Biomedical subjects

M Ghadanfar

Publications and source records attributed to M Ghadanfar.

6 recordsLinked to original sources

PubMed2001

Cardiac and hemodynamic effects of intravenous dofetilide in patients with heart failure.

This study assesses the effects of dofetilide, a new selective Ikr blocker with class III properties, on left ventricular function and hemodynamics of heart failure and compares these effects with those of placebo and amiodarone. Because available antiarrhythmic drugs may depress myocardial performance, an invasive hemodynamic study was performed to assess the safety of this agent. Hemodynamic and angiographic data were obtained at baseline and after 30 minutes of double-blind infusion of dofetilide (8 microg/kg; n = 12), placebo (n = 12), or amiodarone (5 mg/kg; n = 6) in heart failure patients (New York Heart Association class II or III, ejection fraction <35%). Intravenous dofetilide preserved the inotropic indexes and the end-systolic volume index despite a slight but significant decrease in heart rate, whereas intravenous amiodarone increased end-diastolic and end-systolic volume indexes. Amiodarone induced a negative inotropic effect illustrated by a rightward shift of the pressure-volume loop and a reduction in pressure-derived indexes of contractility. Intravenous dofetilide acutely prolonged QT interval more than intravenous amiodarone; however, dofetilide did not slow the overall relaxation rate and reduced QT dispersion. In an acute setting, compared with intravenous amiodarone, intravenous dofetilide preserves cardiac function offering a hemodynamic advantage to treat arrhythmias in patients with impaired left ventricular function.

Adult↗

PubMed2000

Steady-state versus non-steady-state QT-RR relationships in 24-hour Holter recordings.

The aim of the present study was to investigate the QT-RR interval relationship in ambulatory ECG recordings with special emphasis on the physiological circumstances under which the QT-RR intervals follow a linear relation. Continuous ECG recordings make it possible to automatically measure QT duration in individual subjects under various physiological circumstances. However, identification of QT prolongation in Holter recordings is hampered by the rate dependence of QT duration. Comparison of QT duration and QT interval rate dependence between different individuals implies that the nature of the QT-RR relationship is defined in ambulatory ECG. Holter recordings were performed in healthy volunteers at baseline and after administration of dofetilide, a Class III antiarrhythmic drug. After dofetilide, beat-to-beat automated QT measurements on Holter tapes were compared with manually measured QT intervals on standard ECGs matched by time. The QT-RR relationship was analyzed at baseline in individual and group data during three different periods: 24-hour, daytime, and nighttime. Data were collected under steady-state or non-steady-state conditions of cycle length and fitted with various correction formulae. Our study demonstrated an excellent agreement between manually and automated measurements. The classic Bazett correction formula did not fit the QT-RR data points in individual or group data. When heart beats were selected for a steady rhythm during the preceding minute, QT-RR intervals fit a linear relationship during the day and night periods, but not during the 24-hour period in both individual and group data. In contrast, in the absence of beat selection, data fit a more complex curvilinear relationship irrespective of the period. Our study provides the basis for comparison of QT interval durations and QT-RR relationships between individuals and between groups of subjects.

Adolescent↗

PubMed1998

Dynamic analysis of dofetilide-induced changes in ventricular repolarization.

OBJECTIVE: To use dynamic electrocardiographic (ECG) techniques to study the influence of heart rate on dofetilide-induced QT prolongation among healthy volunteers. BACKGROUND: The extent to which heart rate modulates QT prolongation induced by the new class III antiarrhythmic drug dofetilide is a matter of debate. METHODS: Ten healthy volunteers underwent two 24-hour ECG recordings, one in the absence of dofetilide and the other after a single oral dose of 0.5 mg dofetilide. Two 4-hour periods were defined during the second recording: Dh, which corresponded to stable high concentration of the drug, and D1, which corresponded to low concentration of the drug. Corresponding baseline recording periods, Ch and C1, matched by time with Dh and D1 were selected from the control ECG recording in the absence of dofetilide. QT versus R-R relations were compared in the presence and absence of dofetilide. The QT versus R-R relation slope was used as an index of the rate dependence QT prolongation. Rate-independent changes in QT duration were also analyzed. RESULTS: During Dh, dofetilide induced a mean 12% lengthening of ventricular repolarization. Dynamic ECG analysis showed that this prolongation increased as R-R cycles became longer, a phenomenon known as reverse rate dependence. However, QT prolongation persisted at the shortest (600 ms) R-R cycle length that could be analyzed. During D1, dynamic ECG analysis showed a persistent, although small, effect of dofetilide on both QT prolongation (3%) and reverse rate dependence of this effect. CONCLUSIONS: Dofetilide prolongs QT duration, and this class III effect is influenced by heart rate. Although dofetilide-induced QT prolongation decreases when the R-R cycle shortens, this reverse rate dependence is only partial because marked QT prolongation persists at an R-R cycle of 600 ms. The results of our study indicated that dynamic ECG techniques can be useful in detection of subtle, drug-induced changes in the duration of ventricular repolarization.

Administration, Oral↗

PubMed1996

Influence of dofetilide on QT-interval duration and dispersion at various heart rates during exercise in humans.

BACKGROUND: The objective of this study was to assess the influence of heart rate on QT-interval duration and dispersion during administration of the new selective potassium-channel blocker dofetilide in normal subjects. METHODS AND RESULTS: Dofetilide 0.25 and 0.75 mg was administered for 4 days to 12 subjects in a randomized-sequence, double-blind, three-period, placebo-controlled, crossover study. QT-RR pairs were measured on study day 4 over a wide range of RR intervals obtained at rest and during an exercise test. QT-interval durations were calculated at seven predetermined RR intervals ranging from 400 ms (150 bpm) to 1000 ms (60 bpm) by use of monoexponential nonlinear curve fitting. QTmax and QTmin were calculated similarly, and QT-interval dispersion was measured as QTmax-QTmin at each predetermined RR interval. Minimal effects were found with 0.25 mg dofetilide. Two hours after administration of 0.75 mg dofetilide, QT interval was prolonged by 16.7 +/- 8.7% at a heart rate of 60 bpm (P < .01) and by 7.4 +/- 8.2% at a heart rate of 150 bpm (P < .05). QT prolongation at a heart rate of 150 bpm was less pronounced than at lower heart rates. Neither placebo nor dofetilide at either dose significantly increased QT-interval dispersion at any heart rate. CONCLUSIONS: Dofetilide increases QT-interval duration but does not increase QT-interval dispersion in healthy subjects. QT-interval prolongation remains significant at high heart rates, although some degree of reverse rate dependence is observed at high concentrations.

Adult↗

PubMed1991

[Unstable angina and infarction without Q wave treated with verapamil: value of the early exercise test].

Twenty patients aged 56.8 +/- 10 years, hospitalised for unstable angina (12 cases) or infarct without Q wave (8 cases) were treated with IV heparin, aspirin and oral verapamil. The clinical syndrome was controlled by verapamil in 16 cases out of 20 (80% of cases) at the dosage of 360 mg/d in 14 patients and of 480 mg/d in two. An exercise ECG, limited by symptoms, was obtained in 18 patients (90%) between the 8th and 12th day. Coronary arteriography was considered to be indicated in three sets of circumstances: recurrence of angina resistant to nitroglycerin, positive exercise ECG with verapamil, persisting despite triple therapy or strongly positive exercise ECG (total duration less than or equal to 6 minutes). An infarct complicated the early course in 4 patients (20%): twice following angioplasty, once following exercise ECG (spastic angina) and once during triple therapy (refractory angina). Hospital and mid-term (18 +/- 6 months) mortality was nil. With verapamil, the absence of recurrence of angina together with a negative exercise ECG enabled the identification of a large group of patients (40%) with a low risk of a subsequent major accident and in whom early and routine coronary arteriography is probably not indispensable.

Adult↗

PubMedDate not supplied

Electrophysiological effects of dofetilide in an in vitro model of "border zone" between normal and ischemic/reperfused myocardium.

BACKGROUND: To evaluate both class III activity and antiarrhythmic action of dofetilide at the level of the "border zone," we investigated its electrophysiological effects on guinea pig ventricular strips submitted partly to normoxia (normal zone, NZ) and partly to simulated severe ischemia, then reperfusion (altered zone, AZ). METHODS AND RESULTS: Because of the differential class III effects of dofetilide in normal and ischemic regions, the dispersion of the action potential duration at 90% repolarization (APD(90)) between NZ and AZ was reduced by 5 nmol/L of drug during early ischemia (at 10 minutes, APD(90) NZ/APD(90) AZ was 1.68+/-0.22 versus 2.82+/-0.17 in control, P<0.05), whereas 50 nmol/L dofetilide worsened it during late ischemia (at 30 minutes, APD(90) NZ/APD(90) AZ was 4.62+/-0.76 versus 2.57+/-0.21 in control, P<0.05). Concomitantly, dofetilide at 5, 10, and 50 nmol/L abolished the early extrastimulus (ES)-induced arrhythmias, and at 10 and 50 nmol/L, it significantly enhanced the incidence of late spontaneous repetitive responses (in 86% and 75% of preparations treated with 10 and 50 nmol/L, respectively, versus 25% in control, P<0.05). During reperfusion, dofetilide at 5, 10, and 50 nmol/L exhibited concentration-dependent class III effects, as it did in the NZ, and did not modify the incidence of spontaneous arrhythmias. CONCLUSIONS: Dofetilide 5 nmol/L decreased APD(90) dispersion between NZ and AZ and reduced the early ES-induced arrhythmias. However, dofetilide 50 nmol/L increased APD(90) dispersion, and at 10 and 50 nmol/L, it increased the late spontaneous arrhythmias.

Action Potentials↗