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Biomedical subjects

H H Scheld

Publications and source records attributed to H H Scheld.

At least 163 records · Page 9Linked to original sources
PubMed1997

Inducible heat shock protein 70 in rat cardiac allograft and its immunohistochemical localization in cardiac myocytes.

BACKGROUND: Heat shock proteins (HSP) are induced by a variety of stress and are presumed to play an important role in protecting cells from the effects of stress. Some evidence exists that HSP is involved in allograft rejection. Recently, an increase of inducible HSP 70 in heterotopic rat heart allografts was shown by quantitative Western blotting. To determine a possible mRNA induction and the localization of inducible HSP 70, we examined 19 heart transplants in rats. METHODS: Fisher F344 rat hearts were heterotopically transplanted into Lewis recipients (n=10), and nine cardiac isografts (Fisher to Fisher) were performed. The 19 native hearts of the recipients served as controls. Animals were killed on posttransplantation days 1, 3, and 5. The hearts were examined immunohistologically for inducible HSP and analyzed by a semiquantitative polymerase chain reaction for inducible mRNA. RESULTS: The level of HSP 70 mRNA in the allograft increased from day 1 to 3 and day 3 to 5 after transplantation and was significantly higher than that of time-matched isografts (0.92+/-0.49 vs. 0.49+/-0.05 and 1.14+/-0.53 vs. 0.53+/-0.15; P<0.05). The native hearts showed no elevated HSP 70 expression compared with isografts. Immunohistochemically, the majority of inducible HSP was located in cardiomyocytes adjacent to infiltrating lymphocytes, which where consistently negative. CONCLUSIONS: These results demonstrate that HSP mRNA expression in cardiac allografts is time-dependent, and its protein is expressed in cardiomyocytes.

Analysis of Variance↗
PubMed1997

Ischemic versus idiopathic cardiomyopathy: differing neurohumoral profiles despite comparable peak oxygen uptake.

OBJECTIVE: We tested the hypothesis that neurohormonal and immunological activation differs in ischemic and idiopathic dilated cardiomyopathy since recent intervention trials indicate that ischemic cardiomyopathy seems to carry a worse prognosis than idiopathic cardiomyopathy of comparable clinical severity. METHODS: In ten patients with ischemic cardiomyopathy undergoing spiroergometric evaluation venous levels of norepinephrine, epinephrine, renin, angiotensin, atrial natriuretic peptide as well as soluble interleukin-2-receptor were determined before, during and 10 min after exercise. Results were compared to sixteen patients with idiopathic cardiomyopathy with similar peak oxygen uptake (13.3+/-3 vs. 13.6+/-3 ml/kg/min; P=ns). RESULTS: In ischemic patients, norepinephrine, angiotensin, and interleukin-2 receptor levels were significantly higher before, during and after exercise. Interleukin-2-receptor levels correlated with angiotensin. CONCLUSIONS: We conclude that in ischemic as compared to idiopathic cardiomyopathy, a more pronounced activation of the sympathetic, renin-angiotensin and T-cell immune system is present at rest, during and after exercise. These data may contribute to explain differences in response to intervention and in prognosis. They warrant further investigation.

Adult↗
PubMed1997

Quantification of the cAMP response element binding protein in ventricular nuclear protein from failing and nonfailing human hearts.

Alterations in the expression of myocardial regulatory proteins (e.g. beta-adrenoceptor, inhibitory G-proteins) in human heart failure are associated with excessive stimulation of the cAMP signalling pathway by endogenous catecholamines. The transcription factor cAMP response element binding protein (CREB) mediates cAMP-dependent transcriptional activation and is expressed in the human heart. Here, CREB protein was immunologically quantified in ventricular nuclear protein preparations from nonfailing donor hearts (n = 8) and from failing hearts transplanted due to dilative (n = 10) or ischemic cardiomyopathy (n = 6). CREB expression was unchanged in ventricular nuclei from failing hearts compared to the nonfailing controls suggesting that expressional alterations in human heart failure cannot be explained by altered expression of CREB.

Cyclic AMP Response Element-Binding Protein↗
PubMed1997

Patients with valvular heart disease presenting with sustained ventricular tachyarrhythmias or syncope: results of programmed ventricular stimulation and long-term follow-up.

BACKGROUND: Programmed ventricular stimulation is commonly used to guide therapy in post-myocardial infarction patients with sustained monomorphic ventricular tachycardia (VT) or ventricular fibrillation (VF). In patients with valvular heart disease presenting with spontaneous VT, VF, or syncope, the usefulness of this technique is still unclear. The aim of the study was to analyze whether programmed ventricular stimulation was helpful in guiding therapy and determining prognosis in 97 patients with valvular heart disease presenting with VT (60%), VF (18%), or syncope (22%). METHODS AND RESULTS: Patients were classified as having either predominant ventricular pressure or volume overload or no significant pressure or volume overload. Overall, sustained VT or VF was inducible in 38 (39%) and 19 (20%) patients, respectively. Forty-six (47%) patients were discharged on antiarrhythmic drugs, 29 (30%) received an implantable cardioverter-defibrillator, and 22 (23%) remained without therapy. With serial drug testing, inducibility was completely or partially suppressed in 18 (19%) and 9 (9%) patients, respectively. During a mean follow-up of 51 months (n=97), 17 patients (18%) died (sudden death, n=7; heart failure, n=4; noncardiac causes, n=6). One-, 2- and 3-year event-free survival for sudden death, sustained VT, or VF was 77%, 68%, and 61%, respectively. Only inducibility of VT during baseline study (P<.0003) and left ventricular volume overload (P<.008) were significant predictors of arrhythmic events. Recurrence of arrhythmic events occurred in 56% and 56% of patients with complete or partial suppression of inducibility during serial drug testing as well as in 10 of 19 (53%) patients without a change in inducibility. CONCLUSIONS: Although programmed ventricular stimulation seems to predict adverse outcome, serial drug testing is unreliable in guiding therapy. The type of workload imposed on the ventricles influences outcome, being worse in patients with left ventricular volume overload. Therefore, implantation of a cardioverter-defibrillator should be considered early for the management of these patients.

Adolescent↗
PubMed1997

Left ventricular assist device infection is associated with increased mortality but is not a contraindication to transplantation.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used as a bridge to transplantation. Infection is a frequent and major complication associated with the use of these devices, however, the correlation of infection and outcome has not yet been evaluated in a prospective fashion. METHODS AND RESULTS: Twenty-five patients (24 male, 1 female) with end-stage cardiac failure and resulting organ dysfunction were included. Patients were bridged with the Novacor N100 portable LVAD (median duration of support, 55 days) and were evaluated prospectively by device surface cultures on explantation, molecular typing of isolates, and correlation of infection with survival to transplant. Twelve (48%) of 25 patients had LVAD infection as defined by recovery of multiple isolates of identical genotype from the device surface. Whereas only 5 (42%) of 12 patients with LVAD infection survived until transplantation, 11 (85%) of 13 patients without infection were successfully transplanted (P < .05). Death of the 7 patients with proven LVAD infection was associated with multiple organ failure or other signs of acute infection. CONCLUSIONS: LVAD infection is associated with a significantly decreased survival probability. It does not preclude successful bridging but rather may pose an indication for urgent transplantation.

Adult↗
PubMed1997

[Mechanical myocardial support systems 1997: an overview of inta-aortic balloon counterpulsation to implantable left ventricular support systems].

The development of cardiopulmonary bypass (CPB) to support the systemic circulation during cardiac surgical procedures became a clinical reality in 1953. Although the use of CPB for the treatment of post-infarction cardiogenic shock met with little success, intra-aortic balloon counterpulsation was used successfully in 1968 to reduce ischaemic injury in a patient with cardiogenic shock. Today, a broad spectrum of circulatory assist devices for short- and long-term application is available. Three major indication groups for the use of support devices are established. In low-cardiac-output syndrome after cardiac surgical procedures, short-term devices are utilised to enable myocardial recovery. In transplantation candidates suffering from drug-resistant pump failure, the implantation of long-term devices as a bridge to heart transplantation is indicated, and in NYHA class IV patients with contraindications to heart transplantation, the implantation of long-term devices as an alternative to transplantation is under discussion. In the literature, post-cardiotomy support survival is less than 30% on average. About 70% of mechanically bridged patients have survived to undergo heart transplantation and were transplanted with over 90% survival. Major problems during mechanical support are infection, bleeding, and thromboembolism. In view of patients' natural course without support, these clinical results are favourable.

Defibrillators, Implantable↗
PubMed1997

[Evaluation of secondary prevention of coronary heart disease. Results of the EUROSPIRE study in the Munster region].

BACKGROUND: New recommendations for secondary prevention of coronary heart disease (CHD) were issued by the European Society of Cardiology (ESC), the European Atherosclerosis Society (EAS) and the European Society of Hypertension (ESH) in 1994. The main objective of the EUROASPIRE study (European Action on Secondary Prevention by Intervention to Reduce Events) was to evaluate to what degree the new recommendations have been implemented and whether a significant risk factor reduction in patients who presented with CHD has been achieved. The present study was conducted in the region of Münster, Westphalia, Germany, as part of the nine-country EUROASPIRE study. METHODS: A total of 524 patients (58.6 +/- 8.2 years) were included in the study by abstracting data from their medical records. According to the clinical event which led to admission to the hospital, patients belonged to the following four groups: 1) coronary artery bypass graft (CABG), 2) percutaneous transluminal coronary angioplasty (PTCA), 3) acute myocardial infarction, 4) acute myocardial ischemia. Initially, a pre-specified number of patients had been recruited with the goal of having 100 patients in each of the four groups participate in the follow-up interview and examination. At least 6 months and, on average, 20 months after hospital discharge for the acute event, 74.8% of the patients came to an interview and examination for an evaluation of their risk profile. RESULTS: At the interview, 15.6% of the patients smoked, 22.7% were obese, 54.6% had blood pressure levels above 140/90 mm Hg and 31.3% a total cholesterol/HDL-cholesterol-ratio greater than 5. Risk factor modification over time was insufficient as only one-fifth of patients had values of their risk factors within the target range at the time of the interview. CONCLUSION: The goals of secondary prevention have not been achieved in the region of Münster-there is clearly room for improvement. Considering the treatment of patients with CHD, the recommended strategies of secondary prevention need to be applied more intensively in clinical practice.

Adult↗
PubMed1997

[Proinflammatory cytokines and cardiac pump function].

In situations of depressed myocardial function, the role of immunological mechanisms has been studied recently. In different pathophysiological situations, such as chronic heart failure, open heart surgery with extracorporal circulation, cardiac transplantation, myocardial infarction and angina pectoris, patterns have been described with elevation of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1, interleukin-6, and reversible myocardial dysfunction, which may represent a final common pathway. The available data suggest a modulation of important determinants of pump function, i.e., contractility, preload, afterload, and heart rate, by cytokines. Potential mechanisms include the beta-adrenoceptor- and nitric oxide pathway, as well as a direct impact on intracellular calcium homeostasis. Interventional strategies based on this understanding are beginning to emerge.

Animals↗
PubMed1997

Cardiac pacemaker infection: surgical management with and without extracorporeal circulation.

BACKGROUND: Pacemaker infections are rare, but serious complications of pacemaker therapy. The generator pocket, the pacing leads, or both may be involved. METHODS: We report on 12 patients with infected pacemaker systems. Four patients suffered from localized generator pocket infections, 6 had infected leads, and 2 patients had both. Pacemaker systems were completely removed in all patients. When the infection was limited to the generator pocket, the pacemaker system was removed at the original implantation site. Extracorporeal circulation was employed for the explantation of infected pacing leads. RESULTS: No complications occurred in patients with localized generator pocket infections. One patient with infected leads who was preoperatively already in a serious clinical condition died of septic shock in the early postoperative period; another patient died of pulmonary complications after tricuspid valve replacement 14 months after pacemaker explantation. No recurrent infections were observed. CONCLUSIONS: Explantation of the complete pacemaker system has proved a reliable method to eradicate infection. Complications have been rare, except in patients in a critically ill state who undergo cardiopulmonary bypass.

Adult↗
PubMed1997

Comparative analysis of plasminogen activator inhibitor-1 expression in different types of atherosclerotic lesions in coronary arteries from human heart explants.

OBJECTIVES: Clinical manifestations of coronary heart disease result primarily from the progressive development of atherosclerotic plaques and subsequent thrombus formation: processes which may be accelerated by an enhanced expression of plasminogen activator inhibitor (PAI-1) in the vessel wall. In the present study, content and expression of PAI-1 were comparatively analyzed in human coronary arteries in relation to the presence and severity of atherosclerotic lesions. METHODS: Segments of coronary arteries obtained from heart explants (n = 15) were classified by the presence and types of atherosclerotic lesions. Antigen and activity levels of PAI-1 were determined in protein extracts of intimal and medial layers. In situ hybridization and immunohistochemical analyses were performed on serial sections of representative tissue specimens. RESULTS: Total PAI-1 antigen consistently increased from macroscopically normal areas (MNAs) to early lesions (ELs) and to maximal levels in fibrous (FPs) and calcified (CPs) plaques. No PAI activity was detected, although PAI-1 in its free form was present in all vascular specimens. Both free PAI-1 and PAI-1 complexed with plasminogen activators were significantly increased in extracts of advanced lesions. However, there was a 2-3 fold molar excess of free versus complexed PAI-1 in FPs and CPs. These findings suggest the presence of relevant amounts of PAI-1 in its substrate rather than in its inhibitor conformation in areas of advanced lesions. Compared with MNAs, PAI-1 mRNA was strongly expressed within the thickened intima of ELs. The highest PAI-1 expression was observed in FPs and CPs, being mainly localized in areas surrounding the necrotic cores in co-localization with infiltrating macrophages. CONCLUSIONS: PAI-1 content is consistently increased in relation to the severity of the lesions in atherosclerotic coronary arteries. The concomitant elevation of PAI-1 mRNA suggests that the PAI-1 increase in regulated by local synthesis in the areas of atherosclerotic lesions.

Antigens↗
PubMed1997

Novacor LVAD bridge to transplantation in peripartum cardiomyopathy.

We report the case of a 22-year-old woman suffering from peripartum cardiomyopathy who was successfully bridged to cardiac transplantation with a Novacor left ventricular assist device (LVAD). Her course with the device is presented and emphasis is put on the size mismatch between the patient and the device, a fact with normally precludes the implantation of the Novacor LVAD.

Adult↗