Renal Denervation for Hypertension: The Current Landscape and Future Directions.

Hypertension (HTN) is one of the largest contributors to cardiovascular (CV) morbidity and mortality in the USA and is estimated to affect 47% of the US population; however, recent estimates suggest that over 40% continue to have uncontrolled HTN. In the past decade, multiple placebo-controlled randomized studies have shown the safety and efficacy of renal denervation as an adjunctive therapy, culminating in the recent approval of two devices by the US Food and Drug Administration (FDA). These devices use either radiofrequency or ultrasound energies to ablate the perivascular sympathetic nerves in the renal arteries and have been shown to reduce blood pressure.

Advanced Treatment of Hemodynamically Unstable Acute Pulmonary Embolism and Clinical Follow-up.

High-risk acute pulmonary embolism (PE), defined as acute PE associated with hemodynamic instability, remains a significant contributor to cardiovascular morbidity and mortality in the United States and worldwide. Historically, anticoagulant therapy in addition to systemic thrombolysis has been the mainstays of medical therapy for the majority of patients with high-risk PE. In efforts to reduce the morbidity and mortality, a wide array of interventional and surgical therapies has been developed and employed in the management of these patients.

Papillary muscle ventricular arrhythmias in patients with arrhythmic mitral valve prolapse: Electrophysiologic substrate and catheter ablation outcomes.

Background: Mitral valve prolapse (MVP) is a common valve condition and has been associated with sudden cardiac death. Premature ventricular contractions (PVCs) from the papillary muscles (PMs) may play a role as triggers for ventricular fibrillation (VF) in these patients.

Objectives: To characterize the electrophysiological substrate and outcomes of catheter ablation in patients with MVP and PM PVCs.

Imaging characteristics of papillary muscle site of origin of ventricular arrhythmias in patients with mitral valve prolapse.

Background: Mitral valve prolapse has been associated with increased risk of ventricular arrhythmias. We aimed to examine whether certain cardiac imaging characteristics are associated with papillary muscle origin of ventricular arrhythmias in these patients.

Methods And Results: We screened electronic medical records of all patients documented to have mitral valve prolapse on either transthoracic echocardiogram (TTE) or cardiac magnetic resonance imaging (CMR) in our center, who also underwent an electrophysiologic study (EPS) between 2007 and 2016.

Effect of linker substitution on the binding of butorphan univalent and bivalent ligands to opioid receptors.

A series of bivalent hydroxy ether butorphan ligands were prepared and their binding affinities at the opioid receptors determined. Addition of a hydroxy group to a hydrocarbon chain can potentiate binding affinity up to 27- and 86-fold at the mu and kappa opioid receptors, respectively. Two bivalent ligands with sub-nanomolar binding affinity at the mu and kappa opioid receptors were discovered.

Univalent and bivalent ligands of butorphan: characteristics of the linking chain determine the affinity and potency of such opioid ligands.

Bivalent morphinan compounds containing ester linkers were synthesized and their binding affinities at the mu, delta, and kappa opioid receptors determined. Addition of methyl groups adjacent to the hydrolytically labile ester linkage increased stability while only partially affecting binding affinity. The resulting bivalent ligands with optimized spacer length and structure show potent binding profiles with the most potent compound (4b), having K(i) values of 0.

Synthesis and pharmacological evaluation of hydrophobic esters and ethers of butorphanol at opioid receptors.

We synthesized several hydrophobic esters and ethers of butorphanol and assessed their affinities at opioid receptors in CHO cell membranes. Tested compounds displayed moderate to high affinities to the mu and kappa receptors. The findings accord with previous evidence of a lipophilic binding pocket in the opioid receptors that can be accessed to afford good binding affinity without the need for a phenolic hydrogen-bond donor group.

In vivo characterization of (-)(-)MCL-144 and (+)(-)MCL-193: isomeric, bivalent ligands with mu/kappa agonist properties.

Once opioid receptor dimers were postulated, a goal has been to synthesize and screen novel opioids, with the hope of furthering our knowledge of the structure-activity relationship of opioid ligands with the opioid receptors. The aim of the current study was to address whether two isomeric bivalent ligands would have pharmacological differences after central administration, in vivo. The two compounds, (-) bis(N-cyclobutylmethyl-morphinan-3-yl) sebacoylate dihydrochloride (MCL-144) and 1-((+)N-cyclobutylmethylmorphinan-3-yl)-10-((-) N-cyclobutylmethylmorphinan-3-yl)sebacolyate (MCL-193) are each linked by a 10-carbon chain ester.

Revised rates for the stellar triple-alpha process from measurement of 12C nuclear resonances.

In the centres of stars where the temperature is high enough, three alpha-particles (helium nuclei) are able to combine to form 12C because of a resonant reaction leading to a nuclear excited state. (Stars with masses greater than approximately 0.5 times that of the Sun will at some point in their lives have a central temperature high enough for this reaction to proceed.