Thymic Hypoplasia due to a Bis-diamine

Bis(dichloroacetyl)diamine is capable of producing characteristic congenital malformations in high incidence. Wistar rats were given 200 mg/day of bis-diamine via a gastric tube on gestation days 9, 10 and 11. The fetuses of 14, 16, 18, 20 days and new born rats were examined using light and electron microscopes as well as rat T-cell surface markers. The thymus rudiment in rats treated with bis-diamine has been compared to the normal at each stages. A high incidence of aplasia or hypoplasia of the thymus was observed in treated groups. Histological studies of those revealed a short delay in appearance of lymphocytic cells in the thymus, which initially were blast like and later small lymphocytes, and also a delay in cortical and medullary differentiation of the thymus. Immunohistological studies using anti rat T-cell monoclonal antibodies confirmed the histological findings which show a delay of the development of the thymus. Bis-diamine induced anomalies were similar to those of the human primary immunodeficiency syndrome, particularly the DiGeorge syndrome.     

Concentrations of Human Atrial Natriuretic Peptide in the Cord Blood and the Plasma of the Newborn

ABSTRACT. Concentrations of human atrial natriuretic peptide (hANP) in the cord blood and the plasma were measured in 25 newborns. The level of hANP in 0 to 1 post-natal days (212.8±118.1 pg/ml; mean±SD) was significantly higher than that in cord blood (69.7±53.2 pg/ml) ( p < 0.005). There were no significant differences in the levels of hANP at the ages of 0 to 1, 4 and 6 post-natal days. The level of hANP did not show any significant correlation with urinary excretion of Na, urinary Na/Cr or Na/K ratios. Further evaluations should be made in order to clarify the role of hANP during the early post-natal period.     

SEQUENTIAL ULTRASTRUCTURAL CHANGES OF ARTERIES IN RATS INDUCED BY RESTRAINED STRESS

Single and repeated restrained stresses in rats were conducted as a model for evaluating sequential changes of gastric submucosal arteries evoked by stressful stimuli with an emphasis on medial alterations. By single restrained stress, three distinct acute changes of the media were found after a short time of the stress–withdrawal; (1) focal cytoplasmic necrosis, (2) fibrin in–sudation, and (3) leukocyte migration. These acute lesions were readily healed within 20 days without cellular increase or fibrous thickening of the intima. When the stress was repeated over a long period of time, medial smooth muscle cells showed marked degenerative changes ("atrophy with moth–eaten structure") with an increase of granular cell debris and basement membranelike materials. The results suggest that angiopathic effects of stresses may be attributed to the unsuited responsiveness of small artery to vasospasm and its sequential hemodynamic derangements. ACTA PATHOL. JPN. 33: 265 –273, 1983.     

Dynamic Changes of 12-Lead Electrocardiograms in a Patient with Brugada Syndrome

Dynamic ECG Changes in Brugada Syndrome. We present a patient with Brugada syndrome in whom 12-lead ECXis were recorded just before and after an episode of ventricular fibrillation (VF). A progressive elevation of both the RS-T segment and J waves just preceding and following the VF, and a close relationship between the amplitude of the RS-T segment and the preceding R-R intervals during atrial fibrillation, were documented. These findings support the hypothesis that RS-T elevation and a subsequent VF are related to a transient outward current-mediated spike-and-dome morphology of the epicardial action potential.     

A synthetic peptide derived from staphylokinase enhances plasminogen activation by tissue‐type plasminogen activator

Summary. Background: A synthetic nonadecapeptide (SP; GPYLMVNVTGVDGKGNELL) previously enhanced the activation of plasminogen by the SAK/plasmin complex. Objectives: To identify the binding site for SP on plasminogen and elucidate the effects of SP on plasminogen activation by the tissue‐type plasminogen activator (t‐PA). Methods: The effects of SP on plasminogen activation were estimated using a chromogenic substrate and from the cleavage of plasmin on SDS‐PAGE under reduced conditions. The binding to SP of various peptides derived from the amino acid sequence of plasminogen was analyzed with an IAsys biosensor. The SP‐mediated structural change to plasminogen was analyzed by circular dichroism (CD) spectroscopy. The thrombolytic effects of SP were examined using a mouse model of thrombosis. Results: SP enhanced the activation of plasminogen by t‐PA. The catalytic efficiency (k_cat/K_m) of Glu‐plasminogen activation by t‐PA was 11.4‐fold higher in the presence than absence of SP. The binding of SP to plasminogen was greatly inhibited by a synthetic peptide, FEKDKYILQGVTSWGLG, located close to the C‐terminal of the plasminogen B region. Near‐ultraviolet CD spectra of the complex between SP and Glu‐plasminogen significantly differed from those of Glu‐plasminogen. When SP was administered in a mouse model of thrombosis, early recanalization was observed in a dose‐dependent manner. However, SP did not cause recanalization in t‐PA gene‐deficient mice. Conclusions: SP bound to the B region and promoted the activation of plasminogen by t‐PA, and then induced effective thrombolysis.     

Characterization of Atrial Activation (A‐A) Intervals During Atrial Fibrillation Due to a Single Driver: Do They Reflect Atrial Effective Refractory Periods?

Characterization of Atrial Activation Intervals During AF . Background: The mean, median, and minimum local atrial activation (A‐A) intervals have been used to determine the local atrial effective refractory period (AERP) during atrial fibrillation (AF), the underlying assumption being that AF is due to multiple reentrant wavelets. Objective: We tested the hypothesis that when AF is due to a single, rapid, stable reentrant circuit (driver), the minimum and mean local A‐A intervals will be similar at sites in the reentrant circuit, but will vary widely at sites with fibrillatory conduction, making these latter intervals unreliable indicators of AERP. Methods: During sustained AF due to a left atrial (LA) driver in 6 sterile pericarditis dogs, electrograms were recorded from 186 bipolar electrodes from both atria. A‐A intervals were measured from each recording site during 1.2 seconds of AF. Minimum A‐A intervals as well as temporal (within site) and spatial (between sites) variability were determined from all sites. Results: A‐A intervals from each site during AF demonstrated that (1) 90–100% of right atrial (RA) sites and 18–39% of LA sites showed considerable (SD > 6 ms) temporal variability; (2) RA and LA sites with fibrillatory conduction (SD > 6 ms) showed considerable (a) spatial variability (RA: 9–36 ms; LA: 5–27 ms) and (b) variability of the minimum A‐A intervals (RA: 14–35 ms; LA 11–28 ms). Conclusion: During AF due to a driver, areas with fibrillatory conduction manifested considerable variability in the mean and the minimum A‐A intervals. Therefore, it is unlikely that any of the A‐A intervals reflect AERP. (J Cardiovasc Electrophysiol, Vol. 22, pp. 310‐315, March 2011)     

ATP Revealed Extra Pulmonary Vein Source of Atrial Fibrillation after Circumferential Pulmonary Vein Isolation

Noninducibility of atrial fibrillation (AF) by additional electrograms‐guided ablation may benefit the clinical outcome. This report illustrates the effect of adenosine triphosphate (ATP) injection on AF inducibility after pulmonary vein (PV) isolation. AF was triggered twice by ATP without PV reconnection. Meanwhile, complex fractionated atrial electrograms (CFAEs) were observed, and ablation targets on these sites appeared to be essential to the AF elimination. It suggests that CFAEs may contribute to the initiation of some AF. ATP may be useful to induce AF after proven PV isolation, and further ablation might be necessary to ensure efficacy after circumferential PV isolation. (PACE 2010; 33:248–251)     

Acute Effects of Different Atrial Pacing Sites in Patients with Atrial Fibrillation: Comparison of Single Site and Biatrial Pacing

It has been reported that a trial single site or biatrial pacing can suppress the occurrence of AF. However, its mechanism remains unclear. The study population included 32 patients with AF (n = 20: AF group), or without paroxysmal AF (n = 12: control group). The mechanism and efficacy of atrial pacing were investigated by electrophysiological studies to determine which was more effective for suppressing AF induction; single site pacing of the right atrial appendage (RAA) or distal coronary sinus (CS-d), or biatrial (simultaneous BAA and CS-d) pacing. In the AF group, AF inducibility was significantly higher with BAA extrastimulus during RAA (12/20; P < 0.0001) or biatrial paced drive (7/20; P < 0.01) than during CS-d paced drive (0/20). In the control group, AF was not induced at any site paced. In the AF group, the conduction delay and other parameters of atrial vulnerability significantly improved during CS-d paced drive. The atrial recovery time (ART) at RAA and CS-d was measured during each basic pacing mode. ART was defined as the sum of the activation time and refractory period, and the difference between ARTs at RAA and CS-d was calculated as the ART difference (ARTD). The ARTD was significantly longer during BAA pacing in the AF group than in control group (155.0 +/- 32.8 vs 128.8 +/- 32.9 ms, P < 0.05). In the AFgroup, ARTDs during biatrial (52.0 +/- 24.2 ms) and CS-d pacing (51.7 +/- 26.0 ms) were significantly shorter than ARTD during RAA pacing. The CS-d paced drive was more effective for suppressing AF induction than biatrial or RAA paced drive by alleviating conduction delay. CS-d and biatrial pacing significantly reduced ARTD compared with RAA pacing.