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Biomedical subjects

F Weidinger

Publications and source records attributed to F Weidinger.

At least 37 records · Page 2Linked to original sources

Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease.

Flow-mediated vasodilation (FMD) of systemic arteries, a non-invasive parameter of endothelial function, is correlated with cardiovascular risk factors. The relationship between FMD and morphologically and clinically evident coronary artery disease has not been described. This study was performed to test the hypothesis that an impairment of FMD in the brachial artery is related to the presence and/or extent and severity of coronary artery disease (CAD). We examined 74 patients with angina pectoris and 14 control subjects (age 17 36 years). Angiography revealed coronary artery disease (> or = 30% diameter stenosis) in 44 patients (CAD, age 32 67 years) and smooth coronary arteries in 30 patients (non-CAD, age 22-73 years). Vasodilation following reactive hyperemia and after sublingual nitroglycerin (NTG) was assessed in the brachial artery using B-mode high resolution ultrasound. CAD patients showed markedly impaired FMD compared to the non-CAD group (5.7 +/- 4.8 versus 12.6 +/- 6.7%, P < 0.0001) and to controls (5.7 +/- 4.8 versus 15.7 +/- 3.9%, P < 0.00001). NTG induced similar degrees of vasodilation in the CAD and non-CAD groups but less vasodilation in the CAD patients compared to controls (12.2 +/- 6.3 versus 20.4 +/- 6.9%, P < 0.01). On univariate analysis, impaired FMD in CAD patients and non-CAD patients was related to the extent of coronary disease (1-, 2- or 3-vessel disease; r = -0.67, P < 0.0001), to the maximum percent diameter stenosis in one of the major coronary vessels (r = -0.52, P < 0.0001), brachial artery diameter (r = -0.46, P < 0.0001) and plasma cholesterol level (r = -0.34, P < 0.001). On multiple stepwise regression analysis the extent of coronary disease (r = -0.51, P < 0.0001) and the baseline brachial artery diameter (r = -0.37, P < 0.0001) were independently associated with FMD in CAD and non-CAD patients. The present findings suggest that the impairment of FMD in the brachial artery, a marker of systemic endothelial function, is closely related to the angiographic extent of CAD.

Adolescent↗

Is oxidative stress causally linked to unstable angina pectoris? A study in 100 CAD patients and matched controls.

OBJECTIVE: Unstable angina pectoris often leads to acute myocardial infarction. Since lipid peroxidation is thought to be causally related to chronic and acute events in atherosclerosis and coronary artery disease, we measured lipid peroxidation products and vitamin E in 100 patients with coronary artery disease and compared them to a matched control group. METHODS: 50 consecutive patients with stable angina pectoris (SAP) and 50 consecutive patients with unstable angina pectoris (UAP) were studied and compared to 100 clinically healthy individuals. In addition to conventional lipid and lipoprotein analysis, malondialdehydes were measured as thiobarbituric acid reactive substances (TBARS). Lipid hydroperoxides were assayed with the colorimetric methylene blue method. alpha-Tocopherol was quantitated by HPLC after extraction of serum with hexane-ethanol. In the patient group conjugated dienes were also measured. RESULTS: As expected, patients had significantly higher cholesterol, triglyceride LDL-C and Lp(a) values and lower HDL-C values than controls. When patients were divided into groups with SAP and UAP respectively, peroxides and TBARS were significantly higher in the latter group as compared to patients with SAP and to controls. Conjugated dienes were also significantly higher in patients with UAP as compared to patients with SAP. Total plasma alpha-tocopherol was comparable in all three groups, whereas the alpha-tocopherol content per LDL particle was lowest in patients with UAP, followed by patients with SAP and then controls. CONCLUSION: It is concluded that lipid peroxidation parameters are increased in patients with UAP and discriminate SAP from UAP patients.

Aged↗

Regression of coronary atherosclerosis and amelioration of renal function during LDL-immunoadsorption therapy in a renal transplant recipient.

Hyperlipoproteinemia is frequently observed in patients after renal transplantation and contributes to cardiovascular morbidity and mortality. In addition, it was recently shown that hypercholesterolemia accelerates the progression of renal disease. In a renal transplant recipient (RTR) with severe coronary heart disease, familial hypercholesterolemia and decreased renal function, immunospecific LDL-apheresis was instituted since dietary restrictions failed to sufficiently improve hyperlipoproteinemia and medication had to be avoided due to drug interactions. Over a period of 36 months 145 LDL-apheresis treatments were performed at weekly intervals. The desorption of 5600 ml plasma volume allowed a mean reduction of total cholesterol by 56.6% (from 256 mg/dl to 110 mg/dl), of LDL-cholesterol by 63.0% (from 163 mg/dl to 58 mg/dl), of Lp(a) by 68.3% (from 34 mg/dl to 11 mg/dl) and of triglycerides by 49.6% (from 332 mg/dl to 163 mg/dl). Although temporarily decreasing during each apheresis session by 9.0%, HDL-cholesterol values increased during the first 9 months of treatment and remained within the normal range (> 45 mg/dl) thereafter. Cyclosporine A blood trough values were decreased by 32% during LDL-apheresis. Symptoms of angina pectoris rapidly improved and disappeared after 8 months of apheresis treatment. Initial coronary angiography exhibited serious three-vessel-disease, without the possibility of bypass grafting. Coronary angiography repeated after two years of therapy showed a regression of the disease. Serum creatinine levels declined during treatment (from 2.7 mg/dl to 1.8 mg/dl) and proteinuria did not increase further. This is the first report to show that long-term LDL-immunoadsorption is a safe and highly effective treatment of severe hyperlipidemia and coronary heart disease in a RTR, resulting in regression of vascular pathology. Moreover, amelioration of hyperlipidemia may have improved transplant function. Multicenter studies are necessary to confirm our results.

Adult↗

[Dynamic obstruction of the left ventricular outflow tract by prosthesis dysfunction].

We report on a case of dynamic left ventricular (LV) outflow tract obstruction combined with a prosthetic valve dysfunction 13 years following mitral valve replacement with a Hancock bioprosthesis in a 46-year-old patient. Previously, repeated echocardiographic controls had been performed at regular intervals and the prosthesis had been found to be oversized and seated in abnormal position, with projection of the struts into the LV outflow tract. Moreover, a mild chronic LV outflow tract obstruction had been diagnosed upon intermittent findings of relatively high velocity in the outflow tract. Clinically, however, the patient had been stable and the function of the prosthesis had been good. With the onset of the mitral regurgitation due to prosthesis failure, a dynamic obstruction to LV outflow occurred, with severe narrowing of the LV outflow tract by a strut of the bioprosthesis during systole. Subsequently, a low cardiac output syndrome developed. The patient was referred for a mitral valve reoperation. The valve was replaced with a Sorin Bileaflet Carbon prosthesis. On the setting of a mild chronic LV outflow obstruction due to the oversized prosthesis and its abnormal position, hypercontractile cardiac function as a result of mitral regurgitation may have caused the dynamic and symptomatic LV outflow tract obstruction.

Bioprosthesis↗

Blockade of endothelium-derived relaxing factor synthesis with NG-nitro-L-arginine methyl ester leads to enhanced venous reactivity in vivo.

This study was performed to examine whether endothelium-derived relaxing factor (EDRF) influences venous tone and reactivity in vivo. The inferior vena cava and abdominal aorta were studied simultaneously under continuous haemodynamic monitoring in anaesthetised rabbits. In addition, a 20-MHz intravascular ultrasound catheter was placed in the vena cava for on-line two-dimensional imaging of vessel cross-sectional area and calculation of wall stress (T(ension) = P(mean) * r(adius)/2). This approach enabled simultaneous visualisation of both venous (CA(ven)) and aortic (CA(art)) cross-sectional area with continuous recording of vessel dimensions. Measurements were made before and after administration of NG-nitro-l-arginine methyl ester (L-NAME; 10 mg.kg i.v.), a specific inhibitor of EDRF biosynthesis. After L-NAME there was a significant increase in central venous pressure and a decrease in CA(ven). On the arterial side, L-NAME caused a significant increase in mean pressure and CA(art), resulting in a significantly augmented arterial wall stress. The venodilatation elicited by increasing doses of glyceryltrinitrate was markedly enhanced after L-NAME. Norepinephrine caused a parallel shift of the dose-response curve for CA(ven) in the presence of a lower baseline value. These results suggest that EDRF contributes substantially to the control of large capacitance veins in vivo and that L-NAME increases venous reactivity to both norepinephrine and glyceryltrinitrate.

Animals↗

Assessment of changes in vasomotor tone in vivo using intravascular ultrasound.

This study tested the capability of high-frequency, two-dimensional real-time intravascular ultrasound (IVUS) in the detection of dynamic changes of large vessel diameter in vivo. An IVUS-catheter (4.8 French, 20-MHz mechanical transducer) was inserted via the femoral vein, and advanced to the inferior vena cava of anesthetized rabbits (n = 7). The depth of field of the transducer allowed for visualization of the entire cross-sections of both the inferior vena cava (IVC) and the adjacent aorta. Changes in vessel diameter were induced pharmacologically using norepinephrine (NE) and glyceryltrinitrate (GTN), which were injected intravenously before and after the administration of L-NG-nitro-arginine methyl ester) L-NAME, a specific inhibitor of endothelium-derived relaxing factor (EDRF)-biosynthesis. Vasoconstriction and -dilation could be observed continuously from the two-dimensional real-time recordings of vessel cross-sections. Vessel diameters and cross-sectional areas (CA) were measured from still frames at given time intervals of drug infusion, and blood pressure and heart rate were recorded continuously. Following NE, an increase of aortic and a simultaneous decrease of venous CA were observed, while GTN elicited the opposite responses. Inhibition of EDRF was followed by an augmentation of the vascular responses. It is concluded that IVUS is capable of detecting changes in vascular dimensions in vivo. Thus in large vessels, IVUS may become a method for the direct assessment of vasomotion in vivo.

Animals↗

[Intravascular ultrasound: a new dimension of invasive vascular diagnosis].

Intravascular ultrasound is a new imaging modality which allows the visualization of the vessel wall in vivo and could thus become an important adjunct to conventional angiography. Using miniature high-frequency transducers mounted at the tip of flexible catheters, high-resolution cross-sectional images are created and displayed in real-time. Several investigations have shown good correlations between ultrasound and histologic or angiographic techniques for the measurement of cross-sectional dimensions. Atherosclerotic lesions can be characterized by their differences in echo-density as calcified, fibrous or lipoid. Initial clinical studies have demonstrated the possibility to detect acute changes, such as dissections, following PTCA and other interventions. Several potential clinical applications are being discussed, where intravascular ultrasound may yield valuable information in addition to that provided by angiography. If some important current limitations can be overcome, this method may add a new dimension to invasive vascular diagnostics.

Angiography↗

[Direct diagnosis of the atherosclerotic vascular wall: possibilities and limits of intravascular ultrasound].

The clinical application of intravascular ultrasound still awaits established criteria for the interpretation of normal and diseased arterial wall structures. The aim of this preclinical study was to evaluate sonographic features of normal and atherosclerotic human arteries in vitro and to correlate these findings with histological cross-sections. Seventy-four segments from 33 human postmortem arteries of various anatomic locations were studied in saline solution using a mechanical 20-MHz transducer in a 6F catheter. In normal arteries, close correlations were found between sonographic and morphometric measurements of total wall thickness (r = 0.89), lumen circumference (r = 0.99), and of lumen area (r = 0.89, all p less than 0.001). Of 29 histologically verified atherosclerotic lesions, 19 were calcified, and all of them were correctly diagnosed with IVUS; however, acoustic shadowing prevented quantitative plaque evaluation. Of 10 fibromuscular lesions, six (60%) were correctly diagnosed with IVUS, using either direct morphologic criteria (n = 4) or indirect signs of vessel wall irregularity (n = 2), while the remainder (n = 4) were missed by IVUS due to a similar echodensity compared with the surrounding tissue. Thus, there was an overall sensitivity of 86% for the detection of atherosclerotic lesions by IVUS. In animal experiments in vivo, the feasibility of high-quality-imaging in pulsatile arteries was confirmed and pathologic changes in vein grafts were visualized. We conclude that IVUS carries the potential to directly assess arterial wall changes in vivo. The method appears very sensitive in the detection of calcified plaque, whereas fibromuscular lesions may often not be readily distinguished from normal surrounding tissue. This may limit the clinical usefulness of IVUS at the present time.

Adult↗

Platelet survival in patients with dilated cardiomyopathy.

Dilated cardiomyopathy is associated with thromboembolic complications, which correlate poorly, however, with a visible left ventricular thrombus. Therefore, this study was performed to assess whether an abnormality of platelet function in vivo can be detected in patients with dilated cardiomyopathy. Platelet survival was measured after autologous labeling with indium-111 oxine in 28 patients with dilated cardiomyopathy and angiographically normal coronary arteries (mean ejection fraction 21 +/- 9% [standard deviation], range 4 to 39%) and in nine patients with coronary artery disease and similar left ventricular dysfunction (mean ejection fraction 21 +/- 10%). Plasma levels of beta-thromboglobulin and platelet factor 4 were measured in patients with idiopathic cardiomyopathy (n = 15) and platelet scintigraphic images of the heart (n = 24) were obtained in subsets of both patient groups. Platelet survival was significantly and similarly shortened in patients with idiopathic and ischemic cardiomyopathy (67 +/- 34 and 55 +/- 24 h, respectively) compared to controls (209 +/- 9 h, n = 12; p less than 0.001). Of the two platelet-specific proteins, beta-thromboglobulin was increased in the patients compared with controls (42 +/- 17 versus 22 +/- 6 ng/ml, p less than 0.001). Platelet scintigraphy 24 h (n = 24) and/or 48 h (n = 9) after labeling showed a diffuse pattern of enhanced platelet uptake over the heart which varied in intensity among patients, but which was never seen in controls (n = 6). This increased platelet uptake was similar in patients with idiopathic and ischemic cardiomyopathy but did not correlate with either ejection fraction or cardiothoracic ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Heart transplantation: indication, selection criteria and patient management].

Evaluation of potential candidates for cardiac transplantation is a difficult and wearisome process for both physician and patients. As long as we are confronted with the present situation of an increasing chronic donor unavailability, the importance of standardized, rational criteria for evaluation of heart transplantation candidates has to be emphasized, since the success of any organ transplantation depends on adequate selection of potential candidates.

Biopsy, Needle↗

Epoprostenol in patients with Raynaud's disease.

Prostaglandin metabolism and the clinical effect of epoprostenol (prostacyclin, PGI2) infusions were studied in thirteen patients with Raynaud's disease. Epoprostenol was infused at 5 ng/kg/min for six hours daily for two consecutive five day periods, separated by a two day interval. No beneficial effects either during or after infusion could be detected in terms of frequency of severity of attacks or on skin temperature measurement. Raynaud's patients had significantly lower serum thromboxane B2 levels than normal controls though plasma levels of thromboxane B2, 6-oxo-PGF1 and the bicyclic metabolite of PGE2 did not differ between the two groups. Platelets from Raynaud's patients had a significantly lower conversion rate of arachidonic acid into thromboxane B2 and HHT and a significantly higher rate of HETE production than platelets from controls.

6-Ketoprostaglandin F1 alpha↗

Characteristics of transient ischaemic episodes in patients with silent and symptomatic exercise-induced myocardial ischaemia.

To evaluate transient ischaemic episodes during daily life in patients with coronary artery disease and exercise-induced myocardial ischaemia, 38 patients underwent ambulatory ST-segment monitoring over 48 h. Sixteen patients had painless ischaemia during exercise and occasional angina, and 12 patients had symptomatic ischaemia and frequent angina during daily life. Ten patients with proven coronary artery disease but normal exercise electrocardiograms served as controls. The extent of coronary artery lesions and the prevalence of myocardial infarction were similar in all groups. ST-segment monitoring revealed 817 min and 98 episodes of ST depression in 13/16 patients of the asymptomatic group and 111 min and 21 episodes in 5/12 patients of the symptomatic group (P less than 0.03). Subjective scores for physical activity during Holter monitoring were significantly higher in the first group than in the second. The majority of ischaemic episodes in both groups was asymptomatic. No ischaemic ST changes occurred in control patients. Results indicate a higher frequency of transient ischaemic episodes related to a higher level of physical activity in patients with silent ischaemia than in patients with symptomatic exercise-induced ischaemia.

Angina Pectoris↗

[Heavy metal and trace element deviations. A comparison of idiopathic dilated cardiomyopathy and coronary heart disease].

Blood, serum and urine (24-hour-samples) concentrations of cadmium, zinc, calcium and magnesium were determined by means of atomic absorption spectrophotometry in 60 patients, therefrom 30 patients with idiopathic dilated cardiomyopathy (IDC) and 30 patients with coronary heart disease (CHD). The data of heavy metal and trace element concentrations of IDC and CHD patients were compared with each other and furthermore, for each group separately, correlated with patients history data, laboratory evaluations and data from heart catherization protocol. IDC patients showed higher blood cadmium concentrations (p less than 0.001) and lower serum zinc concentrations (p less than 0.001) compared to CHD patients. Serum levels of calcium and magnesium were not different in both groups. In urine samples IDC patients had lower concentrations of calcium (p less than 0.01) and magnesium (p less than 0.01) compared to CHD patients. Urine concentrations of cadmium and zinc were in the same range in both groups. The comparison of heavy metal and trace element concentrations with clinical data did not reveal definite correlations, however, data from experimental studies pointing out interactions of heavy metals and trace elements, could serve as useful interpretations. Hypomagnesemia in both patient groups (IDC, CHD) requires clinical follow up and substitution treatment.

Aged↗

Potential life-threatening cardiac arrhythmias associated with a conventional hypocaloric diet.

Nine obese children (mean age 12.7 years, mean overweight 74.2%) were treated for 3 weeks with a very low calorie diet containing high quality protein. Eight patients (patients A) received a commercially available diet (240 kcal/1004 kJ/day) and 1 patient (patient B) a homemade dietary regimen (500 kcal/2100 kJ/day). Both preparations were supplemented with micronutrients; however, the daily intake of minerals was significantly less in patient B. All patients were monitored for the appearance of cardiac arrhythmias by frequent 24-hour Holter recordings. In patients A the mean loss of body weight was 9.4 +/- 2.4 kg, patient B lost 8.7 kg. The mean daily nitrogen balance was negative (patients A: 10.2 g/day, patient B: 6.8 g/day). Frequent blood chemistry evaluations were unremarkable. On the 14th day of treatment patient B developed arrhythmias (ventricular couplets, non-sustained ventricular tachycardias); in patients A no ventricular dysrhythmias were observed. Our data suggest that very low calorie diets containing protein of high biologic value can be associated with potentially dangerous arrhythmias.

Adolescent↗

Dysrhythmias following the Mustard and Senning operation for transposition of the great arteries.

The prevalence and nature of late dysrhythmias following operative repair of transposition of the great arteries were evaluated in 32 children using pre- and postoperative standard electrocardiograms and postoperative Holter monitoring. The Mustard procedure was performed in 17 patients, the Senning procedure in 15 patients. The mean age at operation was 40 +/- 35 months in the Mustard and 9 +/- 6 months in the Senning group. The mean interval between operation and Holter monitoring 7 +/- 2 years in the Mustard and 1.6 +/- 1 years in the Senning group. All patients had sinus rhythm preoperatively. Following operation, the incidence of sinus rhythm increased from 59% in the Mustard and 87% in the Senning group in the first postoperative week to 76% in the Mustard and 100% in the Senning group at the end of follow-up (mean 4.6 +/- 3.5 years). Holter monitoring revealed dysrhythmias or conduction abnormalities in 12 patients (9 Mustard, 3 Senning). A permanent pacemaker had to be inserted in 2 Mustard patients because of complete atrioventricular block and sinus bradycardia with sinus arrest, respectively. Results indicate a prevalence of late postoperative dysrhythmias of 20% in the Senning and of 59% in the Mustard group (p less than 0.05). However, the significantly longer mean follow-up period of the Mustard group precludes a direct comparison between the 2 types of repair.

Arrhythmias, Cardiac↗

Role of beta-endorphins in silent myocardial ischemia.

The reason for the absence of pain perception in silent myocardial ischemia is unknown. A role of increased endorphinic activity in patients with silent ischemia has been postulated. To further investigate this hypothesis, 10 men with documented coronary artery disease and previous positive electrocardiographic findings during exercise without anginal pain were studied. Six healthy volunteers served as control subjects. The protocol included 2 bicycle exercise tests, the first test serving as baseline and the second performed after administration of naloxone, a specific opiate antagonist. Plasma beta-endorphin levels were measured by radioimmunoassay in both tests at rest, at peak exercise level and after recovery. All patients underwent thallium-201 scintigraphy after coronary vasodilation to provide an additional independent marker of ischemia. All patients showed stress-induced reversible perfusion abnormalities. No patient reported pain after naloxone application. Exercise duration, blood pressure and heart rate were not significantly altered by naloxone. Plasma beta-endorphin levels ranged from 18 +/- 6 pg/100 microliters (mean +/- standard deviation) at rest to 22 +/- 6 pg/100 microliters during exercise in the patient group and from 20 +/- 5 to 27 +/- 9 pg/100 microliters in the control subjects. Thus, there was no significant increase of plasma beta-endorphins during exercise or after naloxone administration, nor was there any difference observed between patients and control group. These data support the view that endorphinic activity does not play an essential role in the pathophysiology of silent myocardial ischemia.

Blood Pressure↗

[R spike potentials in ergometric stress: patients with dilated cardiomyopathy in comparison to coronary heart disease].

R-wave amplitude changes during exercise were compared in patients with cardiomyopathy (n = 32), patients with coronary artery disease (n = 58) and controls (n = 12). Patients with cardiomyopathy (CMP) had a smaller R-wave amplitude (RWA) at rest than those with coronary artery disease (CAD). At comparable levels of exercise patients with CMP showed no change in RWA, while those with CAD demonstrated an increase in RWA. Controls showed a decline in RWA. In patients with CAD changes in RWA during exercise were more sensitive in the detection of disease than ST-segment changes. Left ventricular function was the major determinant of the direction and magnitude of RWA changes both in patients with CMP and CAD, with lesser changes in RWA in patients with more severely reduced left ventricular function.

Blood Pressure↗