Prospective evaluation of a prostacyclin-sparing aspiring formulation and heparin/warfarin in aspirin users with unstable angina or non-Q wave myocardial infarction at rest

The aim of this trial was to compare the efficacy of combinationantithrombotic therapy with a prostacyclin-sparing aspirin plusanticoagulation versus conventional aspirin plus anticoagulation,when added to antianginal therapy, in patients with unstableangina or non-Q wave myocardial infarction already being treatedwith aspirin. In a double-blind (for the aspirin) study, 144prior aspirin users were randomized; 72 patients received controiled-release,prostacyclin-sparing aspirin 75 mg daily plus anticoagulation(intravenous heparin followed by warfarin to maintain the internationalnormalized ratio at 2–3), and 72 patients received conventionalaspirin 75 mg daily plus the same anticoagulation. Controlled-releaseaspirin was formulated to preserve endothelial cell prostacyclinsynthesis. Trial therapy was begun by 13.2 ± 12.3 h ofqualifying pain, and continued for 12 weeks. The frequency of recurrent angina with electrocardiographicchanges, myocardial infarction, or death, was analysed by intentionto treat. At 12 weeks, events were     

PROLONGED EXPRESSION OF THE c-kit RECEPTOR IN GERM CELLS OF INTERSEX FETAL TESTES

Stem cell factor (SCF) and its receptor Kit encoded by the c- kit proto-oncogene are crucial for the development and migration of primordial germ cells in rodents. The expression of Kit has been examined immunohistochemically in gonads obtained from five specimens of fetal tissues with intersex conditions which included 45,X/46,XY mosaicism; androgen insensitivity syndrome; and 46,XY/iso(p)Y mosaicism. Individuals with such disorders of sexual differentiation and Y-chromosome material carry a very high risk of developing testicular neoplasms. Fetal testicular germ cells of the intersex subjects expressed Kit at a later developmental age than controls, in which no Kit protein was detectable beyond the 15th week of gestation. This finding may indicate a disturbance of the chronology of germ cell development, or it may suggest a change of the regulation of c- kit expression in subjects with disorders of gonadal development.     

Synthesis of derivatives of phosphonic glutathione analogs*

Five analogs of S-t-butyl glutathione containing phosphonic analogs of glycine and glutamic acid were obtained by standard procedures of MA activation in solution. Simultaneous deprotection of phosphonic, carboxylic and amino groups was achieved in the silylation reaction.     

Results of Short‐Term and Long‐Term Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation Using Duty‐Cycled Bipolar and Unipolar Radiofrequency Energy

PV Isolation Using Bipolar/Unipolar RF Energy . Background: Electrical disconnection of the pulmonary veins (PV) plays an important role in the ablation of paroxysmal atrial fibrillation (AF). Antral ablation using a conventional steerable ablation catheter often is technically challenging and time consuming. Methods: Eighty‐eight patients (mean age 58 ± 11 years) with symptomatic paroxysmal AF underwent ablation with a circular mapping/ablation decapolar catheter (PVAC). Ablation was performed in the antral region of the PVs with a power‐modulated bipolar/unipolar radiofrequency (RF) generator using 8–10 W delivered simultaneously through 2–10 electrodes, as selected by the operator. Seven‐day Holter monitor recordings were performed off antiarrhythmic drugs at 3‐, 6‐, and 12‐month follow‐up, and patients were requested to visit the hospital in the event of ongoing palpitations. All follow‐up patients were divided into 2 groups: Group 1 with a follow‐up of less than 1 year and group 2 patients completing a 1‐year follow‐up. Results: Overall, 338 of 339 targeted PVs (99%) were isolated with the PVAC with a mean of 24 ± 9 RF applications per patient, a mean total procedure time of 125 ± 28 minutes, and a mean fluoroscopy time of 21 ± 13 minutes. Freedom from AF off antiarrhythmic drugs was found in 82 and 79% of group 1 and group 2 patients, respectively. No procedure‐related complications were observed. Conclusion: PV isolation by duty‐cycled unipolar/bipolar RF ablation can be effectively and safely performed with a circular, decapolar catheter. Twelve‐month follow‐up data compare favorably with early postablation results, indicating stable effects over time. (J Cardiovasc Electrophysiol, Vol. 21, pp. 399–405, April 2010)     

Investigation into Causes of Abnormal Cerebral MRI Findings Following PVAC Duty‐Cycled,Phased RF Ablation of Atrial Fibrillation

Asymptomatic Cerebral Lesions with Phased RF. Introduction: Left atrial catheter ablation of the pulmonary veins (PVs) is an established option for patients with atrial fibrillation (AF). Asymptomatic cerebral emboli (ACE) detected by diffusion weighted MRI (DW‐MRI) following AF ablation has been reported at varying rates. This variability may be linked to procedural variables and demographic risk factors. Animal studies with the multielectrode pulmonary vein ablation catheter (PVAC) have identified potential sources of emboli, including air introduced during PVAC introduction, inadequate anticoagulation, and high current densities when the distal (E1) and proximal (E10) electrodes are in contact. We sought to evaluate the incidence, size, and number of DW‐MRI findings with procedural modifications that potentially reduce the embolic load. Methods: Thirty‐seven AF patients (59 ± 10 years, 73% male, all with paroxysmal AF, left atrial [LA] diameter 44 ± 7 mm, left ventricular ejection fraction 57 ± 7%) underwent MRI sequences preceding ablation, within 24 hours postablation, and at 4–6 weeks. During the procedure all patients were on uninterrupted phenprocoumon, an attempted activated clotting time (ACT) level >300 seconds, had the PVAC introduced under saline, and antral ablation was started with a 2:1 bipolar/unipolar mode. Files from the ablation unit (GENius v14.4) were retrospectively analyzed to determine the relationship between E1 and E10 in close proximity and DW‐MRI findings. Results: Post procedure, 10/37 patients (27%) were positive for new DWI cerebral lesions. Nine of 10 patients had a single lesion, and 1/10 patient had 2 lesions. Average lesion size was 3.1 ± 3.9 mm (2–14 mm). One of 10 (10%) had lesions at MRI follow‐up. No neurological symptoms were observed. Eighteen of 37 (49%) of procedures had evidence of E1/E10 interaction. In the subgroup of patients with and without E1 and E10 in close proximity, the DW‐MRI rate was 8/18 (44%) and 2/19 (11%), respectively (P = 0.029). Conclusions: The source of positive DW‐MRI findings in LA ablation involves several factors. Controlling anticoagulation and careful sheath management helps to reduce the number and size of DW‐MRI lesions. With the PVAC catheter, an ablation with the E1 and E10 in close proximity increases the risk of a DW‐MRI finding. In the future, electrodes E1 and E10 should be kept apart to help reduce the incidence of acute ACE. (J Cardiovasc Electrophysiol, Vol. 24, pp. 121‐128, February 2013)     

Surprising Pharmacological Activity of Analogues Designed by Substitution of Position 3 in Arginine Vasopressin (AVP) and 8-D-Arginine Vasopressin with l-2-Naphthylalanine

In an attempt to develop more active and selective analogues of arginine vasopressin (AVP), two peptides have been designed, synthesized and tested for vasopressor (V₁-receptors) and antidiuretic (V₂-receptors) activities. We also estimated the uterotonic and anti-uterotonic activities of these compounds in-vitro. The first peptide, [(l -2-Nal)³] AVP is a highly active V₂-agonist. The second analogue, [(l -2-Nal)³, (d -Arg)⁸]VP is among the most potent antagonists of the vasopressor response to AVP. Moreover, it is the first V₁-antagonist devoid of anti-uterotonic activity. High antipressor potency of the second peptide was achieved without modification of position 1.     

PLASMA TESTOSTERONE AND ANDROSTENEDIONE LEVELS DURING MONITORED INDUCTION OF OVULATION IN INFERTILE WOMEN WITH 'SIMPLE' AMENORRHOEA AND WITH THE POLYCYSTIC OVARY SYNDROME

Twenty-seven infertile patients with ‘simple’ amenorrhoea-oligomenorrhoea and eighteen with the polycystic ovary (PCO) syndrome were treated for induction of ovulation with clomiphene, human menopausal gonadotrophin and human chorionic gonadotrophin. The treatment was monitored by plasma oestradiol, testosterone, andfostenedione and progesterone estimation. Women with PCO had significantly higher plasma androgen levels than women with ‘simple’ amenorrhoea (P < 0.01 to P < 0.001) both before treatment and during induction of ovulation. When ovulation was induced the pregnancy rate for women with the PCO syndrome with elevated androgens was 21% while for those with uncomplicated amenorrhoea it was 75%. It is concluded that high levels of circulating androgens might be a factor preventing conception in some patients in whom ovulation is apparently successfully induced.     

Atrial natriuretic factor enhances vasopressin-induced bradycardia in normotensive (WKY) but not in spontaneously hypertensive (SHR) rats

Effect of elevation of blood atrial natriuretic peptide (rat 1-28 ANF) level on pressor responses and bradycardia elicited by vasopressin (AVP) was compared in conscious normotensive (WKY) and spontaneously hypertensive (SHR) rats 14-16 weeks old, instrumented with arterial and venous catheters 1-2 days prior to the experiment. Blood pressure and heart rate were determined before and after i.v. injection of 2.5, 5.0 and 10.0 ng of AVP under control conditions (infusion of saline) and during infusion of ANF at a rate of 0.3 micrograms kg-1 min-1. Administration of ANF did not influence pressor responsiveness to AVP (determined as a maximum increase of systolic blood pressure) neither in WKY nor in SHR, however, it elongated the pressor response to the lowest dose of AVP in WKY. Atrial natriuretic factor significantly enhanced bradycardic responsiveness to AVP (determined as a maximum decrease of HR) in WKY but not in SHR. Reduction of heart rate in relation to the corresponding elevation of the systolic pressure (delta HR/delta SP) was also significantly greater in WKY but not in SHR. This effect was significant when blood pressure increases elicited by AVP did not exceed 40 mmHg. The results suggest that ANF potentiates reflex bradycardia elicited by AVP. This action may be a mechanism buffering blood pressure increases in response to AVP. Absence of this effect in SHR may be related to the impairment of the reflex control of blood pressure in this strain.     

Evaluation of Sinus and Atrioventricular Nodes Function in Patients with Vasovagal Syncope

Aim: Evaluation of sinus and atrioventricular nodes function as a potential factor responsible for prolonged bradycardia, asystole, or both in patients with cardioinhibitory and non-cardioinhibitory vasovagal syncope (VVS). The study included 258 patients (mean age = 47.7 ± 17.2 years; range 18–62; 147 females) with a history of VVS. They were divided among four groups, according to results of head-up tilt test (HUTT).
Methods: All patients underwent standard HUTT, carotid sinus massage (CSM), and rapid transesophageal atrial pacing for evaluation of total sinus node recovery time (SNRT), and corrected sinus node recovery time (CNRT), resting and intrinsic heart rate (IHR), and Wenckebach point (WP). Values of SNRT > 1,500 ms, CNRT > 525 ms, WP < 130 bpm, and CSM-induced pause >3 seconds were considered abnormal.
Results: SNRT, CNRT, and WP before and after pharmacological blockade, resting heart rate, and IHR did not differ significantly among the study groups. The prevalence of mild sinus node dysfunction (SND), decreased value of WP, and cardioinhibitory carotid sinus hypersensitivity was similar among all study groups.
Conclusions: The prevalence of mild SND, abnormal atrioventricular conduction, and carotid sinus hypersensitivity (CSH) was similar among patients with VVS regardless of the type of vasovagal reaction. SND and CSH do not seem to play an important role in the pathogenesis of cardioinhibitory vasovagal reaction.