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Biomedical subjects

R Meyer

Publications and source records attributed to R Meyer.

At least 109 records · Page 6Linked to original sources
PubMed1999

A novel perfusion system for the endothelialisation of PTFE grafts under defined flow.

OBJECTIVES: to develop a perfusion system for culturing human endothelial cells on small-diameter PTFE grafts under defined pulsatile shear stress. METHODS: to benefit from a stronger adhesion of endothelial cells to the substrate, we developed a perfusion system which enables culture of endothelial cells on PTFE grafts to confluence under a wide range of shear stress. We also developed an in situ staining method for the determination of the endothelialisation stage by upper light microscopy. RESULTS: the application of pulsatile flow with high shear stress (6.6 dyn/cm2, 5 min) to a graft endothelialised under perfusion did not lead to a disruption of the confluent cell layer. In contrast, a shear stress of 3 dyn/cm2 applied for 5 min was sufficient to wash more than 50% of endothelial cells off the PTFE graft when cultured to confluence under static conditions. CONCLUSIONS: this technique induces a stronger cell adherence of endothelial cells to a PTFE graft in comparison with grafts endothelialised under static conditions. Endothelialised vascular grafts can be pre-conditioned to defined shear stress values.

Blood Vessel Prosthesis↗
PubMed1999

Nuclear DNA fragmentation and immune reactivity in bovine spongiform encephalopathy.

To investigate whether apoptosis contributes to neuronal degeneration in bovine spongiform encephalopathy (BSE), morphological changes consistent with apoptosis were sought and in-situ end labelling (ISEL) was applied, in a series of 20 BSE cases and 10 age-matched normal control cattle. Apoptotic changes were not found in neurons but were occasionally seen in glial cells. Relatively few ISEL-positive neurons were found, but many labelled nuclei were seen in glial cells in certain areas. None of the labelled cells showed morphological features of apoptosis. ISEL(+)cells occurred in areas of spongiform change and other areas of grey matter lacking spongiform change. Some association was found between degree of cellular DNA fragmentation and accumulation of abnormal prion protein (PrP(Sc)). Interestingly, small or moderate numbers of T lymphocytes, not present in the normal central nervous system (CNS), were detected in the CNS parenchyma in most BSE cases. There was a pronounced astrogliosis, but markers of macrophage or microglial activation were only slightly increased. The results indicate that nuclear DNA vulnerability is enhanced in certain neuroanatomical areas in BSE, but evidence that apoptosis plays a role in neuronal loss in BSE was very limited. 1999 Harcourt Publishers Ltd.

Animals↗
PubMed1999

Beware of the heart: the multiple picture of cardiac involvement in myositis.

A 42-yr-old woman with dermatomyositis had two myocardial infarctions, episodes of acute chest pain and an acute lung oedema. These events were initially misinterpreted as atherosclerotic ischaemic heart disease accompanying the autoimmune disease. The lack of improvement of cardiac symptoms with anti-ischaemic and immunosuppressive drugs indicated other mechanisms. Intracoronary drug provocation as well as myocardial biopsy revealed a coincidence of small-vessel disease and vasospastic angina as a cause for the severe cardiac symptoms. After initiating therapy with high doses of calcium channel blockers, marked improvement of cardiac symptoms occurred. In the pathogenesis of cardiac involvement in dermatomyositis, two different mechanisms should be considered: inflammatory processes due to dermatomyositis and vasoconstriction caused by an impaired regulation of vascular tone, such as abnormal vessel reactivity or disturbed neuropeptide release. Signs of this generalized vasopathy are Raynaud's phenomenon, Prinzmetal's angina and small-vessel disease, which can coincide. In patients with severe cardiac symptoms and autoimmune diseases, Prinzmetal's angina should be excluded by intracoronary drug provocation using acetylcholine.

Angina Pectoris, Variant↗
PubMed1999

Getting residents involved in research: a challenge in the era of managed care.

The changing climate of health care, with the associated increasing financial constraints, challenges faculty and residents to find time for mentoring and pursuing research. Departments and institutions can encourage residents to conduct research by assuring them that they have a supportive infrastructure. Only when the institution and faculty value research will residents do the same. More than half of academic surgeons spend less than 20% of their effort in research; how can residency programs expect residents to enthusiastically pursue research when members of the teaching faculty are themselves not writing and publishing? If the ACGME is serious about asking residents to devote their time and energy to becoming more active in research activities, we must be prepared to decrease service commitments, and we must provide clinically active mentors and visible career models.

Academic Medical Centers↗
PubMed1999

[Controlled reperfusion of ischemic extremity musculature to prevent free radical induced lesions].

Tissue injury following reperfusion represents an essential problem of reconstructive vascular surgery. Pathogenetically toxic oxygen radicals are considered to play a pivotal role. Pharmacotherapeutical approaches are based particularly on antioxidants and vasodilators. However, a standardized regimen is not yet clinically introduced. In 48 adult Lewis-rats lower limb ischemia was induced by aortal cross-clamping. Following 3.5 hours of ischemia intravascular flushing perfusion via the distal aorta with a heparinized electrolyte solution (group B). Group C received additionally oxypurinol, group D alprostadil and group E sodium selenite into the flushing solution. At 4 hours recirculation was established. After 10 min, 30 min and 24 hours of reperfusion we determined lactate, creatine kinase, lactate dehydrogenase, urea, malondialdehyde and the laser Doppler flux. At the end of the experiments biopsies were taken from M. tibialis anterior. In comparison to control animals (group A) we observed an attenuation of reperfusion injury in the groups treated with flushing perfusion. Free oxygen radical reactions measured by malondialdehyde release were significantly reduced (30 min: A-209.1 +/- 45.4, B-127.3 +/- 36.9, C-113.2 +/- 14.1, D-99.6 +/- 24.5, E-123.6 +/- 11.2 mmol/l, p < 0.05). The laser Doppler flux measurements corresponded with the biochemical analyses (30 min: A-52.4 +/- 11.1, B-48.0 +/- 11.0, C-72.6 +/- 12.0, D-74.4 +/- 13.3, E-62.6 +/- 10.8% of baseline). Histologically, treatment with alprostadil (PGE1) and oxypurinol revealed superior results. Standardized intraarterial flushing perfusion with antioxidants and vasodilators reduces reperfusion injury. Clinical trials are urgently required to confirm the experimental findings and to optimize the therapy of extremity ischemia/reperfusion injury in humans.

Animals↗
PubMed1999

Brachytherapy in early prostate cancer--early experience.

Use of brachytherapy with radioactive seeds in the management of early prostate cancer is commonly used in the United States. The early experience has been reported from the prostate treatment centers in Seattle for the last 10 years. In this manuscript we are reporting our early experience of 150 radioactive seed implantations in early stage prostate cancer using either Iodine 125 or Palladium 103 seeds. The average age of the patient is 66 years and the median Gleason score is 5.4 with a median PSA of 6. A brief description of the evolution of the treatment of prostate cancer as well as the preparation for the seed implantation using the volume study with ultrasound of the prostate, pubic arch study using CT scan of the pelvis and the complete planning using the treatment planning computers are discussed. We also have described the current technique which is used in our experience based on the Seattle guidelines. We plan a follow-up report with the results of the studies with longer follow-up.

Aged↗
PubMed1998

Control of L-type calcium current during the action potential of guinea-pig ventricular myocytes.

1. During an action potential the L-type Ca2+ current (ICa,L) activates rapidly, then partially declines leading to a sustained inward current during the plateau phase. The reason for the sustained part of ICa,L has been investigated here. 2. In the present study the mechanisms controlling the ICa,L during an action potential were investigated quantitatively in isolated guinea-pig ventricular myocytes by whole-cell patch clamp. To measure the actual time courses of ICa,L and the corresponding L-type channel inactivation (fAP) during an action potential, action potential-clamp protocols combined with square pulses were applied. 3. Within the first 10 ms of the action potential the ICa,L rapidly inactivated by about 50 %; during the plateau phase inactivation proceeded to 95 %. Later, during repolarization, the L-type channels recovered up to 25 %. 4. The voltage-dependent component of inactivation during an action potential was determined from measurements of L-type current carried by monovalent cations. This component of inactivation proceeded rather slowly and contributed only a little to fAP. ICa,L during an action potential is thus mainly controlled by Ca2+-dependent inactivation. 5. In order to investigate the source of the Ca2+ controlling fAP, internal Ca2+ homeostasis was manipulated by the use of Ca2+ buffers (EGTA, BAPTA), by blocking Na+-Ca2+ exchange, or by blocking Ca2+ release from the sarcoplasmic reticulum (SR). Internal BAPTA markedly reduced the L-type channel inactivation during the entire action potential, whereas EGTA affected fAP only during the middle and late plateau phases. Inhibition of Na+-Ca2+ exchange markedly increased inactivation of L-type channels. Although blocking SR Ca2+ release decreased the fura-2-measured cytoplasmic Ca2+ concentration ([Ca2+]i) transient by about 90 %, it reduced L-type channel inactivation only during the initial 50 ms of the action potential. Thus, it is Ca2+ entering the cell through the L-type channels that controls the inactivation process for the majority of the action potential. Nevertheless, SR Ca2+-release contributes 40-50 % to L-type channel inactivation during the initial period of the action potential. However, the maximum extent of inactivation reached during the plateau is independent of Ca2+ released from the SR. 6. For the first time, the actual time course of L-type channel inactivation has been directly determined during an action potential under various defined [Ca2+]i conditions. Thereby, the relative contribution to ICa,L inactivation of voltage, Ca2+ entering through L-type channels, and Ca2+ being released from the SR could be directly demonstrated.

Action Potentials↗
PubMed1998

Overexpression of the sarcolemmal calcium pump in the myocardium of transgenic rats.

The plasma membrane calmodulin-dependent calcium ATPase (PMCA) is a calcium-extruding enzyme controlling Ca2+ homeostasis in nonexcitable cells. However, its function in the myocardium is unclear because of the presence of the Na+/Ca2+ exchanger. We approached the question of the physiological function of the calcium pump using a transgenic "gain of function" model. Transgenic rat lines carrying the human PMCA 4 cDNA under control of the ventricle-specific myosin light chain-2 promoter were established, and expression in the myocardium was ascertained at the mRNA, protein, and functional levels. In vivo hemodynamic measurements in adult homozygous animals showed no differences in baseline and increased cardiac performance recruited by volume overload compared with controls. No differences between transgenic and control cardiomyocytes were found in patch clamp voltage dependence, activation/inactivation behavior of the L-type Ca2+ current, or fast [Ca2+]i transients (assessed by the Fura-2 method). To test whether the PMCA might be involved in processes other than beat-to-beat regulation of contraction/relaxation, we compared growth processes of neonatal transgenic and control cardiomyocytes. A 1.6- and 2.3-fold higher synthesis rate of total protein was seen in cells from transgenic animals compared with controls on incubation with 2% FCS for 24 hours and 36 hours, respectively. An effect of similar magnitude was observed using 20 micromol/L phenylephrine. A 1.4-fold- and 2.0-fold-higher protein synthesis peak was seen in PMCA-overexpressing cardiomyocytes after stimulation with isoproterenol for 12 hours and 24 hours, respectively. Because pivotal parts of the alpha- and beta-adrenergic signal transduction pathways recently have been localized to caveolae, we tested the hypothesis that the PMCA might alter the amplitude of alpha- and beta-adrenergic growth signals by virtue of its localization in caveolae. Biochemical as well as immunocytochemical studies suggested that the PMCA in large part was colocalized with caveolin 3 in caveolae of cardiomyocytes. These results indicate that the sarcolemmal Ca2+-pump has little relevance for beat-to-beat regulation of contraction/relaxation in adult animals but likely plays a role in regulating myocardial growth, possibly through modulation of caveolar signal transduction.

Animals↗
PubMed1998

Characterization of an eag-like potassium channel in human neuroblastoma cells.

1. SH-SY5Y human neuroblastoma cells were investigated with whole-cell and perforated patch recording methods. 2. Besides a quickly activating delayed rectifier channel and a HERG-like channel, a slowly activating potassium channel with biophysical properties identical to those of rat eag (r-eag) channels was detected, here referred to as h-eag. 3. h-eag shows a marked Cole-Moore shift, i.e. the activation kinetics become very slow when the depolarization starts from a very negative holding potential. In addition, extracellular Mg2+ and Ni2+ strongly slow down activation. 4. Application of acetylcholine induces a fast block of the current when recorded in the perforated patch mode. This block is presumably mediated by Ca2+, as about 1 microM intracellular Ca2+ completely abolished h-eag outward current. 5. When cells were grown in the presence of 10 microM retinoic acid in order to synchronize the cell line in the G1 phase of the cell cycle, h-eag current was reduced to less than 5 % of the control value, while the delayed rectifier channel was expressed more abundantly. Down-regulation of h-eag by long-term exposure to retinoic acid was paralleled by a right shift in the activation potential of HERG-like channels. 6. Acute application of 10 microM retinoic acid blocked the delayed rectifier channel but enhanced the h-eag current. 7. Thus, our results show that human neuroblastoma cells express in a cell cycle-dependent manner an [Mg2+]o-dependent potassium channel (h-eag) which is blocked by submicromolar concentrations of intracellular Ca2+.

Acetylcholine↗
PubMed1998

Can cerebrovascular reactivity be assessed by dynamic susceptibility contrast-enhanced MRI?

The acetazolamide (ACZ) test is performed to evaluate the decrease in cerebral perfusion pressure (CPP) by investigation of vasomotor reactivity (VMR). Our aim was to study cerebral blood flow and blood volume changes induced by the ACZ test in healthy control subjects using dynamic susceptibility contrast-enhanced gradient-echo MRI (DSC-MRI). A FLASH sequence was used to produce susceptibility-weighted images during an intravenous injection of 0.1 mmol/kg gadopentetate dimeglumine (Gd-DTPA). After the first dynamic study, 1 g acetazolamide was given intravenously and 10 min later a second bolus of Gd-DTPA was injected. Using the indicator-dilution theory, relative cerebral blood volume and relative cerebral blood flow were estimated. In healthy subjects the ACZ test induced a significant increase in relative blood volume (from 80.5 +/- 10.7 to 113.4 +/- 11.9) and relative blood flow (from 5.73 +/- 0.96 to 7.5 +/- 0.97), symmetrically in the cerebral hemispheres. This approach might be promising in the understanding of cerebral haemodynamics in patients with vascular disorders.

Acetazolamide↗
PubMed1998

The late component of L-type calcium current during guinea-pig cardiac action potentials and its contribution to contraction.

L-Type Ca2+ current (ICa,L) elicited during the action potential (AP) of guinea-pig ventricular myocytes exhibits an early and a late component. The whole-cell patch-clamp technique was used to characterize the process regulating the late ICa,L component and to assess its contribution to excitation-contraction coupling. A stepwise decrease in repolarization rate of AP-like voltage-clamp pulses led to an exponential increase in Ca2+ charge carried by ICa, L. This saturation behaviour was significantly reduced or absent when Ba2+ or monovalent cations were used as charge carriers, which suggests that the late component of ICa,L is controlled mainly by Ca2+-dependent processes. Simultaneously recording ICa,L and zero-load shortening or the internal Ca2+ concentration (fura-2) revealed that Ca2+ carried by the late component of ICa,L markedly contributes to the Ca2+ content of the sarcoplasmic reticulum (SR). Reducing the charge transfer by late ICa,L during a series of AP-like conditioning clamp pulses by 48% reduced the shortening amplitude during a subsequent test stimulation by 56%. This relationship was absent during long rectangular depolarizing conditioning clamps, during which Na+/Ca2+ exchange increased its influence on SR Ca2+ loading. The late component of ICa,L developed only a minor direct influence on the simultaneous cell shortening. Thus, the main contribution of the late ICa,L component is to supply Ca2+ for SR loading.

Action Potentials↗
PubMed1998

Assessment of person-to-person transmission of hantavirus pulmonary syndrome in a Chilean hospital setting.

Person-to-person transmission of Andes hantavirus among healthcare workers was reported in Argentina for the first time in 1996. To determine whether such transmission of the virus occurred during a 1997 outbreak of hantavirus pulmonary syndrome (HPS) in southern Chile due to Andes virus, we conducted a serological and epidemiological study in the Coyhaique Regional Hospital, where the majority of HPS patients were admitted. Workers in every department of the hospital were evaluated for immunoglobulin G (IgG) and IgM hantavirus antibodies using the enzyme-linked immunosorbent assay (ELISA). A standardized questionnaire was used to determine the type and extent of exposure to HPS patients, as well as other potential risk factors and previous febrile respiratory illnesses requiring hospitalization. Less than half (44%) reported always using gloves when touching patients or their secretions; respiratory protection was not used. Of the 319 participants (87.9% of those eligible), 12 (3.7%) had IgG antibodies. This finding is consistent with the antibody prevalence in the community in which the participants lived. Of the 12 positive healthcare workers, six reported contact with HPS patients. A similar exposure was found in those who tested negative [6/140 (4%) compared to 6/179 (3%), P = 0.66]. There was no significant difference in the types of hospital activities performed or the number of hospitalizations for febrile respiratory illnesses between antibody-positive and antibody-negative individuals. These data suggest that there was no person-to-person transmission among healthcare workers during a recent outbreak of HPS in Southern Chile in 1997, despite the inconsistent use of any precautions against transmission.

Chile↗
PubMed1998

Coronary angioplasty, bypass surgery, and retransplantation in cardiac transplant patients with graft coronary disease.

BACKGROUND: Graft coronary disease (GCD) remains the single greatest limitation to long-term survival of heart transplant recipients. Therapeutic strategies for the prevention or retardation of GCD in the cardiac allograft are limited; palliative coronary revascularization has been attempted. Because of the high mortality rate associated with advanced forms of GCD our institution offers the option of retransplantation in selected cases. The aim of this study was by analyzing retrospectively the outcomes of angioplasty, coronary bypass grafting, and retransplantation in cardiac transplant patients to attempt to identify subgroups of transplant recipients with graft coronary disease who may profit from myocardial revascularization. METHODS: Of the 989 patients undergoing 1016 heart transplantations (HTx) at our institution between 10/86 and 12/97, all were screened for the development of GCD. Analyzing routinely annual angiography, intracoronary ultrasound in defined study patients, and autopsy findings, GCD was diagnosed in 124 patients (110 male, 14 female) 2 to 107 months after HTx (mean 30 months). RESULTS: PTCA: Fourty-six out of 124 patients underwent 76 angioplasties at a mean of 50 +/- 30 months (range 4-91 mo) following cardiac transplantation. The primary success rate was 96% (73/76). The reason for the unsuccessful angioplasty attempts (n = 3) was failure to completely penetrate a stenosis of LAD in 2 patients and severe dissection of RCA, which required emergency surgery, in one. Angiographic restenosis occurred in 42% (31 of 76 lesions) and was diagnosed 11 +/- 11 months after the first angioplasty. There was no procedure-related death. CABG: Seven patients underwent bypass surgery at a mean of 67 months (range 6-128 months) after HTx. Elective surgery was performed in 2 patients with proximal severe triple-vessel disease (Type A lesion) and in 1 patient with severe tricuspid regurgitation who received a tricuspid valve replacement and concomitant single-vessel bypass surgery for proximal GCD (Type A lesion). One patient with combined Type A and B/C lesions required emergency surgery for dissection of RCA after an angioplasty procedure. Three patients with post-infarction unstable angina developed worsening congestive heart failure which required emergency surgery. Angiographically all these patients showed diffuse, distal arteriopathy (combined Type B/C lesions). The electively operated patients and the patient with dissection of RCA were successfully treated and survived beyond hospital discharge (overall survival for CABG in GCD patients 4/7 = 57%). After a mean follow-up of 10 months (range 2-32 months) all are in good clinical condition. All 3 patients with distal arteriopathy and emergency surgery died in hospital of left-ventricular failure (43%). Retransplantation: Eight patients underwent retransplantation at a mean of 54 months (range 6-96 months) after HTx. Six of 8 patients had successful operations and survived beyond hospital discharge with a one-year-survival rate of 75%. In a mean follow-up of 31 months (5-68 months) 3 of 6 retransplant recipients developed a recurrence of GCD. CONCLUSION: The presence of angiographic distal arteriopathy should be considered a significant factor in patient selection for coronary revascularization procedure. Coronary angioplasty is to be considered as a method of treatment for severe, local stenoses (Type A lesion). PTCA may be applied in these selected cardiac transplant recipients with primary success and complication rates comparable to routine angioplasty but with an increased rate of restenosis especially in small vessels (diameter < 2.5 mm). The distinction between Type A lesions in large (diameter > or = 2.5 mm) and small vessels may be important not only with respect to restenosis but also with respect to long-term benefit. The overall survival did not differ between GCD patients with and without PTCA, suggesting this treatment to be largely palliative. (ABSTR

Angioplasty, Balloon, Coronary↗
PubMed1998

Rapid modulation of L-type calcium current by acutely applied oestrogens in isolated cardiac myocytes from human, guinea-pig and rat.

Gender-based differences in cardiovascular mortality may be due to a cardio-protective effect of oestrogens on the myocardium. However, mRNA expression of oestrogen receptors in myocardial tissue of the adult heart has yet to be demonstrated. Furthermore, a calcium antagonistic action of 17beta-oestradiol on myocardial tissue has been discussed. Therefore, two subjects were investigated in atrial myocytes of the human, and ventricular myocytes of guinea-pig and rat in this study. (1) Are oestrogen receptors expressed in adult myocardial cells? (2) Is there an influence of oestrogens on the L-type calcium current of cardiac myocytes? Expression of oestrogen receptors was investigated by reverse polymerase chain reaction. L-type calcium current was usually measured by the patch-clamp technique in whole-cell recording mode under selective recording conditions, i.e. overlapping currents were blocked. One series of experiments was performed in perforated patch configuration to avoid internal perfusion. 17beta-oestradiol inhibited L-type calcium current reversibly in all three species. At 10(-5) M, the inhibition was 15-20%. This inhibition was independent of the sex and the species. A full concentration response curve of 17beta-oestradiol on basal L-type current was recorded from female guinea-pig myocytes. The inhibition increased from 2% at 10(-7) M to about 30% at 10(-4) M 17beta-oestradiol. The values could be fitted by a sum of two sigmoidal functions with log EC50 values of -6.5 and -4.9 M and Hill slopes of 2.5 for both. The specificity of the 17beta-oestradiol action was tested by recording the L-type current in the presence of 17alpha-oestradiol and oestrone. 17alpha-oestradiol also inhibited the current, but with a maximal inhibition of only 17%. The concentration-response curve could be fitted by a single sigmoidal function (log EC50 -6-3 M; Hill slope 0.55). Oestrone did not influence the current at all. The decrease in L-type current after the application of 17beta-oestradiol via a rapid perfusion system developed with a time constant of 3-4 s, which was in the same range as that for the influence of isoprenaline. The isoprenaline-stimulated L-type current was much more susceptible to the inhibition by 17beta-oestradiol, i.e. in pre-stimulated cells (1) the inhibitory effect is significantly higher (e.g. at 10(-5) M, inhibition was 36.3% compared with 11.2% in untreated cells) and (2) an inhibitory effect can be seen with oestradiol concentrations as low as 10(-9) M. Although the concentrations needed to gain a calcium antagonistic influence on the basal current were much too high to explain a cardio-protective influence of oestrogens, the presence of oestrogen receptors in cardiac myocytes of all three species, together with the shift in concentration dependence following pre-stimulation by isoprenaline, suggest that myocytes are a potential target for oestrogen.

Animals↗
PubMed1998

Accumulation of chlorpyrifos on residential surfaces and toys accessible to children.

Quantitative examination of major pathways and routes of exposure to pesticides is essential for determining human risk. The current study was conducted in two apartments and examines the accumulation of the pesticide chlorpyrifos in childrens' toys after the time suggested for reentry after application. It has been established for the first time that a semivolatile pesticide will accumulate on and in toys and other sorbant surfaces in a home via a two-phase physical process that continues for at least 2 weeks postapplication. A summation of the above for a 3-6-year-old child yielded an estimated nondietary total dose of 208 microg/kg/day. Potential exposure from the inhalation pathway was negligible, while dermal and nondietary oral doses from playing with toys contributed to 39 and 61% of the total dose, respectively. If children with high frequency mouthing behavior are considered as candidates for acute exposure to chlorpyrifos residues, the estimated acute dose could be as high as 356 microg/kg/day. Routine reapplication of pesticides could lead to continued accumulation in toys and other sorbant surfaces, e.g., pillows, with large sorbant reservoirs, which can become a long-term source of exposure to a child. Estimates of a child's nondietary exposure to chlorpyrifos associated with toys and other sorbant surfaces for a period of 1 week following application appear to be of public health concern, and studies of actual childhood exposure from this pathway are warranted in the home environment. The above information should be used to determine if current procedures for postapplication reentry are sufficient and to evaluate the need for procedures to store frequently used household toys, pillows, and other sorbant objects during insecticidal application.

Air Pollution, Indoor↗
PubMed1998

Treatment of humoral rejection after heart transplantation.

BACKGROUND: Until a few years ago, the incidence of humoral rejection after heart transplantation was underestimated. These episodes were frequently very aggressive and often fatal, because the maintenance and emergency immunosuppression available at the time only inadequately covered the humoral branch of the immune response. In spite of individual case reports, the effects of blood purification procedures or cyclophosphamide in this situation can only be insufficiently estimated. METHODS: To evaluate this therapy concept, 20 dog-lymphocyte-antigen-matched dogs underwent heterotopic neck-heart transplantation. Fourteen dogs underwent transplantation after having been previously sensitized through multiple skin transplantations, 6 dogs were not sensitized (control). The animals received an induction with 3x 250 mg prednisolone, as well as triple immunosuppression (cyclosporine, azathioprine, and cortisone). Biopsy (light microscopy, immunofluorescence), intramyocardial voltage, electric myocardial impedance (>200 kHz, <10 kHz), and echocardiographic (left ventricular wall thickness, diastolic relaxation velocity) examinations were performed daily to monitor rejection. Rejection therapy was continued for 3 days according to the following regimen: apheresis, cortisone boluses (CB), and cyclophosphamide in group A1 (n = 4), apheresis and CB without cyclophosphamide in group A2 (n = 4), and CB only in group C (n = 6). The subsequent course under triple immunosuppression was then observed. RESULTS: In the sensitized animals the onset of severe humoral rejection on the fifth day deteriorated cardiac function down to 75% (70% to 80%) of the initial values. In groups A1 and A2, apheresis resulted in recovery to near-control values (89% to 94%) within two hours, and indeed to complete recovery (97% to 101%) after the second apheresis, that is, within 1 day. In group C recovery was delayed (2 days) and incomplete (84% to 91 %). After therapy was discontinued, rejection-related functional deterioration recurred immediately in group C, and from 2 to 3 days after apheresis, regardless of whether cyclophosphamide therapy was performed (group A1) or not (group A2). In the control group all animals showed a rejection-free posttransplantation course. CONCLUSIONS: By diluting inflammatory mediators, apheresis leads to a rapid improvement in cardiac function during severe humoral rejection after head transplantation. Neither apheresis nor cyclophosphamide therapy are able to have an immediate positive influence on the activation of the immune cascade and to prevent an ongoing rejection.

Animals↗