Genotype-phenotype dilemma in a case of sudden cardiac death with the E1053K mutation and a deletion in the SCN5A gene.

Mutations in the cardiac sodium channel gene SCN5A may result in various arrhythmia syndromes such as long QT syndrome type 3 (LQTS), Brugada syndrome (BrS), sick sinus syndrome (SSS), cardiac conduction diseases (CCD) and possibly dilated cardiomyopathy (DCM). In most of these inherited cardiac arrhythmia syndromes the phenotypical expression may range from asymptomatic phenotypes to sudden cardiac death (SCD). A 16-year-old female died during sleep. Autopsy did not reveal any explanation for her death and a genetic analysis was performed. A variant in the SCN5A gene (E1053K) that was previously described as disease causing was detected. Family members are carriers of the same E1053K variant, some even in a homozygous state, but surprisingly did not exhibit any pathological cardiac phenotype. Due to the lack of genotype-phenotype correlation further genetic studies were performed. A novel deletion in the promoter region of SCN5A was identified in the sudden death victim but was absent in other family members. These findings demonstrate the difficulties in interpreting the results of a family-based genetic screening and underline the phenotypic variability of SCN5A mutations.

Microvascular permeability is increased in both types of diabetes and correlates differentially with serum levels of insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF).

Vascular endothelial growth factor (VEGF) and insulin-like growth factor-I (IGF-I) both play a pivotal role in diabetic microangiopathy. This study assessed the relationship between capillary permeability as a marker of endothelial dysfunction and serum VEGF and IGF-I levels in normotensive diabetics. Subjects were 10 Type 1 (6/4, male/female, age: 30 [mean] +/- 5 [SD] years, HbA1c: 7.5 +/- 1.1 %), 13 Type 2 diabetics (9/4, m/f; 63 +/- 7 years, 8.3 +/- 1.8 %), and 24 age- and sex-matched control subjects. We determined nailfold capillary permeability by intravital fluorescence videomicroscopy after intravenous injection of sodium-fluorescein. Serum VEGF, free and total IGF-I, IGF binding protein (IGFBP)-1, IGFBP-3, and insulin levels were measured by specific immunoassays. Capillary permeability was increased in both types of diabetes patients compared to age- and sex-matched controls. In Type 1 diabetics, fluorescence light intensities increased over time, reaching significance 30 minutes after dye injection. Type 2 diabetics already revealed an early onset of elevated fluorescence light intensities after one minute. Capillary permeability showed a significant positive correlation with VEGF levels in Type 1 diabetics, (r = 0.76, p < 0.05; 20 min after dye injection) but with free IGF-I levels in type 2 diabetics (r = 0.65, p < 0.05; 5 min after dye injection). IGFBP-3 correlated negatively with capillary permeability in both diabetes types, whereas IGFBP-1 levels correlated positively in Type 2 patients. In conclusion, capillary permeability is increased in both types of diabetes mellitus. However, VEGF and IGF-I may differentially affect microvascular permeability depending on the diabetes type.

Loco-regional thrombolysis for deep vein thrombosis: fact or fiction? A study of hemostatic parameters.

Loco-regional thrombolysis for deep-vein thrombosis (DVT) has been claimed to be equally effective and safe compared with systemic thrombolysis. It is not known whether a loco-regional thrombolytic effect exists and of what it might consist. To investigate this issue, we studied eight patients with DVT undergoing loco-regional thrombolysis with 20 mg alteplase infused over 4 h in a dorsal foot-vein of the affected leg, while the leg was kept tightly bandaged; alteplase infusions were repeated every 24 h, the number of therapy cycles (TC) was seven, and full-dose heparin was given. For coagulation analyses, 'loco-regional' blood samples were taken from a vein of the affected leg and 'systemic' samples were taken from an antecubital vein. After a median number of six TC, good partial reperfusion was achieved in 4/8 patients, moderate partial reperfusion in 2/8, major bleedings occurred in 2/8, and minor bleedings in 1/8 patients. During the first TC, recombinant tissue-type plasminogen activator (rtPA) activity and antigen, as well as FgDPs and d-dimers, were elevated significantly loco-regionally over systemic values, and a complete breakdown of plasmin-inhibitor activity occurred with only a slight systemic reduction; no other differences were found. During successive TC, differences in rtPA-activity and -antigen levels decreased, and no significant differences were found for all other parameters. Thus, a local fibrinolytic effect was demonstrable during loco-regional thrombolysis for DVT; the magnitude of this effect diminished during successive TC, giving rise to the hypothesis that the fibrinolytic efficacy may be decreased due to growing, antifibrinolytic activity. The preserved, loco-regional plasmin-inhibitor activities during the later TC, in contrast to the complete breakdown during the first TC, suggest that part of the enhanced antifibrinolytic activity is due to loco-regionally increased plasmin-inhibitor activity. The ultimate goal of loco-regional thrombolysis, the induction of local fibrinolysis without systemic effects, has not, however, been achieved.

[Risk stratification after myocardial infarct]. / Risikostratifizierung nach Myokardinfarkt.

In industrialized countries the rate of sudden cardiac death remains unchanged. The most frequently encountered structural heart disease in these patients is coronary artery disease. Despite the era of thrombolytic therapy of acute myocardial infarction patients carry an increased risk of sudden cardiac arrhythmogenic death within a time period of one to two years following the acute event. Therefore, risk stratification post-MI before patient discharge is furthermore mandatory. The spectrum of non-invasive techniques for risk stratification includes the clinical risk profile, measurement of left ventricular global function (LV ejection fraction), the resting ECG (QT dispersion), an ECG stress test (detection and severity of myocardial ischemia), ambulatory ECG monitoring (number and type of ventricular arrhythmias), surface high resolution ECG (detection of ventricular late potentials), measurement of T wave alternans (TWA, alternans ratio), and measurements of the activity and balance of the autonomous nervous system (heart rate variability, baroreflex sensitivity = BRS). Programmed ventricular stimulation (PVS) serves as an invasive risk stratification technique (detection of an arrhythmogenic substrate). The prognostic power of the non-invasive techniques is limited; in general, the prognostic value of a negative test is reasonably high (90 to 100% depending on the test used), whereas the prognostic value of a positive test is rather low (4 to 42% depending on the test used). Combining several non-invasive tests may significantly improve the positive predictive value above 50%, but this goes along with a significant decreases of sensitivity below 50%. Therefore, a combination of several non-invasive tests (detection and exclusion of a large number of low-risk individuals) with the invasive method of PVS (detection of an arrhythmogenic substrate, i.e. a high-risk patient) seems reasonable, as has been convincingly shown by several smaller prognostic studies.

Intracoronary beta-irradiation with a liquid (188)re-filled balloon: six-month results from a clinical safety and feasibility study.

BACKGROUND: Coronary irradiation is a new concept to reduce restenosis. We evaluated the feasibility and safety of intracoronary irradiation with a balloon catheter filled with (188)Re, a liquid, high-energy beta-emitter. METHODS AND RESULTS: Irradiation with 15 Gy at 0.5-mm tissue depth was performed in 28 lesions after balloon dilation (n=9) or stenting (n=19). Lesions included 19 de novo stenoses, 4 occlusions, and 5 restenoses. Irradiation time was 515+/-199 seconds in 1 to 4 fractions. There were no procedural complications. One patient died of noncardiac causes at day 23. One asymptomatic patient refused 6-month angiography. Quantitative angiography after intervention showed a reference diameter of 2. 77+/-0.35 mm and a minimal lumen diameter of 2.36+/-0.43 mm. At 6-month follow-up, minimal lumen diameter was 1.45+/-0.88 mm (late loss index 0.57). Target lesion restenosis rate (>50% in diameter) was low (12%; 3 of 26). In addition, we observed 9 stenoses at the proximal or distal end of the irradiation zone, potentially caused by the short irradiation segment and the decreasing irradiation dose at its borders ("edge" stenoses). The total restenosis rate was 46% and was significantly lower (29% vs 70%, P=0.042) when the length of the irradiated segment was more than twice the lesion length. CONCLUSIONS: Coronary irradiation with a (188)Re-filled balloon is technically feasible and safe, requiring only standard percutaneous transluminal coronary angioplasty techniques. The target lesion restenosis rate was low. The observed edge stenoses appear to be avoidable by increasing the length of the irradiated segment.

A randomized trial of elective stenting after balloon recanalization of chronic total occlusions.

OBJECTIVES: The aim of this study was to assess the role of Wiktor stent implantation after recanalization of chronic total coronary occlusions with regard to the clinical and angiographic outcome after six months. BACKGROUND: Beside the common use of stents in clinical practice, the number of stent indications proven by randomized trials is still limited. METHODS: Eighty-five patients with a thrombolysis in myocardial infarction grade 0 chronic coronary occlusion were examined. After standard balloon angioplasty, the patients were randomly assigned to stent implantation, or percutaneous transluminal coronary angioplasty (PTCA) alone (no further intervention). Quantitative coronary angiography was performed at baseline and after six months. RESULTS: The minimal lumen diameter did not differ immediately after recanalization (stent group 1.61 +/- 0.30 mm vs. PTCA group 1.65 +/- 0.36 mm), and increased after stent implantation to 2.51 +/- 0.41 mm. After six months, the stent group still had a significantly greater lumen (1.57 +/- 0.59 vs. 1.06 +/- 0.90 mm; p < 0.01) and a significantly lower restenosis and reocclusion rate (32% and 3%) compared with the PTCA group (64% and 24%); restenosis analysis according to treatment was 72% (PTCA) versus 29% (stent, p < 0.01). Late loss was equal in both groups. At follow-up, the stent patients had a better angina class (p < 0.01), and fewer cardiac events (p < 0.03). A meta-analysis including this trial and three other controlled trials with the Palmaz-Schatz stent showed concordant results. CONCLUSIONS: Stent implantation after reopening of a chronic total occlusion provides a better angiographic result, corresponding to a better clinical outcome with fewer recurrence of symptoms and reinterventions after six months.

Heart-rate variability for discrimination of different types of neuropathy in patients with insulin-dependent diabetes mellitus.

It has been shown that patients with insulin-dependent diabetes mellitus (IDDM) may reveal abnormal alterations in heart-rate variability (HRV) due to autonomic neuropathy. This study was performed to prove whether heart-rate variability can be used to stratify diabetic patients with different types of neuropathy. 48 patients with IDDM (age 17-64 yr) underwent standard function tests to assess autonomic and peripheral neuropathy. According to the results of these tests they were divided into 4 groups: Group 1: 18 patients without autonomic or peripheral neuropathy. Group 2: 13 patients with peripheral neuropathy. Group 3: 7 patients with autonomic neuropathy. Group 4: 9 patients with autonomic and peripheral neuropathy. HRV was measured by continuous 24-hours monitoring and time domain parameters were calculated. The results were compared with sex and age-matched healthy controls according to the individual characteristics of the groups and among each subgroup. Our results showed that in Group 1 there was a significant difference of time domain parameters indicative of parasympathetic influence, i.e. rMSSD and pNN50 in comparison to the control subjects (p = 0.002, p = 0.008). These results depended on the duration of diabetes; a subgroup of patients with a duration of IDDM of less than 2 years had no significant differences of HRV values. Group 2 showed the same significant differences. Group 3 and 4 showed significant differences in all measured time domain variables (SDNN, SDANN, SDNN index, rMSSD and pNN50) in comparison to the control subjects (p < 0.04). A comparison of group 1 with group 2 offered significant differences in rMSSD and pNN50 (p = 0.004, p = 0.003). Comparing group 1 with group 3 and 4, all HRV parameters showed significant differences (p < 0.03). In conclusion, HRV is able to distinguish between patients with different types of neuropathy depending on the involvement of parasympathetic or more sympathetic influenced parameters. Furthermore, this method is able to unmask early manifestations of neurological disorders prior to their detection by neurological function tests.

Time-dependent changes of heart rate variability after percutaneous transluminal angioplasty.

OBJECTIVES: It is not known whether the improvement of myocardial perfusion by percutaneous transluminal coronary angioplasty (PTCA) is followed by a response of the autonomic nervous system depending on the recovery of the myocardium. In this study we investigated changes of heart rate variability parameters in patients before and after PTCA at different time intervals. METHODS: In 42 patients with coronary artery disease documented on angiography, before and after PTCA 24-hour measurements of heart rate variability (HRV) were performed from Holter tapes. The time elapsed between the two measurements was 3 to 4 days in 26 patients and 6 to 8 months in 16 patients. Time domain parameters of HRV were calculated. RESULTS: Comparison of the two recordings showed that the parameters rMSSD, pNN50, and SDNN index decreased, whereas SDNN and SDANN increased. These changes were not statistically significant. A subgroup analysis revealed different results for patients with and without previous myocardial infarction: the parasympathetically and more sympathetically influenced parameters revealed different changes in these groups. Other variables such as ejection fraction or severity of coronary artery disease did not influence the HRV results. Although no statistically significant difference was seen on comparison of the patients with different recording intervals, patients with a longer interval between the two measurement periods showed higher values of all HRV parameters closer to normalized values. This observation may be explained by a delayed recovery of myocardial function after successful revascularization by PTCA.

Direct enzyme immunometric measurement of plasma big endothelin-I concentrations and correlation with indicators of left ventricular function.

Recent studies have suggested that the plasma concentrations of endothelin-1, a potent vasoconstrictive peptide, are increased in patients with congestive heart failure. This study aimed to evaluate a new direct ELISA for big endothelin-1 (the precursor of endothelin-1), in comparison with a big endothelin-1 ELISA using plasma sample extraction, and to investigate whether plasma big endothelin-1 concentrations correlate with indicators of left ventricular function. The direct ELISA yielded significantly (P < 0.001) lower results than the assay with extracted samples (0.9 +/- 0.5 pmol/L vs 2.7 +/- 1.9 pmol/L; n = 90); however, the results of the two assays were closely correlated (r = 0.86, P < 0.001). Plasma big endothelin-1 concentrations exhibited a significant (P < 0.001) negative correlation (r = -0.46, r = -0.40) with the left ventricular ejection fraction and a significant positive correlation (r = 0.40, P < 0.001; r = 0.36, P < 0.01) with the left ventricular end-diastolic pressure and the left ventricular end-diastolic (r = 0.42, r = 0.38, P < 0.001) and end-systolic (r = 0.52, r = 0.47, P < 0.001) volume indices. Plasma big endothelin-1 concentrations were notably greater in patients with New York Heart Association (NYHA) class II-IV symptoms than in patients without cardiac disease or in patients categorized to NYHA class I. These data suggest that plasma big endothelin-1 concentrations, measured by a direct ELISA, correlate with hemodynamic indicators and symptoms of left ventricular dysfunction.

Influence of physical activity on 24-hour measurements of heart rate variability in patients with coronary artery disease.

This study assessed the influence of physical activity on time domain variables of heart rate variability (HRV) during 24-hour electrocardiographic registrations. Changes in time domain variables of HRV (in particular SDNN) obtained from Holter recordings were proven as strong predictors of cardiac events in patients with coronary artery disease. Although 24-hour measurements of HRV recordings are a standard technique, little is known about the effects of the environment during the registration period. This applies especially to the type and nature of physical activity. In a prospective study, 106 patients with angiographically proven coronary artery disease were randomized into 2 groups. Group 1 consisted of 54 patients with recordings under normal daily physical activities. Group 2 consisted of 52 patients who were immobilized during the recording. Both groups were comparable concerning clinical parameters. The results of 24-hour measurements of HRV with analysis of time domain variables (SDNN, SDANN, SDNN index, rMSSD, and pNN50) were compared among the 2 patients groups, and with a healthy control group. Comparison of immobilized patients with healthy controls showed statistically significant differences of all HRV parameters (p <0.01). However, when comparing the activity group with healthy controls, none of the parameters showed any significant differences. Comparison of the subgroups revealed statistically significant differences of the parameters SDNN, SDANN (p <0.01), and borderline results for rMSSD and pNN50 (p = 0.05). Our results indicate that time domain variables of HRV calculated from 24-hour recordings are significantly influenced by the level of physical activity and the upright posture during registration. This methodologic aspect has to be considered, especially if HRV measurements are used as prognostic markers in patients with coronary heart disease.

Signal-averaged electrocardiogram in patients with insulin-dependent (type 1) diabetes mellitus with and without diabetic neuropathy.

The purpose of this study was to investigate the presence of ventricular late potentials derived from signal-averaged ECG in patients with IDDM with and without diabetic neuropathy. Eighty patients with IDDM but without evidence of cardiac disease and 80 age-matched healthy control subjects were investigated. The corrected QT interval was measured from the standard surface electrocardiogram. Ventricular late potentials were derived from signal-averaged electrocardiogram. Out of the 80 diabetic patients, 20 had an autonomic neuropathy, 20 had an isolated peripheral neuropathy, and 40 had no symptoms of neuropathy. The corrected QT interval was significantly prolonged in patients with an autonomic neuropathy as compared with the control group (436 +/- 23 ms(x 5) vs 384 +/- 23 ms(x 5), p < 0.001). In the other patient groups there was no significant prolongation of the corrected QT interval. Ventricular late potentials were present in 3 diabetic patients with an isolated peripheral neuropathy and in 1 control subject (NS). No diabetic patient with an autonomic neuropathy had ventricular late potentials. Our data did not indicate an increased incidence of ventricular late potentials derived from signal-averaged electrocardiogram in diabetic patients independent of a coexisting diabetic neuropathy or a prolonged corrected QT interval.

Increased endothelin release by cultured human smooth muscle cells from atherosclerotic coronary arteries.

OBJECTIVES: Endothelin, a 21-amino acid peptide initially purified from the medium of cultured endothelial cells, is a potent vasoconstrictor exerting its effects predominantly in a paracrine or autocrine manner. Recent data indicate that endothelin is also synthesized by cultured vascular smooth muscle cells and that endothelin is an effective stimulator of smooth muscle cell proliferation. This study aimed to investigate the endothelin release of cultured human smooth muscle cells, isolated from coronary plaques and from normal coronary tunica media, and to determine circulating endothelin concentrations in patients with coronary artery disease compared to control subjects. METHODS: Coronary plaque material was extracted by thrombendarterectomy during aorto-coronary bypass grafting (n = 19). Segments of normal coronary arteries were obtained at autopsy (n = 33). Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells with antibodies against smooth muscle alpha-actin. Venous blood samples were drawn from patients with coronary artery disease undergoing cardiac catheterization (n = 32) and from control subjects (n = 38). Endothelin concentrations in culture medium and in plasma samples were measured by radioimmunoassay after Sep Pak C18 extraction. RESULTS: Cultured smooth muscle cells, isolated from coronary plaques, released a significantly (P < 0.001) higher amount of immunoreactive endothelin into the culture medium (39.2 +/- 3.9 pg/10(4) cells, mean +/- s.e.m., 31 supernatant samples) than smooth muscle cells from normal coronary tunica media (3.9 +/- 0.8 pg/10(4) cells, 28 samples). Circulating endothelin concentrations were slightly elevated (P < 0.01) in patients with coronary artery disease (3.8 +/- 0.2 pg/ml) compared to control subjects (3.0 +/- 0.2 pg/ml). CONCLUSIONS: These data suggest that the endothelin production is markedly increased in smooth muscle cells of coronary atherosclerotic plaques. The enhanced endothelin release may stimulate smooth muscle cell proliferation in a paracrine or autocrine manner and thus may contribute to the development or progression of coronary artery disease.

QRS morphologies of the surface ECG of nonsustained ventricular tachycardias during holter monitoring compared with QRS morphologies of spontaneous sustained ventricular tachycardias.

The purpose of this study was to compare electrocardiographic (ECG) morphologies of nonsustained ventricular tachycardias (VTs) during Holter monitoring with the ECG morphology of documented, sustained, monomorphic VTs during the spontaneous event of tachycardia in 14 patients (9 with coronary artery disease), in whom a sustained, spontaneous monomorphic VT had been documented in a 12-lead ECG. All patients had a 24-hour Holter ECG without antiarrhythmic medication. Channel 1 of the Holter ECG was compared with leads V1, V2, and V3, and channel 2 with leads V4, V5, and V6. The Holter ECG of 10 patients in whom the QRS complex during sinus rhythm was similar to the QRS complex in the corresponding ECG leads was accepted for analysis. In 8 of the 10 patients, nonsustained VTs were detected during Holter monitoring. In one of these eight, the ECG morphology of at least one nonsustained VT in the Holter recordings was identical with the sustained VTs. Thus, incidences and ECG morphologies of nonsustained VTs during Holter monitoring do not correlate closely with those of spontaneous sustained monomorphic VTs. Therefore, most ventricular runs during Holter monitoring may have a mechanism different from that of spontaneous sustained VTs.

Management of unstable angina in patients over 75 years old.

BACKGROUND: Although there have been reports of successful percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) in elderly patients, few data are available on the optimal management of unstable angina in such patients. This study was therefore designed to identify the preferred revascularization strategy in patients with unstable angina over 75 years of age. METHODS: Early and late results were evaluated for patients over 75 years with unstable angina undergoing PTCA (n = 51) or CABG (n = 53). The two groups were comparable with respect to age, sex distribution, clinical manifestation of symptoms, left ventricular ejection fraction and accompanying non-cardiac diseases. In the CABG group, significantly more patients had left main coronary artery stenosis (13 and 2%, respectively). RESULTS: Both PTCA and CABG treatment showed similar procedural success rates (91 and 94% respectively) and hospital mortality rates (4 and 6% respectively). Procedural complications were comparable regarding Q-wave myocardial infarction, stroke, renal failure and vascular complications. Patients undergoing CABG received significantly more blood transfusions than those undergoing PTCA (17 and 2% respectively). During follow-up, the mortality rate was comparable in both groups (4% with CABG and 8% with PTCA), but significantly fewer patients in the CABG group developed unstable angina (8 versus 21% in the PTCA group), fewer patients were readmitted to hospital for cardiac reasons (CABG group 17%, PTCA group 31%) and fewer patients needed repeat coronary interventions (CABG group 4%, PTCA group 18%). CONCLUSION: Both PTCA and CABG were comparable with regard to short- and long-term mortality, but CABG treatment was favourable with regard to clinical symptoms, readmission to hospital and repeat coronary interventions.

A prescreening system for potential antiproliferative agents: implications for local treatment strategies of postangioplasty restenosis.

BACKGROUND: Recent advances in the understanding of the biology of restenosis indicate that it is predominantly caused by a multifactorial stimulation of smooth muscle cell proliferation. The aim of this study was to investigate the in vitro effect of five potential antiproliferative agents on smooth muscle cells from human atherosclerotic femoral arteries. METHODS AND RESULTS: Primary stenosing plaque material of 24 patients (aged 63 +/- 14 years) and restenosing plaque material of 7 patients (aged 65 +/- 9 years) was selectively extracted from femoral arteries by the Simpson atherectomy device. Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells by positive reaction with smooth muscle alpha-actin. Dalteparin sodium (0.001-100 anti-Xa units/ml), cyclosporine A (0.005-500 micrograms/ml), colchicine (0.00004-4 pg/ml), etoposide (0.002-200 micrograms/ml), and doxorubicin (0.0005-50 micrograms/ml) were added to the cultures. Six days after seeding, cells were trypsinized and cell number was measured by a cell counter. All five agents tested exhibited a significant inhibition of smooth muscle cell proliferation (P < 0.001). After an incubation time of 48 h, the cytoskeletal components, alpha-actin, vimentin, and microtubules were investigated. At peak concentrations, all five tested agents except dalteparin sodium caused severe damage to the cytoskeleton. CONCLUSIONS: All five potential antiproliferative agents exhibited a significant inhibition of smooth muscle cell proliferation. The development of new intravascular delivery systems may open the way for local antiproliferative treatment strategies in interventional cardiology.

[Effect of a pressure dressing on angiologic complications after diagnostic coronary angiography]. / Einfluss des Druckverbandes auf angiologische Komplikationen nach diagnostischer Koronarangiographie.

500 consecutive patients undergoing diagnostic coronary angiography were studied for vascular complications using either a conventional (n = 250) or a special mechanical device for compression dressing (n = 250). In both groups one case of arterial occlusion occurred. Using the conventional pressure dressing, we observed four pseudoaneurysms, whereas there were none in the special mechanical device dressing group (p < 0.05). In contrast, eight patients developed a deep vein thrombosis after mechanical device pressure dressing compared to only 1 venoust in the conventional dressing group (p < 0.02). Five patients, four of the eight patients with mechanical device dressing, suffered from clinical apparent pulmonary embolism (p = 0.1801). Thus, a mechanical device pressure dressing may decrease the number of arterial pseudoaneurysms but is associated with an increased risk of deep vein thrombosis and pulmonary embolism. Therefore, we recommend the use of the mechanical device pressure dressing only in selected patients with severe obesity.

Improved detection of transient myocardial ischemia by a new lead combination: value of bipolar lead Nehb D for Holter monitoring.

The investigations of ST-segment changes by Holter monitoring demonstrate asymptomatic and symptomatic episodes of myocardial ischemia, which may occur during daily activities. One factor, which is of great importance for the detection of silent myocardial ischemia during ambulatory monitoring, is the combination of the leads. Former studies showed that the analysis of two channels alone may not adequately detect silent myocardial ischemia. We therefore used a three-channel ambulatory ECG monitoring system with a new lead combination. The Holter monitoring results were correlated with the distribution of coronary stenosis detected by coronary angiography. In 54 patients with single coronary vessel disease and ischemic ST-segment depressions during exercise testing, standard Holter lead combination CM2/CM5 was extended by a bipolar Nehb D-like lead. Lead combination CM2/CM5 identified 23 patients (43%) with ST-segment depressions (total number of ischemic episodes = 372). Additional Nehb D-like lead identified 30 patients (55%) with ST-segment depressions (total number of ischemic episodes = 1048). The combination of leads CM2/CM5 and Nehb D raised the number of patients with documented ST-segment depressions to 33 of 54 (61%). Lead Nehb D showed the highest sensitivity for the detection of inferior wall ischemia (stenosis of the right coronary artery); nevertheless, this lead may not be regarded as specific for ST-segment alterations only caused by inferior wall ischemia. The correlation of ischemic ST-segment depressions during exercise testing (classified as anterior, inferior, or anterior and inferior type of ischemia) and documented ST-segment changes in the different Holter leads underline these results.(ABSTRACT TRUNCATED AT 250 WORDS)

Corticosteroid agents inhibit proliferation of smooth muscle cells from human atherosclerotic arteries in vitro.

We studied the in vitro effect of steroid agents on smooth muscle cells from human atherosclerotic arteries. Recent advances in the understanding of the biology of restenosis indicate that restenosis is predominantly caused by a multifactorial stimulation of smooth muscle cell proliferation. Primary stenosing plaque material of 24 patients (aged 63 +/- 14 years) and restenosing plaque material of 7 patients (aged 65 +/- 9 years) was selectively extracted from femoral arteries by the Simpson atherectomy device. Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells by positive reaction with smooth muscle alpha-actin. The steroid agents prednisolone (0.0075-750 micrograms/ml), hydrocortisone (0.0125-1250 micrograms/ml), and dexamethasone (0.0004-40 micrograms/ml) were added to the cultures. Six days after seeding the cells were trypsinized and the cell number was measured by a cell counter. All three steroid agents exhibited a significant antiproliferative effect on smooth muscle cell proliferation. At high concentrations of hydrocortisone, cytoskeletal elements of smooth muscle cells such as actin, microtubules, and vimentin, were largely altered. Our data indicate that the proliferation of smooth muscle cells from human atherosclerotic arteries in vitro can be inhibited by steroid agents and thus may open the way for local post-angioplasty treatment strategies.