The Histological Basis of Frank's Sign.

Frank's sign is a diagonal crease of the ear lobe, supposedly related to cardiac pathology, and has strongly been associated with coronary artery atherosclerosis. A total of 45 consecutive adult patients referred for autopsy in a one-and-a-half-year period were extensively studied. Samples from both the ear lobes were obtained for histopathology, as well as cardiac samples from all four cardiac compartments. When compared patients with Frank's sign and those without it had no statistical difference in age (p = 0.0575). There was however a statistically significant increased cardiac weight (p = 0.0005), left ventricular wall thickness (p = 0.0002), and right ventricular wall thickness (p = 0.0043). Histopathology obtained from the ear lobes revealed myoelastofibrosis in an arterial vessel, located at the base of the crease, diffuse fibrosis, and Wallerian-like degeneration, with eosinophilic inclusions in the peripheral nerves. These changes suggest a time-related progression of the crease-associated changes. Our data suggest a significant correlation between the morphological changes of the myocardium and the presence of the ear lobe creases, with arterial myoelastofibrosis, Wallerian-like degeneration in peripheral nerves and deep tissue fibrosis found in the base of the crease.

Decreased Activity of the Protein C Anticoagulant Pathway in the Early Hours of Paroxysmal Atrial Fibrillation.

BACKGROUND: Increased coagulation activity has been established in paroxysmal atrial fibrillation (PAF), but data on the anticoagulant system are scarce. PURPOSE: To examine the protein C anticoagulant pathway in the early hours of the disease. MATERIALS AND METHODS: Fifty-one patients (26 men and 25 women; mean age 59.84 ± 1.60 years) and 52 controls (26 men and 26 women; mean age 59.50 ± 1.46 years) were selected for the study. Protein C antigen and its activity, total protein S, free protein S and its activity, soluble forms of endothelial protein C receptor (sEPCR), and thrombomodulin (sTM) were examined in the plasma. RESULTS: The indicators were studied in patients between the 2nd and the 24th hour after the onset of arrhythmia. Levels of protein C were significantly elevated in patients compared to controls (111.40% ± 6.66% vs 94.83% ± 4.47%; P = .039). Protein C activity showed significant reduction in PAF (73.13% ± 5.80% vs 103.3% ± 3.80%; P < .001). Total protein S levels did not differ significantly (108.20% ± 4.07% vs 102.40% ± 3.65%; P = .30). Free protein S (76.81% ± 6.01% vs 122.10% ± 3.97%; P < .001) and its activity (71.39% ± 6.27% vs 119.50% ± 6.54%; P < .001) were reduced in patients. Higher levels of sEPCR (203.10 ± 10.33 vs 133.10 ± 7.37 ng/mL; P < .001) and sTM (6.50±0.40 vs 4.48±0.28 ng/mL; P < .001) were measured in PAF. CONCLUSION: Protein C activity is reduced still in the first hours (until the 24th hour) of PAF clinical manifestation, determining reduced activity of the anticoagulant pathway as a whole. The established low levels of free protein S and its activity as well as low sEPCR and sTM levels are a possible explanation of the changes in protein C activity.

Early effects of paroxysmal atrial fibrillation on plasma markers of fibrinolysis.

There are no studies to date on the early changes in the hemostasis profile of patients with paroxysmal atrial fibrillation (PAF).Given the key role of the fibrinolytic system in maintaining blood fluidity, our aim was to examine its activity in patients with clinical manifestation of the disease <24 hours.We studied 51 nonanticoagulated patients with a first episode of the disease (26 men, 25 women; mean age 59.84 ±â€Š1.60 years) and 52 controls (26 men, 26 women; mean age 59.50 ±â€Š1.46 years) who matched the patients in terms of gender, age, comorbidities, and conducted treatment. Using enzyme-linked immunoassays and colorimetric assays we assessed the plasminogen activity, tissue plasminogen activator level (t-PA), plasminogen activator inhibitor 1 activity (PAI-1), α2-antiplasmin activity (α2-AP), D-dimer level, and vitronectin level. Blood samples were collected immediately after hospitalization.Patients were hospitalized between the second and twenty fourth hours (mean 8.14 ±â€Š0.76 hours) after the onset of PAF. Compared to controls, plasminogen (159.40 ±â€Š4.81 vs 100.2 ±â€Š2.88%, P < 0.001) and t-PA levels (11.25 ±â€Š0.35 vs 6.05 ±â€Š0.31 ng/mL, P < 0.001) were significantly higher in the patient group. PAI-1 activity (7.33 ±â€Š0.37 vs 15.15 ±â€Š0.52 AU/mL, P < 0.001) and α2-AP (112.9 ±â€Š2.80 vs 125.60 ±â€Š3.74%, P < 0.05) as well as vitronectin plasma levels (134.7 ±â€Š5.83 vs 287.3 ±â€Š10.44 mcg/mL, P < 0.001) were lower in the PAF group. Conversely, the levels of D-dimer in patients were significantly higher (0.53 ±â€Š0.07 vs 0.33 ±â€Š0.02 ng/mL, P < 0.05).Early changes in the fibrinolytic system occur in PAF, suggesting their close relationship with the manifestation of the disease. There is high plasma fibrinolytic activity, during the very first 24 hours of the disease, which is most likely a pathophysiological response to the intensified procoagulation process.

Significant Increase in C-Reactive Protein and Serum Amyloid A in the Early Hours of Paroxysmal Atrial Fibrillation.

BACKGROUND: A number of data have been accumulated on inflammation in persistent and permanent atrial fibrillation (AF). Our aim was to study the process in paroxysmal AF (PAF) by measuring plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA) and fibrinogen in dynamics. METHODS: The markers were investigated in 51 patients (26 males and 25 females; 59.84 ± 1.60 years) at hospital admission (baseline), 24 hours and 28 days after sinus rhythm restoration. Fifty-two controls (26 males and 26 females; 59.50 ± 1.46 years) were selected. RESULTS: At baseline, hs-CRP and SAA concentrations were higher in patients (8.12 ± 0.82 vs. 5.57 ± 0.21 mg/L, P = 0.003; 16.04 ± 0.93 vs. 5.12 ± 0.23 ng/mL, P < 0.001, respectively) and these changes persisted 24 hours after sinus rhythm restoration (8.16 ± 0.71 vs. 5.57 ± 0.21 mg/L, P < 0.001; 12.99 ± 0.75 vs. 5.12 ± 0.23 ng/mL, P < 0.001, respectively). On the 28th day, no significant difference was measured (5.42 ± 0.29 vs. 5.57 ± 0.21 mg/L, P = 0.68; 5.89 ± 0.38 vs. 5.12 ± 0.23 ng/mL, P = 0.08, respectively). At any measurement, fibrinogen levels did not differ between patients and controls (3.30 ± 0.17 vs. 3.22 ± 0.11 g/L, P = 0.70; 3.32 ± 0.11 vs. 3.22 ± 0.11 g/L, P = 0.52; 3.24 ± 0.13 vs. 3.22 ± 0.11 g/L, P = 0.90, respectively). CONCLUSION: PAF is associated with dynamics in hs-CRP and SAA plasma levels. The results suggest that inflammation is closely related to the arrhythmia initiation.

Early Changes in the Antithrombin and Thrombin-Antithrombin Complex in Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: Data on coagulation changes in paroxysmal atrial fibrillation (PAF) are scarce. The aim of this study was to examine plasma antithrombin (AT) levels and activity as well as thrombin-antithrombin (TAT) complex levels in the early hours of the clinical manifestation of PAF. METHODS: Fifty-one patients (26 men and 25 women; mean age 59.84 ± 1.60 years) were consecutively selected with PAF duration < 24 hours, and 52 controls (26 men and 26 women; mean age 59.50 ± 1.46 years) matched the patients in terms of gender, age and comorbidities. Plasma levels and activity of AT and levels of the covalent TAT complex were studied once in each study participant. RESULTS: AT plasma levels in PAF patients were statistically significantly lower compared to controls (164.69 ± 10.51 vs. 276.21 ± 8.29 µg/mL, P < 0.001). Plasma activity of the anticoagulant was also significantly lower in PAF (71.33±4.87 vs. 110.72±3.09%, P < 0.001). TAT complex concentration in plasma was higher in the patient group (5.32 ± 0.23 vs. 3.20 ± 0.14 µg/L, P < 0.001). CONCLUSION: We can say that PAF is associated with significantly reduced AT levels and activity and increased levels of TAT complex during the first 24 hours after its manifestation. These changes indicate a reduced activity of AT anticoagulant system, which is a probable prerequisite for the established enhanced coagulation (high TAT complex levels).

Paroxysmal atrial fibrillation: dynamics of the main antioxidant enzymes--superoxide dismutase and catalase.

INTRODUCTION: Researchers have a particularly strong interest in the mechanisms implicated in the clinical manifestation of atrial fibrillation. OBJECTIVE: To examine dynamically the activity of the antioxidant enzymes, superoxide dismutase and catalase in patients with paroxysmal atrial fibrillation (duration < 48 hours). MATERIALS AND METHODS: The studied parameters were examined in the erythrocytes of 51 patients (59.84 +/- 1.60, 26 men) immediately after their hospitalization, at 24 hours and 28 days after restoration of sinus rhythm. 52 controls (59.50 +/- 1.46, 26 men) were also included, none of which had a history of arrhythmia. Propafenone was used to manage the rhythm abnormality. The enzyme activity was determined by a spectrophotometric method. RESULTS: The average duration of atrial fibrillation episodes until the time of hospitalization was 8.14 hours (from 2 to 24 hours). During patient hospitalization the activity of superoxide dismutase and catalase was considerably higher compared to that of the controls (8.46 +/- 0.26 vs 5.81 +/- 0.14 U/mg Hb; 7.36 +/- 0.25 vs 4.76 +/- 0.12 E240/min/mg Hb; P < 0.001). This difference was maintained 24 hours after the rhythm regularization (7.19 +/- 0.25 vs 5.81 +/- 0.14 U/mg Hb, p < 0.001; 5.30 +/- 0.21 vs 4.76 +/- 0.12 E240/min/mg Hb, p < 0.05). Twenty-eight days after the restoration of sinus rhythm, the activity of catalase remained increased (5.11 +/- 0.08 vs 4.76 +/- 0.12 E240/min/mg Hb, p < 0.05). CONCLUSION: The paroxysmal atrial fibrillation in our study was characterized with significantly increased activity of superoxide dismutase and catalase even in the early hours of clinical manifestation of the disorder, which then slowly decreased with the restoration of sinus rhythm. Therefore, we can conclude that changes in oxidative status are closely related to the disease and are probably a part of the intimate mechanisms related to its initiation and clinical course.