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Biomedical subjects

B Reichart

Publications and source records attributed to B Reichart.

At least 235 records · Page 13Linked to original sources
PubMed1994

Reduction of cyclosporine-induced nephrotoxicity by cilastatin following clinical heart transplantation.

The objective of this prospective, randomized, placebo-controlled, single-blinded study in 28 heart-transplanted patients was to investigate whether the dehydropeptidase inhibitor cilastatin reduces cyclosporine-induced nephrotoxicity. Cilastatin is available only in combination with imipenem, a beta-lactam antibiotic to which it is added for reduction of nephrotoxic side-effects of the antimicrobial agent. Patients received either 100 ml placebo (n = 12) or 100 ml (500 mg) imipenem/cilastatin (n = 16) twice perioperatively, and 4 times daily for the first 7 postoperative days. Serum creatinine and urea, as well as urine concentrations of N-acetyl-beta-D-glucosaminidase, which is directly correlated with tubular cell damage, were used as markers for renal function. Thromboxane B2 and 6-keto-prostaglandin F1-alpha serum concentrations were determined to investigate whether there is an imbalance in synthesis of thromboxane A2 and prostacyclin as a possible mechanism for cyclosporine-induced nephrotoxicity. Two placebo patients and 6 patients receiving imipenem/cilastatin had to be excluded from further analysis. Three of 10 placebo patients required hemofiltration, and 2 of them even required hemodialysis, as compared with none in the imipenem/cilastatin group. Creatinine concentrations increased significantly from the second to the fourth postoperative day in the placebo group, but remained nearly normal in cilastatin patients (P < 0.05 for intergroup comparison on postoperative days 2-4). The same trend was observed in urea and N-acetyl-beta-D-glucosaminidase concentrations, without the difference reaching statistical significance. For thromboxane B2 and 6-keto-prostaglandin F1-alpha no differences between the groups could be found. These results suggest that imipenem/cilastatin can counteract acute cyclosporine-induced nephrotoxicity, which appears to be associated with alterations of tubular cell function. The combined use of cyclosporine and imipenem/cilastatin appears to be advantageous in patients following heart transplantation during the initial postoperative period.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Intragraft events after heart transplantation: an experimental study comparing cytology in coronary sinus blood, peripheral blood, and daily histology.

Acute rejection is a frequent consequence after heart transplantation. To expand our knowledge of the rejection process and to investigate some intragraft events during acute rejection, the following experimental transplantation model was designed. Right cervical heart transplantation was performed in 12 mongrel dogs. Two experimental groups of six animals each received different immunosuppressive regimens. All animals were treated with daily triple drug therapy. In contrast to group 1, the animals in group 2 received high-dose steroids during rejection. The condition of the hearts was examined by daily transmural biopsies, graded according to the Billingham classification. To detect and quantify alterations in the mononuclear cell subsets of the myocardial venous return, blood samples from the coronary sinus blood (CS) and from peripheral blood (PB) were taken simultaneously with the biopsy. The total number of lymphoblasts and activated lymphocytes was determined and an activation index (AI) was calculated. The data referred to was established from 337 transmural biopsies. The AI of PB (n = 287) correlated well with the different stages of acute rejection (grade B0: AI = 2.2 +/- 2.1; grade B1 + 2: AI = 6.3 +/- 1.7; grade B3: AI = 10.0 +/- 4.7; P < 0.001). The rejection kinetics of both groups, including the rejection-free interval following high-dose steroid administration in group 2, could be expressed accurately by the AI. The time course of the total number of lymphoblasts in CS versus PB demonstrated that the lymphoproliferative response started 4 days prior to the first intramyocardial signs of rejection (mean = 3.8 +/- 0.7; n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Changes in cAMP formation in mononuclear leukocytes of heart and renal transplant recipients.

In mononuclear leukocytes (MNL) of renal transplant recipients treated with cyclosporine A and prednisone, an increase of basal cAMP generation has been observed. In order to characterize the mechanisms underlying changes of cAMP generation in patients who were treated with immunosuppressives following heart transplantation, we investigated the beta-adrenoceptor--G protein--adenylate cyclase signal transduction cascade in heart transplant recipients and for comparison in renal transplant recipients as well as controls. Basal cAMP formation in MNL was elevated in heart transplant recipients by 272% and in renal transplant recipients by 148% compared to controls. Following beta-adrenoceptor stimulation with isoprenaline, cAMP formation in MNL of heart transplant recipients was similar to the controls, but was enhanced in renal transplant recipients to 138%. Investigation of beta-adrenoceptor density on MNL as a possible cause for increased cAMP formation revealed similar receptor numbers in controls and in cardiac or renal transplant recipients. Furthermore, the increase of the beta-adrenoceptor density on MNL, which is observed following infusion of isoprenaline, was similar in controls and heart transplant recipients. The amount of pertussis- and cholera toxin substrates was the same in heart transplant recipients as in controls. In contrast, MNL of renal transplant recipients showed a marked increase of Gs alpha by 45% and a smaller albeit significant increase of Gi alpha by 15%, as judged by cholera toxin and pertussis toxin labeling, respectively. Investigation of inotropic parameters by echocardiography under control conditions and during the infusion of increasing concentrations of isoprenaline revealed no difference in the basal contractility and the inotropic response to beta-adrenergic stimulation in controls and heart transplant recipients. It is concluded that changes of G-protein expression are involved in the increase of the cAMP-generation in MNL of heart transplant recipients. These alterations in MNL cannot be taken as a model of cellular function in the transplanted heart, but it is reasonable to suggest that elevations of cAMP formation in MNL may contribute to the immunosuppressive effects of the treatment with cyclosporine A or corticosteroids, the mechanism of which could be an alteration of Gs alpha or the catalyst in renal transplant recipients and the catalyst in heart transplant recipients which occurs without any changes of beta-adrenoceptors.

Adenylate Cyclase Toxin↗
PubMed1994

Heart-lung transplantation in a patient with pulmonary atresia and ventricular septal defect.

Operation for pulmonary atresia and ventricular septal defect is challenging, as in most patients the pulmonary arteries are hypoplastic, nonconfluent, or in part absent. In these cases, combined heart-lung transplantation may be the surgical treatment of choice. In the described case, the morphology of pulmonary atresia and ventricular septal defect was present in combination with completely atretic main, left, and right pulmonary arteries. In this patient, successful heart-lung transplantation was performed.

Adult↗
PubMed1994

One-incision approach for insertion of implantable cardioverter defibrillators.

The placement of a transvenous implantable cardioverter defibrillator (ICD) system through a single infraclavicular skin incision has been a surgical goal for years. The development of a new investigational model of ICD with substantially reduced dimensions (volume, 83 cm3; mass, 132 g) has made the one-incision approach a clinical reality. Between March and September 1993, 4 female and 19 male patients (mean age, 60 +/- 9.6 years; range, 46 to 73 years) underwent implantation of this device for the treatment of ventricular fibrillation (n = 14) or ventricular tachycardia (n = 9). One transvenous lead was placed in the right ventricular apex and another in the left subclavian vein. A subpectoral pocket was formed in the infraclavicular area from the same incision to house the ICD generator and, if necessary, the subcutaneous patch. The mean operation time (81.5 +/- 32.7 minutes; range, 54 to 195 minutes) was significantly shorter than that noted for a previous series made up of patients undergoing traditional transvenous ICD implantations. In 20 patients (87%), endovenous defibrillation without a subcutaneous patch successfully caused externally induced ventricular fibrillation to revert with a mean minimum energy output of 21.9 +/- 3.5 J (range, 12 to 24 J). Endovenous defibrillation was more successful when biphasic (n = 16/17 [94%]) shocks rather than monophasic shocks (n = 4/6 [67%]) were used. No mortality, morbidity, or surgical complications were observed. These results indicate that the one-incision approach and the small size of the ICD generator can substantially facilitate ICD implantation and result in a reduction in the surgical trauma, the operation time, and the amount of material implanted.

Aged↗
PubMed1994

Cytoimmunological monitoring after homograft valve replacement.

Examination results concerning immunological reactions in cryopreserved allograft valves during the early postoperative course are so far not available. Cytoimmunological monitoring (CIM) is a well established method to prove rejection reaction after allograft transplantation and was used in this study. Allograft valves were harvested from patients who underwent heart transplantation, and did not require sterilizing in antibiotic solutions. The valves were dissected, conserved and subsequently frozen to -40 degrees C and stored in a freezing system at -196 degrees C. During the first 3 weeks following allograft implantation, CIM was performed daily. An activation index (AI) was determined from the cytological evaluation of the mononuclear concentrate in the peripheral blood. An increase of the AI > 1 was defined as an immunological reaction. As control we performed 98 CIM examinations in eight patients who underwent bioprosthetic valve replacement in the aortic position. Echocardiography (TTE and TEE) was used postoperatively as function control. Out of 16 patients who underwent cryopreserved aortic valve implantation in the aortic position, 336 CIM-results were obtained. An immunological reaction could be detected in all patients, starting on the 5th day on average. Comparing ABO-compatible (group I, n = 9) with ABO-incompatible (group II, n = 7) allografts, the AI-maximum in group I was 1.4 with a mean duration of 1.5 days. Group II was characterized by more intensive immunoreactions (mean = 2.3) which proved to be even more prolonged (mean = 3.3 days, P < 0.05). Nevertheless it became apparent that all observed immunological events were completely reversible without the need for immunosuppressive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗
PubMed1994

Integrity and viability of homograft valves.

Since it has been suggested that the leaflet tissue viability influences durability after homologous valve replacement, we compared different harvest and preservation techniques in order to examine the quality and smoothness of homograft conservation. We analyzed human aortic and pulmonary valve leaflets obtained from 'heart-beating donors' (HBD) during heart transplantation and from 'non-heart-beating donors' (NHBD) during coroner's autopsies. Valves were either cryopreserved in liquid nitrogen or stored at 4 degrees C in nutrient medium similar to the procedure reported in our protocols of the homograft bank system. All grafts from NHBD had been antibiotically sterilized for 3 days beforehand. Morphological observations were made using light and electron microscopy and, in order to characterize the endothelial cell viability, a non-radioactive cell proliferation assay was used. The PGI2 secretion of the remaining endothelium was defined as the 6-keto-prostaglandin F1 alpha metabolite by an enzyme immunoassay. Observations in the scanning electron microscope revealed that, after cryopreservation, homografts show an almost confluent endothelium when processed within 24 h after harvest from HBD, but lack endothelial cells when obtained from NHBD. Cryopreserved grafts from NHBD exhibited an altered tissue structure with edema and vacuolization within the spongiosa of the leaflets as well as irreversible cell damage when examined under the light and transmission electron microscope. That the metabolic activity of HBD homografts was maintained was confirmed by proven PGI2 secretion (6150 +/- 1200 pg/3 ml M199 after cryopreservation), whereas specimens from NHBD showed a reduced (1950 +/- 730 pg/3 ml M199) and, after cryopreservation, almost no release (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Influence of halothane on the effect of cAMP-dependent and cAMP-independent positive inotropic agents in human myocardium.

Volatile anaesthetics have a variety of effects on the myocardium, namely a negative inotropic effect and a catecholamine sensitizing effect. The present study was designed to see if the hydrocarbon anaesthetics interact specifically with subcellular targets of the myocardial cell, by examining the effects of halothane in the presence of positive inotropic agents with different mechanisms of action. Experiments were performed in isolated electrically driven left ventricular preparations (1 Hz, 37 degrees C, Ca2+ 1.8 mmol litre-1) from human hearts obtained at cardiac surgery. The concentration-response curves of noradrenaline, milrinone, BayK 8644 and Ca2+ were investigated in the absence and in the presence of halothane. Halothane enhanced the efficacy of noradrenaline and milrinone but not of Ca2+ or BayK 8644. The potency of milrinone was also increased by halothane, whereas the potency of BayK 8644 was decreased and those of noradrenaline and Ca2+ were unchanged. Halothane differentially influences the effects of agents with different positive inotropic mechanisms. This experimental approach can be taken as a functional method to localize the mechanisms of action of the inhalation anaesthetics in human myocardium, namely sensitization of cAMP formation and interaction with L-type Ca2+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Comparison of UW versus HTK solution for myocardial protection in heart transplantation.

In order to evaluate the protective effect of University of Wisconsin (UW) solution in heart transplantation, a retrospective comparative study with histidine-tryptophane-ketoglutarate (HTK) solution was initiated. In group I, we included 160 patients with HTK preservation, while group II consisted of 50 patients who had their transplant protected with UW solution. All patients received standard quadruple drug therapy for immunosuppression. The average ischaemic time of the donor hearts in group I was 142+/-44 min, ranging from 83 to 235 min. Acute immediate perioperative graft failure occurred in six cases (3.8%). Statistical analysis including the chi-square test, revealed a significant increase in the incidence of acute perioperative graft failure when compared with duration of ischaemic time (P < 0.01). Within the first 30 postoperative days, 24 patients died (15% early mortality). The same statistical correlation was evident between the incidence of early mortality and duration of graft ischaemic time. The 30-day and 6-month survival rates were 81% and 78%, respectively. The average ischemic time of the donor hearts in group II was 193+/-50 min ranging from 100 to 360 min, which was significantly longer in comparison with the group I (P < 0.05). Acute perioperative graft failure occurred once (2%); the patient was retransplanted successfully. Five patients died within the first 30 postoperative days (10% early mortality). There was no correlation between length of ischaemic time and incidence of acute graft failure or early mortality. The 30-day and 6-month survival rates were 90% and 88%, respectively and, thus, better when compared with group I. In both groups similar results were achieved with regard to postoperative NYHA status of the patients and incidence of cardiac arrhythmias. Myocardial preservation with HTK solution showed satisfying results as long as the ischaemic time did not exceed 4 h. The early functional results achieved with UW graft protection were excellent, even with ischaemic times longer than 4 h and not depending on lenght of ischaemic period.

Adenosine↗
PubMed1994

Studies of the nucleoside transporter inhibitor, draflazine, in the human myocardium.

1. The aim of the present study was to determine the effect of the nucleoside transporter inhibitor, draflazine, on the force of contraction in human myocardium and the affinity of the compound for the nucleoside transporter. Nucleoside transport inhibitors, like draflazine, are of potential importance for cardiopreservation of donor hearts for heart transplantation. 2. Functional experiments were performed in isolated electrically driven (1 Hz, 1.8 mmol l-1 Ca2+) human atrial trabeculae and ventricular papillary muscle strips. The affinity of draflazine for the myocardial nucleoside transporter was studied in isolated membranes from human ventricular myocardium and human erythrocytes in radioligand binding experiments using [3H]-nitrobenzylthioinosine ([3H]-NBTI). Dipyridamole was studied for comparison. 3. In membranes from human myocardium and erythrocytes, [3H]-NTBI labelled 1.18 pmol mg-1 protein and 23.0 pmol mg-1 protein, respectively, nucleoside transporter molecules with a KD value of 0.8 nmol l-1. Draflazine concentration-dependently inhibited binding of [3H]-NBTI to myocardial and erythrocyte membranes with a K(i)-value of 4.5 nmol l-1. The potency as judged from the K(i) values was ten times greater than that of dipyridamole in both myocardial and erythrocyte membranes. 4. Draflazine, at concentrations up to 100 mumol l-1, did not produce negative inotropic effects in atrial and ventricular myocardium. (-)-N6-phenylisopropyladenosine (R-PIA) and carbachol did not reduce force of contraction in ventricular myocardium, but exerted concentration-dependent direct negative inotropic effects in atrial myocardium. 5. The data provide evidence that draflazine specifically binds to the nucleoside transporter of the human heart and erythrocytes with high affinity. The compound does not produce negative inotropic effects at concentrations as high as 100 micromol 1-1.6. Draflazine could be a useful agent for cardio preservation because it does not produce cardio depressant effects. Thus, it may be possible to perfuse explanted hearts directly with this agent without the hazard of cardiodepression.

Adult↗
PubMed1994

The failing human heart is unable to use the Frank-Starling mechanism.

There is evidence that the failing human left ventricle in vivo subjected to additional preload is unable to use the Frank-Starling mechanism. The present study compared the force-tension relation in human nonfailing and terminally failing (heart transplants required because of dilated cardiomyopathy) myocardium. Isometric force of contraction of electrically driven left ventricular papillary muscle strips was studied under various preload conditions (2 to 20 mN). To investigate the influence of inotropic stimulation, the force-tension relation was studied in the presence of the cardiac glycoside ouabain. In skinned-fiber preparations of the left ventricle, developed tension was measured after stretching the preparations to 150% of the resting length. To evaluate the length-dependent activation of cardiac myofibrils by Ca2+ in failing and nonfailing myocardium, the tension-Ca2+ relations were also measured. After an increase of preload, the force of contraction gradually increased in nonfailing myocardium but was unchanged in failing myocardium. There were no differences in resting tension, muscle length, or cross-sectional area of the muscles between both groups. Pretreatment with ouabain (0.02 mumol/L) restored the force-tension relation in failing myocardium and preserved the force-tension relation in nonfailing tissue. In skinned-fiber preparations of the same hearts, developed tension increased significantly after stretching only in preparations from nonfailing but not from failing myocardium. The Ca2+ sensitivity of skinned fibers was significantly higher in failing myocardium (EC50, 1.0; 95% confidence limit, 0.88 to 1.21 mumol/L) compared with nonfailing myocardium (EC50, 1.7; 95% confidence limit, 1.55 to 1.86 mumol/L). After increasing the fiber length by stretching, a significant increase in the sensitivity of the myofibrils to Ca2+ was observed in nonfailing but not in failing myocardium. These experiments provide evidence for an impaired force-tension relation in failing human myocardium. On the subcellular level, this phenomenon might be explained by a failure of the myofibrils to increase the Ca2+ sensitivity after an increase of the sarcomere length.

Calcium↗
PubMed1994

Endothelialization of cardiac valve bioprostheses.

The main disadvantage of implanted xenograft valves used in cardiac surgery is their poor clinical long-term result, due to early tissue degeneration. In order to improve the performance of such glutaraldehyde fixed bioprostheses, a biological coating with viable endothelial cells was suggested. Therefore, glutaraldehyde preserved bovine pericard patches, as well as commercially available xenograft valves, were lined using human venous endothelial cells or microvascular cells from the subcutaneous fat tissue. Before cells were transplanted into their new environment, grafts were treated with an amino acid solution in order to neutralize the cytotoxic effect of free aldehydes, and precoated with fibronectin-heparin and basic fibroblast growth factor (bFGF) or endothelial cell growth supplement (ECGS) in order to enhance cell proliferation. Coated specimens were kept in culture conditions for a further seven days. Proliferation of transplanted cells was verified by an increase of activation following 3H-thymidine incorporation, while the maintained metabolic cell activity was demonstrated via Prostacycline (PGI2) measurement. Morphology was evaluated by means of scanning electron microscopy (SEM). As evaluated by the beta-Counter, 7 ng/ml bFGF (288,727 +/- 39,668 counts on day 4) substantially enhanced cell proliferation after seeding, opposed to the stimulation with 30,000 ng/ml ECGS (91,924 +/- 1129 counts on day 4), (p < 0.001). The PGI2 release of transplanted cells was stimulated with 25 microM Na arachidonic acid by the factor 2.6 +/- 0.3 and inhibited with 5 mM acetylsalicylic acid by the factor 0.7 +/- 0.2 on day 4 when compared with the basic level.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1994

[Can hyperlipidemia after heart transplantation be optimally and safely treated?].

"Is there any safe and optimal treatment of hyperlipidemia following heart transplantation?" The problem of hypercholesterolemia following heart transplantation if often underestimated. Up to now there is no concept of therapy allowing an optimal adjustment of lipid parameters. Therapeutical trials using ion exchange resins, derivatives of nicotinic acids and fibrates were not successful due to cyclosporine A interaction, hepatotoxicity and limited efficacy of the applied substances. In a prospective, randomized and controlled trial we investigated the effects of the HMG-CoA-reductase inhibitor simvastatin in heart transplant recipients. The study included 70 patients (simvastatin n = 37, control group n = 33). 8 patients died within the first three months following heart transplantation. Purpose of the study was the adjustment of the LDL-cholesterol values in the simvastatin treated group to < or = 110 mg/dl. Following 24 months of treatment a mean LDL-cholesterol plasma level of 110 mg/dl was obtained. The corresponding mean value of the control group was 150 mg/dl. The difference between both groups was significant (p < 0.001). In the same period the mean HDL-cholesterol values increased by approx. 15% in both groups (no significant difference [p > 0.05]). The ratio of LDL/HDL-cholesterol was significant lower in the simvastatin treated group (2.28) than in the control group (2.94) (p < 0.05). There was no significant difference in Lp(a) values. No adverse side effects were observed within the observation period of 24 months, particularly no increase in the frequency of rejection episodes. Summarizing the above, we recommend low-dose simvastatin therapy as a safe and optimal treatment of hypercholesterolemia following heart transplantation.

Adult↗
PubMed1994

[Malignant angiosarcoma of the right atrium in pregnancy. Diagnostic and therapeutic problems].

Primary tumors of the heart, in contrast to secondary metastatic tumors show a very rare occurrence. About 25% of all primary cardiac tumors are malignant with angiosarcomas being the most frequent type of tumor. The clinical presentation include pericardial tamponade by hemorrhagic pericardial effusion, right heart failure, lung embolism and thoracal pain. Diagnostic procedures include echocardiography, magnetic resonance imaging, CT scan, angiography, pericardioscopy and finally surgical exploration. We report on a 27-year old pregnant woman (23rd week) with a malignant primary angiosarcoma of the right atrium. The patient was admitted to the hospital with progressive shortening of breath due to pericardial tamponade from pericardial effusion. A tumor of the right atrium was detected by echocardiography. Diagnostic procedures had to consider the pregnancy of the patient. Transesophageal echocardiography, magnetic resonance imaging and finally angiography of the right heart with tumor biopsy were performed. Histological examination did not show any signs of malignancy. After corticosteroids pericardial effusion disappeared. Surgical exploration of the tumor was not performed because of the pregnancy. Two weeks later the patient underwent emergency surgery because of progressive heart failure due to obstruction of the tricuspidal valve by the tumor. Thereby intrauterine death of the fetus occurred. The tumor was removed and the right atrium was reconstructed using a Dacron patch. Adjuvant chemotherapy was performed. Eight months later the tumor recurred and heart transplantation was performed. two months later pulmonary metastases were found. the patient died 20 months after onset of symptoms. This is a rare case of the very unusual coincidence of pregnancy and a primary malignant heart tumor.

Adult↗
PubMed1994

Homograft aortic root replacement for destructive valve endocarditis. The benefit of an in-house homograft bank.

This report concerns the surgical treatment of a 45-year old patient with active staphylococcus-endocarditis of the aortic valve which resulted in an aortic root abscess and consequently in a ventricular aortic discontinuity. A technique of homograft aortic root replacement after removal of all infected and necrotic areas is described. After a six month follow-up, the patient is asymptomatic (New York Heart Association functional class I) and shows no signs of recurrence of endocarditis. This case report makes the benefit of an in-house homograft-bank system obvious.

Abscess↗