Is the Atrial High Rate Episode Diagnostic Feature Reliahle in Detecting Paroxysmal Episodes of Atrial Tachyarrhythmias?

The atrial high rate episode diagnostic in The Thera® pacemaker reports frequency, duration, and date/time of atrial tachyarrbytbmias according to programmed criteria. The aim of The study was to validate The atrial high rate episode diagnostic feature. Episodes of atrial fibrillation recorded by Holter monitoring were compared to episodes detected by the pacemaker. Eorty five ambulatory (Holter) recordings were used for evaluation. Thirty of 45 ambulatory (Holter) recordings showed sinus rhythm. On 4 of these 30 ambulatory (Holter) recordings, The Thera® detected 12 episodes of atrial tachyarrbythmias as false-positives (sinus rhythm was detected as atrial tacbyarrbytbmia). The main reason was far-field R and T wave oversensing. On 15 of 45 ambulatory (Holter) recordings, 125 episodes of atrial tachyarrhytbmias were recorded. Ninety-three of these events also were detected by the pacemaker, while for 32 events the Thera® reported sinus rhythm. The main reason was that the episodes were of too short duration. Therefore, the Thera® (programmed with detection rate 160 beats/min, detection beats 40, termination beats 10) was unable to detect atrial tachycardias. Software simulation of The diagnostic algorithm under several programming settings using the digitized Holter files demonstrated highly reliable detection of atrial tachyarrhythmias (sensitivity 98%, specificity 100%) when programmed as follows: detection rate 220 beats/min, detection beats 10, termination beats 20. It can be concluded that Thera®'s high rate episode monitor is a reliable tool for detection of a trial tachyarrhythmias, if programmed as recommended.     

Intracoronary Beta-Radiation Therapy for In-stent Restenosis: Long-Term Success Rate and Prediction of Failure

Objective: The following retrospective observational study assesses the long-term results of intracoronary beta-radiation therapy for patients with in-stent restenosis.
Background: Beta-radiation has been used to treat patients with coronary in-stent restenosis. However, long-term clinical success using this technique has not at this time been established.
Methods: Two-hundred and thirteen consecutive patients received intracoronary brachytherapy (noncentered beta-emitter, Novoste BetaCath™) for in-stent restenosis and were followed up over a period of 39.1 ± 18.4 months. The combined end-point was defined as a major adverse clinical event (MACE) and comprised mortality, acute myocardial infarction, or target vessel revascularization (TVR).
Results: MACE occurred in 110 patients (51.6%): death in 27 patients (12.7%), acute myocardial infarction in 8 patients (3.8%), TVR in 90 patients (42.3%). TVR comprised percutaneous coronary reinterventions in 76 patients (35.7%) and coronary bypass surgery in 24 patients (11.3%). Secondary end-point was determined as target vessel failure and occurred in 93 patients (43.7%). Of note, the frequency of at least two previous target lesion interventions as well as impairment of left ventricular function was associated with reduced success rate, whereas other clinical parameters did not indicate outcome after treatment with intracoronary radiation therapy.
Conclusion: During the mean, a period of 3 years, more than half of the patients receiving intracoronary radiation therapy reached primary end-point, representing, in the main, TVR. During this period a mortality rate of nearly 13% was documented. These results signify a delayed, though continued, restenotic process after index procedure. (J Interven Cardiol 2010;23:60–65)     

New Trends in Coronary Revascularization: Neoangiogenesis by Human Growth Factors

This article is a report of our clinical experience with the human growth factor FGF as applied to the ischemic human myocardium. After the completion of extensive preliminary animal experiments, the growth factor FGF, obtained from genetically manipulated Escherichia coli bacteria and highly purified, was introduced into aortocoronary bypass surgery as an additional therapeutic agent. A double-blind study was carried out on 40 patients with coronary heart disease, separated into "growth factor" and control groups, each containing 20 members. All patients were treated for coronary three-vessel vascular disease, in each case with an IMA bypass for the LAD and single venous bypasses for the RCX and or RCA. To bridge over additional peripheral stenoses in the LAD or one of its branches, human growth factor FGF was injected into the myocardium of those in the growth factor group. Twelve weeks later, the IMA bypasses were selectively demonstrated by intraarterial DSA. These angiographs were then quantitatively evaluated. In all patients of the growth factor group, the formation of new vessels could be demonstrated in the region where FGF had been administered in a manner strictly reminiscent of our experimental results. A capillary net sprouting from the coronary artery and making further connection with this vessel could be demonstrated, and the computer-supported evaluation of the angiographs showed a significant increase in the blood supply of the region of the myocardium injected. The use of FGF may be the appropriate treatment for patients with peripheral stenosis or diffuse coronary arteriosclerosis who cannot be treated surgically. However, large randomized studies are required to confirm these results.     

Evaluation of the in vitro and in vivo activity of the l-, d,l- and d-Cit6 forms of the LH-RH antagonist Cetrorelix (SB-75)

The objective of this study was to examine the in vivo and in vitro gonadotropin-inhibiting potencies, edematogenic activities and the receptor binding affinities of the d -Cit⁶, d,l -Cit⁶ and l -Cit⁶ forms of the LH-RH antagonist Cetrorelix (SB-75) [AC-d -Nal(2)¹,d -Phe(4Cl)²,d -Pal(3)³,d -Cit⁶,d -Ala¹⁰]LH-RH. In order to demonstrate the suppressive effects of two different diastereomers of SB-75 and their racemic mixture on LH and FSH release, [d -Cit⁶] SB-75 was injected subcutaneously in doses of 2.5 and 10 μg/rat, [d,l -cit⁶]-SB-75 in doses of 5 and 20 μg/rat and [l -Cit⁶] SB-75 in doses of 12.5 and 50 μg/rat to castrated male rats. Two hours after administration, there was no difference in LH levels between rats injected with the l -form and control animals, indicating a low activity and/or a rapid enzymatic degradation of this peptide. The (1:1) diastereomeric mixture was only about half as potent in suppression of LH release compared to [d -cit⁶] SB-75. Serum FSH levels were suppressed significantly (p<0.01) for more than 48 h after the administration of 10 μg [d -Cit⁶] SB-75 and 20 μg of [d,l -Cit⁶] SB-75, respectively. [d -cit⁶] SB-75 administered at a dose of 2 μg/rat induced 100% inhibition of ovulation, while 4 μg/rat of the d,l -Cit⁶ peptide were necessary to produce the same effect. [l -Cit⁶] SB-75 given at a high dose of 40 μg/rat produced only 14% inhibition of ovulation. The d -Cit⁶ form of SB-75 produced skin lesions with a much smaller diameter than the l -isomer, and was about 34 times less edematogenic. [d -Cit⁶] SB-75 was bound more powerfully to high-affinity pituitary LH-RH receptors than either d,l -Cit⁶ or l -Cit⁶ analogues. In vitro assays based on the superfusion of dispersed rat pituitary cells on a column, followed by radioimmunoassay for LH, also demonstrated a lower inhibitory activity for the l -Cit⁶ analogue, but the differences between d -, d,l - and l -citrulline analogues were smaller than in vivo. Our results indicate that the LH-RH antagonist [d -Cit⁶] SB-75 is more effective in suppression of gonadotropin release In vivo and in vitro, less edematogenic and possesses higher binding anity to pituitary LH-RH receptors than the d,l - and l -citrulline decapeptide analogues. © Munksgaard 1995.     

Interaction of laxatives with enzymes of cyclic AM P metabolism from human colonic mucosa

Abstract The mechanism by which laxatives such as dioctyl sodium sulfosuccinate and ricinoleic acid evoke colonic fluid secretion has been suggested to involve mucosal cyclic AMP. Ricinoleic acid and dioctyl sodium sulfosuccinate were tested for their capacity to modulate the key enzymes of cAMP-metabolism– adenylate cyclase and cAMP-phosphodiesterase–in human colonic mucosa.
Both laxatives were ineffective stimuli of human colonic adenylate cyclase. In contrast to ricinoleic acid, dioctyl sodium sulfosuccinate was a competitive inhibitor of soluble cAMP-phosphodiesterase activity. These experiments suggest that the cathartic properties of dioctyl sodium sulfosuccinate in human colonic mucosa might be mediated by cyclic AMP via inhibition of soluble phosphodiesterase activity.     

Radiofrequency Catheter Ablation of Frequent Monomorphic Ventricular Ectopic Activity

INTRODUCTION: Frequent ventricular ectopic beats can result in severe symptoms and may even be incapacitating in some patients. Although radiofrequency catheter ablation is an effective and safe therapy for drug refractory idiopathic ventricular tachycardia, it has not been widely used in ventricular ectopy. The purpose of this study was: (1) to assess the potential role of catheter ablation in eliminating monomorphic ventricular ectopy in symptomatic patients regarding feasibility and safety and (2) to determine the usefulness of various mapping strategies. METHODS AND RESULTS: Forty-one patients with symptomatic ventricular ectopic activity (right ventricular origin in 23 patients, left ventricular origin in 18 patients) were enrolled. The mean frequency of ventricular ectopic beats was 1512+/-583/hour documented by Holter ECG monitoring. These patients had previously been unable to tolerate or had been unsuccessfully treated with a mean of 3+/-1 antiarrhythmic agents. The site of origin was mapped using earliest endocardial activation times, unipolar electrograms and pace mapping. Radiofrequency ablation was successful in 34 (83 %) of 41 patients. Multivariate logistic regression analysis revealed pace mapping as the only independent predictor for a successful ablation site (P < 0.01). After a follow-up of 3 months, the overall success rate was 71%. The mean frequency of ventricular ectopic beats after successful ablation was 12+/-10 ventricular premature beat/hour. CONCLUSION: Radiofrequency catheter ablation is an effective and safe treatment for frequent symptomatic drug refractory monomorphic ventricular ectopic activity. Pace mapping predicts best successful ablation of ventricular ectopic beats.