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Biomedical subjects

Roland Hetzer

Publications and source records attributed to Roland Hetzer.

At least 73 records · Page 4Linked to original sources
PubMed2005

Transfusion-free cardiopulmonary bypass in Jehovah's Witness patients weighing less than 5 kg.

Performing cardiac surgery on pediatric Jehovah's Witness patients is a great challenge for the surgical team and especially for the perfusionist. Jehovah's Witnesses reject blood transfusions on the grounds of their literal interpretation of passages of the Bible. In accordance with this belief, Jehovah's Witnesses feel that it is also forbidden to retransfuse autologous blood that has been separated from their own circulatory system. We report the use of cardiopulmonary bypass (CPB) during open-heart surgery in three infants with a body weight of 4.5 kg, 3.5 kg, and 3.1 kg, respectively, without transfusion of blood components. A small-volume CPB circuit with a priming volume of 200 mL, including the arterial line filter, was designed to decrease the degree of hemodilution. A dedicated pediatric heart lung machine console with remote pump heads and intensive blood conservation efforts allowed the operation without the use of donor blood. The CPB circuits were primed with crystalloid solution only. The procedures were performed in normothermia or in moderate hypothermia. Pre-CPB hemoglobin levels were 10.8 g/dL, 10.6 g/dL, and 8.5 g/dL. The hemoglobin concentrations measured during CPB ranged from 5.9 to 6.5 g/dL, 6.4 to 6.8 g/dL, and 5.5 to 5.9 g/dL, respectively. The patients did not receive any blood or blood products during their entire hospital stay.

Anticoagulants↗
PubMed2004

Regulation of matrix metalloproteinases and their inhibitors in the left ventricular myocardium of patients with aortic stenosis.

Aortic stenosis (AS) results in myocyte and extracellular matrix remodeling in the human left ventricle (LV). The myocardial renin-angiotensin system is activated and collagens I and III and fibronectin accumulate. We determined the yet unknown regulation of enzymes that control collagen turnover, i.e., LV matrix metalloproteinases (MMP) and their tissue inhibitors (TIMPs) in human AS. We compared LV samples from AS patients undergoing elective aortic valve replacement (n=19) with nonused donor hearts with normal LV function (controls, n=12). MMP-2, MMP-9, MT1-MMP, and extracellular matrix metalloproteinase inducer (EMMPRIN), TIMP-1, TIMP-2, TIMP-3, and TIMP-4 mRNA were quantitated by real-time RCR. MMP-1, MMP-2, MMP-3, TIMP-3, TIMP-4, and EMMPRIN protein were measured by immunoblotting and MMP-9 and TIMP-1 protein by ELISA. Gelatinolytic MMP-2 and MMP-9 activity was measured by zymography. MMP-2 was increased in AS at mRNA, protein, and activity levels (131%, 193%, and 138% of controls). MMP-3 protein (308%) and EMMPRIN mRNA and protein were also upregulated (171% and 200%). In contrast, MMP-1 (37%) and MMP-9 mRNA, protein, and activity (26%, 21%, and 52%) were downregulated. MMP-9 activity was inversely correlated with LV size. TIMP-1 mRNA and protein were decreased (55% and 73%). In contrast, TIMP-2 mRNA (358%), TIMP-3 mRNA and protein (145% and 249%) were increased. TIMP-4 mRNA was not altered, but TIMP-4 protein was upregulated to 350%. Changes were similar in AS patients with normal and impaired LV ejection fraction. The dysregulation of myocardial MMPs and TIMPs in human AS starts at an early disease stage when LV function is still normal. In spite of upregulation of some MMPs the balance between MMP and TIMP is shifted towards MMP inhibition in human AS and may contribute to collagen accumulation.

Aged↗
PubMed2004

Upregulation of myocardial estrogen receptors in human aortic stenosis.

BACKGROUND: Estrogen receptor (ER)-mediated effects have been associated with the modulation of myocardial hypertrophy in animal models and in humans, but ER expression in the human heart and its relation to hypertrophy-mediated gene expression have not yet been analyzed. We therefore investigated sex- and disease-dependent alterations of myocardial ER expression in human aortic stenosis together with the expression of hypertrophy-related genes. METHODS AND RESULTS: ER-alpha and -beta, calcineurin A-beta, and brain natriuretic peptide (BNP) mRNA were quantified by real-time polymerase chain reaction in left ventricular biopsies from patients with aortic valve stenosis (n=14) and control hearts with normal systolic function (n=17). ER protein was quantified by immunoblotting and visualized by immunofluorescence confocal microscopy. ER-alpha mRNA and protein were increased 2.6-fold (P=0.003) and 1.7-fold (P=0.026), respectively, in patients with aortic valve stenosis. Left ventricular ER-beta mRNA was increased 2.6-fold in patients with aortic valve stenosis (P<0.0001). ER-alpha and -beta were found in the cytoplasm and nuclei of human hearts. A strong inverse correlation exists between ER-beta and calcineurin A-beta mRNA in patients with aortic valve stenosis (r=-0.83, P=0.002) but not between ER-alpha or -beta and BNP mRNA. CONCLUSIONS: ER-alpha and -beta in the human heart are upregulated by myocardial pressure load.

Adrenergic beta-Antagonists↗
PubMed2004

RNA-binding proteins heterogeneous nuclear ribonucleoprotein A1, E1, and K are involved in post-transcriptional control of collagen I and III synthesis.

Collagen types I and III, coded by COL1A1/COL1A2 and COL3A1 genes, are the major fibrillar collagens produced by fibroblasts, including cardiac fibroblasts of the adult heart. Characteristic for different cardiomyopathies is a remodeling process associated with an upregulation of collagen synthesis, which leads to fibrosis. We report identification of three mRNA-binding proteins, heterogeneous nuclear ribonucleoprote (hnRNP) A1, E1, and K, as positive effectors of collagen synthesis acting at the post-transcriptional level by interaction with the 3'-untranslated regions (3'-UTRs) of COL1A1, 1A2, and 3A1 mRNAs. In vitro, binding experiments (electromobility shift assay and UV cross-linking) reveal significant differences in binding to CU- and AU-rich binding motifs. Reporter gene cell transfection experiments and RNA stability assays show that hnRNPs A1, E1, and K stimulate collagen expression by stabilizing mRNAs. Collagen synthesis is activated via the angiotensin II type 1 (AT1) receptor. We demonstrate that transforming growth factor-beta1, a major product of stimulated AT1 receptor, does not activate solely collagen synthesis but synergistically the synthesis of hnRNP A1, E1, and K as well. Thus, post-transcriptional control of collagen synthesis at the mRNA level may substantially be caused by alteration of the expression of RNA-binding proteins. The pathophysiological impact of this finding was demonstrated by screening the expression of hnRNP E1 and K in cardiovascular diseases. In the heart muscle of patients experiencing aortic stenosis, ischemic cardiomyopathy, or dilatative cardiomyopathy, a significant increase in the expression of hnRNP E1, A1, and K was found between 1.5- and 4.5-fold relative to controls.

3' Untranslated Regions↗
PubMed2004

Consumption of blood products during mechanical circulatory support in children: comparison between ECMO and a pulsatile ventricular assist device.

OBJECTIVE: Different mechanical circulatory support (MCS) systems are used in children with intractable heart failure. However, the need for anticoagulation leads to hemorrhage with subsequent use of blood products. We compared the coagulation disorders and the need for blood products in children treated either with extracorporeal membrane oxygenation (ECMO) or with the Berlin Heart pulsatile pneumatic ventricular assist device. PATIENTS: We retrospectively reviewed the first 8-day course of 64 children who were on MCS for more than 2 days between 1990 and 2002. Thirty children (median age 7.4 years, weight 25.5 kg) received Berlin Heart support and 34 children (median age 1.8 years, weight 9.2 kg) ECMO. Anticoagulation was accomplished by continuous infusion of heparin. Red blood cell count, platelet count, aPTT, AT III, fibrinogen, and ACT were measured regularly. Depending on blood loss and the coagulation disorder, red blood cells, fresh frozen plasma, platelets, and AT III were substituted. RESULTS: There were no preoperative differences in hematological parameters between the two groups. In the Berlin Heart group platelet transfusion was 4.3 ml x kg x day vs 24.6 ml x kg x day in the ECMO group. Red blood cell substitution was 17.2 vs 60.3 ml.kg.day. Fresh frozen plasma substitution was 8.5 ml x kg x day vs 46.9 ml x kg x day (P<0.001). Even in the congenital heart defect subgroups, when MCS was implanted without recent cardiotomy, the differences were significant. Nevertheless, the mean daily values for hemoglobin, platelets, and fibrinogen were lower in the ECMO group. There was lower overall mortality in the Berlin Heart group. CONCLUSIONS: Compared to ECMO, use of the Berlin Heart in children results in less blood loss and lower consumption of red blood cells, platelets, and fresh frozen plasma.

Adolescent↗
PubMed2004

Effectiveness of bivalirudin as a replacement for heparin during cardiopulmonary bypass in patients undergoing coronary artery bypass grafting.

We investigated the use of bivalirudin as an anticoagulant therapy during cardiopulmonary bypass in 20 patients who underwent coronary artery bypass grafting. Primary end points consisted of clinical outcome data, whereas secondary end points focused on blood loss, transfusions, pharmacokinetics, and monitoring. Our data provide the first evidence of clinical feasibility of anticoagulation with bivalirudin during cardiopulmonary bypass.

Aged↗
PubMed2004

[Surgical revascularization in patients with diabetes mellitus].

Patients with coronary artery disease (CAD) and diabetes mellitus have an increased risk of mortality when undergoing either interventional or surgical revascularization. However, the rate of necessary reinterventions is significantly lower after surgical revascularization than after percutaneous transluminal coronary angioplasty (PTCA). As yet, no results of long-term follow-up after stent implantation are available. The risk for a patient with diabetes mellitus and CAD of dying of myocardial infarction after a bypass operation is significantly lower than after PTCA. Bypass operation with sternotomy in patients with diabetes mellitus carries, however, an increased risk of postoperative mediastinitis, especially when both internal thoracic arteries are used for "totally arterial" revascularization. For this reason the internal thoracic artery should be used only unilaterally in surgical revascularization in these patients. Preoperative and postoperative stabilization of the blood sugar level is very important. Sclerosis of the vessels in close proximity to the heart (ascending aorta, carotid arteries) must be clarified preoperatively. The operation should be carried out particularly carefully, with the wound area kept as small as possible. Reexploration should definitely be avoided. If these guidelines are followed, surgical revascularization in patients with CAD and diabetes mellitus can achieve very good results.

Coronary Artery Bypass↗
PubMed2004

[Contrast echocardiography for detection of incomplete rupture of the left ventricle after acute myocardial infarction].

Myocardial rupture is a major complication after acute myocardial infarction. With complete rupture of the free left ventricular wall cardiac tamponade occurs with fatal outcome in most cases. With partial rupture, however, hemorrhage is slower, allowing days or weeks for diagnosis. Survival of these patients strongly depends on early recognition of this complication followed by immediate surgical intervention. Echocardiography is the diagnostic tool of choice to detect myocardial rupture with consecutive hemopericardium but diagnosis remains difficult even if suspected. We describe the case of a patient with inferior infarction who presented with cardiogenic shock, echocardiographic signs of pericardial effusion and abnormal motion and myocardial irregularities of the inferior wall. With Doppler echocardiography no flow across the wall was detected. Left heart contrast echocardiography confirmed the diagnosis of suspected myocardial rupture by clear deliniation of the defect. Immediate surgical repair was successfully performed in this patient with favorable long-term outcome. Thus, echocardiography early after acute myocardial infarction is useful in detecting subsequent complications and the use of contrast echocardiography should be considered in suspected myocardial rupture.

Echocardiography↗
PubMed2004

Clinical significance of PlA polymorphism of platelet GP IIb/IIIa receptors during long-term VAD support.

BACKGROUND: Although bleeding and thromboembolism remain major complications after implantation of ventricular assist devices (VADs), no standard anticoagulation protocols are available. Genetic polymorphism of platelet glycoprotein IIb/IIIa may contribute to the development of complications. The present study demonstrates a relationship between the PlA genotype and postoperative complications in patients implanted with pulsatile and axial flow VADs. METHODS: The PlA genotype was determined in 41 consecutive patients treated with a VAD who received anticoagulation with phenprocoumon and aspirin. Pulsatile Novacor (Novacor Corp, Oakland, CA) and Berlin Heart VADs (Berlin Heart, Berlin, Germany) were implanted in 28 patients and the axial flow MicroMed DeBakey VAD (MicroMed Technology, Inc, Houston, TX) in 13. The relationship between the PlA genotype, the anticoagulation regime, and bleeding and thromboembolic events was analyzed. RESULTS: There were no differences between patients with the A1A1 and A1A2 genotype regarding demographic characteristics, weight, or infection episodes. The international normalized ratio (INR), platelet activation tests, and doses of aspirin and dipyridamol before events were similar in both groups. Patients with the A1A1 genotype developed more bleeding complications (39% vs 0%, p = 0.021), while patients with the A1A2 genotype showed a tendency toward more thromboembolic events (13% vs 30%, p = 0.33). With regard to different types of VAD, patients with the axial flow DeBakey VAD and the A1A1 genotype developed significantly more bleeding complications (70% vs 0%, p = 0.033). CONCLUSIONS: In patients with a long-term VAD determination of PlA polymorphism and subsequent adjustment of the anticoagulation regime may lead to a reduction of bleeding and thromboembolic complications.

Anticoagulants↗
PubMed2004

Initial experience with miniature axial flow ventricular assist devices for postcardiotomy heart failure.

BACKGROUND: The recently introduced Impella Recover (Impella CardioSystems AG, Aachen, Germany) microaxial flow left and right ventricular assist devices (LVAD/RVAD) were evaluated as they provide circulatory support in the setting of postcardiotomy heart failure refractory to high-dose inotropic and intra-aortic balloon pump (IABP) support. METHODS: Between May 2002 and November 2002, the Recover LVAD was implanted in six patients (64 +/- 11 years) with acute left heart failure following coronary artery bypass procedures. Preoperative left ventricular (LV) ejection fraction was compromised (28% +/- 12%, 12% to 45%). Three patients presented with unstable circulation or cardiogenic shock following acute myocardial infarction, with a predicted mortality rate of 44% +/- 11% (EuroSCORE). Intraoperatively, severe heart failure was present with a more than 70% mortality rate predicted by the IABP score. The Recover RVAD and LVAD were combined to provide biventricular assist device (BVAD) support in one case of post-transplant graft failure. RESULTS: The Recover LVAD delivered blood flows of up to 5 L/min. A moderate degree of hemolysis and a reduction in platelet count were noted. Four patients were weaned from the LVAD after 169 +/- 34 hours, two of whom remain long-term survivors. Full recovery of graft function allowed weaning of the patient from BVAD support after six days. CONCLUSIONS: The initial experience with the Impella Recover VADs proved the new systems to be advantageous regarding the ease of implantation and device removal, low anticoagulation requirements, and advanced weaning features. In cases of severe heart failure, survival was improved by using LVADs when compared to that predicted by solely continuing IABP and drug support.

Aged↗
PubMed2004

New onset arrhythmias after the extracardiac conduit Fontan operation compared with the intraatrial lateral tunnel procedure: early and midterm results.

BACKGROUND: Arrhythmias are one of the main causes of postoperative morbidity superseding Fontan operations. Comparative data on the incidence of sinus node dysfunction after the extracardiac Fontan operation (ECFO) and the intraatrial lateral tunnel Fontan operation (LTFO) are very limited and controversial. The aim of this study was to evaluate whether ECFO decreases the risk of postoperative arrhythmias compared with LTFO. METHODS: Seventy-four consecutive patients received either an LTFO (n = 29, 5 recordings in 1992 to 9 recordings in 1997) or an ECFO (n = 45, 11 recordings in 1995 to 5 recordings in 2001). The rhythm was documented preoperatively and postoperatively with standard electrocardiogram (ECG) recording and ECG monitoring. During follow-up all patients had 2-8 (median 3) standard ECG recordings per year. Additionally 45 patients (65%) had a Holter ECG at least once a year. RESULTS: Median follow-up post-ECFO was 4.4 years (1.6-7.2) and post-LTFO it was 7.9 years (5.4-11.1). There were 5 early deaths (3 LTFO, 2 ECFO) and 1 late death (LTFO) (total mortality 8%). Sinus rhythm persisted in 37 ECFO patients (86%) as compared with 13 LTFO patients (50%) (p < 0.001). The incidence of new onset supraventricular tachyarrhythmias (SVTs) post-ECFO compared with LTFO was lower: 5 patients (11%) versus 11 patients (38%) early postoperatively (p < 0.001) and none versus 7 patients (27%) during follow-up (p < 0.001), respectively. Early postoperatively 10 LTFO patients (34%) and another 3 patients during follow-up required permanent pacemaker implantation due to bradyarrhythmias, but none of the ECFO patients required this. CONCLUSIONS: Our data suggest that ECFO decreases the incidence of postoperative new onset arrhythmias during early and midterm follow-up compared with LTFO.

Adolescent↗
PubMed2004

Permanent mechanical circulatory support in patients of advanced age.

OBJECTIVE: This study details our initial results of long-term left ventricular assist device (LVAD) support in patients suffering from catecholamine-dependent end-stage heart failure or cardiogenic shock with age above 65 years or age above 60 and contraindications to cardiac transplantation. METHODS: Between September 2000 and July 2002, 27 patients received implantation of left ventricular assist devices (Micromed DeBakey (n=15), Berlin Heart Excor (n=6), Arrow Lion Heart (n=4) and Novacor N100 (n=2)). The mean age of this group was 66.2+/-4.1 (60-77) years. The patients presented with the following features by the time of LVAD implantation: failure of weaning from inotropic support (78%), either profound cardiogenic shock (37%) or instable hemodynamic status (22%), high-dose inotropic (52%) or intraaortic balloon pump support (11%), dialysis (15%), artificial ventilation (15%), and at least one previous cardiac procedure (44%). RESULTS: The cumulative survival rate for the whole group was 63% at 30 days, 30% at 180 days, and 22% at 2 years. The presence of preoperative cardiogenic shock was associated with a higher perioperative mortality rate. Late complications (n=7) included replacement of two thrombosed DeBakey LVADs and five late deaths secondary to thrombembolism/intracranial hemorrhage (DeBakey LVAD, n=3) or septicemia (n=2). As of May 15, 2003, six patients remain on LVAD support for an average of 653 (339-953) days, three patients now for more than 2 years. Ten patients were discharged home to spend 73% of their life span on out-of-hospital long-term LVAD support. CONCLUSION: This study reports the first single-center experience of permanent LVAD support in patients of advanced age. For this initial experience, many patients with critical circulatory status and previous cardiac operations were included and a high postoperative mortality rate was encountered among them. Older age and associated multimorbidity are the key determinants rendering the conditions of LVAD therapy for this patient cohort to be different from the bridge-to-transplant experience. The LVADs employed in this study showed different capabilities with regard to long-term support. Our experience shows that permanent mechanical circulatory support does have the potential to evolve as a treatment option in selected elderly patients with end-stage heart failure.

Aged↗
PubMed2004

First experiences with a novel magnetically suspended axial flow left ventricular assist device.

UNLABELLED: Axial flow pumps have gained increased acceptance since their first clinical use in 1998. The present report summarizes the clinical experience with patients treated for severe cardiogenic shock for the first time with a newly developed axial flow pump with magnetically levitated bearings. MATERIAL AND METHODS: The axial flow pump Incor was implanted in 24 patients between June 2002 and June 2003. All except one patient were men. In 16 patients dilative cardiomyopathy, in seven ischemic and in one restrictive cardiomypathy had been diagnosed. All patients presented with catecholamine-dependent end-stage heart failure, seven of them were on an artificial ventilator and three were dependent on intraaortic balloon pump support. All patients suffered from organ dysfunction resulting from low cardiac output. RESULTS: There were no perioperative deaths. The 30-day mortality rate was 8% (n = 2); 79% ( n = 19) of patients reached a condition to be discharged home. The cumulative time on the device is 6.9 years; the longest individual time up to July 1, 2003 is 12.6 months. There were no structural defects or failures of the system. In one case the controller had to be exchanged because of intermittent malfunction. Cardiac output ranged between 4 and 6 l in all instances and there were no cases of infection of the drive-line or the system. Hemolysis was present initially but was not detectable in the later course. There were three instances of transient ischemic attacks. Two patients developed late cardiac tamponade with re-opening of the chest after 9 and 14 days. In one patient persistent gastrointestinal bleeding required re-hospitalization and transfusion therapy. Two patients were weaned from the device after 6 and 7 months of support, respectively. CONCLUSION: The preliminary clinical experience with Incor is promising. The flow is sufficient for recovery from multiorgan failure and the pump allows long-term hemolysis-free support. The concept of magnetically levitated bearings has proven to be durable and reliable. In the case that the heart may recover through unloading, weaning from the pump is possible.

Adult↗