Animal model considerations to evaluate prosthetic tricuspid valve implants.

Aims: Determining tricuspid valve comparative anatomy and appropriate animal models for preclinical evaluation of prosthetic tricuspid valve implants.

Methods And Results: We described and measured 81 heart specimens: 12 humans, 22 dogs, 21 sheep and 26 pigs. Tricuspid annulus circumference varied in humans from 109 to 149 mm, in pigs from 85 to 140 mm, and were ≤125 mm in dogs and sheep.

Current challenges for clinical trials of cardiovascular medical devices.

Several features of cardiovascular devices raise considerations for clinical trial conduct. Prospective, randomized, controlled trials remain the highest quality evidence for safety and effectiveness assessments, but, for instance, blinding may be challenging. In order to avoid bias and not confound data interpretation, the use of objective endpoints and blinding patients, study staff, core labs, and clinical endpoint committees to treatment assignment are helpful approaches.

Chronic electrical stimulation of the carotid sinus baroreflex improves left ventricular function and promotes reversal of ventricular remodeling in dogs with advanced heart failure.

Background: Autonomic abnormalities exist in heart failure and contribute to disease progression. Activation of the carotid sinus baroreflex (CSB) has been shown to reduce sympathetic outflow and augment parasympathetic vagal tone. This study tested the hypothesis that long-term electric activation of the CSB improves left ventricular (LV) function and attenuates progressive LV remodeling in dogs with advanced chronic heart failure.

Implantable carotid sinus stimulator for the treatment of resistant hypertension: local effects on carotid artery morphology.

Background: The Rheos System is a chronically implanted carotid sinus baroreflex activating system with a pulse generator and bilateral perivascular carotid sinus leads (CSLs) that is being evaluated in prospective clinical trials for the treatment of drug-resistant hypertension. We evaluated carotid artery structural integrity after implantation of the CSLs.

Methods: To assess the effect of chronic CSL attachment, 29 CSLs were implanted on the common carotid arteries of eight sheep.

Chronic baroreceptor activation enhances survival in dogs with pacing-induced heart failure.

Much of the current pharmacological therapy for chronic heart failure targets neurohormonal activation. In spite of recent advances in drug therapy, the mortality rate for chronic heart failure remains high. Activation of the carotid baroreceptor (BR) reduces sympathetic outflow and augments vagal tone.

Acute device-based blood pressure reduction: electrical activation of the carotid baroreflex in patients undergoing elective carotid surgery.

Carotid sinus baroreceptors are involved in controlling blood pressure (BP) by providing input to the cardiovascular regulatory centers of the medulla. The acute effect of temporarily placing an electrode on the carotid sinus wall to electrically activate the baroreflex was investigated. We studied 11 patients undergoing elective carotid surgery.

Prolonged activation of the baroreflex abolishes obesity-induced hypertension.

Prolonged electrical activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure in normotensive dogs. The main goal of this study was to assess the influence of prolonged baroreflex activation on arterial pressure and neurohormonal responses in 6 dogs with obesity-induced hypertension. After control measurements, the diet was supplemented with cooked beef fat for 6 weeks, whereas sodium intake was held constant.

An implantable carotid sinus baroreflex activating system: surgical technique and short-term outcome from a multi-center feasibility trial for the treatment of resistant hypertension.

Objectives: To assess perioperative outcomes and blood pressure (BP) responses to an implantable carotid sinus baroreflex activating system being investigated for the treatment of resistant hypertension.

Methods: We report on the first seventeen patients enrolled in a multicenter study. Bilateral perivascular carotid sinus electrodes (CSL) and a pulse generator (IPG) are permanently implanted.

Renal denervation does not abolish sustained baroreflex-mediated reductions in arterial pressure.

Recent studies indicate that suppression of renal sympathetic nerve activity and attendant increments in renal excretory function are sustained baroreflex-mediated responses in hypertensive animals. Given the central role of the kidneys in long-term regulation of arterial pressure, we hypothesized that the chronic blood pressure-lowering effects of the baroreflex are critically dependent on intact renal innervation. This hypothesis was tested in 6 dogs by bilaterally activating the carotid baroreflex electrically for 7 days before and after bilateral renal denervation.

An implantable carotid sinus stimulator for drug-resistant hypertension: surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial.

Background: A large number of patients have hypertension that is resistant to currently available pharmacologic therapy. Electrical stimulation of the carotid sinus baroreflex system has been shown to produce significant chronic blood pressure decreases in animals. The phase II Rheos Feasibility Trial was performed to assess the response of patients with multidrug-resistant hypertension to such stimulation.

Lessons learned combining N-of-1 trials to assess fibromyalgia therapies.

Objective: Applying population research to individual treatment requires understanding the connections between patient-specific characteristics, population-based studies, and treatment responses. Conducting practice-based research using individual-focused (N-of-1) trials may aid this process. We combined N-of-1 trials to compare fibromyalgia therapies and to assess the feasibility and outcomes of this approach for practice-based effectiveness research.

Influence of prolonged baroreflex activation on arterial pressure in angiotensin hypertension.

Despite recent evidence indicating sustained activation of the baroreflex during chronic infusion of angiotensin II (Ang II), sinoaortic denervation does not exacerbate the severity of the hypertension. Therefore, to determine whether Ang II hypertension is relatively resistant to the blood pressure-lowering effects of the baroreflex, the carotid baroreflex was electrically activated bilaterally for 7 days in 5 dogs both in the presence and absence of a continuous infusion of Ang II (5 ng/kg per minute) producing high physiological plasma levels of the peptide. Under control conditions, basal values for mean arterial pressure (MAP) and plasma norepinephrine concentration (NE) were 93+/-1 mm Hg and 99+/-25 pg/mL, respectively.

Prolonged activation of the baroreflex produces sustained hypotension.

The role of baroreflexes in long-term control of arterial pressure is unresolved. To determine whether chronic activation of the baroreflex produces sustained hypotension, we developed a method for prolonged activation of the carotid baroreflex in conscious dogs. This was achieved by chronically implanting electrodes around both carotid sinuses and using an externally adjustable pulse generator to electrically activate the carotid baroreflex.

Assessment of permanent dual-chamber pacing as a treatment for drug-refractory symptomatic patients with obstructive hypertrophic cardiomyopathy. A randomized, double-blind, crossover study (M-PATHY).

Background: Dual-chamber pacing (DDD) has been proposed as a treatment alternative to surgery for severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), based largely on uncontrolled studies.

Methods And Results: This prospective, multicenter trial assessed pacing in 48 symptomatic HCM patients with >/=50 mm Hg basal gradient, refractory to drug therapy. Patients were randomized to 3 months each of DDD pacing and pacing backup (AAI-30) in a double-blind, crossover study design, followed by an uncontrolled and unblinded 6-month pacing trial.

Mechanism of acute mechanical benefit from VDD pacing in hypertrophied heart: similarity of responses in hypertrophic cardiomyopathy and hypertensive heart disease.

Background: Dual-chamber pacing can improve symptoms in hypertrophic cardiomyopathy (HCM), but the mechanism remains unclear. We hypothesized that pacing generates discoordinate contraction and a rightward shift of the end-systolic pressure-volume relation (ESPVR) and that benefits from this mechanism do not depend on the presence of resting outflow pressure gradients or obstruction.

Methods And Results: Eleven patients with NYHA class III symptoms, 5 with HCM, and 6 with hypertensive hypertrophy and cavity obliteration, were studied by invasive conductance catheter methods.

Sensitivity and positive predictive value of Medicare Part B physician claims for rheumatologic diagnoses and procedures.

Objective: To examine the sensitivity and positive predictive value of Medicare physician claims for select rheumatic conditions managed in rheumatology specialty practices.

Methods: Eight rheumatologists in 3 states abstracted 378 patient office records to obtain information on diagnosis and office procedures. The Medicare Part B physician claims for these patient visits were obtained from the Health Care Financing Administration.

Polymyalgia rheumatica in patients with a normal erythrocyte sedimentation rate.

Objective: To ascertain the frequency of polymyalgia rheumatica (PMR) with a normal erythrocyte sedimentation rate (ESR; < or = 30 mm/hour) and to determine any defining clinical characteristics.

Methods: A retrospective chart review study of all patients meeting the clinical criteria for PMR seen over a 5-year period in a hospital and an office-based rheumatology practice.

Results: We evaluated 117 patients; 26 (22.

Carotid sinus hypersensitivity and syndrome in patients with chronic atrial fibrillation.

Carotid sinus hypersensitivity (CSH) has been studied in subjects in sinus rhythm, but it has never been studied in patients with chronic atrial fibrillation (AF). After a finding of CSH in a patient with chronic AF and syncope, we studied the effects of carotid sinus stimulation in a group of patients with AF. Ten patients with chronic AF and normal ventricular rates who complained of dizziness or loss of consciousness underwent right and left carotid sinus massage (CSM) during ECG monitoring.

Sodium/calcium exchanger in heart muscle: molecular biology, cellular function, and its special role in excitation-contraction coupling.

The Na/Ca exchanger has been examined with respect to its molecular biology, its cellular function, and its role in excitation-contraction coupling. The Na/Ca exchanger plays a central part in excitation-contraction coupling, setting the level of sarcoplasmic reticular calcium and contributing to the triggering of sarcoplasmic reticular calcium release. Functional biophysical studies with isolated single cells and caged calcium provide evidence that the Na/Ca exchanger works as a two step sequential transporter.

Mapping of the human cardiac Na+/Ca2+ exchanger gene (NCX1) by fluorescent in situ hybridization to chromosome region 2p22-->p23.

The cDNA that encodes the human Na+/Ca2+ exchanger (NCX1) involved in regulation of intracellular calcium levels has been isolated from a cardiac cDNA library. Using fluorescent in situ hybridization, the human cDNA was mapped to chromosome region 2p23-->p22 by co-hybridization with fluorescinated alu517-PCR amplified total human DNA to obtain an R-banding pattern.

Expression of the Na-Ca exchanger in diverse tissues: a study using the cloned human cardiac Na-Ca exchanger.

In many cells including cardiac myocytes, cytoplasmic Ca is importantly controlled by the plasmalemmal Na-Ca exchanger (3, 8). The tissue diversity and differences in cellular environment raise the question whether the same exchanger is found in all tissues. Recent experiments using rod cells have demonstrated that at least two forms of Na-dependent Ca transport exist.

Effect of coronary perfusion of heptanol or potassium on conduction and ventricular arrhythmias.

Abnormalities in cellular coupling, modulated in part by intracellular gap junctions, have an important role in the genesis of reentrant arrhythmias in the setting of chronic myocardial infarction. The effects of heptanol, which has a relatively selective action on gap junctional resistance at low concentrations, and potassium, which primarily affects active membrane properties, were assessed using a localized intracoronary infusion system in 11 normal dogs in vivo. Both agents caused a dose-related slowing of conduction.