower peri-interventional morbidity than conventional transabdominal surgery. In this study the long-term morbidity of the procedure was evaluated. METHODS AND RESULTS: Between September 1994 and December 1998, 150 patients (age, 69.6 +/- 8.49 years; 142 men, 8 women) with abdominal aortic aneurysms were treated with the placement of an intravascular nitinol stent-graft (Stentor [55] and Vanguard-System [95]); there were eight tubular grafts and 142 bifurcated grafts. Initial placement of the stent-graft was successful in 144 patients. Mean follow-up was 49 +/- 25 months. In 13.3% of stent-graft placements we encountered the following complications: 4 cases of migration or dislocation of the prosthesis (30.5 +/- 7.4 months after placement); 2 ruptures of the aorta (26.7 and 15.0 months after placement); 3 recurrent thromboses of the stent-graft (25.5 +/- 5.3 months after placement); 3 endoleaks (27.5 +/- 15.7 months after placement); and 5 infections of the prosthesis (26.6 +/- 16.5 months after placement). There was no correlation between the complications and the type of stent used. All of these patients were treated by surgical replacement of the prosthesis with a Dacron graft. CONCLUSIONS: (1) The results suggest that most complications are due to a continuation of the disease process leading to loosening of the prosthesis. (2) Explantation of the prosthesis and surgical repair is feasible but bears additional risks. (3) Because the onset of reperfusion of the excluded aneurysm cannot be predicted, all patients with infrarenal aortic stent-grafts require frequent computer tomographic follow-up. (4) Finally, the results call for further improvements in the design of the stent-graft.

Aged↗
PubMed2000

Insulin-stimulated glucose transport is dependent on Golgi function in isolated working rat heart.

UNLABELLED: Insulin and epinephrine stimulate glucose uptake through distinct mechanisms. We tested the hypothesis that the golgi apparatus is involved in insulin-stimulated but not epinephrine-stimulated glucose transport and phosphorylation. METHODS: We perfused isolated working rat hearts with Krebs-Henseleit buffer containing [2-(3)H]glucose (5 mmol/l, 0.05 microCi/ml) and Na-oleate (0.4 mmol/l). In the absence or presence of the inhibitor of golgi function, brefeldin A (30 micromol/l), either insulin (1 mU/ml), epinephrine (1 micromol/l), or phenylephrine (100 micromol/l) plus propranolol (10 micromol/l, selective alpha -adrenergic stimulation) were added to the perfusate. RESULTS: Cardiac power was stable in all groups (between 8.56+/-0.61 and 10.4+/-1.11 mW) and increased (34%) with addition of epinephrine, but not with selective alpha -adrenergic stimulation. Insulin, epinephrine, and selective alpha -receptor stimulation increased glucose transport and phosphorylation (micromol/min/g dry wt, basal: 1.19+/-0.13, insulin: 3.89+/-0.36, epinephrine: 3.46+/-0.27, alpha -stimulation: 4.08+/-0.40). Brefeldin A increased basal glucose transport and phosphorylation and blunted insulin-stimulated but not epinephrine-stimulated glucose transport and phosphorylation. Selective alpha -stimulated glucose transport and phosphorylation was also blunted by brefeldin A. CONCLUSIONS: Both insulin and alpha -adrenergic stimulation result in glucose transporter translocation from a pool that requires golgi function. Stimulation with epinephrine results in glucose transporter translocation from a pool that does not require golgi function. The stimulating effects of the alpha -adrenergic pathway on glucose transport and phosphorylation are independent of changes in cardiac performance.

Adrenergic alpha-Agonists↗
PubMed2000

Controlled limb reperfusion with a simplified perfusion system.

UNLABELLED: The goal of revascularisation of an acutely ischemic limb is to prevent the loss of the extremity and to enable return of normal function. Although reperfusion of an ischemic limb is a prerequisite for the preservation or reestablishment of function, it may, in itself, cause further injury. Controlled reperfusion after revascularisation may reduce this injury and may facilitate return of normal function. Thus far, the technique of controlled limb reperfusion required the use of cardiosurgical equipment and has therefore been reserved for cardiac surgery centers. However, the majority of patients with acute limb ischemia are referred to hospitals, where the technical equipment for controlled reperfusion is not available. We modified the technique of controlled limb reperfusion using a simplified perfusion system with a pressure-cuffed bag, which allows controlled reperfusion without the use of a roller pump. The modified reperfusion technique was applied to 9 patients with acute and persistent ischemia of the limbs (mean ischemic period: 21 +/- 21 hours). Controlled reperfusion consisted of a 30 min infusion of a normothermic reperfusate solution, which was mixed with the patient's blood (6:1, blood/reperfusate ratio) distally to the proximal obstruction. RESULTS: Five patients (56%) recovered with normal function of the limb. Two patients (22%) lost the ischemic limb (ischemic periods: 77 h and 9h; creatine kinase before operation: 6230 U/I and 1045 U/I): another two patients (22%) died, who were in profound cardiogenic shock. CONCLUSION: The simplified perfusion system allows to put controlled limb reperfusion into practice in any operating room. The results support the notion that controlled limb reperfusion should be applied in any patient with acute ischemia of an extremity.

Arterial Occlusive Diseases↗
PubMed2000

Palliative treatment of a secondary aortoduodenal fistula by stent-graft placement.

A 64-year-old male was admitted with suspected aortoduodenal fistula 16 years after transabdominal aortic reconstruction for aortoiliac occlusive disease. Computed tomography (CT) and angiography revealed an aortoduodenal fistula and a suture-line aneurysm at the proximal anastomosis. Due to the patient's poor general condition at the time of diagnosis, endoluminal stent-graft implantation was chosen rather than conventional surgery. Successful placement of the stent graft without leakage of contrast medium and with complete exclusion of the fistula was demonstrated by CT. The patient recovered uneventfully and was discharged 10 days after the intervention. Five months later contrast CT indicated a recurrence of the aortoduodenal fistula. Since the patient was now in good general condition the stent graft was removed surgically and an extra-anatomic axillofemoral bypass was implanted. Endoluminal stent-graft Implantation is effective as palliative therapy for aortoduodenal fistulas and is especially valuable in patients with high risk for conventional surgery.

Aortic Diseases↗
PubMed2000

Kinetic differences and similarities among 3 tracers of myocardial glucose uptake.

UNLABELLED: Two glucose tracer analogs, uniformly labeled [14C]2-deoxyglucose ([U-14C]2DG) and FDG, are widely used to assess myocardial glucose uptake. Despite the similar electron configuration of the fluorine and hydrogen atoms, uptake of the 2 tracer analogs may not be the same because of their different electronegativity. METHODS: To test this hypothesis, we determined glucose uptake in isolated rat hearts simultaneously from the accumulation of [U-14C]2DG radioactivity in the tissue, by continuous monitoring of FDG accumulation with a pair of coincidence detectors and by cumulative release of 3HOH from [2-3H]glucose. A first group of hearts was perfused at physiologic workload with Krebs-Henseleit buffer containing 10 mmol/L glucose; a second group, with the buffer containing 5 mmol/L glucose plus 0.4 mmol/L oleate and 1 mU/mL insulin. Third and fourth groups were subjected to ischemia (i.e., a 75% reduction in coronary flow) and reperfused. For the third group, the buffer contained 5 mmol/L glucose; for the fourth, 5 mmol/L glucose plus 0.4 mmol/L oleate. RESULTS: No difference in the total amount of tracer accumulation in any group was seen between the 2 tracer analogs. The ratio [+/-SD] of [U-14C]2DG to FDG ranged from 0.93+/-0.09 to 1.31+/-0.11. However, both tracer analogs paralleled glucose uptake in the absence of insulin but underestimated glucose uptake significantly in the presence of insulin. Changes in 2DG uptake with ischemia and reperfusion could be detected only with FDG. CONCLUSION: Although uptake of [U-14C]2DG equals uptake of FDG quantitatively, acute changes in 2DG uptake (and, thus, in the tracer-tracee relationship) are detectable only with the fluorine-labeled tracer.

Animals↗