Early restenosis after eversion carotid endarterectomy versus carotid stenting: a single-centre retrospective study.

AIM: The aim of our study was to compare the early restenosis rate between patients undergoing carotid artery stenting (CAS) and carotid endarterectomy (CEA) at a single cardiovascular institution. METHODS: In 2004, 368 carotid endarterectomies were carried out on 347 patients and 144 internal carotid artery stentings were performed on 140 patients. The mean follow-up time was 18.4 months (range 6-38 months). Restenosis rates were calculated with the Kaplan-Meyer method and the two groups were compared by using log-rank test. Perioperative outcome was also evaluated and the groups were compared with chi-square test. RESULTS: Significantly more perioperative complications occurred in the CAS group, mainly transient neurological (7.60% vs 2.20% in the CEA group, P<0.05) and cardiovascular symptoms (4.10% vs 1.10% in the CEA group, P<0.05). Moderate restenosis (50-69%) occurred in 11.41% (42/368) of CEA cases and in 4.86% (7/144) of CAS cases (P<0.05). Severe (70%) restenosis rates were 10.05 % in the CEA group and 3.47% in the CAS group (P<0.05). CONCLUSIONS: Incidence of restenosis after carotid artery stening was less common than after carotid endarterectomy. On the other hand, perioperative complications were recorded more often after CAS than following CEA.

Intrapericardial infusion of endothelin-1 induces ventricular arrhythmias in dogs.

OBJECTIVES: Recently, extremely high levels of endothelin-1 (ET-1) were detected in the pericardial fluid of patients with heart disease; however, the pathophysiological importance of this finding is not known. The present study was designed to characterize ET-1 levels in canine pericardial fluid and to investigate the effects of local high concentrations of exogenous ET-1 in vivo. METHODS: In anesthetized, open-chest dogs ET-1 (Groups 1 and 2: 11 and 33 pmol.kg-1.min-1; n = 6 and 6, respectively) or physiological saline (Group 3, n = 5) were infused into the closed pericardial sac for 40 min. In serial pericardial fluid and aortic blood plasma samples, ET-1 levels were measured by radioimmunoassay, and analysed by high-performance liquid chromatography (HPLC). Systemic arterial blood pressure, heart rate, cardiac output (CO), standard ECG and right ventricular endocardial monophasic action potentials (MAPs) were recorded. RESULTS: Basal pericardial fluid ET-1 levels were significantly higher than respective plasma levels (342 +/- 210 vs. 8.0 +/- 5.2 pmol.l-1, n = 14, P < 0.001. In HPLC analysis pericardial fluid ET-1 was indistinguishable from ET-1(1-21). Infusion of exogenous ET-1 into the pericardial space induced ventricular arrhythmias in all instances, which were associated with 9.7-fold increase in pericardial fluid ET-1 levels. Ventricular tachycardias developed in 9 of 12 animals. The arrhythmogenic effect of ET-1 was more apparent in dogs with the larger dose. Before the onset of arrhythmias, intrapericardial infusion of ET-1 increased QT time (Group 1: 207 +/- 18 to 230 +/- 23 ms, P < 0.01; Group 2: 220 +/- 12 to 277 +/- 17 ms, P < 0.01) and MAP duration at 90% repolarization (at 300 ms cycle length) (Group 1: 192 +/- 9 to 216 +/- 9 ms, P < 0.01; Group 2: 205 +/- 9 to 255 +/- 9 ms, P < 0.001). Hemodynamic variables did not change significantly prior to the onset of ventricular tachyarrhythmias. In Group 3, arrhythmias were not observed and all electrophysiological and hemodynamic parameters remained unchanged. CONCLUSIONS: Administration of exogenous ET-1 into the pericardial space induces ventricular arrhythmias associated with prolongation of QT time and MAP duration. Whether pericardial fluid ET-1 under pathophysiological conditions can ever reach sufficiently high levels to induce ventricular arrhythmias remains to be elucidated.

Modification of the cardiac transmembrane potentials and currents by polyamines.

Spermine up to 10(-5) M increased the resting potential (RP) and maximum rate of rise (Vmax) of the action potential (AP) and accelerated the initial (20, 50%) repolarization in isolated guinea-pig and cat atria. These effects were not modified by pindolol (4 X 10(-7) M) or atropine (3 X 10(-7) M) but were prevented by indomethacin (10(-6) M). The right papillary muscle of guinea-pig only showed the acceleration of repolarization while the other parameters were not changed. Spermine did not influence the inward membrane currents under voltage clamp conditions in frog sinoatrial fibers. Spermidine up to 10(-5) M increased RP, Vmax and the duration of AP in guinea pig papillary muscle. RP, Vmax and AP duration were moderately enhanced by spermidine in guinea pig atrium and were not changed in cat atrium. Spermidine was found to stimulate the inward membrane current. Its stimulatory effect was confined to the fast component of the inward current. Neither spermidine nor spermine were able to induce the Ca2+-dependent slow AP in 25 mM K+-depolarized atrium. It is suggested that polyamines influence cardiac membrane events which are responsible for AP and ionic currents.

A sensitive microplate-based continuous-monitoring (kinetic) assay for serum neutral endopeptidase (EC 3.4.24.11) activity.

A sensitive microplate-based continuous monitoring (kinetic) assay is described for the determination of serum neutral endopeptidase (EC 3.4.24.11) activity. The relatively simple technique is suitable for routine and serial measurements of neutral endopeptidase activity in human serum and other body fluids using a kinetic microplate reader. In 38 healthy blood donors (27 males, 11 females, age range 19-51 years) the mean activity of the enzyme was 3.43 +/- 1.02 U/l. The activities did not differ between sexes (P = 0.895, N.S.).

Diuretic and natriuretic actions of extract prepared from rat erythrocytes.

Freeze-dried preparation of rat erythrocytes was extracted into distilled water and after heat treatment the extract was chromatographed on Sephadex G-25 column. The effluent fractions were pooled, freeze-dried, dissolved in Ringer's solution and bioassayed for diuretic and natriuretic responses in anaesthetized non-diuretic rats. The active fractions potently enhanced urine output (about 9-fold control) and urinary sodium excretion (about 7-fold control). The responses started to develop after a lag period of approximately 10-20 min, peaked between 60-80 min post-injection and then diminished. The augmentation of sodium excretion persisted longer than the increased diuresis. The biological activity of the extract was retained after dialysis in a tube with nominal molecular weight cut-off below 1,000.

Investigating the dual nature of endothelin-1: ischemia or direct arrhythmogenic effect?

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, which may also elicit severe ventricular arrhythmias. The aims of our study were to compare the effects of total left anterior descending coronary artery (LAD) occlusion to intracoronary (ic.) ET-1 administration and to investigate the pathomechanism of ET-1 induced arrhythmias in 3 groups of anesthetized, open-chest mongrel dogs. In group A (n=10) a total LAD occlusion was carried out for 30 min, followed by a 60 min reperfusion period. In groups B and C ET-1 was administered into LAD for 30 min at a rate of 30 pmol/min (n=6) and 60 pmol/min (n=8). Epi- and endocardial monophasic action potential (MAP) recordings were performed to detect electrophysiologic changes and ischemia Blood samples for lactate measurements were collected from the coronary sinus (CS) and from the femoral artery. Infrared imaging was applied to follow epimyocardial heat emission changes. At the end of the ET-1 infusion period coronary blood flow (CBF) was reduced significantly in groups B and C (deltaCBF30MIN B: 21+/-2%, p<0.05; C: 35+/-2%, p<0.05), paralleled by a significant epimyocardial temperature decrease in group C (deltaT30MIN: -0.65+/-0.29 degrees C, p<0.05). Two dogs died of ventricular fibrillation (VF) in the reperfusion period in group A. Ventricular premature contractions and non-sustained ventricular tachycardic episodes appeared in group B, whereas six dogs died of VF in group C. Significant CS lactate level elevation indicating ischemia was observed only in group A from the 30th min occlusion throughout the reperfusion period (control vs. 30 min: 1.3+/-0.29 vs. 2.2+/-0.37 mmol/l, p<0.05). Epi- and endocardial MAP durations (MAPD90) and left ventricular epicardial (LV(EPI)) upstroke velocity decreased significantly in group A in the occlusion period. ET-1 infusion significantly increased LV(EPI) MAPD90 in group B and both MAPD90-s in group C. In conclusion, ischemic MAP and CS lactate changes were observed only in group A. Although ET-1 reduced CBF significantly in groups B and C, neither MAP nor lactate indicated ischemic alterations. ET-1 induced major ventricular arrhythmias appeared before signs of myocardial ischemia developed, though reduced CBF presumably contributed to sustaining the arrhythmias.

Presence of immunoreactive endothelin-1 and atrial natriuretic peptide in human pericardial fluid.

This study was undertaken to characterize endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) concentrations in human pericardial fluid, blood plasma, right atrial appendage and papillary muscle by use of specific radioimmunoassays. In patients undergoing cardiac surgery (n=16) pericardial fluid mean immunoreactive (ir-) ET-1 and ir-ANP levels were 36-fold and 4-fold higher than corresponding plasma levels, respectively. In high performance liquid chromatography (HPLC) pericardial fluid ir-ET-1 was indistinguishable from human ET-1[1-21] and the majority of pericardial fluid ir-ANP coeluted with human ANP[99-126]. Atrial tissue ir-ET-1 and ir-ANP concentrations were 17-fold and 870-fold higher than in ventricular tissue. Our present study demonstrated for the first time the presence of ir-ET-1 in the pericardial fluid in humans. Human pericardial fluid contained far the highest concentrations of ET-1 among all biological fluids tested thus far. The functions of pericardial fluid ET-1 and ANP on cardiac performance and coronary vascular tone require further investigations.

Characterization and stimuli for production of pericardial fluid atrial natriuretic peptide in dogs.

Recently high immunoreactive atrial natriuretic peptide (ir-ANP) levels have been found in the pericardial fluid of patients undergoing cardiac surgery. The present study was designed to characterize pericardial fluid ANP in anesthetized dogs. Pericardial fluid ir-ANP levels were 3.4-fold higher than plasma levels and the molecular form, revealed by high performance liquid chromatography, was indistinguishable from ANP[99-126]. Elimination of [125I]ANP was 5-fold slower in the pericardial space than in plasma. Activity of the major ANP degrading enzyme, neutral endopeptidase (NEP, EC 3.4.24.11), was 15-times higher in the pericardial fluid than in plasma. Right atrial balloon distension and rapid right ventricular pacing induced maximally 2.3-fold and 1.5-fold increases of pericardial fluid ir-ANP, respectively. Pericardial fluid ir-ANP concentrations and right atrial pressure values showed significant correlation during the stimuli. Our present results show that high concentrations of ir-ANP can be found in the dog pericardial fluid even under unstimulated conditions. Slow elimination of ANP from the pericardial fluid compartment may contribute to the high peptide levels. However this slow elimination cannot be attributed to a lower NEP activity. High basal levels of ANP in the pericardial fluid could be further increased by atrial balloon stretch and rapid ventricular pacing. The increase of pericardial fluid ir-ANP appeared to be a stretch-dependent response. ANP released into the pericardial fluid may be involved in the regulation of cardiac function and coronary vascular tone.

Enhanced accumulation of pericardial fluid ferritin in patients with coronary artery disease.

BACKGROUND: Ferritin is a storage protein for iron that can either represent a source of iron or perform a cytoprotective action as an iron sequestrant. OBJECTIVE: To compare the concentrations of ferritin in pericardial fluid of patients with valvular heart disease, serving as controls, and in patients with coronary artery disease. DESIGN: We studied a total of 59 consecutive male patients undergoing elective heart valve replacement (group 1: n = 22, mean +/- SD age 55 +/- 11 years) or elective coronary artery bypass grafting (group 2: n = 37, mean +/- SD age 59 +/- 9 years). METHODS: Iron status indicators, total protein and albumin concentrations, and lactate dehydrogenase activities were determined in pericardial fluid and serum samples obtained from patients during surgery. RESULTS: Pericardial fluid concentrations of ferritin in both patient populations were significantly (P < 0.001) greater than the concentrations in sera: group 1, 375 (107-2030) micrograms/l compared with 146.5 (21-407) micrograms/l; group 2, 1115 (226-2500) micrograms/l compared with 152.0 (16-398) micrograms/l (median (range)), respectively. Moreover, pericardial fluid ferritin concentration was significantly (P < 0.01) greater in patients undergoing coronary artery bypass grafting than in those undergoing heart valve replacement, whereas serum ferritin concentrations did not differ between the two patient populations. CONCLUSIONS: As pericardial fluid reflects the composition of the myocardial interstitium, we suggest that ferritin released can serve as a potential source of iron in the cardiac interstitium that may promote the generation of oxygen free radicals. Conversely, we presume that induction of ferritin synthesis, representing an important mechanism by which tissue adapts to hypoxic damage, can afford myocardial cytoprotection.

Altered polyamine levels in skeletal muscle of patients with myasthenia gravis.

Forty patients with myasthenia gravis were tested for polyamine content of the musculus sternothyreoideus removed during thymectomy. Cases with slight muscle alteration were found to show elevated values for all the three polyamines (putrescine, spermidine and spermine) examined with an increased spermidine/spermine ratio. In severe muscular atrophy, however, the high spermidine and spermine levels were accompanied by unchanged putrescine content and spermidine/spermine ratio. Denervational changes in polyamine levels parallel to the degree of muscular damage are useful indicators of the actual grade of muscle atrophy associated with myasthenia gravis. In histologically intact samples, without apparent signs of muscular atrophy the spermidine level and spermidine/spermine ratio were increased in comparison to the control. In addition to being very early signs of denervation, these higher values are possibly the biochemical expression of some adaptive, compensatory hyperfunction of the muscle fibers.

[New method for the intraoperative biochemical monitoring of cerebrospinal fluid in surgery of thoracoabdominal aortic aneurysms]. / Uj módszer a cerebrospinalis fluidum (CSF) intraoperatív biokémiai monitorozásában thoracoabdominalis aortaaneurysma-mútétek során.

Paraplegia remains to be one of the most dangerous complications following thoracoabdominal aortic surgery with an incidence of 0.5 to 40%. Therefore, intraoperative monitoring of spinal cord function is very important when choosing the appropriate surgical technique. Early detection of spinal cord injury continues to be a crucial problem, moreover, the currently applied electrophysiological methods appear to be inaccurate. The aim of the study was to detect prospective spinal cord injury intraoperatively by monitoring the biochemical parameters of the cerebrospinal fluid (CSF). The authors studied the reversible aerobic/anaerobic metabolic changes by monitoring CSF lactate levels, moreover S-100 protein and neuron-specific enolase (NSE) concentrations--specific for neuroglia and neuronal injury, respectively. One of the important methods to prevent paraplegia is the intraoperative CSF drainage, which may improve spinal cord perfusion. Between 1996-1998 51 patients underwent reconstructive thoracic or thoracoabdominal aortic aneurysm operation. The continuously drained CSF was collected in 10 ml fractions during the preparation, whereas during aortic cross-clamping and de-clamping 10 minute fractions were used. All CSF samples were immediately analysed intraoperatively for pH, pCO2, HCO3, potassium and lactate levels, S-100 protein and NSE were analysed by immunoluminescence. CSF lactate levels increased slightly during aortic clamping and a moderate, but non-significant increase was found in the hyperemic phase (reperfusion) in patients without spinal cord ischemia. Spinal cord injury was detected in 7 cases. These patients exhibited a significant CSF-lactate increase (control vs aortic cross-clamping: 1.9 vs 5.3 mmol/l), moreover CSF-lactate remained elevated throughout the whole operation. Paraplegia did not occur, Tarlov 2 paraparesis developed in four cases and three patients displayed cerebral damage. Intraoperative CSF--especially CSF-lactate--monitoring may help the operating team to detect early anaerobic changes of the metabolism the spinal cord.

[Activity of neutral endopeptidase in serum of patients with primary biliary cirrhosis]. / Neutrális endopeptidáz-aktivitás primer biliaris cirrhosisos betegek szérumában.

Neutral endopeptidase (neprilysin; EC 3.4.24.11) is present in the brush border membrane, for example in the bile ducts. We investigated serum neprilysin activity and its correlation with cholestatic markers in patients with primary biliary cirrhosis. Sera of 39 patients with primary biliary cirrhosis (37 females, 2 males, mean age 45 years, range 24-71 years) were investigated. Twenty-seven healthy volunteer subjects served as control. Serum neprilysin activity was measured by a sensitive microplate-based continuous monitoring kinetic assay. Succinyl-alanyl-alanyl-phenyl-alanyl-4- nitroanilide was used as substrate. For statistical analysis Kruskal-Wallis ANOVA by ranks and Mann-Whitney U test were used. The neprilysin activities were significantly higher in stages III (mean 13.2 +/- SD 10.8 U/l) and IV (21.8 +/- 17.5) than in the control subjects (2.4 +/- 2.9, p < 0.01). There was no significant difference in neprilysin activity between the patients with stages I and II, or between stage I + II (2.88 +/- 3.0) and the control. Positive correlation was found between the activity of neprilysin and serum bilirubin, alkaline-phosphatase and gamma-glutamyl-transferase (p < 0.005 for each). In this study we confirmed that serum neprilysin activity is elevated in patients with primary biliary cirrhosis at advanced stages and the elevation correlated with the cholestatic markers. The increased neprilysin activity seems to be an indicator for the severity and progression of the disease.

[Effect of regional hypothermia on cerebrospinal fluid parameters during thoracoabdominal aorta clamping in dogs]. / Regionális gerincveló hypothermia hatása a liquor összetételére thoracoabdominalis aortakirekesztés során állatkísérletben.

The most feared complication of thoracoabdominal clamping is the paraplegia or paraparesis following ischemic injury of the spinal cord. Early intraoperative recognition of this complication has not been solved yet. In our earlier experiment we found significant alterations of CSF glucose, lactate, pCO2 and Neuron Specific Enolase (NSE) levels during 60 minutes thoracoabdominal aortic clamping in dogs. The analysis of these parameters proved to be proper to follow metabolism of the spinal cord during this type of surgery. In our present paper we studied protective effect of regional hypothermia using peridural cooling by registration of above parameters. Statistical analysis of our data showed prevention of production of anaerobe metabolites in animals with icy peridural irrigation. The biochemical approach is appropriate for monitoring effectiveness of regional hypothermia of the spinal cord during aortic surgery.

[Thrombolytic therapy as pretreatment before vascular operations and radiologic interventions]. / Ersebészeti és intervencionális radiológiai beavatkozások elókészítése trombolízis alkalmazásával.

The authors describe their 60 cases of thrombolysis with steptokinase (SK). Thrombolysis was required in 55 patients because of arterial, while in 5 patients because of venous side thrombosis. The 73% of the patients with arterial occlusion where thrombolysis was applied belonged Fountain stage IV, while 27% to Fountain stage III. Graft occlusion occurred in 60% of all cases and the acute or subacute thrombosis of the native vessels required thrombolysis in 40%. The thrombolysis alone was sufficient in 26 patients, while it was completed with PTA in 9, with PTA and implantation of stent in 1 and with vascular surgical procedure in 10 cases. Reconstruction surgery was the final solution in 4 patients, for whom the thrombolysis was inadequate. Amputation was unavoidable in 8 cases. The thrombolysis therapy was successful in 77% in our experience. The high number of hemorrhagic complications was due to the bleeding of puncture hole. It needed surgical suture in 10 cases.

Kinetic assay for the determination of the oxidative stress biomarker, advanced oxidation protein products (AOPP) in the human blood plasma.

UNLABELLED: A number of human diseases and pathological conditions were found to be associated with increased oxidative stress. In the literature several techniques are available for the assessment of oxidative stress, but most of them are not applicable for a routine medical laboratory due to the complex methodology and/or financial reasons. We report here on a simple, inexpensive, kinetic assay for the determination of the oxidative stress biomarker, advanced oxidation protein products (AOPP) in the human blood plasma. METHODS: This study involved 70 patients (47M/23F; mean age: 64.6 y; range: 16-85) admitted to our Department with a wide range of cardiovascular and peripheral vascular diseases. Three critically ill patients were assigned for monitoring purposes. Plasma AOPP were simultaneously determined using an end-point assay as reference method and by a kinetic method developed in our laboratory. Plasma fibrinogen concentration was measured according to the Clauss method. RESULTS: There was a highly significant correlation (r2 = 0.588; p < 0.0001) between AOPP concentration (reference method) and AOPP reactivity (kinetic method). Both AOPP concentration and AOPP reactivity also significantly correlated with plasma fibrinogen concentration (r2 = 0.780; p < 0.0001; r2 = 0.564; p < 0.0001). The three representative cases presented appear to support the relevance of our novel method in the monitoring of critically ill patients. CONCLUSIONS: This simple and inexpensive kinetic assay can be widely used in any routine laboratory interested in oxidative stress research. It is especially recommended for monitoring critically ill or other patients.

Changes in the plasma concentration of soluble thrombomodulin in patients with severe carotid artery stenosis after eversion endarterectomy.

OBJECTIVE AND DESIGN: The purpose of the study was to investigate the putative role of soluble thrombomodulin (sTM) in severe carotid artery stenosis. MATERIALS AND METHODS: We prospectively studied 64 patients who were undergoing carotid endarterectomy (2001-2003). Plasma sTM concentration was determined in each patient before surgery and at 14 months postsurgery. -308 TNF-alpha promoter polymorphism was also determined. RESULTS: Strong negative correlation was found between the preoperative duplex scan values and the plasma sTM concentrations (R = -0.418, p = 0.0006). Patients with 308 A TNF-alpha genotype had significantly lower (p = 0.0415) preoperative sTM values than their counterparts with no such polymorphism. Soluble TM concentrations measured in plasma samples taken at the end of the postsurgical follow-up period of 14 months duration were significantly higher compared to the preoperative values (p < 0.0001). CONCLUSIONS: Our present findings indicate that sTM may be adsorbed to the atherosclerotic plaques or inflamed endothelium in carotid arteries. The pathological significance of this adsorption remains to be determined.