EFFECT OF EARLY BLOCKADE OF BRADYKININ B2-RECEPTORS ON THE BLOOD PRESSURE PHENOTYPE OF NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS

We evaluated if chronic blockade of bradykinin B₂-receptors by the long-acting antagonist Icatibant (D-Arg,‘Hyp³,Thi⁵,D-Tic⁷,Oic⁸’-bradykinin) affects blood pressure of rats. Pairs of normotensive Wistar Kyoto rats or spontaneously hypertensive rats were mated and their offspring received Icatibant (25 nmol day⁻¹per kg body wt., s.c.) or vehicle from the 2nd day until the 7th week of life. Then, the administration of Icatibant or vehicle was continued by i.p. infusion using Alzet osmotic pumps. At 9 weeks of age, normotensive rats given Icatibant showed greater systolic blood pressure (135±1vs115±1 mmHg in vehicle-treated rats,P<0.01), while heart rate was similar. The group difference regarding blood pressure levels was confirmed by direct intra-arterial measurement. No difference was detected between vehicle- and Icatibant-treated spontaneously hypertensive rats regarding blood pressure increase with aging. In conclusion, chronic blockade of bradykinin receptors by Icatibant alters the adult cardiovascular phenotype of Wistar Kyoto rats, provided that the antagonist is given at the early phases of life. These results suggest that the B₂-receptor is essential for the maintenance of cardiovascular homeostasis during development, whereas it does not exert a protective role against the progression of hypertension in a rat model of genetic hypertension.     

Inhibition of Feline Immunodeficiency Virus Infectionin Vitroby Envelope Glycoprotein Synthetic Peptides

Sixty-six 20- to 23-amino-acid synthetic peptides, partially overlapping by 10–12 amino acids, spanning the entire sequence of the envelope SU and TM glycoproteins of the Petaluma isolate of FIV, have been used to investigate the Env domains involved in viral infection. Peptides 5 to 7, spanning amino acids²²⁵E–P²⁶⁴located in a conserved region of the SU protein, and peptides 58 to 61, spanning amino acids⁷⁵⁷N–P⁸⁰⁶and encompassing hypervariable region 8 of TM protein, exhibited a remarkable and specific antiviral effect against the homologous and one heterologous isolate, as judged by inhibition of FIV-induced syncytium formation and p25 production in CrFK cells. Peptides 5 and 7, but not peptides 58 and 59, also inhibited viral replication of a fresh FIV isolate on nontransformed lymphoid cells. By flow cytometry, peptides 5, 7, 58, and 59 were shown to bind the surface of FIV permissive cells. The antiviral activity of peptides 5 and 7, however, was time-dependent, as inhibition of FIV replication was seen when the peptides were administered before or within 3 hr after virus inoculation; in contrast, TM peptides 58 and 59 exerted a potent inhibitory effect when added up to 24 hr after virus inoculation. Circular dychroism analysis showed that peptide 5 folds to a helical conformation in the presence of a hydrophobic environment. Although the basis for the antiviral action of the peptides is not understood, our data suggest that the inhibitory peptides may act by interacting with cell-surface molecules involved in viral infection.     

Tobacco smoking and risk of haematological malignancies in adults: a case–control study

A retrospective study was conducted in 1216 cases to investigate the possible association between tobacco smoking and the risk of haematological malignancies. A small, but not significant, increase in malignancy was observed in smokers. Significant association was demonstrated between tobacco smoking and acute non-lymphoblastic leukaemia, and myelodysplastic syndromes. The duration and amount smoked increased the risk; heavy smokers presented significant positive associations with overall malignancies, acute nonlymphoblastic leukaemia, myelodysplastic syndromes, and monoclonal gammopathy of undetermined significance, whereas light smokers did not present any significant association. These data support a causal relationship between certain haematological malignancies and tobacco smoking. Further research is needed to examine the risk according to dose–response effect, and the variation in risk according to the histological subtype of the malignancy.     

Short-chain fatty acid topical treatment in distal ulcerative colitis

Background: Some evidence indicates that short-chain fatty acid (SCFA) enemas are effective in the treatment of distal ulcerative colitis. Methods: In a randomized, double-blind, placebo-controlled study, we tested the efficacy of a 6-week course of topical SCFA (100 mL, twice daily enemas of sodium acetate 80 mmol/L, sodium propionate 30 mmol/L and sodium butyrate 40 mmol/L) in 40 patients with mild to moderate distal colitis. Clinical, endoscopic and histological data were collected at the beginning and end of the study. Results: Fourteen patients on SCFA improved (overall score 11.3 ± 2.0 vs. 7.4 ± 3.5) as compared to five in the placebo group (overall score 10.0 ± 1.9 vs. 8.9 ± 2.5). In the SCFA-treated group all parameters significantly improved except the number of bowel motions, whereas no significant changes were recorded in the control group. A statistically significant difference between the two treatment regimens, however, was observed only for intestinal bleeding (P < 0.05), urgency (P < 0.02) and the patient self-evaluation score (P < 0.05). This was probably due to the random inclusion of more patients with moderate disease into the SCFA-treated group, thus causing pre-trial differences between the two groups. Conclusion: the present study confirms that irrigation with SCFA enemas is effective in distal colitis, and may represent an alternative therapeutic tool in the treatment of the disease.     

Increasing Cardiac Rate by Tracking the Respiratory Rate

Un stimulateur asservi qui utilise la fréquence venlilatoire comme capteur a été implunté chez 22 patients, dont 19 pour la stimulation ventriculaire et 3 pour la stimulation auriculaire. Le niveau d'exercice atteint en utilisant ce système a été toiijours supérieur à celui de la stimulation ventriculaire à fréquence fixe. En plus, aucun capteur chimique ou mécanique n'était utilisé; le capteur même est simple, durable et utilise une faible énérgie. Done, ce système s'adapte facilement à chaque patient individuel.     

The QT-Sensitive Cybernetic Pacemaker: A New Role for an Old Parameter?

A critical review of the available data on QT interval is presented to delineate techniques useful to the development of a QT-sensitive cybernetic pacemaker. The reason for the development of this unit stems from the ability of QT prolongation to predict the onset of life-threatening ventricular arrhythmias in some clinical situations; the QT interval is physiologically related to the cardiac cycle length, therefore providing adequate information to drive both ventricuiar and atrioventricuiar sequential rate-responsive pacemakers. This unit might also monitor cardiac rhythm and detect the pathophysioiogic precursors of advanced grades of ventricular arrhythmias. A therapeutic role, both pharmacologic and electrical, may also be possible in the future. Integration of these concepts and cooperation between interested physicians, technicians and manufactors will be necessary to produce such a unit at a low cost-benefit ratio. The potential clinical application of this pacemaker deserves attention for the prophylaxis and treatment of sudden arrhythmic death.     

A New Approach to the Prevention of Endless Loop Tachycardia in DDD and VVD Pacing

Endless loop tachycardia (ELT) is a possible complication in dual chamber pacing; it is usually prevented by programming the atrial refractory period (PVARP) longer than the retrograde ventriculoatrial (VA) conduction interval; this in some patients limits the upper rate. In 15 patients with a DDD (nine patients) or a single-pass lead VDD pacemaker (six patients) and retrograde atrial activation, telemetric recording documented a significant difference in amplitude of antegrade, and retrograde atrial potentials (VDD 1.21 ± 0.32 mV vs 0.56 ± 0.23 mV, P = 0.008; DDD 2.7 ± 1 vs 1.8 ± 1 mV, P - 0.038; Student's t-test for paired data). In 3/15 patients ELT stopped after programming of atrial sensitivity to a value. greater than the retrograde P wave amplitude; in 11/15 patients this occurred at a sensing value lower than or equal to retrograde P wave amplitude with a high pass band filter operating. One patient required PVARP lengthening. Holter monitoring showed no more ELTs. In most patients with a DDD or single-pass lead VDD pacemaker with widely programmable sensing amplitude and Hi/Low bandpass filters. individual programming of atrial channel sensitivity prevents ELT without affecting the PVARP and, consequently, upper rate limit.     

Impact of the Main Implantable Cardioverter-Defibrillator Trials for Primary and Secondary Prevention in Italy: A Survey of the National Activity During the Years 2001–2004

Background: Several trials demonstrated the lifesaving role of implantable cardioverter-defibrillator (ICD) in high-risk groups of patients. Aim of this review was to report the clinical characteristics of patients enrolled in the ICD Registry of the Italian Association of Arrhythmology (AIAC) in the years 2001–2004.
Methods: The Registry collects prospectively 85% of national ICD implantation activity on the basis of European ICD form (EURID).
Results: The number of implanted ICDs in Italy was 2,418 in the year 2001, 3,992 in the year 2002, 5,595 in the year 2003, and 7,190 in the year 2004. The number of ICDs per million of inhabitants was 42.1 in the year 2001 (+11.8% respect to 2000), 70.0 in the year 2002 (+65.1% respect to 2001), 98.3 in the year 2003 (+40.4% respect to 2002), and 125.0 in the year 2004 (+27.2% respect to 2003). The median age was 67 years in the years 2001–2002, 68 years in the years 2003–2004. The main indications during the study were syncope (24.2–14.9%) and cardiac arrest (28.5–17.3%), followed by palpitations and dizzy spells (15.5–17.2%, and 9.4–6.9% of patients, respectively). The use of prophylactic ICD had a fourfold increase in the examined period (5.8% in 2001, 22.9% in 2004). Ventricular tachycardia was the main arrhythmic indication in 44.4–54.6% of cases, ventricular fibrillation in 11.8–18.0%, both in 3.5–6.5%. In the years 2002, 2003, and 2004 single chamber ICDs were implanted in 45.5%, 38.8%, and 33.7% of patients, dual chamber ICDs in 35.1%, 32.3%, and 30.5%, biventricular ICDs in 19.4%, 28.9%, and 34.7%, respectively.
Conclusion: The ICD implantation rate in Italy increased significantly in the period 2001–2004, similarly to the trend in other western countries. The Registry showed an important increase of prophylactic and dual or triple chamber ICDs use.     

Permanent Overdrive Atrial Pacing in the Chronic Management of Recurrent Postoperative Atrial Reentrant Tachycardia in Patients with Complex Congenital Heart Disease

This study investigated the value of permanent atrial pacing as an adjunct to the current therapy in the chronic management of recurrent postoperative atrial reentrant tachycardia in patients with complex congenital heart disease. We studied the postpacing clinical course in 18 patients with recurrent atrial reentrant tachycardias unresponsive to conventional therapy who had an implanted atrial pacemaker. The pacemaker was programmed at a lower pacing rate 20% faster than the spontaneous mean daily rate previously determined with 24-hour Holter monitoring. Serial Holter recordings and pacemaker programming sessions were subsequently performed trying to mantain a paced atrial rhythm overdriving the spontaneous rhythm as long as possible. Twenty-four hour Holter monitoring documented a prevalent (> 80%) paced rhythm during the daily hours in all patients during the follow-up; all patients, however, required at least once a variation In programmed mode and pacing rate. Antiarrhythmic medications were discontinued after 6 months if the patient remained arrhythmia free while on pacing. Recurrences of atrial reentrant tachycardia occurred in five patients (29%) during the initial 6 months interval after the pacemaker implantation, while late recurrences occurred in only two patients (11 %). One patient died suddenly 10 months after the pacemaker implant. At the end of the follow-up, 15 patients (83%) were arrhythmia-free and only 2 of them were still on antiarrhythmic drugs. We conclude that permanent atrial overdrive pacing can be an important tool in the management of patients with atrial reentrant tachycardia following repair of congenital heart disease.