Long-Term Follow-Up After Right Atrial Radiofrequency Catheter Treatment of Paroxysmal Atrial Fibrillation

Catheter ablation of paroxysmal atrial fibrillation using long linear lesions in the right atrium is still under investigation, and its long-term follow-up is unknown. Methods: Thirty-six men and nine women (aged 51 ± 12 years) with symptomatic daily episodes of AF for 6 ± 5 years despite the use of 4.7 ± 1.5 antiarrhythmic drugs were studied between July 1994 and January 1996. Progressively longer ablation lines were performed in 3 groups of 15 consecutive patients each, using a 14-electrode catheter or a single-electrode dragging technique. Success was defined as atrial fibrillation elimination or recurrence for no longer than 6 hours over 3 months of observation. Patients who had fewer than 6 hours of atrial fibrillation per month were considered "improved." Medium- (11 ± 4 months) and long-term (26 ± 5 months) results were assessed clinically from a patient's diary and from Holter recordings. Results: After a follow-up of 11 months, 24 patients had a favorable result of the ablation procedure with or without additional antiarrhythmic drug therapy, representing 53% of the original cohort. After 26 ± 5 months of follow-up, these successful results were reduced to 17 patients (37%). Conclusions: After linear atrial ablation, a significant long-term attrition of arrhythmia-free patients was observed. This may be due to a combination of disease progression, incomplete linear block, and ineffective ablation of arrhythmogenic triggers.     

Synthesis of Thiazolotriazine Derivatives and Their Antinociceptive Effects in Mice

A series of 2-(4-arylpiperazin-1-yl-methyl)-4-methyl-1-oxo-5,6,8,8a-tetrahydro-thiazolo[3,4-d] [1,2,4]triazines was prepared and tested for antinociceptive activity. The compounds were prepared by the Mannich reaction from the corresponding 2-unsubstituted thiazolotriazines. When administered intraperitoneally most were found to have potent analgesic activity in the mouse during tests of phenylbenzoquinone-induced abdominal constriction; ED50 values (doses resulting in half the maximum effect) ranged from 10 to 87 mg kg^?1. Derivatives with a 3-chloro- or 4-fluorophenylpiperazinylmethyl side-chain in the 2-position of the bicyclic system were, when administered intraperitoneally at doses greater than 25 mg kg^?1, also effective in the hot-plate test without associated sedative effects. The compounds have a large therapeutic index; intraperitoneal LD50 values (doses which result in the death of half the animals) were > 700 mg kg^?1. Naloxone attenuated the analgesic activity of the 3-chloro derivative, suggesting the participation of μ-receptors in the antinociceptive effects of this drug. In addition, a non-opioid mechanism, probably related to enhancement of the release of 5-hydroxytryptamine and noradrenaline, or inhibition of the neuronal re-uptake of these compounds, has been evinced to explain the analgesic properties of the 3-chloro or 4-fluoro derivatives. These results provide evidence for the involvement of noradrenergic and 5-hydroxytryptaminergic pathways in the analgesic activity of 3 and 4. Because of their potential effectiveness, the 3-chloro- or 4-fluorophenylpiperazinylmethyl derivatives might be suitable for treatment of a wide variety of painful conditions and could be attractive reserve agents for patients dissatisfied with opioids.     

Fractional Flow Reserve: The Ideal Parameter for Evaluation of Coronary, Myocardial, and Collateral Blood Flow by Pressure Measurements at PTCA

To overcome the fundamental limitations of coronary arteriography to assess the functional significance of coronary artery disease, it is necessary to obtain direct information about coronary blood flow. Recently we validated three pressure flow equations, which enable calculation of maximum coronary, myocardial, and collateral flow by merely measuring aortic, central venous, and distal coronary pressures under the condition of maximum vasodilation and using an ultra thin pressure monitoring guide wire for distal coronary pressure recording. In this paper, the first clinical experiences of this method are described. For that purpose, the concept of fractional flow reserve (FFR) is important. Fractional coronary flow reserve (FFR_cor) is defined as the maximum achievable blood flow in a stenotic artery, divided by normal maximum flow in that same artery, i.e. maximum flow in that artery in the case that it would be completely normal. Fractional myocardial flow reserve (FFR_myo) is defined in a similar way, and recruitable collateral blood flow is expressed as a fraction of normal maximum myocardial flow. Fractional flow reserve, defined in this way, is easy to obtain at percutaneous transluminal coronary angioplasty (PTCA) by the pressure-flow equations, is independent of pressure changes, applicable to three vessel disease, and enables calculation of the separate contribution of coronary and collateral flow to total myocardial perfusion. In 18 patients a very close correlation was demonstrated between FFR_myo, calculated by pressure recordings at PTCA by the first pressure flow equation, and FFR_myo obtained by positron emission tomography, which is considered the gold standard for myocardial perfusion. In 60 other patients, maximum recruitable collateral blood flow at balloon inflation (Q_c/Q^N) was calculated according to the third pressure-flow equation and correlated to the presence or absence of ischemia. It could be demonstrated that Q_C/Q^N exceeds 22% in all 23 patients without ischemia, whereas Q_c/Q^N was less than 22% in 34 out of 37 patients who experienced ischemia during balloon inflation. This margin value of 22% is very close to the theoretically expected value of 20%. based upon a coronary flow reserve of 5 under standard physiologic conditions. It can be concluded that the concept of fractional flow reserve provides a rapid, accurate, and elegant way for quantitative assessment of maximum coronary and myocardial blood flow before and after PTCA. Moreover, this is the first method that enables quantitative calculation of collateral blood flow in clinical practice. (J Interven Cardiol 1993; 6:331–344)     

Release of platelet-activating factor (PAF-acether) from alveolar macrophages by the calcium ionophore A 23187 and phagocytosis

Platelet-activating factor (PAF-acether) was recovered from rabbit, rat and human alveolar macrophages stimulated with the Ca++ ionophore A23187. PAF-acether release was also obtained from rat and rabbit macrophages in the presence of zymosan, but not from human alveolar preparations in spite of the phagocytic activity exhibited by the latter cells. Observed releases were active, Ca++ dependent, and plateaued at 45 min. No PAF-acether was released from lungs washed out of their macrophages, another argument against the mastocyte origin of this mediator. Given the potent bronchoconstrictive activity of PAF-acether, its release from alveolar macrophages may provide an alternative explanation for non IgE-dependent asthmas and the implication of platelets in pulmonary diseases.