Isomerism finds its importance in the field of clinical pharmacology and pharmacotherapeutics, as isomers differ in their pharmacokinetic and pharmacodyanmic properties. Drug isomerism has opened a new era of drug development. Currently, knowledge of isomerism has helped us in introducing safer and more effective drug alternatives of the newer as well as existing drugs. Many existing drugs have gone chiral switch i.e., switching from racemic mixture to one of its isomers. Cetrizine to levocetrizine is one of such examples, where effective and safer drug has been made available. In this article, we have attempted to review the basic concepts of stereochemistry and chirality and their significance in pharmacotherapeutics. Various pharmacological aspects such as pharmacokinetic and pharmacodynamic variations resulting out of chirality has been discussed in detail in this article.

No abstract

Background Ventricular tachycardia (VT) and premature ventricular complexes (PVC) most frequently occur in the context of structural heart disease. However, the burden of idiopathic ventricular arrhythmias (VA) in the general population is unknown. Methods and Results We identified incident cases of idiopathic VA between 2005and 2013 from Olmsted County, MN using the Rochester Epidemiology Project database. For PVC cohorts, we included those with frequent (defined as ≥100 PVC/24 hours) symptomatic PVCs. We defined idiopathic VA-associated cardiomyopathy as an EF drop of ≥10% from baseline. Between 2005 and 2013, we identified 614 individuals with incident idiopathic VA. (229 [37.3%] were male, average age was 52.1 ± 17.2 years). Of these, 177 (28.8%) had idiopathic VT, 408 (66.5%) had symptomatic PVCs and 29 (4.7%) had idiopathic VA-associated cardiomyopathy. The age- and sex- adjusted incidence rates in 2005–2007, 2008–2010 and 2011–2013 were 44.9 per 100,000 (95% CI 38.0–51.8), 47.6 per 100,000 (95% CI 40.8–54.5) and 62.0 per 100,000 (95% CI 54.4–69.6), respectively. In idiopathic VT, there was an increase in incidence rate with age s (P<0.001) but not between sexes (P=0.12). The age-adjusted incidence of symptomatic PVC was higher in females than males (46.2 per 100,000 [95% CI 40.9–51.6] versus 20.5 per 100,000 [95% CI 16.8–24.3], p<0.001). The small number of individuals with idiopathic VA-associated cardiomyopathy precluded any formal testing. Conclusions The incidence of idiopathic VA is increasing. Furthermore, overall incidence increases with age. While the rate of idiopathic VT is similar across genders, women have a higher incidence of symptomatic PVC.

No abstract

No abstract

Background Endocardial radiofrequency ablation of epicardial ganglionic plexus (GP) for atrial fibrillation (AF) is complicated by myocardial damage. Objectives We hypothesized that an epicardial approach with a novel nitinol catheter system capable of causing irreversible electroporation (IRE) with direct current (DC) could selectively and permanently destroy GP without collateral myocardial injury. Methods Acute studies and medium‐term terminal studies (mean survival, 1137 days) were performed with seven dogs. In the acute studies, DC was used to target epicardial GP within the transverse sinus, oblique sinus, vein of Marshall, and right periaortic space. Successful electroporation was defined as the presence of ablative lesions in the GP without collateral myocardial damage. A four‐point integer system was used to classify histologic changes in tissue harvested from the ablation sites. Atrial effective refractory period (AERP) was measured during the acute and medium‐term studies. Results For six dogs in the medium‐term studies, the postablation period was uneventful without complications. Lesions were successfully created at 20 of 21 sites (95.2%) with more than minimal myocardial damage in one dog. An increase in AERP occurred in both atria during the acute studies but was maintained only in the right atrium at medium‐term follow‐up (5032 milliseconds). No dog had damage to the esophagus, adjacent great arteries, or pulmonary veins. Conclusions This proof‐of‐concept study suggests that safe, effective, and selective epicardial ablation of GP can be performed with DC by IRE with minimal collateral myocardial damage.

BackgroundCurrent thermal ablation methods for atrial fibrillation, including radiofrequency and cryoablation, have a suboptimal success rate. To avoid pulmonary vein (PV) stenosis, ablation is performed outside of the PV, despite the importance of triggers inside the vein. We previously reported on the acute effects of a novel direct current electroporation approach with a balloon catheter to create lesions inside the PVs in addition to the antrum. In this study, we aimed to determine whether the effects created by this nonthermal ablation method were associated with irreversible lesions and whether PV stenosis or other adverse effects occurred after a survival period.Methods and ResultsInitial and survival studies were performed in 5 canines. At the initial study, the balloon catheter was inflated to contact the antrum and interior of the PV. Direct current energy was delivered between 2 electrodes on the catheter in ECG‐gated 100 μs pulses. A total of 10 PVs were treated demonstrating significant acute local electrogram diminution (mean amplitude decrease of 61.2±19.8%). After the survival period (mean 27 days), computed tomography imaging showed no PV stenosis. On histologic evaluation, transmural, although not circumferential, lesions were seen in each treated vein. No PV stenosis or esophageal injury was present.ConclusionsIrreversible, transmural lesions can be created inside the PV without evidence of stenosis after a 27‐day survival period using this balloon‐based direct current ablation approach. These early data show promise for an ablation approach that could directly treat PV triggers in addition to traditional PV antrum ablation.

No abstract