Effect of 2-Aminoethoxydiphenyl Borate (2-APB) on Heart Rate and Relation with Suppressed Calcium-Activated Potassium Channels: Larval <i>Drosophila</i> Model

Cardiac contractile cells depend on calcium in order to function. Understanding the regulation of calcium influx, efflux, and release from the sarcoplasmic reticulum is essential. The focus of this investigation is to address how a reduction of functional Ca2+-activated K+ (KCa) channels, via a mutational line, might impact the heart rate in larva when the SER is also modulated through Ca2+ loading and stimulation. The larval heart tube is exposed in situ and flushed with saline. With a known saline composition, a potential therapeutic pharmacological agent, 2-Aminoethyl diphenylborinate (2-APB), was examined for its effect on heart rate, as well as to determine the contribution from KCa channels. In this study, it was determined that mutation in the K(Ca) channel (i.e., Slo) showed a different trend than the wild-type CS strain. Exposure to high concentrations of 50 µM 2-APB decreased heart rate in the Slo strain and increased it in the wild-type CS strain. Serotonin increased heart rate in both thapsigargin- and 2-APB-treated larvae, with no significant difference between the strains

Update on the Talent aortic stent-graft: a preliminary report from United States phase I and II trials.

PURPOSE: Phase I and phase II trials were conducted to determine the safety and efficacy of the Talent aortic stent-graft (Medtronic World Medical, Sunrise, Fla) in the treatment of infrarenal abdominal aortic aneurysms (AAA). This is a preliminary report of the technical results and 30-day clinical outcome of these trials. METHODS: Multicenter prospective trials were conducted to test the Talent stent-graft in high-risk and low-risk patient populations with AAA, including phase I feasibility and phase II clinical trials. The low-risk study included concurrent surgical controls. RESULTS: In the phase I trial, deployment success was achieved in 92% (23/25 patients), and initial technical success was 78% (18/23 implants without endoleak). The 30-day technical success rate was 96%, with six endoleaks that resolved spontaneously (without need for further intervention); and the 30-day mortality rate was 12% (3/25 patients). The phase II high-risk trial demonstrated a deployment success of 94% (119/127 patients) and an initial technical success of 86% (102/119 implants). The 30-day technical success rate was 96%, and the 30-day mortality rate was 1.5% (2/127 patients). The phase II low-risk trial included a first-generation and a second-generation Talent stent-graft. Deployment success rates were 97% and 99%, respectively, and technical success rates at 30 days were 97% and 96%, respectively. The 30-day mortality rate was 2% in the phase II low-risk first-generation device trial, and the adverse-event rate was 20%. Corresponding figures for the second-generation device were 0% and 1.8%, respectively. CONCLUSION: The Talent stent-graft can be deployed successfully and achieves endovascular exclusion in a large proportion of patients with AAA. Morbidity and mortality rates are acceptable. One-year clinical results and the comparison with concurrent surgical control subjects remain to be evaluated

Effect of Doxapram, a K2p Channel Blocker, and pH on Heart Rate: Larval <i>Drosophila</i> Model

Two-P-domain K+ (K2p) channels are responsible for maintaining the resting membrane potential. K2p channels have varied expression in healthy tissue, but they also change in cancerous or diseased states. The correlation and causation as regards the alteration of K2p channel expression are still being investigated. The compound doxapram seems to block K2p channels and depolarize cells. Using Drosophila, the increased expression of the ORK1 K2p channel in cardiac and skeletal muscle was investigated. The heart rate in larval Drosophila is very sensitive to pH, and since doxapram blocks a subset of the K2p channels that are known to be acid-sensitive, it was postulated that doxapram would affect heart rate. A pH change from 7.1 to 6.5 increased the rate, while that from 7.1 to 7.5 decreased the rate. An amount of 0.1 mM of doxapram had no effect, but 0.5 of mM depressed Drosophila heart rates within five minutes. Exposure to 5 mM of doxapram immediately decreased the rate. Lipopolysaccharides (LPSs) from Gram-negative bacteria acutely increased the rate. LPSs activate K2p channels in the skeletal muscle of larvae and are blocked by doxapram. LPSs slightly reduce depression in the rate induced by doxapram. The overexpression of K2p channels in the heart and skeletal muscle depressed the heart rate and heightened pH sensitivity. At larval neuromuscular junctions, the overexpression in skeletal muscle increases the frequency of spontaneous quantal events and produces a more negative resting membrane potential

Brachial artery catheterization to facilitate endovascular grafting of abdominal aortic aneurysm: safety and rationale.

PURPOSE: Endovascular treatment of abdominal aortic aneurysms (AAAs) is a technically demanding procedure that is based on the complexity and multiplicity of steps and the guidewire and catheter manipulations required. Brachial artery catheterization is an adjunctive technique that can facilitate the placement of an endoluminal prosthesis. METHODS: Brachial access was used during endoluminal AAA repair in 79 of 103 consecutive patients with a modular-design stent-graft prosthesis at two institutions. RESULTS: Left brachial access facilitated (1) angiography to guide juxtarenal device deployment, (2) antegrade contralateral limb access, (3) device delivery through disadvantaged iliac arteries by means of a brachial femoral wire, (4) access to renal arteries when necessary, and (5) catheter exchanges and a reduction in fluoroscopic positional changes. Complications included one puncture-site pseudoaneurysm, seven hematomas, and 29 patients with extensive ecchymosis. The length of stay was not prolonged in any case. There were no embolic, oculocerebral, or ischemic upper extremity events. CONCLUSIONS: Brachial artery catheterization, as an adjunctive technique to endoluminal AAA repair, offers noteworthy technical advantages with few, but self-limiting complications

Safety of coil embolization of the internal iliac artery in endovascular grafting of abdominal aortic aneurysms.

PURPOSE: During endovascular grafting of an abdominal aortic aneurysm (AAA), iliac limb extension to the external iliac artery may be indicated when the common iliac artery is ectatic or aneurysmal. Preliminary or concomitant coil embolization of the internal iliac artery (IIA) is thus necessary to prevent potential reflux and endoleak. We sought to determine the safety of hypogastric flow interruption in this setting. METHODS: We retrospectively reviewed 156 patients who underwent stent-graft AAA repair at two institutions between February 1, 1998, and January 31, 1999. Coil embolization of one or both IIAs was undertaken when the diameter of the common iliac artery was more than 20 mm to enable limb endograft extension to the external iliac artery. Bilateral procedures were staged. RESULTS: Thirty-nine (25%) of 156 patients were selected for coil embolization of one (n = 28) or both (n = 11) IIAs. The interventions were performed before (n = 31) or during (n = 8) the stent-graft procedure. Complications included groin hematomas in 3 patients, iliac artery dissection in 1, failure to catheterize the IIA in 2, and transient rise in the serum creatinine level in 3. One patient had erectile dysfunction, and five patients (13%) had buttock claudication after unilateral occlusion. Serious ischemic complications were not observed. CONCLUSION: Coil embolization of one or both IIAs appears to be safe in the setting of endovascular grafting of AAA. Buttock claudication is a relatively significant problem and may limit applicability of this strategy to patients who are unfit for standard open repair

The Effect of Doxapram on Proprioceptive Neurons: Invertebrate Model

The resting membrane potential enables neurons to rapidly initiate and conduct electrical signals. K2p channels are key in maintaining this membrane potential and electrical excitability. They direct the resting membrane potential toward the K+ equilibrium potential. Doxapram is a known blocker for a subset of K2p channels that are pH sensitive. We assessed the effects of 0.1 and 5 mM doxapram on the neural activity within the propodite-dactylopodite (PD) proprioceptive sensory organ in the walking legs of blue crabs (Callinectes sapidus). Results indicate that 0.1 mM doxapram enhances excitation, while the higher concentration 5 mM may over-excite the neurons and promote a sustained absolute refractory period until the compound is removed. The effect of 5 mM doxapram mimics the effect of 40 mM K+ exposure. Verapamil, another known K2p channel blocker as well as an L-type Ca2+ channel blocker, reduces neural activity at both 0.1 and 5 mM. Verapamil may block stretch activated channels in sensory endings, in addition to reducing the amplitude of the compound action potential with whole nerve preparations. These findings are notable as they demonstrate that doxapram has acute effects on neurons of crustaceans, suggesting a targeted K2p channel. The actions of verapamil are complex due to the potential of affecting multiple ion channels in this preparation. Crustacean neurons can aid in understanding the mechanisms of action of various pharmacological agents as more information is gained