Biomedical subjects
Publications and source records attributed to M Grazzini.
In a patient with hepatic failure of middle grade diltiazem at standard therapeutic dosis for unstable angina caused collateral fuss on atrioventricular conduction. This event is not considered in medical literature or on the schedule of the product. Because of the pharmacokinetics features of diltiazem, a higher risk of side effects can be expected if a abnormality of hepatic function is present.
BACKGROUND: Immunization with cardiac myosin induces experimental autoimmune heart disease in genetically predisposed mice. These mice produce heart-specific autoantibodies, some of which are directed against the cardiac myosin isoform. METHODS AND RESULTS: We have reported the presence of circulating heart-specific autoantibodies in 26% of patients with idiopathic dilated cardiomyopathy (DCM) using indirect immunofluorescence. To identify the autoantigen(s) recognized by heart-specific autoantibodies in human disease, we tested, by Western blotting, sera from 26 DCM patients, 14 of whom were cardiac antibody-positive and 12 antibody-negative, as well as sera from 12 patients with cardiac failure from ischemic or valvular heart disease and from 13 normal subjects who were cardiac antibody-negative. Crude myofibrillar proteins and myosin preparations extracted from human atrial or ventricular specimens were used as antigens. Sodium dodecyl sulfate polyacrylamide gel electrophoresis was performed. The proteins were electrophoretically transferred to nitrocellulose sheets. The paper strips were incubated in sera from patients or controls at 1:100 dilution; the reaction was revealed with a peroxidase-labeled second antibody against human immunoglobulin. Twelve of the 14 DCM sera (86%) containing heart-specific antibodies reacted with both the alpha- (atrial specific) and beta- (ventricular and slow skeletal) myosin heavy chain isoforms; none of the 13 normal sera (p = 0.0001) and one of the 24 heart failure-negative control sera (4%, p = 0.0001) contained antibodies against myosin heavy chain. CONCLUSIONS: These findings indicate that alpha- and beta-cardiac myosin heavy chain isoforms as in the murine model of autoimmune heart disease are major autoantigens in patients with idiopathic DCM.
Aetiology and pathogenesis of idiopathic dilated cardiomyopathy (DCM) are uncertain. The two major pathogenetic hypotheses are: 1) autoimmunity; 2) persistent viral infection. Indirect evidence for virus association comes from the finding of raised titres of antibody to coxsackievirus in DCM, but infectious virus has never been isolated in myocardium from DCM patients. Bowles et al. using the slot-blotting technique reported that enteroviral RNA was commonly detectable in the myocardium of patients with myocarditis (53%) and with DCM (52%). Other groups using this as well as more refined hybridization techniques have failed to confirm such a high prevalence. Detection of enteroviral genomic RNA in cardiac tissue does not, however, imply active infection or pathogenicity. Thus the mechanisms of chronic myocardial damage in the absence of whole competent infectious virus remain uncertain. The other major pathogenetic hypothesis in DCM involves autoimmune mediated damage to myocytes. Circulating organ specific autoantibodies have been reported in a quarter of a group of patients with idiopathic DCM. This suggests that there may be autoimmune mechanisms operating at least in this subset of patients, but the exact relation of these antibodies to the pathogenesis and prognosis needs to be defined. The abnormal expression of major histocompatibility complex class II antigens on cardiac microvascular endothelium in endomyocardial biopsy tissue from DCM patients, and the reported association with HLA-DR4 phenotype lend further support to the autoimmune hypothesis. The viral and the autoimmune hypothesis in chronic myocarditis and in DCM are not mutually exclusive. In experimentally murine virus-induced myocarditis infectious virus can no longer be recovered from the myocardium after two weeks, although nucleic acid sequences of the viral genome are still detectable. The development of chronic inflammation takes place only in mice with a predisposing genetic background. Chronic myocyte damage is associated with the production of circulating heart-specific autoantibodies and autoreactive lymphocytes. In this animal model chronic myocarditis appears to be a virus-triggered or precipitated autoimmune disease, rather than a persistent viral infection with tissue damage due to active virus synthesis and replication. A similar transition from acute myocarditis into DCM may occur in man.
In a multicentre double-blind, inpatient, placebo-controlled trial the effects on premature ventricular beats (PVBs) of mexiletine in a standard, submaximal dose were studied by Holter monitoring in 144 outpatients. After wash-out, mexiletine was administered for 14 days. The effects were re-tested, after one week of a placebo, in a second 14-day period of mexiletine administration. Of the patients 73% in the first period and 82.5% in the second period responded to mexiletine (a reduction of 75% or more of PVBs/24 h--p less than 0.001 compared with the placebo for both periods). Mexiletine also significantly reduced the Lown class of PVBs and the frequence of paired PBVs, ventricular tachycardia, multiform beats and R on T wave phenomenon. Mexiletine showed an equivalent effectiveness in the four main aetiological groups of arrhythmias. Fifty nine patients complained of adverse effects (gastrointestinal or neurological) the intensity of which led to the stopping of the treatment in 16 of them. These results show that mexiletine is highly effective, even in submaximal doses, in preventing ventricular arrhythmias of whatever origin.
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Two cases of Ebstein's anomaly in apparently asymptomatic adult patients are described. The chances of non invasive recognition of the malformation by means of electro-vectorcardiography and echocardiography are discussed. Unlike their useful diagnostic contribution, their prognostic valve seems to be negligible. For this purpose clinical course of malformation would remain very important, even if some unusual electrocardiographic and radiological features can provide interesting informations.
The Authors evaluated by graded speed treadmill exercise the maximal walking tolerance in two groups of patients with isolated obstruction of femoral (15 cases) and iliac (11 cases) respectively, recognized by non invasive methods. Clinical and instrumental patterns at rest were nearly the same. In the two groups studied the following data have been considered: ankle systolic pressure at rest, arm-thigh pressure gradient, pressure index, maximum walking tolerance and baseline pressure recovery time after exercise. Mean and standard deviation of each parameter were calculated; statistical significance of the observed differences was tested by Student's t test. Since walking tolerance resulted significantly higher (p < 0.01) in femoral obstructions, factors associated with the level of the obstructive lesion are analyzed and discussed, which can explain such functional behaviour.
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Electrocardiograms of 27 patients with the Wolff-Parkinson-White syndrome (12 A Rosenbaum and 15 B Rosenbaum type) were studied. Planimetrically it was determined mean polarity of the delta were on both frontal (DI and DIII bipolar leads) and horizontal (V1 and V3 precordial leads) planes. In order to identify anatomical site of pre-excitation, all data were statistically analyzed. It was allowed to distinguish 5 delta wave groups and 5 relative anatomical sites of pre-excitation: posterior paraseptal, left ventricle free wall, right ventricle free wall, left ventricle posterior wall and dorsal portion of the interventricular septum.
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