PubMed Health⌕ Search

Biomedical subjects

D V Exner

Publications and source records attributed to D V Exner.

27 records · Page 2Linked to original sources
PubMed1999

Prolonged sinus node recovery time in humans after the intracoronary administration of a nitric oxide synthase inhibitor.

In vitro studies indicate that nitric oxide synthase (NOS) inhibitors alter sinus node automaticity. Moreover, whereas the systemic delivery of N(G)-monomethyl-L-arginine (L-NMMA), a NOS inhibitor, results in sinus bradycardia and arterial hypertension, its intracoronary administration has little effect on sinus heart rate. Therefore whether L-NMMA directly alters sinus node function in humans is not known. By using a crossover design, we evaluated the effect of intracoronary L-NMMA (20 micromol/min x 10 min) on corrected sinus node recovery time (CSNRT), heart rate, mean arterial blood pressure, electrocardiographic intervals, and coronary artery blood flow in nine men and 13 women aged 48+/-12 years. All were in sinus rhythm and had normal baseline CSNRTs. Baseline measurements were made during a dextrose infusion, and then L-NMMA was administered, and these parameters remeasured. In 11 patients, the infusions were near the origin of the sinus node artery (Concordant), whereas in the remaining 11, they were into the opposite coronary circulation (Discordant). After L-NMMA, significant prolongations in CSNRT were seen in Concordant (p < 0.001) and Discordant patients (p < 0.05), but were most pronounced in the Concordant group (p < 0.05). Although a significant reduction in coronary artery blood flow and nonsignificant changes in blood pressure and heart rate were observed after L-NMMA, these changes were not related to changes in CSNRT (r2 < or = 0.2; p > or = 0.2). These data support the notion that NO is a modifier of human sinus node automaticity.

Blood Pressure↗
PubMed1998

Telemetry-documented, pace-terminable ventricular tachycardia in patients with ventricular fibrillation.

The follow-up prevalence of electrogram-confirmed spontaneous ventricular tachycardia with a cycle length of >280 ms (53%) exceeds the prevalence of ventricular fibrillation (23%) in patients whose only spontaneous arrhythmia before implantable cardioverter defibrillator implantation was ventricular fibrillation. Antitachycardia pacing therapy safely terminates most (89%) of these slower ventricular tachycardia episodes, recommending the use of tiered-therapy devices and anticipatory activation of ventricular tachycardia detection and treatment algorithms for ventricular fibrillation patients who receive an implantable cardioverter defibrillator.

Electrocardiography↗
PubMed1998

A high affinity binding site for [3H]-Dofetilide on human leukocytes.

Certain Class III anti-arrhythmic agents have been shown to interact with human leukocytes and after antigenic and mitogenic activation. We hypothesized that a binding site for the Class III anti-arrhythmic agent, dofetilide, would exist on human leukocytes. Analysis of binding isotherms defined the presence of a single high affinity binding site on mononuclear cells and neutrophils: Kd 26+/-4 nm, Bmax 61+/-14 fmol/10( 6) cells and Kd 33+/-14 nm, Bmax 163+/-45 fmol/10(6) cells, respectively. Other Class III drugs inhibited [3H]-dofetilide binding at physiologically relevant concentrations, but the IC50 values of E4031 and quinidine were significantly higher for leukocytes than for cardiac myocytes. Interestingly, verapamil inhibited [3H]-dofetilide binding to leukocytes, but not to cardiac myocytes at physiologic concentrations (10 microM). Charybdotoxin and tetraethlyammonium inhibited [3H]-dofetilide binding to leukocytes at microM mm concentrations, respectively, however, apamin did not inhibit binding even at 1 microM concentrations. These data suggest that a Ca2+-activated K+ channel, like K(Ca) mini (apamin-insensitive isoform), is a candidate for the leukocyte [3H]-dofetilide binding site. To assess the functional significance of defetilide binding to leukocyte biology, we evaluated fMLP-stimulated superoxide production in the presence or absence of dofetilide. Dofetilide, at 30 nm suppressed of superoxide production. In conclusion, dofetilide binds to human leukocytes at physiologic concentrations and this binding alters leukocyte function possibly through interaction with a Ca2+-activated K+ channel.

Animals↗
PubMed1998

Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction.

OBJECTIVE: This study undertook to determine if the presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular dysfunction was associated with increased mortality and, if so, whether the increase could be attributed to progressive heart failure or arrhythmic death. BACKGROUND: Atrial fibrillation is a common condition in heart failure with the potential to impact hemodynamics and progression of left ventricular systolic dysfunction as well as the electrophysiologic substrate for arrhythmias. The available data do not conclusively define the effect of atrial fibrillation on prognosis in heart failure. METHODS: A retrospective analysis of the Studies of Left Ventricular Dysfunction Prevention and Treatment Trials was conducted that compared patients with atrial fibrillation to those in sinus rhythm at baseline for the risk of all-cause mortality, progressive pump-failure death and arrhythmic death. RESULTS: The patients with atrial fibrillation at baseline, compared to those in sinus rhythm, had greater all-cause mortality (34% vs. 23%, p < 0.001), death attributed to pump-failure (16.7% vs. 9.4%, p < 0.001) and were more likely to reach the composite end point of death or hospitalization for heart failure (45% vs. 33%, p < 0.001), but there was no significant difference between the groups in arrhythmic deaths. After multivariate analysis, atrial fibrillation remained significantly associated with all-cause mortality (relative risk [RR] 1.34, 95% confidence interval [CI] 1.12 to 1.62, p=0.002), progressive pump-failure death (RR 1.42, 95% CI 1.09 to 1.85, p=0.01), the composite end point of death or hospitalization for heart failure (RR 1.26, 95% CI 1.03 to 1.42, p=0.02), but not arrhythmic death (RR 1.13; 95% CI 0.75 to 1.71; p=0.55). CONCLUSIONS: The presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular systolic dysfunction is associated with an increased risk for all-cause mortality, largely explained by an increased risk for pump-failure death. These data suggest that atrial fibrillation is associated with progression of left ventricular systolic dysfunction.

Adult↗
PubMed1998

Unipolar sensing in contemporary pacemakers: using myopotential testing to define optimal sensitivity settings.

Bipolar lead use has increased due to oversensing concerns with older unipolar systems. Data on contemporary unipolar devices with improved hardware design and greater programming flexibility is lacking. Using a randomized crossover design, unipolar and bipolar sensing characteristics of 22 atrial and 16 ventricular leads were compared in 34 patients who had pulse generators of programmable polarity. Unipolar and bipolar intracardiac electrogram amplitudes, pacing and sensing thresholds at rest were similar. Provocative maneuvers were used to assess for myopotential inhibition. At atrial sensitivities of 0.625-1.50 mV, myopotential inhibition occurred in 11 (50%) atrial leads in the unipolar mode compared to 1 (5%) in the bipolar mode (p < 0.001). At sensitivities of > 1.50 mV myopotential inhibition occurred in only 1 ventricular (unipolar) lead. An optimal sensitivity setting for each polarity was derived using clinic test results and assessed by ambulatory ECG (AECG). At these optimal settings, oversensing occurred in 1 (6%) atrial and 1 (8%) ventricular unipolar lead during AECG monitoring, whereas oversensing was not seen in any leads programmed to the bipolar mode. Undersensing occurred in 5 (29%) atrial unipolar versus 1 (6%) bipolar lead (p = 0.08). Undersensing was not observed in any of the ventricular leads. Myopotential inhibition may be frequently provoked by provocative maneuvers at higher sensitivity settings in atrial unipolar leads. The frequency of oversensing can be significantly reduced by defining an optimal sensitivity setting using simple isometric maneuvers. Given present day concerns over bipolar lead longevity, increased utilization of unipolar ventricular leads should be considered.

Action Potentials↗
PubMedDate not supplied

Beta blockers with ACE inhibitors in mild heart failure.

ACE inhibitors are standard therapy for treating both symptomatic and asymptomatic patients with left ventricular dysfunction. However, recent clinical trials have shown that beta blockers further reduce mortality in patients with symptomatic heart failure treated with ACE inhibitors. However, the evidence in support of adding beta blockers to ACE inhibitor therapy in patients with asymptomatic left ventricular dysfunction is less certain. The mechanisms by which ACE inhibitors and beta blockers may exert benefit in patients with heart failure are discussed, and studies assessing the association of beta blockade with outcome in patients with mild heart failure receiving ACE inhibitor therapy are reviewed. (c)2000 by CHF, Inc.

Journal Article↗