Biomedical subjects

H G Olbrich

Publications and source records attributed to H G Olbrich.

At least 37 records · Page 2Linked to original sources

PubMed1996

Analysis of adhesion molecules in myocardial biopsies of cardiac allografts and coronary artery disease with CABG.

Interactions of leukocytes with vascular endothelium are important components of inflammation tissue reactions and have been implicated in cardiac transplant rejection and demonstrated to be mediated by cell adhesion molecules (CAM's). The expression of ICAM-1, VCAM-1 and E-selectin in human myocardium is variable and little is known about the expression of LFA-1 and Mac-1 during allograft rejection. This study investigated these CAM's in myocardial biopsies of transplanted hearts (HTX) and of coronary artery disease eligible for coronary artery bypass grafting (CABG) as non-inflammatory controls and explicitly examines vascular endothelium, cardiomyocytes and infiltrating cells. Immunohistochemistry was performed using the APAAP-method and directing specific mouse anti-human monoclonal antibodies against ICAM-1 (CD54), VCAM-1 (CD106), E-selectin (CD62E), alpha-LFA-1 (CD11a), alpha-Mac-1 (CD11b), alpha-p150/95 (CD11c) and the beta2-integrin chain (CD18). CD18, LFA-1 (CD11a), Mac-1 (CD11b) and p150/95 (CD11c) were markedly expressed on infiltrating immunocytes in HTX compared to CABG where no expression of beta2-integrins was observed. Cardiac allografts demonstrated a strong expression of ICAM-1 on vascular endothelium and on infiltrating cells. ICAM-1 was not detected on cardiomyocytes. In CABG a weak expression of ICAM-1 was observed on endothelial cells but not on myocytes. VCAM-1 was expressed on vascular endothelium and perivascular infiltrating cells in HTX but not in CABG. VCAM-1 was not found to be expressed on myocytes. There was no evidence for the presence of E-selectin in any of our biopsy specimens. Our study shows that the study of cell adhesion molecules adds to the pathophysiological understanding of inflammation after transplantation in cardiac disease. This offers a potential for the development of diagnostic tools and new therapeutic strategies.

Biopsy↗

PubMed1995

Efficiency of beta-adrenoceptor subtype coupling to cardiac adenylyl cyclase in cardiomyopathic and control hamsters.

Densities of beta-adrenoceptor subtypes and their contributions to stimulation of adenylyl cyclase were studied in heart ventricles from cardiomyopathic (BIO 8262) and control Syrian hamsters (CLAC) at 4 different ages: 30, 100, 200, and 300 days. In BIO ventricles neither total beta-adrenoceptor density nor that of the beta 1-adrenoceptor subtype differed from the controls, whereas the density of beta 2-adrenoceptors was significantly higher in myocardium from 200- and 300-day-old BIO compared to that from age-matched CLAC hamsters. Stimulation of adenylyl cyclase by the non-selective beta-adrenoceptor agonist isoprenaline did not differ between strains, but the beta 1-adrenoceptor mediated component was significantly reduced in cardiomyopathic hamsters of all age groups. In 300-day-old animals beta 1-adrenoceptors accounted for 83% (CLAC) and 68% (BIO) of total beta-adrenoceptor binding sites, whereas only 26% (CLAC) and 6% (BIO) of the isoprenaline effect on cAMP formation were mediated via beta 1-adrenoceptors. Thus, the present study shows a lower coupling efficiency of beta 1-adrenoceptors compared to the beta 2-adrenoceptor subtype in ventricles from healthy Syrian hamsters and a progressive, further reduction in beta 1-adrenergic function in cardiomyopathic animals.

Adenylyl Cyclases↗

PubMed1994

Risk of endomyocardial biopsy in immunosuppressed patients after cardiac transplantation.

OBJECTIVES: Central venous puncture is required for endomyocardial biopsy to identify rejection after cardiac transplantation. We evaluated our use of the Seldinger technique to determine the safety of this invasive method. METHODS: In 42 immunosuppressed patients central venous puncture was performed after cardiac transplantation using the Seldinger technique for right heart biopsy. Together with physical examinations, chest X-ray and cardiac ultrasonography were performed during the inhospital follow-up. Outpatient follow-up continues and all reported adverse effects were evaluated by the attending cardiologist. RESULTS: There were a total of 620 central venous punctures, most via the right internal jugular vein (77.9%). The planned puncture could not be performed in 3.2% of the cases and an alternative site was used. The femoral approach was associated with the longest radiation time. No severe adverse effects were observed and no complications (infection, large haematoma, pneumothorax, severe rhythm disorders) were recorded. CONCLUSION: Even in immunosuppressed patients frequently requiring central venous puncture, right heart endomyocardial biopsy can be safely performed to evaluate rejection.

Adult↗

PubMed1994

Correlation between long-chain acylcarnitine in serum and myocardium after heart transplantation in humans.

The concentrations of free, short-chain, and long-chain acylcarnitine were determined in 19 right ventricular endomyocardial biopsies and in serum from 14 patients after orthotopic heart transplantation and 3 nontransplanted control patients with normal cardiac function. Coronary angiography was normal in all patients. Left ventricular ejection fraction as measured by radionuclide ventriculography was not different between heart-transplanted and control patients (60.3 +/- 6.7% and 61.7 +/- 10.7%, respectively). Myocardial and serum carnitine concentrations in heart-transplanted patients were not different from control patients (myocardium: free carnitine 11.8 +/- 4.8 vs 7.1 +/- 7.1, short-chain acylcarnitine 4.5 +/- 2.1 vs 5.8 +/- 2.0, long-chain acylcarnitine 4.9 +/- 3.8 vs 3.9 +/- 3.2 mumol/g noncollagen protein; serum: free carnitine 32.6 +/- 11.2 vs 32.0 +/- 9.9, short-chain acylcarnitine 7.3 +/- 5.2 vs 5.1 +/- 1.3, long-chain acylcarnitine 4.1 +/- 2.7 vs 4.8 +/- 4.0 mumol/L). There was a highly significant correlation between myocardial and serum long-chain acylcarnitine (r = 0.76, P < 0.001). The data suggest that carnitine metabolism is not altered after heart transplantation.

Adult↗

PubMed1994

Endothelium-dependent and endothelium-independent vasomotion in large coronary arteries and in the microcirculation after cardiac transplantation.

Endothelium-dependent and endothelium-independent vasodilation of the epicardial conduit vessels and the microcirculatory coronary vessels was investigated with cumulative doses of acetylcholine (ACh 50 micrograms and 100 micrograms i.c.), nitroglycerin (0.3 mg i.c.) and dipyridamole (0.56 mg.kg-1 i.v.) in 17 patients (3 female/14 male; age: 47 +/- 3.6 years) with angiographically normal coronary arteries 40 +/- 5.1 months after cardiac transplantation. The effect of ACh on large conduit arteries was evaluated angiographically. Coronary blood flow velocity changes were measured utilizing an 8F Judkins style 20 MHz Doppler catheter positioned in the left main coronary artery. A coronary flow index was calculated from the mean Doppler flow velocity and the computed cross-sectional vascular area. After 50 micrograms of ACh the diameter of proximal, middle and distal segments of the left anterior descending coronary artery decreased significantly by 7.6 +/- 2.06% (P < 0.05), 10.6 +/- 3.5% (P < 0.01) and 12.6 +/- 3.29% (P < 0.01) and after 100 micrograms ACh by 10.5 +/- 2.4% (P < 0.05), 13.0 +/- 3.7% (P < 0.01) and 15.3 +/- 3.9% (P < 0.01). The endothelium-independent vasodilator nitroglycerin (0.3 mg i.c.) induced an increase in vascular diameter of 14.4 +/- 3.1% (P < 0.01), 18.6 +/- 4.1% (P < 0.01) and 20.8 +/- 2.9% (P < 0.01) in proximal, mid and distal segments of the left anterior descending coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1993

Uncoupling of beta 1-adrenoceptors from cardiac adenylyl cyclase in cardiomyopathic and control hamsters.

The beta-adrenoceptor-adenylyl cyclase system was studied in heart ventricles from Wistar rats, cardiomyopathic (BIO 8262) and nonfailing control hamsters (CLAC) using the beta 1-adrenoceptor antagonist CGP 20712A. In radioligand binding studies, the majority of beta-adrenoceptors in ventricles from rats as well as from CLAC hamsters was of the beta 1-subtype (72.2% and 76.6%, respectively). In BIO ventricles a significant (CLAC vs. BIO, P < 0.05) reduction in the beta 1-subtype (62.9%) was found. In Wistar rats the subtype-mediated stimulation of adenylyl cyclase reflected the beta 1:beta 2 ratio as determined by binding studies. In hamster ventricles the effect of isoprenaline was mediated predominantly (CLAC) or exclusively (BIO) via the beta 2-subtype, indicating that cardiac beta 1-adrenoceptors were partly (CLAC) or completely (BIO) uncoupled from the adenylyl cyclase.

1-Methyl-3-isobutylxanthine↗

PubMed1993

[Heart volume determination as an indication of rejection after orthotopic heart transplantation].

Endomyocardial biopsy in cardiac transplantation is still the most exact test (gold standard) to confirm or exclude a suspected rejection. Up to now, all available noninvasive tests suffer from a low sensitivity and specificity. For a further reduction of biopsies early available noninvasive methods are desirable. In the data presented a comparison between histological findings and heart volume measurements is shown in 40 patients (112 histological findings) after orthotopic cardiac transplantation. In 46 cases with no evidence of histological rejection the echocardiographically or radiologically determined heart volume was 869 +/- 142 ml/1.73 m2 body surface area, compared to 1026 +/- 178 ml/1.73 m2 in 29 cases with mild cardiac rejection. In 37 cases with a moderate or severe rejection heart volume as 1094 +/- 181 ml/1.73 m2. The diagnosis of a moderate or severe rejection by biopsy is combined with a heart volume above 950 ml/1.73 m2 with a sensitivity of 78% and a specificity of 73%. Intramyocardial edema as well as an increase in right and left ventricular volumes due to heart failure may be the causes for heart volume increase in rejection. Thus, heart volume measurement which can be performed easily during routine echocardiography gives additional information about whether a rejection has to be assumed or can be excluded. Today, sensitivity and specificity of the test does not allow a reduction of biopsy frequency. Further investigations are necessary to analyze the course of heart volume changes during an episode of rejection.

Biopsy↗

PubMed1992

[Ventricular function in hypertrophic cardiomyopathy. Systolic and diastolic ventricular function].

BASIC CONSIDERATION: Hypertrophic cardiomyopathy is defined as a primary myocardial disease associated with a hypertrophic non-dilated left ventricle with no other heart or systemic disease that might lead to hypertrophy of the left ventricle. The leading symptoms are effort-associated angina and dyspnea, rapid fatigue, dizziness and syncope. MAIN POINTS DISCUSSED: The hemodynamic situation is characterized by a hyperdynamic systole and impaired diastole and left-ventricular filling. In the obstructive form, hypertrophy of the basal septum and an anteriorly moving mitral valve during systole result in an end-systolic reduction in the cross-section of the outflow tract associated with considerable intraventricular pressure gradients. Disturbances in the myocardial calcium metabolism are presently suspected to be causally involved in the diastolic function impairment.

Cardiomyopathy, Hypertrophic↗

PubMed1992

Right ventricular volumes and hemodynamics after successful orthotopic heart transplantation. A comparison to coronary artery disease using thermodilution.

Only few data exist concerning right ventricular function in the chronic stage after cardiac transplantation. Therefore, we investigated hemodynamic and right ventricular volumetric data by a computerized thermodilution Swan-Ganz catheter in 17 patients (median age: 53, range: 18-63 yr) at a median of 24 (4 to 44) months after cardiac transplantation during rest and supine bicycle exercise. Myocardial biopsy showed grade one or less according to the classifications of Billingham. Sixteen patients with coronary artery disease, but without prior myocardial infarction, served for comparison. While angiographic left ventricular ejection fraction was nearly identical in transplant recipients [77 (60-92)%, median (range)] and in patients with coronary artery disease [78 (64-94)%], right ventricular ejection fraction was lower (p < 0.001) in patients after cardiac transplantation [37 (16-58)%] as compared to patients with coronary artery disease [56 (46-62)%]. In transplant recipients right atrial pressure was significantly higher both at rest [10 (2-18) mmHg] and exercise [18 (8-30) mmHg] than in patients with coronary artery disease [5 (1-11) and 8 (3-18) mmHg]. Pulmonary capillary wedge pressure behaved similar in both groups. To further evaluate reasons for right ventricular impairment, a correlation analysis was performed. This showed a negative correlation between right ventricular ejection fraction and the time interval after transplantation (p < 0.0002). However, there was no correlation between right ventricular ejection fraction and acute rejection or a rejection score. In conclusion, right ventricular function may be severely altered in transplant recipients, in contrast to an only slight impairment of left ventricular function.

Adolescent↗

PubMed1992

Effect of magnesium pyridoxal 5-phosphate glutamate on the hamster cardiomyopathy.

30-day-old polymyopathic hamsters (strain BIO 82.62) were orally treated with either magnesium pyridoxal 5-phosphate glutamate 100 mg/kg, equimolar amounts of magnesium alone (MgCl2 55 mg/kg), or water b.i.d. for 30 days, or sacrificed before treatment. 60-day-old healthy hamsters (strain CLAC) served as controls. Magnesium pyridoxal 5-phosphate glutamate lowered the myocardial calcium content (42.8 +/- 13.1 mmol/kg dry weight) as compared to MgCl2 (70.3 +/- 11.9 mmol/kg dry weight) and water (72.7 +/- 13.6 mmol/kg dry weight). The serum and tissue lipid pattern did not differ between BIO 82.62 and normal hamsters except high serum cholesterol and triglyceride levels in 30-day-old BIO 82.62 hamsters. Myocardial necroses were influenced by neither magnesium pyridoxal 5-phosphate glutamate nor MgCl2. Cytochemical investigation of the ultrastructural calcium localization in the aorta revealed less calcium precipitates with magenesium pyridoxal 5-phosphate glutamate in media myocytes. It is concluded that magnesium pyridoxal 5-phosphate glutamate exerts a calcium antagonistic effect in the cardiomyopathy of the Syrian hamster which is related neither to the magnesium content of magnesium pyridoxal 5-phosphate glutamate nor to its lipid lowering activity.

Animals↗

PubMed1991

Beat-to-beat variation of heart rate in diabetic patients with autonomic neuropathy and in completely cardiac denervated patients following orthotopic heart transplantation.

Dysfunction of the vagal nerve, an early symptom in the development of autonomic neuropathy, can be assessed reliably by the beat-to-beat variation in heart rate. Patients after a cardiac transplantation are a unique model to investigate the beat-to-beat variation of a completely denervated heart. Heart rate and the beat-to-beat variation during normal and deep respiration were investigated in diabetic subjects with an autonomic neuropathy (n = 10), age and sex matched healthy controls (n = 10) and cardiac transplanted patients (n = 10). Further studies during pharmacological blockade of the parasympathetic nervous system with atropine were performed. In the denervated heart the coefficient of variation of the beat-to-beat interval was 0.38 +/- 0.02% during normal respiration, compared to 1.32 +/- 0.13% (P less than 0.0001) and 2.56 +/- 0.13% (P less than 0.0001) in the diabetic and control subjects, respectively. Administration of atropine (2 mg intravenously) decreased the coefficient of variation of the RR-interval to 0.73 +/- 0.09% in the diabetic patients (P less than 0.0005) and to 0.67 +/- 0.07% in the controls (P less than 0.0001), whereas the coefficient of variation remained unaffected in the cardiac denervated patients (0.39 +/- 0.02%). In the three groups an almost parallel increase of the RR-variation was observed during deep respiration at a rate of 6 breaths/min (from 0.38 +/- 0.02% to 1.99 +/- 0.38% in cardiac transplanted patients, P less than 0.0025; from 1.32 +/- 0.13% to 3.10 +/- 0.43% in diabetic patients, P less than 0.0025; from 2.56 +/- 0.13% to 5.42 +/- 0.94% in healthy controls, P less than 0.005). We conclude that a beat-to-beat variation of heart rate is present in the completely denervated heart. This RR-variation can not be influenced by a pharmacological blockade of the parasympathetic nervous system with atropine. The beat-to-beat variation increases during deep respiration not only in healthy controls but also in diabetic patients with autonomic neuropathy (partially denervated hearts) and cardiac transplanted patients (completely denervated hearts). This indicates an intracardiac mechanism in the modulation of heart rate.

Atropine↗

PubMed1991

Nebivolol increases survival in cardiomyopathic hamsters with congestive heart failure.

The genetically inbred cardiomyopathic Syrian hamster provides a valuable model of congestive cardiomyopathy: myocytolytic necrosis at 30-50 days of age is followed by cardiac hypertrophy at 150-250 days, and finally by congestive failure and death at 250-350 days. Successful drug treatment has been reported in the prenecrotic stage, but not when started during congestive failure. The present study evaluated survival of the cardiomyopathic hamster treated with the new beta-adrenoceptor blocker nebivolol, which was initiated during congestive failure. Fifty animals (BIO82.62, either sex, age 200 days) were acclimated to an environmentally controlled room for 20 days, receiving food and water ad libitum; seven hamsters died, indicating development of congestive failure. The remaining animals were then randomly assigned to one of three groups: 15 animals received control food; food for the others was supplemented with nebivolol, yielding a daily intake of either 0.1 mg/kg (n = 14) or 1 mg/kg (n = 14). At the lower nebivolol dose, death rate was unaltered in comparison with controls. However, at 1 mg/kg, survival was markedly improved (p = 0.042). Nebivolol treatment, started during congestive failure, thus significantly delays mortality in the cardiomyopathic hamster.

Adrenergic beta-Antagonists↗

PubMed1991

The effect of cyclosporine on electrically paced isolated rat cardiomyocytes.

The acute cardiotoxicity of cyclosporine was investigated in isolated cardiomyocytes from adult rats. In a first study, myocytes were incubated with CsA ranging from 1 to 10 micrograms/ml and paced by electrical-field stimulation. After 30 min of stimulation the number of surviving rod-shaped myocytes was significantly reduced at 2.5 micrograms/ml (77.9%) and 5 micrograms/ml CsA (64.2%) as compared with the drug vehicle methanol (88.8%, P less than 0.05) with a further decrease at 10 micrograms/ml CsA (30.1% vs. 81.2%, P less than 0.005). In a second study, with the use of digital image processing of fura-2 fluorescence, the mean intracellular free calcium concentration, integrated over 1 sec, of single myocytes in the presence of 5 micrograms/ml CsA, the solvent methanol, or pure Krebs Ringer Hepes buffer was measured. Starting 2 Hz field stimulation increased the intracellular free calcium concentration from 100.1 to 177.9 nM in buffer and from 145.7 to 200.6 nM calcium with methanol. In contrast, there was a 3-fold increase of the intracellular free calcium concentration with 5 micrograms/ml CsA from 128.8 to 376.1 nM calcium. The intracellular free calcium during electrical stimulation was significantly higher with CsA than with the solvent (376.1 nM vs. 200.6 nM, P less than 0.001). In a further study, myocytes were incubated with calcium ranging from 0.5 to 8 mM calcium in the presence of 5 micrograms/ml CsA or the solvent methanol and electrically stimulated. Here, with increasing extracellular calcium the number of rod-shaped myocytes decreased significantly with CsA as compared with the solvent (P less than 0.02). The data suggest that CsA exerts a dose-dependent toxic effect on isolated rat cardiomyocytes that depends on the extracellular calcium concentration. There is direct evidence that CsA increases the intracellular free calcium concentration in rat cardiomyocytes.

Animals↗

PubMed1991

[Vascular problems in patients with transplants from the interdisciplinary viewpoint].

From 1979 to 12/1990 795 organ transplants have been performed at our hospital (kidney n:737, liver n:23, heart n:35). Our data reveal vascular problems in 10 percent of the transplanted patients - not concerning the vascular anastomosis. The therapeutic approach should be determined interdisciplinary. Due to the low complication rate of operative or interventionel procedures in this patients, even relative indications--to improve "quality of live"--can be accepted.

Adult↗

PubMed1991

[Course of dilatative hypertrophic cardiomyopathy].

Five patients with hypertrophic cardiomyopathy developed left-ventricular dilatation and congestive heart failure during an observation period of 16-29 years. In one patient cardiac transplantation had to be performed. The initial predominant symptoms of outflow-tract obstruction and diastolic dysfunction developed into progressive left-ventricular systolic failure. The question of whether this is a well-defined subgroup of patients with hypertrophic cardiomyopathy, or whether hypertrophic cardiomyopathy turns into a phase of left-ventricular dilatation and failure after some years remains to be elucidated by long-term studies.

Adult↗

PubMed1991

[Experiences with the application of monoclonal Indium-111 antimyosin scintigraphy in the diagnosis of rejection episodes following orthotopic heart transplantation].

Indium-111-labeled Fab fragment imaging using a murine antimyosin monoclonal antibody (Myoscint, Centocor, Leiden) was evaluated for efficacy in detecting cardiac allograft rejection. Diagnosis of rejection was made by endomyocardial biopsy with four to five samples taken for each procedure. Eighty-one studies were performed in 25 patients (21 men, four women, mean age 50 +/- 9 years) from 2 weeks to 45 months after cardiac transplantation. 0.5 mg of the monoclonal antibody labeled with 60 MBq Indium-111 (Antimyosin-Fab-DTPA) was administered i.v. Planar scintigraphic images were obtained in LAO 45 and anterior projections as well as "half-body-scintigrams" 48 h after injection. Using the regions-of-interest-(ROI)technique the relative uptake over the lung and the heart was determined and an index of In-111 uptake was calculated. A heart-to-lung ratio of 1.5 or higher was considered indicative for moderate to severe rejection. Specificity was 86% (nine false-positive In-111 studies in 68 negative biopsy studies), sensitivity was 85% (two false-negative In-111 studies in 13 pathological biopsy studies). It is concluded that the In-111 method has a high sensitivity and specificity in detecting heart transplant rejection and may be useful in the monitoring of patients in the chronic phase after heart transplantation. The 48-h delay in establishing the diagnosis limits the applicability in acute severe rejection.

Adult↗

PubMed1991

[Multiparametric analysis using radionuclide ventriculography in the assessment of left ventricular function following heart transplantation].

Left ventricular systolic and diastolic performance was evaluated by radionuclide angiography in 17 patients following cardiac transplantation and compared with normal persons. Both groups performed supine bicycle exercise during the investigation, the control group at 102 +/- 73 W and the transplanted patients at 61.2 +/- 15 W. The ejection fraction increased in the normal persons from 61 +/- 8 to 69 +/- 10% whereas in the transplanted patients it did not increase significantly. There were no relevant changes in systolic parameters during exercise in the transplant recipients. The changes in diastolic parameters were significantly smaller in transplant patients than in normals. After correction for heart rate-induced changes a significantly different time course of the systolic-diastolic sequence during the cardiac cycle became evident in the transplanted group at rest. During exercise the systolic-diastolic sequence during the cardiac cycle became similar in both groups. It is concluded that the reduced exercise capacity of patients in the late phase after cardiac transplantation is partially due to the absence of an EF increase and a limitation of diastolic reserve during exercise.

Adult↗

PubMed1990

In vivo evidence that human atrial natriuretic factor-(99-126) (hANF) stimulates parasympathetic activity in man.

In a double-blind study 8 healthy male subjects received 100 micrograms human atrial natriuretic facotr-(99-126) (hANF) and NaCl0.9% in random order on different days. Following hANF injection a significant increase in cardiac beat-to-beat variation was observed (4.65% vs 5.95%). This shows that in vivo human atrial natriuretic factor stimulates cardiac parasympathetic activity in man.

Adult↗