Reduced thrombin generation and soluble P-selectin after intravenous enoxaparin during PCI.

PURPOSE: The objective of our study was to identify changes in the coagulation and serum concentration of soluble P-selectin (sP-sel) after i.v. bolus of 0.75 mg/kg enoxaparin in a group of 33 patients during PCI. METHODS AND RESULTS: As compared to baseline, i.v. enoxaparin increased anti -Xa activity and FIIa inhibition together with APTT and thrombin time tests within 20 min, that persisted for 60 min. At 6 h, the results of all tests had returned to baseline. In contrast, the level of prothrombin fragments (F1 + 2) decreased persistingly for a period of 6 h (baseline 1.19 ± 0.42 nmol/l, after 20 min 1.03 ± 0.46 nmol/l, after 60 min 1.06 ± 0.43 nmol/l, after 6 h 0.95 ± 0.40 nmol/l, p < 0.001 vs. baseline for all values). In addition, i.v. enoxaparin decreased serum sP-sel level (baseline 111.80 ± 37.05 ng/ml, after 20 min 87.80 ± 33.17 ng/ml, after 60 min 86.45 ± 29.15 ng/ml, after 6 h 92.24 ± 31.34 ng/ml, p < 0.001 vs. baseline value for all). sP-sel level mildly correlated with both F Xa inhibition (r = -0.275, p < 0.05) and F1 + 2 level (r = 0.274, p < 0.05). CONCLUSION: Intravenous enoxaparin induced target F Xa inhibition (>0.6 IU/ml) for 60 min in 82% of study patients. During the 6 h of monitoring, a decrease of thrombin generation (F1 + 2) and sP-selectin levels were observed.

Hemodynamic response to thoracoscopy and thoracotomy.

Operations in the pleural cavity are connected with circulatory changes in pulmonary circulation and general changes of hemodynamics. These changes are influenced by the position of patient's body on the operation table and by the introduction of artificial pneumothorax. Thoracoscopy is an advanced surgical approach in thoracic surgery, but its hemodynamic effect is still not known. The aim of the present study was to compare the hemodynamic response to surgeries carried out by open (thoracotomy - TT) and closed (thoracoscopy - TS) surgical approach. Thirty-eight patients have been monitored throughout the operation--from the introduction of anesthesia to completing the surgery. Monitored parameters were systolic blood pressure (BPs), diastolic blood pressure (BPd), O2 saturation (SaO2), systolic blood pressure in pulmonary artery (BPPAs), diastolic blood pressure in pulmonary artery (BPPAd), wedge pressure (P(W)), central venous pressure in right atrium (CVP), cardiac output (CO) and total peripheral resistance (TPR). No significant difference has been found in hemodynamic response between TT and TS groups. Significant changes of hemodynamic parameters occurring during the whole surgical procedure were detected in both technical approaches. The most prominent changes were found after the position of patients was changed to the hip position (significantly decreased BPs, BPd, MAP, SaO2 and BPPAs) and 5 min after the pneumothorax was established (restoration of the cardiac output to the initial value and significant decrease of the TPR). It can be concluded that the thoracoscopy causes almost identical hemodynamic changes like the thoracotomy.

[The isolated form of cardiac amyloidosis in the form of beginning infiltrative cardiomyopathy without restrictive physiology]. / Izolovaná forma srdecní amyloidózy v podobe pocínající infiltrativní kardiomyopatie bez restriktivní fyziologie.

The authors describe an interesting case of isolated cardiac manifestation of AL-amyloidosis manifesting as an incipient infiltrative cardiomyopathy with heart failure symptoms due to moderate left ventricular diastolic dysfunction. Restrictive cardiomyopathy with severe diastolic dysfunction is considered as the characteristic manifestation of fully developed cardiac amyloidosis. However, the organ deposition of amyloid is progressive and left ventricular filling worsens continuously, starting with less advanced forms of diastolic dysfunction; the restrictive physiology is characteristic only for advanced phases of the disease. Therefore, the possibility of the incipient infiltrative cardiomyopathy due to the amyloidosis should be considered in patients with heart failure symptoms and echocardiographic findings of unexplained left ventricular hypertrophy with only mild or moderate diastolic dysfunction.

Characterization of gene therapy products and the impact of manufacturing changes on product comparability.

Gene therapy products represent a novel and complex class of products. Ensuring product safety, identity, purity and potency following a manufacturing change extends not only to assessing the final formulated product but also all the components used during product manufacturing. CBER has implemented a stepwise approach to product characterization and compliance with cGMPs, which increases as the study moves from phase 1 toward phase 3 and licensing. It is important that product characterization be performed early in product development because without full product characterization it will be difficult to determine the impact of the manufacturing process on the product as well as the impact any manufacturing change will have on the product. To demonstrate product comparability a thorough understanding of the manufacturing process, including product characterization, is necessary, so that the impact of a manufacturing change can be accurately assessed.

Effect of acute hyperglycaemia on sodium handling and excretion of nitric oxide metabolites, bradykinin, and cGMP in Type 1 diabetes mellitus.

AIMS: The aim of this study was to evaluate the effect of acutely induced hyperglycaemia on renal sodium handling and to explore the role of the bradykinin-nitric oxide-cGMP signalling pathway. PATIENTS AND METHODS: We compared 20 Type 1 diabetic (DM1) patients without microalbuminuria with 15 weight-, age-, and sex-matched healthy controls (C). Clearances of para-aminohippuric acid (CPAH), inulin (Cin), lithium, sodium, and urinary nitrite/nitrate (NOx), cGMP and bradykinin excretion rates were measured in two 90-min periods: a glycaemic clamp-induced euglycaemia (5 mmol/l-period I) and hyperglycaemia (12 mmol/l-period II) (Study 1) and during time-controlled euglycaemia (5 mmol/l-period I and 5 mmol/l-period II) to avoid the effects of time and volume load (Study 2). RESULTS: Cin and CPAH were not significantly different during euglycaemia (period I of Study 1) in DM1 and controls, whereas fractional excretion of sodium was decreased in DM1 (1.84 +/- 0.75 vs. 2.36 +/- 0.67%; P < 0.05) due to an increase in fractional distal tubular reabsorption of sodium (94.01 +/- 1.94 vs. 92.24 +/- 2.47%; P < 0.05). A comparison of changes during Study 1 and Study 2 revealed acute hyperglycaemia did not change renal haemodynamics significantly, while fractional distal tubular reabsorption of sodium increased (DM1: P < 0.05; C: P < 0.01) and fractional excretion of sodium decreased (P < 0.01) in both groups. The urinary excretion rates of NOx were comparable during euglycaemia in DM1 and C. While in C, they significantly increased during Study 1 (period I: 382 +/- 217 vs. period II: 515 +/- 254 nmol/min; P < 0.01) and Study 2 (period I: 202.9 +/- 176.8 vs. period II: 297.2 +/- 267.5 nmol/min; P < 0.05) as a consequence of the water load, no changes were found in DM1. The urinary excretion of bradykinin was lower in DM1 compared with C (0.84 +/- 0.68 vs. 1.20 +/- 0.85 micro g/min; P < 0.01) during euglycaemia; it was not affected by hyperglycaemia. There were no significant differences between DM1 and C and in cGMP urinary excretion rates following hyperglycaemia. CONCLUSION: This study demonstrates that DM1 without renal haemodynamic alterations is associated with impaired renal sodium handling. Moreover, we did not find a relationship between the renal excretion rates of vasoactive mediators and sodium handling due to hyperglycaemia.

[Effect of primary coronary angioplasty on long-term prognosis in patients with diabetes mellitus]. / Vliv prímé koronární angioplastiky na dlouhodobou prognózu nemocných s diabetes mellitus.

OBJECTIVES: To investigate feasibility and safety of primary PCI in diabetic patients. BACKGROUND: Diabetic patients with acute myocardial infarction (AMI) have been shown to be at high risk for adverse clinical outcomes. Limited data is available on long term prognosis of diabetics treated with primary PCI. METHODS: Retrospective analysis of consecutive 67 diabetic patients and 211 non diabetic patients treated with primary PCI from 1/1995 to 12/1999, follow up for 38 +/- 12 months. RESULTS: The baseline characteristics were comparable in both groups. The mean age was 62 years in diabetic patients and 59 years in non diabetic patients. Hypertension (50% vs. 36%, p = 0.05), contraindications to thrombolytic treatment (13.4% vs. 5.7%, p = 0.037), cardiogenic shock (16.4% vs. 7.1%, p = 0.023), multivessel disease (34% vs. 23%, p = 0.07) and longer time delay to treatment (240 vs. 180 min., p = 0.05) were more often present in diabetic group. 47% of diabetic and 42% of nondiabetic patients received stents. The TIMI 2 or 3 flow rates were reached in 91% of diabetic patients and in 90% of nondiabetic patients, but TIMI 2 flow was found more often in diabetics (9% vs. 2.4%, p = 0.016). Higher rate of bleeding complications leading to significant change in the blood count (7.5% vs. 1.4%, p = 0.01) and higher 30 day mortality (11.9% vs. 5.2%, p = 0.05) was observed in diabetic group. However when the shock patients were excluded from the analysis, the 30 day mortality was different insignificantly in both groups (4.5% vs. 2.4%, p = 0.36). During follow up of 259 acute phase survivors 24 patients died. There was a trend to higher total long term mortality (22.3% vs. 13.2%, p = 0.07) and higher rate of nonfatal reinfarction (13.4% vs. 6.2%, p = 0.05) in diabetic group. CONCLUSIONS: Primary PCI is safe and effective treatment of diabetic patients presenting with AMI. The higher rate of slow flow in infarct related artery after PCI observed in diabetics can be one of reasons for higher 30 day mortality in this group. Mean ischemic time in diabetics is behind the 4 hour border, where the possible benefit from reperfusion decreases. The main reason for higher mortality in our diabetic group was the higher rate of cardiogenic shock. Higher risk of bleeding complications at puncture site in diabetic patients can be explained by the lower quality of vessel wall.

Tobacco use amongst high school students in the Czech Republic.

OBJECTIVE: We were interested in the prevalence of smoking amongst teen-age students, its possible causes, and their understanding of its associated health risks. METHODS: We constructed a questionnaire that was responded to by a total of 419 students from 5 high schools in Prague, Czech Republic. Students were classified as non-smokers, mild (1-10 cigarettes daily), moderate (11-20 cigarettes daily), and severe smokers (>20 cigarettes daily). The survey also contained questions about passive smoking, motivation for smoking, the understanding of its associated health risks, alcohol consumption, and drugs. RESULTS: We found that amongst 16-20 years old high school students there are 37.5% smokers (38.0% men, and 37.0% women). The majority are mild smokers (82.3%), 15.8% moderate smokers and 1.9% heavy smokers. 29.0% of non-smokers reported passive smoking; i.e. that 65.7% of students are exposed to harmful effect of tobacco smoke. The average onset of smoking is at 14 years of age. The youngest smoker started smoking at the age of 5 years. Parents of 52.0% of students smoke (69.4% of smokers and 41.6% of non-smokers). Most of students know about the risk of lung cancer and cardiovascular diseases (86-99%). CONCLUSIONS: The prevalence of active and passive smoking among high school students is high. Parents smoking is significantly more frequent in teen-age smokers than in non-smokers. We consider the "teen-age" population together with their parents to be the key target for a successful antismoking campaign.

[Comparison of the morphology of atherosclerotic plaques in patients with stable angina pectoris and acute coronary syndrome using intravascular ultrasonography]. / Srovnání morfologie aterosklerotických plátu u nemocných se stabilní anginou pectoris a akutním koronárním syndromem pri vysetrení intravaskulárním ultrazvukem.

The article summarises present knowledge on the differences in the structure of atherosclerotic plaques in patients with stable angina pectoris and in those with acute coronary syndrome during intravascular ultrasound examination. Authors describe differences in the pathologic anatomy and also in the clinics. The review includes pictures of the typical structural features and references of papers with similar topics.

[Long-term prognosis in patients with acute myocardial infarct and treatment with direct coronary angioplasty]. / Dlouhodobá prognóza nemocných s akutním infarktem myokardu pri lécbe prímou koronární angioplastikou.

BACKGROUND: Primary coronary angioplasty (PTCA) has a beneficial effect on the immediate prognosis for patients with acute myocardial infarction. Number of information about effects of direct PTCA on the long-term prognosis are less numerous. The aim of the work was to establish the long-term prognosis for not-selected patients treated by direct PTCA. METHODS AND RESULTS: The studied group consisted of 279 patients with acute myocardial infarction treated by direct PTCA in years 1995 to 1999 for the period of 38 +/- 12 months. Part of them were out-door patients of our clinic. The necessary data of the other patients were obtained by a questionnaire and by a telephone contact. 45 (16%) patients were lost from the follow up. The mortality rate of the study group was compared with data in the central register of Czech Republic. Positive angiographic effect of the direct PTCA (residual stenosis < 50% + flow TIMI 3) was achieved in 90% of patients. 30-day mortality was 6.8%, after excluding patients with cardiogenic shock it decreased to 3.2%. 6 patients (2.2%) had non-fatal infarction within 30 days after the first attack. From 259 patients who survived the acute infarction phase 24 died during the next period of follow up, 18 (7%) patients had a relapse of non-fatal infarction. PTCA of the infarcted artery was done in 15% of patients, PTCA of another artery in 9% of patients. The aorthocoronary bypass was indicated in 6% of patients. Almost half of relapses occurred during the first year after the hospitalisation. The risk factors of the death during the follow up were the age > 70 years, ejection fraction < 35%, impairment of 3 or more coronary artery branches, i.m. in the history, duration of ischemia > 4 hours, and diabetes mellitus. The total mortality was 11.4% in the first year, 1.4% in the second and 3.3% in the third year of the follow up. CONCLUSIONS: The beneficial prognostic effect of the direct PTCA on patients with acute infarction carries through the whole period of follow up. Prognosis of the risk patients remains critical. Next revascularization of the infarcted artery was in our cohort of patients necessary in 21% of patients.

Interventional treatment of multiple vascular involvement in young male with heterozygous familial hypercholesterolemia.

We report a case of 31 year old man with heterozygous familial hypercholesterolemia and excessive tobacco use leading to acute myocardial infarction as the first manifestation of premature atherosclerosis. The patvent was treated by primary PTCA of occluded first marginal artery and at this time an attempt of recanalisation of occluded LAD was unsuccessful. The patient was referred for mini coronary bypass graft of the LIMA to LAD. During evaluation of carotid arteries we found a significant stenosis of the left internal carotid artery and occlusion of the left subclavian artery which made the use of LIMA unsuitable. Therefore, another attempt of PTCA of the occluded LAD was performed, this time with success. Hence PTA of the occluded subclavian artery was performed with good result. The patient was treated with the standard therapy of CAD and combined lipid lowering agents with significant reduction of plasma cholesterol. However, 2 years after the first MI, he suddenly died after swimming at the age of 31. In this patient the risk of premature CAD was increased by the presence of another powerful risk factor--the excessive tobacco use. Acute physical exercise probably acted as a trigger of acute coronary events at the time of both MI. Interventional methods were very effective in the treatment of multiple atherosclerotic lesions in this patient and provided significant relief of symptoms. Treatment of heterozygous FH is briefly discussed in this article.

[Comparison of the cost effectiveness of treatment of acute myocardial infarct with primary angioplasty and thrombolysis ]. / Srovnání cenové efektivity lécby akutního infarktu myokardu primární angioplastikou a trombolýzou.

INTRODUCTION: Primary angioplasty (PTCA) or intravenous thrombolysis are the recommended treatment of acute myocardial infarction. According to results of clinical investigations however primary PTCA provides a more favourable short-term as well as long-term prognosis. As this method is much more expensive we were interested in its cost-effectiveness as compared with cheaper intravenous thrombolysis. METHODS: We constructed an decision analysis model (programme DATA 3.5, TreeAge Software) to compare the strategy of primary PTCA and intravenous thrombolysis in acute myocardial infarction. Probabilities of clinical outcomes were obtained from a long-term randomized clinical trial (Zijlstra et al. NEJM, 1999). The relative risk of death in PTCA was 0.54, rehospitalization 0.52 and reinfarction 0.27. The costs of PTCA (100,000,- crowns), of streptokinase thrombolysis (4000,- crowns) and hospitalization (2820,- crowns) were estimated from costs of the catheterization laboratory and information obtained from health insurance companies. We assumed that the subsequent costs of treatment and quality of life after the first infarction were the same in both strategies. In patients with reinfarction we anticipated a reduced quality of life (coefficient of life quality 0.9). The average effect of treatment and costs of both strategies were evaluated in the course of five years. As an acceptable cost-effectiveness (ratio of difference in costs and effect) we considered costs up to 200,000,- crowns per one gained year of life. RESULTS: In the basic analysis we revealed that after 5 years the strategy of primary PTCA is more expensive (125,000,- crowns vs. 4500,- crowns) but has a greater effect, i.e. a longer life span (4.38 vs. 3.81) adjusted to quality of life). The cost-effectiveness (ratio of difference in costs and effect) expressing the costs of one gained year of life when using primary PTCA as compared with thrombolysis was despite the high cost of PTCA acceptable and amounted to 140,350,- crowns. Analysis of the sensitivity of the model confirmed the stability of favourable cost-effectiveness within a wide range of costs and therapeutic effect. CONCLUSION: Primary PTCA is in acute myocardial infarction a cost-effective strategy) providing effect for an acceptable cost) despite the markedly higher costs of the procedure.

[Effect of delaying reperfusion therapy with PTCA on long term prognosis in patients with acute myocardial infarct]. / Vliv délky zpozdení reperfuzní lécby prímou PTCA na dlouhodobou prognózu nemocných s akutním infarktem myokardu.

BACKGROUND: The benefit of thrombolysis in patients with acute myocardial infarction (AMI) strongly depends on the time from onset of symptoms to the initiation of treatment. For AMI patients treated with PTCA this time seems to be important only to a certain time level. The aim of this study was to assess the influence of time to treatment of AMI with coronary angioplasty on short term and long term prognosis. METHODS: We followed 339 consecutive AMI patients treated with coronary angioplasty from 1995 to 1999 in a cardiac care unit. Patients were divided to five groups according to time to treatment. RESULTS: Time to treatment < 90 min. was achieved in 35 (10.5%); 91-210 min. in 105 (31%); 211-330 min. in 72 (21%); 331-690 min. in 74; > 691 min. in 53 (15.5%) patients. Ischemic time (time from symptom onset to reperfusion) in the groups was < 2 h.; 2-4 h.; 4-6 h; 6-12 h; > 12 h. respectively. The ejection fraction of left ventricle 3-5 days after AMI was 50%, 51%, 45%, 40%, 46% and the 30 day mortality was 5.7%, 2.9%, 11.1%, 10.8%, 11.3% in the groups respectively, showing no significant differences between the groups. However the higher rate of TIMI 3 flow was achieved in patients with time to treatment shorter than 3.5 h. compared to patients treated later (93.6% vs. 83.9%, p = 0.007). The lower 30 day mortality (3.6% vs. 11.1%, p = 0.012), lower 3 year mortality (8.6% vs. 19.1%, p = 0.003), lover frequency of heart failure during hospitalisation (11.4% vs. 28.1%, p < 0.001) as well as lower maximal level of released kreatinkinase (32 +/- 29 vs. 44 +/- 39 mukat/l, p = 0.005) was observed in patients treated within 3.5 h. from symptoms onset compared to patients treated later. CONCLUSION: The success rate of primary PTCA to achieve normal flow in infarct related artery is high, but decreases when treatment is started later than 3.5 h. from AMI onset. The short term and long term mortality as well as incidence of heart failure during acute phase is lowest when the intervention was started within 3.5 h. from symptoms onset. Initiation of intervention after 3.5 h. resulted in significant mortality increase, but further delay of treatment had minimal impact on patients prognosis. Great effort needs to be paid to start the primary PTCA within 3.5 h. from AMI onset in as many patients as possible. From our data we can indirectly conclude: patients without a chance for reperfusion with thrombolytic therapy within 4 h. from symptoms onset should be considered candidates for PTCA regardless the time of transportation. In patients with chance to reperfuse infarct related artery within 4 h. from symptoms onset with thrombolytic treatment (thrombolysis needs to be started before 2.5-3rd h.) while having low probability to start PTCA within 3.5 h., the thrombolysis should be given first and PTCA performed later if needed.

[Direct percutaneous transluminal coronary angioplasty in patients with acute myocardial infarct treated at the Cardiac Center of the General Medical School Hospital in Prague: a 1-year retrospective study]. / Prímá perkutánní transluminální koronární angioplastika u pacientu s akutním infarktem myokardu v Kardiocentru Vseobecné fakultní nemocnice Praha: jednorocní retrospektivní studie.

UNLABELLED: Direct percutaneous transluminal coronary angioplasty (d-PTCA) in patients with acute myocardial infarctions (AIM) has become an alternative of thrombolytic treatment. If the involved department has adequate experience the success rate of the procedure is high and the immediate and long-term results are better than those of thrombolysis. Moreover contrary to thrombolytic treatment successful percutaneous coronary intervention in AIM is more beneficial for patients also later than 6 hours after the development of infarction pain. In the Cardiocentre of the General Faculty Hospital (GFH) patients with AIM are constantly attended, i.e. those indicated for reperfusion therapy are treated solely by the d-PTCA method. OBJECTIVE AND METHOD: Retrospective analysis of d-PTCA in AIM made during the annual period from Jan. 1 2000 to Dec. 31 2000. Into the observation study patients were included with clinical and/or ECG signs of AIM when the period from the onset of pain to the beginning of intervention did not exceed 12 hours. All patients were given before the procedures 500 mg of acetylsalicylic acid and 10,000 u. heparin. Cardiac catheterization was implemented by the percutaneous Seldinger technique via the a. femoralis l.dx., in exceptional cases from the left femoral artery. An approach via the a. radialis and/or a. brachialis was not used in any of the patients. From the investigation patients were excluded who had before the percutaneous coronary intervention (PCI) a thrombolytic preparation (so-called rescue-PTCA). RESULTS: During the mentioned period in the Cardiocentre of the GFH a total of 673 PTCA were performed, incl. 127 (18.9%) d-PTCA in patients with AIM. In the mentioned group of 127 patients subjected to intervention were 87 (68.5%) men and 40 (31.5%) women. The mean age of the men was 59.1 +/- 12 years and the mean age of the women 68.2 +/- 12 years. As to the main risk factors of coronary atherosclerosis arterial hypertension was present in 48%, smoking in 42%, diabetes in 23% and hyperlipoproteinaemia in 31% of the treated patients. More than one third of the patients had a history of myocardial infarction (38%). The infarcted artery was the r. interventricularis anterior (LAD) in 51 (40.2%), the right coronary artery (RCA) in 54 (42.5%), the r. circumflex (LCX) in 16 (12.6%), the left main coronary artery in 2 (1.6%) and the bypass in 4 (3.1%). Multiple coronary affections were recorded in 80 (63%) patients, affections of one artery in 47 (37%). Primary procedural success (flow TIMI 3/2) was achieved in 121 patients (95.3%). Normal flow through the infarcted artery TIMI 3 was achieved in 118/127 (85.8%) patients. In 91 (71.7%) into the infarcted artery a coronary stent was implanted, during hospitalization no subacute stenosis of the stent developed. The mean period between the onset of infarction pain--injection was 4.4 +/- 2.3 hours. The mean period of the entire procedures was 48 +/- 14.5 minutes. As contrast material only non-ionic contrast substances were used (Iomeron 350) with a mean consumption of 150 ml per patient. The mean skiascopic time was 13.6 +/- 1.8 min. A total of 9 (7.1%) patients were treated with GP IIb/IIIa receptor blockers (abciximab). The total hospitalization mortality of the intervened group was 7.1% (9 patients). In a sub-group of 9 patients who at the onset of the procedure were in cardiogenic shock 3 (33%) died. The hospitalization mortality of the sub-group of patients with AIM without cardiogenic shock, treated with d-PTCA was 5.1% (6/118). During hospitalization the authors did not observe any intracranial haemorrhage. DISCUSSION: The group of subjects with AIM subjected to catheterization who are treated by d-PTCA is relatively numerous in our department. According to a number of clinical studies successful d-PTCA in AIM gives better short-term and long-term results as compared with thrombolytic therapy. The primary success rate of d-PTCA was high and the hospital mortality was low and comparable with contemporary data in the literature. CONCLUSION: Direct PTCA is effective treatment in patients with acute myocardial infarction. The authors results confirm the high procedural success rate and acceptable hospital mortality. These favourable results of an invasive approach to treatment of AIM must be compared in future with bolus thrombolytic treatment by new types of thrombolytic preparations in combination with anti-platelet treatment with blockers of platelet glycoprotein receptors IIb/IIIa with/or without subsequent percutaneous coronary intervention.

[Complications in administration of contrast media in the catheterization laboratory: a 5-year retrospective study]. / Komplikace podání kontrastních látek v katetrizacní laboratori: petiletá retrospektivní studie.

UNLABELLED: Iodine contrast substances (CS) are used since the twenties of the 20th century. From the chemical aspect benzoic acid derivatives are involved which are classified according to their osmolality (high-low- and isoosmolar) tendency of ionization (ionic and non-ionic) and according to the molecular structure monomers and dimers). Side-effects are due to their osmotic, ionic and chemical action on tissues. They include a number of systemic and organ symptoms (cardiovascular, immunological, haemocoagulation, neurological and renal), from the clinical aspect divided into mild, medium severe and severe. The relatively high incidence of undesirable reactions when ionic high-molecular CS are used led to the-development of non-ionic preparations with a lower osmolality, the more extensive use of which is limited by economic factors. Moreover so far convincing clinical data are lacking that the higher incidence of undesirable reactions after the use of CS has a clinical impact. OBJECTIVE: To summarize experience with administration of CS in the catheterization laboratory of the Cardiocentre of the General Faculty Hospital during diagnostic and intervention procedures within 5 years with regard to the occurrence of undesirable effects when comparing ionic and non-ionic CS. METHOD: Retrospective analysis of a group of patients examined in the catheterization laboratory to whom a CS was administered during the period between Jan. 1 1995 and Dec. 31 1999. RESULTS: In 1995-1999 (5 years) in the catheterization laboratory a total of 10,149 procedures where implemented where ionic (ioxitalam-Telebrix 350) and non-ionic (iopromide Ultravist 370, ioversol--Optiray 370 and iomeprol-Iomeron 350) contrast substances were administered. Ionic CS were administered in 4,668 (46%) and non-ionic CS in 5,481 (54%) instances. Undesirable effects were recorded in a total of 107 (1.1%) patients, incl. ventricular fibrillation in 76 (0.75%), cardiac arrest in 12 (0.12%) and in 19 (0.19%) there were other undesirable effects (weakness, nausea, hypotension, flush, urtica etc.). Ionic and non-ionic CS participated equally in complications: ionic CS in 53 (49.5%) cases and non-ionic CS in 54 (50.5%), whereby no difference was observed in the type of complications. No death in conjucntion with administration of CS was observed. CONCLUSION: The use of contemporary contrast substances in the catheterization laboratory for diagnostic and intervention procedures on the heart is relatively safe with a minimal risk of development of serious complications. No difference was observed between the use of ionic and non-ionic CS.

Time course of endothelin-1 plasma level in patients with acute coronary syndromes.

An elevated plasma level of endothelin-1 was reported in several cardiovascular conditions including unstable angina pectoris and myocardial infarction. The present study was designed to evaluate the time course of the endothelin-1 release in unstable angina pectoris and to assess its relationship to the development of myocardial infarction and coronary vessel occlusion. The cohort studied included 32 patients with the clinical diagnosis of unstable angina pectoris who had been admitted to the coronary care unit and subsequently underwent coronary angiography (group A). Fourteen patients with chronic stable angina pectoris referred to routine diagnostic coronary angiography served as the control group (group B). A significant difference in the endothelin-1 plasma level was found between both groups, the values being 10.2 +/- 5.3 and 6.0 +/- 3.1 pg/ml (p < 0.01), respectively. There were, however, no significant differences between the following subdivisions of group A: patients with and without subsequent myocardial infarction; those with angiographically documented occlusion of at least one major branch of the coronary artery and no occlusion; and finally, those with persisting symptoms of angina pectoris and with favorable response to treatment. Neither was there any difference found among the subgroups differing in the time interval between the onset of chest pain and blood sampling. The time course of endothelin plasma concentrations showed elevated values lasting for more than 96 h after the index episode of prolonged chest pain. No correlation with the subsequent clinical course could be inferred. Thus, plasma endothelin level was elevated in patients with unstable angina pectoris and myocardial infarction and the increase persisted for several days after the onset of symptoms.

The immunophilin FKBP65 forms an association with the serine/threonine kinase c-Raf-1.

FKBP65 is a member of the FK506-binding protein class of immunophilins and is the only member reported to contain four peptidylprolyl cis-trans isomerase domains and an unrelated COOH-terminal domain. In this report, we show that the heat shock protein hsp90 and the serine/threonine protein kinase c-Raf-1 are components of FKBP65 immune complexes. The NH2-terminal regulatory domain of c-Raf-1 appears to be required for its interaction with FKBP65. Using GST-FKBP65 fusion protein and purified Raf proteins, we show that full-length FKBP65 can interact with c-Raf-1 but not B-Raf. The activation kinetics of c-Raf-1 after v-H-RasV12 injection of Xenopus oocytes appear to correlate with FKBP65/c-Raf-1 interaction, suggesting that FKBP65 may preferentially associate with forms of c-Raf-1 that are more posttranslationally modified. The interaction of FKBP65 with the c-Raf-heat shock protein 90 heterocomplex implicates this immunophilin in signal-transduction processes.

Local changes in the plasma endothelin level in the coronary artery immediately after percutaneous transluminal coronary angioplasty.

Endothelin plays an important role in cardiovascular pathology. As one of the most important endothelium-derived vasoconstrictor substances, endothelin together with endothelium-derived vasodilating factor control vascular tone and contribute to the vasoconstrictory response if the production of endothelium-derived vasodilating factor is impaired. The aim of the study was to assess the changes of the local endothelin level in coronary circulation immediately after percutaneous transluminal coronary angioplasty (PTCA). Plasma endothelin levels were measured in blood samples from the peripheral vein and ostium of the coronary artery before the angioplasty, and from the distal coronary artery just beyond the dilated segment and the peripheral vein immediately after the procedure. The plasma endothelin level was significantly higher in the ostium of the coronary artery already prior to PTCA as compared to the peripheral vein (10.9 +/- 3.4 vs. 7.2 +/- 2.1 pg/ml, p < 0.005). There was no change in the endothelin level in the coronary artery distal to the dilated segment immediately after the procedure as compared to the initial level, although this level was higher than the postangioplasty venous level (9.8 +/- 2.9 vs. 7.7 +/- 2.0 pg/ml, p < 0.005). Individual changes in coronary-artery plasma endothelin levels as a response to coronary angioplasty were disparate. An increase and a decrease in coronary artery plasma endothelin levels by more than 2 pg/ml after coronary angioplasty were observed in 3 and 6 subjects, respectively. In conclusion, increased plasma endothelin levels were found in blood samples drawn from the coronary artery as compared to the peripheral vein. There was no further change in the plasma endothelin level in the coronary artery distal to the dilated segment after angioplasty; however, the individual responses were disparate.

Molecular cloning, DNA sequence analysis, and biochemical characterization of a novel 65-kDa FK506-binding protein (FKBP65).

We have identified a mouse gene encoding a 65-kDa protein (FKBP65) that shares homology with members of the FK506-binding protein (FKBP) class of immunophilins. Predicted amino acid sequence shows that this protein shares significant homology with FKBP12 (46%), FKBP13 (43%), FKBP25 (35%), and FKBP52 (26%). FKBP65 contains four predicted peptidylprolyl cistrans-isomerase (PPIase) signature domains, and, although similar in size, is distinct from FKBP52 (also identified as FKBP59, hsp56, or HBI), which contains three FKBP12-like PPIase domains. With N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as the substrate, recombinant FKBP65 is shown to accelerate the isomerization of the prolyl peptide bond with a catalytic efficiency similar to other family members. This isomerization activity is inhibited by FK506 and rapamycin, but is not sensitive to Cyclosporin A. Based on Northern blot analysis, FKBP65 mRNA transcripts are present in lung, spleen, heart, brain, and testis. A polyclonal antibody, raised against a COOH-terminal peptide (amino acid residues 566-581), was used to immunoprecipitate FKBP65 from NIH3T3 cells and demonstrate that FKBP65 is a glycoprotein. In addition, [32P]orthophosphate labeling experiments show that FKBP65 is also a phosphoprotein. These results suggest that FKBP65 is a new FKBP family member.

Changes in proximal and distal coronary artery diameter during atrial pacing-induced myocardial ischemia.

BACKGROUND: The present study was designed to evaluate the role of tachycardia-induced dynamic coronary artery diameter changes in the development of myocardial ischemia. METHODS: Coronary angiography at rest and during atrial pacing-induced myocardial ischemia was performed in 22 patients. The diameter of the proximal and the corresponding distal coronary artery segments at rest and during pacing was measured using quantitative coronary angiography. Plasma levels of noradrenaline, adrenaline, dopamine and endothelin were determined in a subset of 14 patients in blood drawn from aorta and coronary sinus at rest and during pacing. RESULTS: Luminal diameter in normal proximal and distal segments increased, respectively, from 2.93 +/- 0.34 and 1.40 +/- 0.04 mm at rest to 3.03 +/- 0.25 and 1.58 +/- 0.07 mm during atrial pacing. The diameter of the proximal coronary artery segments with significant concentric stenosis decreased from 1.28 +/- 0.4 mm at rest to 0.95 +/- 0.34 mm during pacing, whereas segments with either significant eccentric or non-significant stenosis did not change significantly. A correlation was found between the noradrenaline level in the coronary sinus and the distal coronary artery diameter. CONCLUSIONS: A decrease in diameter of coronary artery segments with concentric stenosis during tachycardia might contribute to the development of myocardial ischemia. Some of the dynamic coronary artery changes may be influenced by the plasma level of noradrenaline. No evidence was found to suggest that dynamic changes in the diameter of proximal segments are related to the changes in diameter of the corresponding distal segments.