[Clinical aspects of infectious endocarditis].
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Biomedical subjects
Publications and source records attributed to B Maisch.
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The vascular endothelium plays a key role in immunologic reactions that also involve the heart: Increased expression of class 1 and 2 antigens of the major histocompatibility complex a common finding in acute rejection after heart transplantation whereas in myocarditis this finding is less pronounced. Another form of involvement of the endothelial cells in the secondary immune response has been reported only infrequently; anti-endothelial antibodies, which may be cytolytic to living cultured human endothelial cells, were demonstrated to be bound to the endomyocardial biopsies of patients with different forms of rejection and with biopsy proven myocarditis and circulating in the peripheral blood of the patients as cytolytic autoantibodies.
Five frequently used hemodynamic oxygen consumption parameters were compared with the directly measured myocardial oxygen consumption (MVO2) in 28 patients with different heart diseases (4 without heart disease, 2 with mitral valve prolapse, 20 with coronary artery disease with or without left ventricular dysfunction, 2 with mitral regurgitation, 1 with hypertrophic obstructive cardiomyopathy and 3 with left ventricular hypertrophy due to hypertension). In most patients pressure-rate product (r = 0.908), tension-time index (r = 0.977), triple product (r = 0.970), pressure-work index (r = 0.954) and the additive parameter Et (r = 0.994) correlated relatively close with MVO2 under conditions of normal or low inotropic stimulation. Already during a moderately enhanced contractile state, tension-time index (r = 0.855), triple product (r = 0.873) and pressure-work index (r = 0.906) lose their close correlations with MVO2. Only pressure-rate product (r = 0.933) and Et (r = 0.982) remained reliable predictors of MVO2 also under these conditions of moderate positive inotropic stimulation.
It is still difficult to differentiate between the various stages of myocarditis and primary dilated cardiomyopathy (DCM). Hence, we analyzed the history, as well as the laboratory and virological data of 22 children with a dilated, poorly functioning left ventricle, aged 2 months to 16.7 years (m = 4.2 y), on whom we had performed endomyocardial biopsies about 4 months after the beginning of the illness. Specimens were investigated by light and electron microscopy and, in addition immunoserological (n = 15) and immunohistological investigations (n = 7) were performed. On the basis of cellular infiltration in the histological examination we diagnosed resolving/resolved myocarditis in 6 patients and DCM in 15 patients. Previous respiratory infection or sudden onset were found in 40-50% of patients in both groups. Antimyolemmal and antisarcolemmal antibodies showed no preference. Follow-up (3.1 +/- 2.8 years) of the patients showed equal mortality (33% vs. 38%) in the post-myocarditis and DCM group. Complete normalization of all findings in 3 patients of the DCM group makes the classification among the post-myocarditis group probable, which would, then give a lower mortality rate (22% vs. 46%) and a chance of restitution in 55% of cases. In any one specific case all the diagnostic methods do not allow undoubted distinction between both entities. The prognosis of myocarditis seems to be better than that of DCM in childhood.
In cats anaesthetized with nitrous oxide and sodium pentobarbital, multireceptive lumbar dorsal horn neurones excited by controlled noxious radiant heating of glabrous hind paw skin were recorded by extracellular microelectrodes. These noxious heat responses were inhibited by concomitant noxious stimulation of the ipsilateral forepaw or pinna, or repetitive electrical stimulation of the ipsilateral forelimb deep radial nerve. Similar extents of inhibition were produced by noxious peripheral stimulation and by deep radial nerve stimulation in repetitive trains at intensities sufficient to excite small myelinated fibres or unmyelinated fibres. A greater inhibitory effect was produced by continuous repetitive high-intensity stimulation of the deep radial nerve. With a constant frequency (5 Hz) of continuous deep radial nerve stimulation, graded increases in stimulation intensity revealed the threshold for inhibition in the small myelinated fibre range, and an additional increment of the inhibitory effect when unmyelinated fibres were also activated. When suprathreshold for unmyelinated fibres, the efficacy of continuous deep radial nerve stimulation increased with graded increases in stimulation frequency, with a threshold frequency for inhibition between 0.5 and 1 Hz and maximal effect at 5 Hz. Two nociceptive-specific neurones studied were also inhibited by deep radial nerve stimulation. The results indicate that 'diffuse noxious inhibitory controls' (DNIC) occur in the cat and can be activated by remote electrical or natural noxious stimulation.
Endomyocardial biopsy in this study of 1250 biopsied patients (mean of five samples/patient) proved to be a remarkably safe technique with no lethal complications. It may help to detect the underlying cause of heart failure but is handicapped by sampling error in focal disease processes (such as myocarditis and sarcoid heart disease) when conventional light and electron microscopy are used. In this biopsy series 123 patients (9.8%) suffered from severe heart failure; lymphocytic infiltrates were found in only 10 (8%). Immunohistological data suggested a secondary humoral immunopathogenesis in all patients with myocarditis and perimyocarditis, in 75% of patients with postmyocarditic heart muscle disease and in 48% of patients with primary dilated cardiomyopathy. There may thus be a need for a new classification of heart muscle diseases that includes immunological parameters of humoral and cellular autoreactivity.
We investigated the course of symptoms and the spontaneous ECG retrospectively in 308 patients who had received a pacemaker because of atrioventricular (AV) block (n = 115), sick sinus syndrome (SSS, n = 107), bradyarrhythmic atrial fibrillation (bradyarrhythmia, n = 51), carotid sinus syndrome (CSS, n = 16), complete bifascicular block associated with 1st degree AV block (n = 13) and with other indications (n = 6). The mean implantation time was 63 months. The clinical state of 93% of all patients improved after pacemaker implantation; their symptoms decreased markedly. Persisting syncopy in some patients with SSS, however, supports a restricted implantation policy. We rarely saw improved AV conduction in patients with AV block (11%). Furthermore, in patients with SSS, atrial fibrillation occurred significantly more often (35%) than in those with AV block (17%; P less than 0.01). Only 3% of patients with SSS developed 2nd and 3rd degree AV block within the observation period. In all patients with initial bifascicular block and additional 1st degree AV block, pacing prevented further syncopal attacks; four of them showed 3rd degree AV block at control, indicating that pacemaker implantation is mandatory in symptomatic patients with bifascicular disease and 1st degree AV block.
UNLABELLED: Atrial fibrillation (AF) and thromboembolism are discussed to be complications of the VVI mode. We reinvestigated the spontaneous ECG and the anamnesis of 246 pacemaker patients with the indications second and third degree atrioventricular block (AV block, n = lll), sick sinus syndrome (SSS, n = 101) and other indications (n = 34), all had shown sinus rhythm at implantation. The mean implantation time was 63 +/- 45 months (203 VVI and 43 dual chamber pacemakers). THE RESULTS: (1) Atrial fibrillation was found in 63 patients (26%). Only one of them had a DDD pacemaker inserted, the implantation time of dual chamber devices being shorter, however, (2) The incidence of AF in patients with SSS (37%) was significantly higher (P less than 0.01) than in patients with AV block (19%). (3) Three patients suffered from strokes or transitory ischemic attacks in the follow-up, only one of them had AF at control. CONCLUSIONS: Our results confirm that VVI stimulation favors AF long-term which is most likely due to irritation of the atrial rhythm by retrograde conduction. In our patients the incidence of thromboembolic complications was not higher in the group of patients with AF. However, from this study in surviving patients, we cannot exclude that we lost some patients due to severe stroke.
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In anesthetized cats, extracellular recordings were made from lumbar spinal dorsal horn neurons, driven by noxious radiant skin heating. Heat-evoked responses were inhibited during electrical stimulation in the medullary nucleus raphe magnus (NRM). To identify the spinal pathways mediating this descending inhibition, reversible blocks in the spinal cord white matter were produced by microinjection of the local anesthetic lidocaine. Descending inhibition from the NRM was significantly reduced during blocks in the dorsal and medial, but not ventral parts of the contralateral lateral funiculus (LF). Blocks at any site in the ipsilateral LF failed to affect NRM-induced descending inhibition. These results indicate that NRM-induced inhibition of nociceptive dorsal horn neurons is conveyed primarily in fibers descending in the contralateral spinal white matter.
In anesthetized cats, lumbar dorsal horn neurons were excited by brief noxious radiant heating of glabrous hindpaw skin. These nociceptive responses were inhibited by concomitant repetitive electrical stimulation of the ipsilateral deep radial nerve. Noxious heat responses were linearly correlated with skin temperature during heating. The slope of this stimulus-response function was decreased, and the response threshold increased, by deep radial nerve stimulation. Microinjection of lidocaine into the medullary raphe attenuated the inhibition induced by deep radial nerve stimulation. The results indicate that in the cat, 'diffuse noxious inhibitory controls' (DNIC) involve medial medullary regions.
The time course and extent of local anaesthetic blocks within the spinal cord of cats were evaluated. A monopolar stimulation electrode with the tip lowered into the dorsal columns (DC) 1000 microns below cord surface was used to activate antidromically DC fibers at the T13 level and evoke cord dorsum potentials at the level of the lumbar spinal cord. The amplitude of the negative deflection, the N-wave, was determined for various stimulation intensities (stimulation-response-function, SRF). Lidocaine (1%) was microinjected in volumes of 0.5 or 1.0 microliter into the DC from a glass micropipette 1 mm caudal to the stimulation site. Conduction block was characterized by a reversible shift of the SRFs to higher stimulation intensities. The diameter of the blocked area in the transverse plane was evaluated from threshold intensities and was found to be 0.9 +/- 0.1 mm 4 to 30 min after the injection of 0.5 microliter lidocaine and 1.6 +/- 0.36 mm 10 to 45 min after the injection of 1.0 microliter lidocaine. In the sagittal plane, the diameter of the blocked area following 1.0 microliter lidocaine was found to be up to 2.8 mm. The DC-block was reversible within 92 min following injection of 1.0 microliter and 69 min after the injection of 0.5 microliter lidocaine. The application of the present findings for blocks in other CNS structures is discussed.
In 60 pediatric patients, aged from 1 month to 22 years (median 3.54) and a bodyweight of 3 to 67 kg (median 12.6 kg) transvascular endomyocardial biopsy was performed from the right (35 patients) or left ventricle (30 patients). The specimens were investigated by light and electron microscopy. Immune serological investigations were performed in 22 patients, immune histological examinations in eight. There were three indications for biopsy: a. 29 children had a poorly functioning, dilated left ventricle. Of these, seven suffered from endocardial fibroelastosis, 16 from dilated cardiomyopathy, six (plus one control-biopsy) from healing/healed or chronic myocarditis. b. 17 children showed inadequate left ventricular hypertrophy. Of these, ten suffered from HCM, four from secondary hypertrophy, three from storage diseases. c. Various questions were answered in eight children - four with hypoxic, two with cytotoxic myocardial damage. There were five misindications, retrospectively. We observed no serious complications. Evaluation of biopsy revealed diagnostic findings in 11.7%, was helpful in 71.7% and of no help in 16.6%. Hence, even in childhood, endomyocardial biopsy is a diagnostic tool which can contribute useful information on the etiology or pathogenesis of the underlying myocardial disease.
In anaesthetized cats, nociceptive responses of lumbar dorsal horn neurons were studied during administration of salmon calcitonin (sCT). Systemic sCT administration (4-95 IU/kg i.v.) produced no change in neuronal responses produced by noxious skin heating or by impulses evoked electrically in afferent C-fibres. Responses to skin heating were reduced during electrical stimulation in the brainstem, but the efficacy of this descending inhibition was not altered by systemic sCT administration. In contrast, noxious heat responses were clearly reduced by microinjection of sCT into the mesencephalic periaqueductal grey or the medullary raphe regions. These results suggest that calcitonin or a related peptide could act at specific brainstem sites to inhibit the spinal transmission of nociceptive information.
In acute perimyocarditis we found that OKIAI-positive cells were increased, and in dilated cardiomyopathy OKMI-positive cells were increased. No significant alteration in suppressor T cell activity was observed in our patients with either disease. The characteristic immunofluorescent pattern in carditis and postmyocarditic heart disease is the presence of antimyolemmal antibodies with intact rat and human cardiocytes in titers of 1:40-1:320 as antigens. The antimyolemmal fluorescence can be absorbed with the respective causative virus in Coxsackie B, influenza, mumps and EBV-myocarditis, indicating that the antibodies are a cross-reactive. AMLA-positive sera induce cytolysis of vital rat cardiocytes in vitro, suggesting that the antibodies are of pathogenetic relevance. Cytolytic serum activity could be absorbed out with the respective virus. Immunohistologic specimens obtained from patients with carditis demonstrate the fixation of IgG and IgM antibodies; IgG antibodies also occur in dilated cardiomyopathy and coronary artery disease. In dilated postmyocarditic heart disease both antimyolemmal fluorescence and cytolytic activity are preserved at a lower level when compared to carditis. These antibodies can also fix complement. In the acute phase of carditis circulating immune complexes can be demonstrated. Cellular effector mechanisms against vital cardiocytes were maintained or even slightly enhanced in carditis, postmyocarditic and primary dilated cardiomyopathy. In vitro NK cell activity against K 562, however, was decreased. This is compatible with a sustained target-specific cytotoxicity whereas reduced NK cell activity may indicate impairment of this effector organ.
Sera and lymphocytes from a 37-year-old male patient with acute perimyocarditis during a Q-fever endemic were analyzed for antibody and cell-mediated immune reactions and followed up 28 months later. Circulating autoantibodies against myocardial tissue were assessed by indirect immunofluorescence. Cytolysis of vital contracting rat cardiocytes, by antimyolemmal antibodies and complement, and lymphocytotoxicity, with and without the patient's serum, were evaluated and compared with the results obtained in ten patients suffering from Q-fever without perimyocardial involvement and with 40 healthy subjects. Antimyolemmal antibodies (AMLA), a muscle-specific subtype of antisarcolemmal antibodies, were demonstrated by immunofluorescence in the one patient with Q-fever perimyocarditis in titers of up to 1:320 but not in the controls. AMLA induced cytolysis of myocytes in the presence of complement. Both AMLA and cytolytic serum activity could be absorbed in all sera of this patient by using Coxiella burnetii. Only marginal lymphocytotoxicity against heterologous cardiocytes was detected in the early phase and again during the follow-up 2 years later in the Q-fever myocarditis patient but not in any of the noncarditic Q-fever cases nor in controls. It is postulated that cross-reacting, complement-fixing, cytolytic autoantibodies against the cardiac myolemma are operative either as a cause of cardiac damage or a consequence, pointing to a secondary immunopathogenesis of chronic Q-fever perimyocarditis.
Physiological stimulation can be achieved by either bifocal or rate responsive pacing. The latter pacemakers adapt the heart rate to physical activity by biological signals. Out of many possible approaches only three pacemaker systems for rate responsive pacing are available: the QT-pacemaker (Tx or Quintech), the respiratory biorate pacemaker, and the activity detecting Activitrax. Our own experiences (8 QT, 6 Biorate, 8 Activitrax pacemakers) and a survey of 95 QT- and 37 Biorate pacemakers from 11 centers are reported. The Biorate pacemaker functions without any problems; its present disadvantage is limited programmability. With the Tx pacemaker failing, frequency adaptation (26%) was found more often in the early series, mostly due to voltage polarization at the tip of the electrode. The Activitrax pacemaker gives satisfactory frequency adaptation, largely depending on the activity of the muscles of the shoulder and pectoral region.