PubMed Health⌕ Search

Biomedical subjects

P Dorian

Publications and source records attributed to P Dorian.

At least 19 recordsLinked to original sources
PubMed1992

Pathophysiology and prognostic significance of Holter-detected ST segment depression after myocardial infarction. The Tissue Plasminogen Activator: Toronto (TPAT) Study Group.

OBJECTIVES: We performed Holter monitoring on days 4 and 7 after acute myocardial infarction in 109 patients to assess whether ST segment shift would identify those with more severe coronary artery disease, left ventricular dysfunction and unfavorable prognosis. BACKGROUND: Silent myocardial ischemia is a frequent and prognostically significant event after acute myocardial infarction. However, the specific pathophysiologic mechanisms and the impact of thrombolytic therapy are uncertain. METHODS: In addition to Holter monitoring, patients underwent exercise testing, radionuclide angiography on days 1 and 9 and quantitative coronary angiography on day 9. RESULTS: Thirty-five patients (32%) had ST segment depression and had similar recombinant tissue-type plasminogen activator (rt-PA) treatment assignment and a reduced cross-sectional area of the infarct-related artery (0.59 +/- 0.57 vs. 1.04 +/- 1.26 mm2, p < 0.05). Global left ventricular function improved from day 1 to day 9 in patients without (4% +/- 11%, p < 0.001) but not in those with (0% +/- 7%) ST segment depression. In-hospital event rates were similar; however, follow-up 18 +/- 11 months after hospital discharge revealed a greater frequency of death and recurrent myocardial infarction in patients with compared with those without ST segment depression (27% vs. 6%, p = 0.03). CONCLUSIONS: After acute myocardial infarction, approximately one third of patients have ST segment depression on Holter monitoring, independent of the use of thrombolytic therapy. The unfavorable prognosis observed in these patients may be related to greater lumen obstruction in the infarct-related artery and lack of improvement in left ventricular function.

Cardiac Catheterization↗
PubMed1992

Use of telemetry functions in the assessment of implanted antitachycardia device efficacy.

Twenty patients (aged 50 +/- 21 years and mean left ventricular ejection fraction 37 +/- 17%) with recurrent ventricular arrhythmias were treated with an investigational, implantable combined antitachycardia-pacing cardioverter defibrillator. The device's telemetry capabilities include both stored (1-second snapshots) and real-time display of endocardial and device-circuit signals. The device can store these before, during and after up to 50 tachycardia and antitachycardia pacing episodes. All stored events are indexed to a 24-hour internal clock. During 10.1 +/- 5.1 months of follow-up, the device was used in 11 of 20 patients. In the entire group, antitachycardia pacing was activated on 44 +/- 14 occasions per patient (total 874) and shock delivery occurred on 8 +/- 14 occasions per patient (total 156). Reconstruction by stored telemetry of all device-therapy episodes was possible. Twenty-six percent of all shocks delivered were not appropriate and were due to atrial arrhythmias in 2 patients and dysfunction of the sensing lead in 3. The absence of a relation between symptoms and appropriate shock delivery was documented in 1 patient. Antitachycardia pace acceleration occurred in 5.3% of cases; 7% of attempts at pacing were unsuccessful and needed shock therapy. It is concluded that the enhanced telemetry available in newer antitachycardia devices enables more accurate assessment of device use and enhances diagnosis of inappropriate therapy delivery.

Electric Countershock↗
PubMed1992

The effects of cardiac transplantation and cyclosporine therapy on digoxin pharmacokinetics.

Most patients needing cardiac transplantation are treated with digoxin for heart failure. Because of its narrow therapeutic range, even recommended doses of digoxin may cause severe toxicity. Several drugs, including quinidine, amiodarone, verapamil, and propafenone can interact with digoxin, leading to toxic accumulation of the glycoside. The authors have recently reported two cases of severe digitalis toxicity after the initiation of cyclosporine treatment in patients awaiting cardiac transplantation. A preliminary study on two additional patients suggested that cyclosporine reduced the plasma clearance and volume of distribution of digoxin. To assess the mechanism of this interaction, the authors studied digoxin pharmacokinetics in patients awaiting cardiac transplantation and again after the surgery, during chronic cyclosporine therapy. To separate the effects of transplantation and cyclosporine on digoxin pharmacokinetics, pharmacokinetic studies were subsequently performed in dogs to allow controlled experimental conditions for evaluation of the digoxin-cyclosporine interaction.

Administration, Oral↗
PubMed1992

Isoproterenol increases defibrillation energy requirements in dogs.

The effect of intravenous isoproterenol on the energy requirements for successful defibrillation (DF) was examined in anesthetized dogs following cholinergic blockade with atropine (n = 5) and following treatment with d- and d,l-sotalol (n = 16). Defibrillation shocks were administered through left and right ventricular epicardial patch electrodes and the energy requirements for DF were studied using two different methods. Multiple shocks of varying energies were delivered and the energies required for 50% success (E50) and 80% success (E80) in DF were estimated using logistic regression. Atropine (0.04 mg/kg) increased E50 by 32 +/- 30% (p = 0.046) and E80 by 39 +/- 38% (p = ns). Subsequent administration of isoproterenol (10 micrograms/ml), increasing the heart rate by 52 +/- 35% (p = 0.025), resulted in a further 108 +/- 21% (p = 0.015) and 88 +/- 55% (p = 0.02) rise in E50 and E80 values, respectively. In a second set of experiments, d- (n = 9) and d,l-sotalol (n = 7) (4 mg/kg bolus followed by 0.025 mg/kg/min maintenance infusion) were administered and baseline curves relating delivered energy to % success in DF were calculated. Isoproterenol (10 +/- 4 micrograms/min) was given to increase the heart rate by 54 +/- 32% (p less than 0.025), and resulted in decreases in % success at each of two energy levels, falling in the midrange of the dose-response curve. Following d,l-sotalol, % successful shocks fell from 60 +/- 15 to 42 +/- 28% (p less than 0.05); following d-sotalol, the % success fell from 66 +/- 13 to 38 +/- 36% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Psychiatric treatment strategies for patients at risk of dying suddenly.

This paper outlines the development of psychiatric treatment approaches to certain patients with life-threatening ventricular arrhythmias which may affect outcome, both psychological and, at times, medical. Three cases sketches which illustrate psychiatric management strategies are presented. One case history indicates how lack of adherence to such treatment contributed to a negative outcome. Emphasis is placed on an integrated approach to psychiatric treatment which is individualized for each patient. The importance of close liaison with cardiologist, selective psychotherapy, stress management skills and family involvement is highlighted.

Adaptation, Psychological↗
PubMed1991

Oral clofilium produces sustained lowering of defibrillation energy requirements in a canine model.

The effect of long-term oral administration of antiarrhythmic drugs on defibrillation energy requirements is not well understood. We examined the effect of clofilium, a drug that prolongs cardiac action potential duration without slowing cardiac conduction, on defibrillation energy requirements and ventricular effective refractory periods in a canine model during a 3-week period. Epicardial patch electrodes were implanted in 12 dogs, and baseline testing was conducted under fentanyl anesthesia on day 7. An oral clofilium (100 mg/day) regimen was started on day 8. Six clofilium-treated and six control dogs underwent repeated testing on days 14, 21, and 28 after surgery. Truncated trapezoidal shocks were given repeatedly at various stored energies in random order; delivered current and impedance were measured; and delivered energy was calculated. The energy and current for 50% success in defibrillation (E50 and I50, respectively) were determined. For control animals, E50 increased by a mean 34 +/- 78%, 60 +/- 83%, and 69 +/- 122% compared with baseline (day 7) on days 14, 21, and 28, respectively. In contrast, E50 in clofilium-treated dogs decreased by 39 +/- 62%, 24 +/- 33%, and 32 +/- 15% on days 14, 21, and 28, respectively. Mean current requirements (I50) remained relatively stable compared with baseline in control animals (-7 +/- 39%, +25 +/- 36%, +40 +/- 75% on days 14, 21, and 28, respectively). After clofilium administration I50 decreased by 36 +/- 22%, 32 +/- 17%, and 33 +/- 17% on days 14, 21, and 28, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

DL and D sotalol decrease defibrillation energy requirements.

We examined the acute effects of intravenous DL and D sotalol on the energy requirements for internal defibrillation (DF) in 44 dogs anesthetized with pentobarbital (n = 18), enflurane (n = 8), and fentanyl (n = 18). Multiple shocks of varying energies were applied through left and right ventricular epicardial patch electrodes to relate delivered energy to percent success in DF. The energies required for 50% success in DF (E) were estimated by logistic regression. DL or D sotalol was administered in a loading (4 mg/kg over 10 min) and maintenance (1.5 mg/kg/hr) infusion and the energy--success curve was again measured 30 minutes after drug administration. The effect of DL and D sotalol on E50 was compared to controls given saline. Both DL and D sotalol significantly lowered E50 by 16% +/- 14% (P less than 0.05) and 24.5% +/- 8.2% (P less than 0.05), respectively, in fentanyl anesthetized animals; this was accompanied by a 22% +/- 8% (P less than 0.05) and 16% +/- 5% (P less than 0.01) increase in ventricular effective refractory period (VERP), respectively. In pentobarbital anesthetized dogs, DL and D sotalol decreased E50 by 16% +/- 27% (P = ns) and 11% +/- 16% (P less than 0.05), respectively, and were associated with a 23% +/- 5% (P less than 0.01) and 12 +/- 4% (P less than 0.05) prolongation of VERP. DL and D sotalol decrease defibrillation energy requirements, possibly as a result of their Class III antiarrhythmic drug action.

Animals↗
PubMed1988

Effects of magnesium on ischemic and reperfusion arrhythmias in the rat heart and electrophysiologic effects of hypermagnesemia in the anesthetized dog.

Magnesium sulfate, reportedly clinically effective against some ventricular arrhythmias, has not been extensively studied for its effects on experimental ischemic and reperfusion arrhythmias. We evaluated the effects of three high extracellular concentrations of magnesium (Mg2+) 1.19, 2.38, and 4.76 mM in 70 isolated perfused rat hearts following coronary artery ligation and reperfusion, at each of three different perfusate ionized calcium (Ca2+) concentrations (0.9, 1.25, and, 2.5 mM), where 1.25 mM is close to physiologic. At 0.9 mM Ca2+, higher concentrations of Mg2+ increased the sinus node cycle length (p less than 0.02) and virtually abolished ischemic ventricular tachycardia (VT) and reperfusion ventricular fibrillation (VF) (p less than 0.01), otherwise consistently found in this model. At 1.25 and 2.5 mM Ca2+ increasing Mg2+ had no effect on the incidence of ischemic or reperfusion arrhythmias, although at 1.25 mM Ca2+ ischemic VT had longer cycle lengths and VT appeared after a longer delay (p less than 0.01). In the nonischemic dog heart, marked increases of serum Mg2+ progressively prolonged the A-H, H-V, and QR S intervals, the ventricular effective refractory period, and the sinus cycle length, while the arterial blood pressure fell. Because of its relatively modest electrophysiologic and hemodynamic effects, it is inferred that intravenous magnesium may be given therapeutically with relative safety.

Anesthesia↗
PubMed1988

Defibrillation current and impedance are determinants of defibrillation energy requirements.

The relationship between various electrical descriptors of shocks for cardiac defibrillation is incompletely understood. Defibrillating energy, current, impedance and pulse duration were measured in 18 dogs. They were subject to repeated fibrillation--defibrillation through epicardial patches, with shocks of preset energy and voltage and variable pulse duration, impedance and peak current. Current and energy requirements for defibrillation were calculated. Energy requirements were positively correlated with pulse duration and interelectrode impedance (r = .70, P less than 0.01). Correcting for heart weight, these correlations were no longer present. However, peak current was correlated with energy requirements both before (r = -0.62, P less than 0.05) and after (r = 0.76, P less than 0.01) correcting for heart weight, with energy requirement decreasing as peak current/g heart increased. Current requirements were significantly less variable between animals than energy requirements (.027 +/- .012 joules/g vs .016 +/- .003 Amps/g), suggesting that current per unit heart weight may be a better descriptor than energy for the ability to defibrillate.

Animals↗
PubMed1988

Digoxin-cyclosporine interaction: severe digitalis toxicity after cyclosporine treatment.

Digoxin toxicity developed in two patients awaiting cardiac transplantation upon the initiation of cyclosporine. Toxicity was associated with elevated digoxin concentrations (10.6 and 5.7 nmoles/L), gastrointestinal symptoms, and arrhythmias classic for digoxin toxicity (bidirectional ventricular tachycardia and AV nodal block with accelerated junctional rhythm respectively). A previously unreported drug interaction between cyclosporine and digoxin was suspected and digoxin pharmacokinetics were studied in two additional patients both before and after cyclosporine therapy prior to cardiac transplantation. The study confirmed a significant interaction between cyclosporine and digoxin; the apparent volume of distribution of digoxin decreased by 71% and its plasma clearance decreased by 53%. Until further information regarding the cyclosporine-digoxin interaction is available, this combination should be used with great caution.

Coronary Disease↗
PubMed1987

The relationship between successful defibrillation and delivered energy in open-chest dogs: reappraisal of the "defibrillation threshold" concept.

The traditional assessment of the energy required for successful ventricular defibrillation involves the measurement of a "defibrillation threshold" (DFT), implying a clear-cut distinction between effective and ineffective energies. We examined the relationship between delivered energy and the likelihood of successful defibrillation in 10 open-chest pentobarbital anesthetized dogs, with the use of an internal spring/patch electrode system. An initial DFT was determined by decreasing the energy discharged until a failure first occurred (10.3 +/- 3.4 J). Six energy levels in 1 to 2 J increments were then selected surrounding this value and each was administered eight times in balanced random order (total 48 trials). The relationship between energy and percent success in defibrillation exhibited a shallow slope, with a gradual increase in success from 0% to 100% over several energy increments. The initial DFTs showed actual success rates varying from 25% to 87.5% (mean 71 +/- 26%). The results were fitted to a sigmoidal dose-response curve by logistic regression analysis and the energy associated with 50% success (E50) and 80% success (E80) was determined, as no single value for DFT could be defined in any animal. In 12 other dogs, a defibrillation curve was similarly constructed at baseline and was repeated after 90 minutes. No significant change in E50 (5.0 +/- 2.1 J vs 5.2 +/- 2.7 J) or E80 (6.3 +/- 2.5 J vs 6.6 +/- 3.2 J) was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Ethmozine: electrophysiology, hemodynamics, and antiarrhythmic efficacy in patients with life-threatening ventricular arrhythmias.

Thirteen patients with drug-resistant, life-threatening ventricular arrhythmias and inducible sustained ventricular tachycardia (VT) at electrophysiologic study received moricizine HC1 (ethmozine), 10 mg/kg/day orally. Eight patients underwent electrophysiologic study before and after drug administration; the arrhythmia became noninducible in one. In five other patients, spontaneous sustained VT occurred after 1 to 5 days of drug therapy, and one patient had a worsening of arrhythmias on ethmozine. Ethmozine prolonged infranodal conduction time (HV interval) (51.4 +/- 13.8 msec to 69.3 +/- 17.7 msec [mean +/- SD]), PR interval (201 +/- 28.1 msec to 244 +/- 62.2 msec), and QRS interval (123 +/- 27 msec to 147 +/- 32 msec). Ventricular refractory periods were not consistently affected, and only the one patient who became noninducible had an increase in effective ventricular refractory period (280 to 310 msec). The drug had no significant effect on sinus cycle length or sinus node recovery time, atrial conduction or refractoriness, or atrioventricular nodal refractoriness. Ethmozine had no effect on radionuclide ejection fraction (25.5 +/- 12.7% to 28.2 +/- 13.8%) or cardiac index (2.4 +/- 0.7 to 3.0 +/- 0.6 ml/min/m2) and caused no significant changes in mean aortic, right atrial, pulmonary arterial, or pulmonary capillary wedge pressures. Although the drug is well tolerated and produces no untoward hemodynamic effects, ethmozine is relatively ineffective in patients with sustained VT refractory to conventional antiarrhythmic agents.

Adult↗
PubMed1986

Effect of quinidine and bretylium on defibrillation energy requirements.

We examined the effect of bretylium and quinidine on the energy requirements for internal defibrillation in 14 pentobarbital-anesthetized dogs. Bretylium, 6 or 10 mg/kg (n = 6), did not affect the relation between energy and the likelihood of successful defibrillation. The mean energy required to achieve 50% success (E50) or 90% success (E90) in defibrillation was not significantly altered; E50 was 5.3 +/- 1.9 J (X +/- s.d) before and 6.1 +/- 3.5 J after bretylium (n.s.), and E90 was 7.2 +/- 2.1 J before and 8.6 +/- 3.3 J after drug (n.s.). Quinidine was administered in a series of two loading and maintenance infusions to achieve mean plasma concentrations of 2.4 +/- 0.63 and 2.95 +/- 0.88 microgram/ml, respectively (n = 8). No significant effect on defibrillation energy requirement was observed; mean E50 before and after treatment was 6.3 +/- 3.3 J and 6.2 +/- 2.9 J, respectively, and mean E90 was 8.3 +/- 4.4 J and 8.3 +/- 4.1 J, respectively. Similarly, saline administration to control dogs (n = 12) resulted in no change in E50 or E90. At concentrations or doses similar to those in patients with serious arrhythmias, neither quinidine nor bretylium appears to have consistent effects on the energy requirements for internal defibrillation in our dog model.

Animals↗
PubMed1986

Lidocaine causes a reversible, concentration-dependent increase in defibrillation energy requirements.

To investigate the influence of lidocaine on the energy requirements for internal defibrillation, lidocaine (n = 8) or saline solution (n = 12) was administered by intravenous infusion to 20 pentobarbital-anesthetized dogs, and the likelihood of successful defibrillation was examined at various shock energy levels before and after treatment. After lidocaine administration to a mean steady state concentration of 5.6 +/- 2.7 micrograms/ml, the mean energy required to achieve 50 and 90% success in defibrillation (E50 and E90) increased by 61.1 +/- 34.1% (mean +/- SD, p less than 0.005) and 47.1 +/- 28.6% (p less than 0.005), respectively. The steady state log lidocaine concentration correlated positively with the observed increase in E50 (r = 0.887, p less than 0.01) over a concentration range from 1.95 to 9.8 micrograms/ml. In a related experiment, lidocaine infusion was administered to five dogs and then abruptly discontinued. At energy levels achieving a mean 90.0 +/- 10.0% success in defibrillation before treatment, only 43.3 +/- 23.4% success was achieved after 60 minutes of the lidocaine infusion (p less than 0.01) at a mean plasma concentration of 8.4 +/- 2.1 micrograms/ml. The percent of successful defibrillations returned to baseline value (92.0 +/- 18.0%, p less than 0.01) after drug washout at a time when mean lidocaine concentration had declined to 1.8 +/- 0.5 microgram/ml. Lidocaine causes a reversible, concentration-dependent increase in the energy requirements for successful defibrillation; recommendations to administer lidocaine to patients with ventricular fibrillation resistant to defibrillation may need to be reviewed.

Animals↗