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Biomedical subjects

Roland Hetzer

Publications and source records attributed to Roland Hetzer.

At least 127 records · Page 7Linked to original sources

Effects of therapeutic beta blockade on myocardial function and cardiac remodelling in congenital cardiac disease.

BACKGROUND: Cardiac remodelling is now recognised as an important aspect of cardiovascular disease progression and is, therefore, emerging as a therapeutic target in cardiac failure due to different etiologies. Little is known about the influence of different therapies for cardiac failure on the remodelling seen in infants with congenital cardiac disease. METHODS: During follow-up of a prospective and randomized trial, we investigated therapeutic effects on neurohormonal activation, ventricular function, and myocardial gene expression. We compared the data from 8 infants with severe congestive heart failure due to left-to-right shunts, who received digoxin and diuretics alone, to 9 infants who received additional treatment with propranolol. RESULTS: In these infants, beta-adrenergic blockade significantly reduced highly elevated levels of renin, from 284 +/- 319 microU/ml compared to 1061 +/- 769 microU/ml. Systolic ventricular function was normal in both groups, but diastolic ventricular function was improved in those receiving propranolol, indicated by significantly lower left atrial pressures, lower end-diastolic pressures, and less pronounced ventricular hypertrophy, the latter estimated by lower ratios of myocardial wall to ventricular cavity areas on average of 42%. Further hemodynamic parameters showed no significant differences between the groups, except for the lower heart rate in infants treated with propranolol. In those treated with digoxin and diuretics, there was a significant downregulation of beta2-receptor and angiotensin-2 receptor genes, and up-regulation of endothelin A receptor and connective tissue growth factor genes, that were partially prevented by additional treatment with propranolol. CONCLUSIONS: Beta-blockade is a new therapeutic approach for congestive heart failure in infants with congenital cardiac disease, producing with significant benefits on neurohormonal activation, diastolic ventricular function, and cardiac remodelling.

Adrenergic beta-Antagonists↗

Beneficial hemodynamic and renal effects of intravenous enalaprilat following coronary artery bypass surgery complicated by left ventricular dysfunction.

OBJECTIVE: Angiotensin-converting enzyme inhibitors are an effective therapy for all stages of heart failure due to reduced systolic left ventricular function. Because sufficient data on intravenous angiotensin-converting enzyme inhibitors following coronary artery bypass surgery complicated by postoperative left ventricular dysfunction are unavailable, the efficacy and safety of intravenously administered enalaprilat were evaluated. DESIGN: A placebo-controlled, randomized, double-blind protocol. SETTING: Postoperative intensive care unit at the German Heart Institute Berlin. PATIENTS: Forty patients with a left ventricular ejection fraction <35% following coronary artery bypass surgery on the second postoperative day or after weaning from intra-aortic balloon counterpulsation. INTERVENTIONS: A loading dose of enalaprilat 0.625 mg infused over 1 hr was followed by 5 mg/24 hrs administered continuously for up to 72 hrs. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary hemodynamic variables, blood gases, hormonal variables, renal function, and electrolytes were measured before and repeatedly during therapy. Acute effects were as follows: At 1 hr, enalaprilat increased the cardiac index (p <.001), stroke volume index (p <.001), and right ventricular stroke work index (p <.03) compared with placebo, whereas mean arterial pressure (p <.008) and both systemic (p <.001) and pulmonary (p <.02) vascular resistance decreased. Continuous effects were as follows: Over 72 hrs, enalaprilat decreased diastolic pulmonary artery pressure (p <.019), pulmonary artery occlusion pressure (p <.02), and central venous pressure (p <.02). The cardiac and stroke volume indexes were consistently higher in the enalaprilat group, whereas systemic and pulmonary vascular resistances were lower. The arterial blood-pressure lowering effect was blunted and heart rate remained unchanged. Mixed venous oxygenation (p <.02) was higher and arterial oxygenation was not modified. Finally, enalaprilat increased creatinine clearance (p <.002) and decreased creatinine (p <.02) and urea (p <.03). CONCLUSIONS: Intravenous enalaprilat safely and effectively improves cardiac and renal function following coronary artery bypass surgery complicated by postoperative left ventricular dysfunction.

Adult↗

Coronary artery calcium scoring: diagnostic accuracy of different software implementations.

PURPOSE: To compare the diagnostic power of different software implementations for the quantification of coronary artery calcium. MATERIALS AND METHODS: Electron beam computed tomography was performed in 109 heart transplant recipients at the same time as catheter coronary angiography and intracoronary ultrasound. Electron beam computed tomography images were analyzed by 3 software packages marketed for the quantification of coronary calcifications using the same software settings, and the resultant calcium scores correlated with the invasive reference methods by Bland-Altman plots and analysis of the receiver operating characteristics. RESULTS: Although all scoring systems displayed close correlations upon regression analysis (r2=0.94-0.99), their ability to detect disease as per the invasive reference method varied significantly in some instances. The area under the ROC curve varied between Az=0.78 and 0.85 for the detection of coronary artery stenosis upon coronary angiography (P=0.05-0.13), and between Az=0.75 and 0.83 for the detection of accelerated intimal proliferation (P=0.03-0.18). CONCLUSIONS: Different software implementations for the quantification of coronary artery calcium load may display diagnostically relevant differences in spite of close direct correlation.

Adolescent↗

Prebypass filtration of cardiopulmonary bypass circuits: an outdated technique?

Filtration of cardiopulmonary bypass (CPB) priming fluid before connection of the circuit to the patient was first accomplished by arterial line filtration. When dedicated prebypass filters (PBFs) with smaller pore sizes became available, a large number of particles could be found on the filter surface. In recent years, modern manufacturing methods for CPB circuit components were believed to be associated with a reduced number of particles found in components of extracorporeal circuits, making separate filtration of CPB priming solution unnecessary. Microemboli generated during the preparation and priming procedure of the CPB circuit may consist of either solid particles or gaseous emboli and may contribute to patient morbidity. Endotoxins found in infusion solutions and CPB priming solutions may trigger inflammatory responses when administered into the circulatory system. Filtration of crystalloid CPB priming solutions with a PBF consisting of a filter membrane with a pore size of 0.2 microm was found to effectively reduce the number of microemboli. Infusion filters with a filter pore size of 0.2 microm were found to reduce the endotoxin contamination in infusion solutions. Prebypass filtration with filters containing pores of 0.2 pm should be a necessity for contemporary perfusion practice.

Cardioplegic Solutions↗

Safe minimization of cardiopulmonary bypass circuit volume for complex cardiac surgery in a 3.7 kg neonate.

Over recent years, increasing awareness has been aroused to the hazards of the utilization of donor blood products. Particularly in neonate cardiac surgery employing cardiopulmonary bypass (CPB), the relative high priming volume of the CPB system and its adjunctive components, such as hemofilters, causes severe hemodilution and, therefore, particularly during extended perfusions, customarily requires priming of the system with autologous blood components. We report on our efforts to minimize the CPB system and adjust the perfusion strategy to the goal of transfusion-free CPB in a 3.7 kg neonate scheduled for repair of transposition of the great arteries.

Blood Transfusion↗

Clinical value of prostacyclin and its analogs in the management of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is associated with changes in vascular tone as well as vascular structure, with the relative contribution of each dependent upon the etiology of the increased vascular resistance. Prostacyclin treatment has markedly improved both the therapeutic options and the prognosis of PAH. The beneficial effect of prostacyclin in PAH is linked to the powerful vasodilating capacity and, even more importantly, to the inhibition of platelet aggregation, smooth muscle proliferation and antiinflammatory actions. Since prostacyclin has a very short plasma half-life, continuous intravenous administration via a portable infusion pump must be carried out. Because of the complexity of the delivery and the associated complications, intravenous prostacyclin (epoprostenol) therapy is restricted to patients with late NYHA Class III and Class IV and thus alternative modes of delivery in less advanced PAH are desirable. Recent clinical studies with more stable prostacyclin analogs such as subcutaneously delivered treprostinil, orally active beraprost and aerosolized iloprost have demonstrated beneficial effects of each of these prostanoids, especially in NYHA Class II and III patients and, therefore, these agents should be considered first for prostanoid therapy in the early stages of PAH. Prostaglandins may be more effective in conjunction with endothelin receptor antagonists or phosphodiesterase inhibitors and an increasing number of studies are now addressing the combined efficiency and safety of these combinations. This update will focus on the current development status of PAH therapy with prostacyclin and its analogs. Special attention will be accorded to the selection of patients for prostanoid therapy, therapy monitoring and improvement of therapeutic efficacy by addition of other new therapeutic agents to prostaglandins. Survival benefits and special aspects of bridging-to-transplant therapy are also important aspects of the review.

Antihypertensive Agents↗

[Pre- and post-interventional follow-up of stent graphs with single and multi-slice spiral computerized tomography].

PURPOSE: Could contrast enhanced computed tomography replace conventional catheter angiography in the preoperative evaluation of aortic aneurysms before stentgraft implantation? Does multi slice computed tomography have advantages comparing to single slice computed tomography? METHODS: We compared 15 single slice with 13 multi slice computed tomography studies and reconstructions according to there ability to replace conventional catheter angiography in the preoperative evaluation. In the postoperative follow-up 60 single slice computed tomography studies were compared to 60 multi slice studies. RESULTS: By using appropriate reconstructions the spiral computed tomography studies could deliver all information necessary for implantation. In our study no advantage of multi slice computed tomography could be detected. In the postoperative evaluation of stentgrafts our computed tomography scan protocol could detect all relevant complications in single and multi slice computed tomography. No significant advantage of multi slice computed tomography could be detected. CONCLUSION: Contrast enhanced computed tomography is equal to conventional catheter angiography in the pre- and postoperative evaluation of stengrafts. No significant advantage of multi slice versus single slice could be detected.

Aortic Aneurysm, Abdominal↗

Pulsatile mechanical cardiac assistance in pediatric patients with the Berlin heart ventricular assist device.

Mechanical cardiac assistance for neonates, infants, children and adolescents may be accomplished with pulsatile ventricular assist devices (VAD) instead of extracorporeal membrane oxygenation or centrifugal pumps. The Berlin Heart VAD consists of extracorporeal, pneumatically driven blood pumps for pulsatile univentricular or biventricular assistance for patients of all age groups. The blood pumps are heparin-coated. The stationary driving unit (IKUS) has the required enhanced compressor performance for pediatric pump sizes. The Berlin Heart VAD was used in a total number of 424 patients from 1987 to November 2001 at our institution. In 45 pediatric patients aged 2 days-17 years the Berlin Heart VAD was applied for long-term support (1-111 days, mean 20 days). There were three patient groups: Group I: "Bridge to transplantation" with various forms of cardiomyopathy (N = 21) or chronic stages of congenital heart disease (N = 9); Group II: "Rescue" in intractable heart failure after corrective surgery for congenital disease (N = 7) or in early graft failure after heart transplantation (N = 1); and Group III: "Acute myocarditis" (N = 7) as either bridge to transplantation or bridge to recovery. Seventeen patients were transplanted after support periods of between 4 and 111 days with 12 long-term survivors, having now survived for up to 10 years. Five patients (Groups I and III) were weaned from the system with four long-term survivors. In Group II only one patient survived after successful transplantation. Prolonged circulatory support with the Berlin Heart VAD is an effective method for bridging until cardiac recovery or transplantation in the pediatric age group. Extubation, mobilization, and enteral nutrition are possible. For long-term use, the Berlin Heart VAD offers advantages over centrifugal pumps and ECMO in respect to patient mobility and safety.

Adolescent↗

Reduction of microemboli count in the priming fluid of cardiopulmonary bypass circuits.

Microemboli may impair cognitive function in patients undergoing heart surgery. Prebypass filtration has been shown to reduce particle load in the cardiopulmonary bypass (CPB) priming fluid. This study was performed to detect the embolic load of CPB priming fluid, to determine the efficacy of a 0.2 microm prebypass filter (PBF) in reducing emboli in the range of 0.1-5 microm and to provide guidelines for the handling of the device. A total of 12 CPB circuits were tested in two groups, using a laser light scattering particle counter, sensitive to microemboli in the range of 0.1-5 microm. In control group A, priming fluid before administration to the CPB circuit was analyzed. Group B circuits contained microporous membrane oxygenators (N = 5); group C consisted of CPB circuits with excluded membrane oxygenators (N = 7). When group A was compared to groups B and C, significantly more microemboli were found in the categories 0.2 microm, 0.5 microm, 0.8 microm for both groups B and C (p < .05). Group C circuits had higher microemboli counts in the categories 1.5 microm and 3 microm (p < .05) when compared to group B. Microemboli bigger than 0.2 microm could be eliminated after 2 min of prebypass filtration with a CPB flow of 5 L/min. The number of microemboli smaller than 0.2 microm was reduced substantially. Small microemboli with a size of 0.1 microm originate mainly from the priming solution. Microemboli in the range of 0.2 microm, 0.5 microm, and 0.8 microm originate mainly from the CBP circuit. In circuits with bypassed membrane oxygenators, a higher microemboli count in the range of 1.5 microm and 3 microm may be explained by a possible filtering capacity of membrane oxygenators. The 0.2 microm PBF is an effective tool to reduce the particle load in the CPB priming fluid.

Cardiac Surgical Procedures↗

Release patterns of astrocytic and neuronal biochemical markers in serum during and after experimental settings of cardiac surgery.

OBJECTIVE: Brain injury and altered psychomotor development in infants, children and adults after cardiac surgery using cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) is still a matter of concern. Early diagnosis and identification of brain injury that has occurred or is ongoing by measurement of biochemical markers in serum may have diagnostic and prognostic value. The aim of the experimental studies in an animal model was therefore to investigate the release patterns of astroglial and neuronal markers in serum and to determine the morphological and immunohistochemical changes in the brain of animals undergoing similar perfusion conditions of CPB and a period of DHCA. METHODS: Fourteen New Zealand rabbits, (weight, 3.1 +/- 0.25 kg) were anesthetized, intubated and mechanically ventilated. Four animals were sham operated and served as controls. After median sternotomy the animals were connected to CPB by cannulation of the aorta and right atrium. Full flow CPB (200-250 ml/kg/min) was initiated to achieve homogeneous systemic cooling. Circulatory arrest of 60 minutes was induced when rectal and nasopharyngeal temperature of 14 degrees C was achieved. After rewarmed reperfusion and establishment of stable cardiac ejection the animals were weaned from CPB and monitored for 6 hours. Then the animals were killed, the brain was immediately removed and cut in standardized sections. These were fixated, embedded in paraffin and stained for further quantitative histological studies. In the brain astrocyte reactivity for S-100B was assessed immunocytochemically (DPC Immustain Los Angeles, USA). Monoclonal mouse anti-human neurospecific enolase (NSE) antibody was used for the localization of NSE in the fixed and paraffin embedded brain (NSE-DAKO, H14). The concentrations of S-100B protein and neurospecific enolase (NSE) in the serum were analyzed using a commercially available immunoluminometric assay (LIA-mat, Sangtec 100, Byk-Sangtec). Immunospecific monoclonal anti-parvalbumin antibody was used for the detection of parvalbumin in the brain. Serum concentrations of parvalbumin were analyzed using a newly developed ELISA method. RESULTS: In all experimental animals a significant increase of the serum concentration of the astroglial protein S-100B was found immediately after reperfusion and the termination of CPB. In contrast the serum levels of the neuronal proteins parvalbumin and NSE were not increased, but rather decreased. Light microscopy and electron microscopy revealed perivascular astrocytic swelling and minor neuronal cell injury. In comparison to the sham operated animals, increased immunohistochemical staining of S-100B was found. This increased reactivity of S100B antibody was found in the astrocytic processes with immediate connection to the perivascular space and around the perivascular oedema. The immunocytochemical stainings for NSE and parvalbumin in the neuronal cells was not different from that of sham-operated animals and indicated well preserved neurons.

Animals↗

The MicroMed DeBakey VAD--part I: The pump and the blood flow.

The results obtained in over 100 patients implanted with the MicroMed DeBakey VAD in several centers in Europe and USA (September 2001, M. Loebe, personal communication) demonstrate that the effectiveness of the MicroMed DeBakey VAD is comparable to that of the pulsatile devices and that it also shows some superior properties. Recently, other axial pumps--the Jarvic 2000 (72) and HeartMate II (73)--have come into clinical use. Because the patients show good tolerance of the nonpulsatile blood flow in the early postoperative period, and pulsatility increased with recovery of the left ventricle because of unloading, we believe that the axial pumps will gain wide acceptance and provide a new option in the treatment of heart failure.

Heart-Assist Devices↗

Novel mutations in sarcomeric protein genes in dilated cardiomyopathy.

Mutations in sarcomeric protein genes have been reported to cause dilated cardiomyopathy (DCM). In order to detect novel mutations we screened the sarcomeric protein genes beta-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), troponin T (TNNT2), and alpha-tropomyosin (TPM1) in 46 young patients with DCM. Mutation screening was done using single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. The mutations in MYH7 were projected onto the protein data bank-structure (pdb) of myosin of striated muscle. In MYH7 two mutations (Ala223Thr and Ser642Leu) were found in two patients. Ser642Leu is part of the actin-myosin interface. Ala223Thr affects a buried residue near the ATP binding site. In MYBPC3 we found one missense mutation (Asn948Thr) in a male patient. None of the mutations were found in 88 healthy controls and in 136 patients with hypertrophic cardiomyopathy (HCM). Thus mutations in HCM causing genes are not rare in DCM and have potential for functional relevance.

Adult↗

Prognosis after the implantation of an intra-aortic balloon pump in cardiac surgery calculated with a new score.

BACKGROUND: Over the past decade, the use of a ventricular-assist device (VAD) in patients with postcardiotomy cardiogenic shock has resulted in hospital discharge rates of 25% to 40% and is improving. Nevertheless, indications for and timing of the implantation of a VAD in patients who have received an intra-aortic balloon pump (IABP) remain unclear. METHODS AND RESULTS: From July 1996 to March 2000, 391 patients with cardiac low-output syndrome who underwent open-heart surgery and had an IABP implanted were analyzed in a retrospective pilot study. The perioperative mortality was 34% (133 patients). Clinical parameters were analyzed 1 hour after IABP support began. Statistical multivariate analysis showed that patients with an adrenaline requirement higher than 0.5 microg x kg(-1) x min(-1), a left atrial pressure >15 mm Hg, urine output <100 mL/h, and mixed venous saturation (SVO(2)) <60% had poor outcomes. Using this data, we developed an IABP score (0 to 5 points) to predict survival early after IABP implantation in cardiac surgery. We evaluated our score by monitoring another 101 patients as a control group prospectively. Additionally, 210 patients who received coronary artery bypass grafting (CABG) exclusively were analyzed. All investigations confirmed the validity of the score. CONCLUSIONS: The IABP score can predict survival early after IABP implantation. In patients with a high IABP score, implantation of a VAD should be considered.

Aged↗

Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing.

BACKGROUND: Primary pulmonary hypertension (PPH) is a life-threatening disease. Prognostic assessment is an important factor in determining medical treatment and lung transplantation. Whether cardiopulmonary exercise testing data predict survival has not been reported previously. METHODS AND RESULTS: We studied 86 patients with PPH (58 female, age 46+/-2 years, median NYHA class III) between 1996 and 2001 who were followed up in a tertiary referral center. Right heart catheterization was performed and serum uric acid levels were measured in all patients. Seventy patients were able to undergo exercise testing. At the start of the study, the average pulmonary artery pressure was 60+/-2 mm Hg, average pulmonary vascular resistance was 1664+/-81 dyne x s x cm(-5), average serum uric acid level was 7.5+/-0.35 mg/dL, and average peak oxygen uptake during exercise (peak VO(2) was 11.2+/-0.5 mL x kg(-1) x min(-1). During follow-up (mean: 567+/-48 days), 28 patients died and 16 underwent lung transplantation (1-year cumulative event-free survival: 68%; 95% CI 58 to 78). The strongest predictors of impaired survival were low peak VO(2) (P<0.0001) and low systolic blood pressure at peak exercise (peak SBP; P<0.0001). In a multivariable analysis, serum uric acid levels (all P<0.005) and diastolic blood pressure at peak exercise independently predicted survival (P<0.05). Patients with peak VO(2) < or =10.4 mL x kg(-1) x min(-1) and peak SBP < or =120 mm Hg (ie, 2 risk factors) had poor survival rates at 12 months (23%), whereas patients with 1 or none of these risk factors had better survival rates (79% and 97%, respectively). CONCLUSIONS: Peak VO(2) and peak SBP are independent and strong predictors of survival in PPH patients. Hemodynamic parameters, although also accurate predictors, provide no independent prognostic information.

Exercise Test↗