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Biomedical subjects

M A Ruder

Publications and source records attributed to M A Ruder.

10 recordsLinked to original sources
PubMed1991

Disposition kinetics of orally administered enoximone in patients with moderate to severe heart failure.

Enoximone is a phosphodiesterase inhibitor, which has been studied extensively for use in the management of patients with moderate-to-severe heart failure. The authors have studied the absorption and disposition kinetics of enoximone and its primary metabolite, enoximone sulfoxide, after both single oral doses of enoximone and at steady-state after short-term chronic oral therapy. A total of ten patients (two female, eight male) with moderate-to-severe heart failure (NYHA class II-IV) were enrolled into the study after giving written informed consent. The plasma levels of enoximone sulfoxide were greater than those of enoximone at all sampling times. The peak enoximone sulfoxide plasma concentrations ranged from 3.5 to 17.3 times the peak enoximone plasma levels for individual patients. The average steady-state plasma concentrations for enoximone were 115 +/- 40 ng/mL and 190 +/- 78 ng/mL for 50 mg every 8 hours and 100 mg every 8 hours dosage regimens, respectively. The absorption and disposition kinetics of enoximone were found to be significantly variable between patients. The authors also evaluated the relationship between dose administered and steady-state plasma levels as well as the relationship between the observed and predicted steady-state plasma levels. The authors found a linear relationship between the dose that was administered and the accrued plasma levels, as well as a good correlation between the predicted and observed steady-state levels. Although these data confirm previous reports that the sulfide metabolite of enoximone accumulates extensively in the plasma during oral therapy, reaching levels much higher than those of enoximone, these data do not support previous suggestions that the disposition of enoximone is nonlinear.

Administration, Oral↗
PubMed1991

Clinical pharmacology of intravenous enoximone: pharmacodynamics and pharmacokinetics in patients with heart failure.

Twenty-one patients with heart failure (New York Heart Association [NYHA] class II to IV) received a 24-hour infusion of enoximone followed by a 12-hour washout period. Patients were randomly assigned to one of four treatment groups. Groups I to III received an 0.5 mg/kg bolus, followed by a maintenance infusion of 2.5, 5.0, or 10.0 micrograms/kg/min. Group IV patients received a maintenance infusion of 5.0 micrograms/kg/min without a loading dose. Serial assessment of hemodynamics, plasma levels of enoximone and enoximone sulfoxide, and ventricular ectopy were performed. Enoximone produced a clinically significant increase in cardiac index, and a decrease in mean pulmonary artery wedge pressure and systemic vascular resistance in all groups. Enoximone mildly increased heart rate, and had a minimal effect on mean arterial pressure. There was no statistically significant change in ventricular ectopy during the infusion. Significant hemodynamic improvement was noted at even the lowest infusion rate, and did not increase in linear fashion at higher infusion rates. In patients who did not receive an initial loading bolus of 0.5 mg/kg, the increase in cardiac index was delayed by approximately 1 hour. Plasma concentrations of both enoximone and its major metabolite continued to rise throughout the 24-hour infusion in group III (10.0 micrograms/kg/min), rather than reaching steady state as predicted by the terminal exponential half-lives of these compounds. This is suggestive of nonlinear pharmacokinetics and indicates a potential for excessive accumulation of enoximone and its metabolite during prolonged infusion. These findings may have important implications in guiding the intravenous administration of enoximone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Comparison of pre- and postoperative conduction patterns in patients surgically cured of atrioventricular node reentrant tachycardia.

Patients with atrioventricular (AV) node reentrant tachycardia characteristically have short and constant retrograde His-atrium conduction times (H2A2 intervals) during the introduction of ventricular extrastimuli. It has therefore been suggested that the tachycardia circuit involves retrograde conduction up an accessory pathway located in perinodal tissue. If the mechanism of surgical cure of AV node reentrant tachycardia is interruption of this accessory pathway, postoperative changes in retrograde conduction would be expected. Thirteen patients with drug-refractory AV node reentrant tachycardia underwent surgery. Preoperatively, H2A2 intervals were short and constant. During AV node reentrant tachycardia, earliest atrial activation was seen near the His bundle and was 0 to 25 ms before ventricular activation in all patients except one. Surgery consisted of dissection of right atrial septal and anterior inputs to the AV node and central fibrous body. Postoperatively, the H2A2 interval remained short and constant compared with preoperative values although it was slightly prolonged (74 +/- 18 versus 61 +/- 21 ms, p less than 0.005). Twelve of the 13 patients are free of tachycardia after 28 +/- 13 months and no patient has had evidence of AV node block. Thus, surgical cure of AV node reentrant tachycardia is highly successful; however, there is no reason to postulate an accessory pathway or use of perinodal tissue as part of the tachycardia circuit and the mechanism of surgical success remains obscure.

Adult↗
PubMed1990

Pharmacodynamics of enoximone during intravenous infusion.

Twenty-one patients with heart failure (NYHA class II-IV) received a 24-hour infusion of enoximone, followed by a 12-hour washout period. Patients were randomly assigned to one of four treatment groups. Groups I-III received a 0.5 mg/kg bolus, followed by a maintenance infusion of 2.5, 5.0 or 10.0 micrograms/kg/minute. Group IV patients received a maintenance infusion of 5.0 micrograms/kg/minute without the bolus. Serial assessments of haemodynamics, plasma levels of enoximone and enoximone sulphoxide, and ventricular ectopy were performed. Enoximone produced a significant increase in cardiac index (28.1-46.7%) and a decrease in mean pulmonary artery wedge pressure (6.4-35.7%) and systemic vascular resistance (34.7-78.9%). Enoximone had minimal effect on heart rate and blood pressure. In patients who did not receive an initial bolus of 0.5 mg/kg, haemodynamic changes were delayed by approximately 1 hour. Significant haemodynamic improvement was noted at even the lowest infusion rate and did not increase in linear fashion at higher infusion rates. During infusion of enoximone at 10.0 micrograms/kg/minute, both enoximone and its sulphoxide accumulated non-linearly and did not achieve a steady state. No significant adverse effects were noted in these patients. Enoximone infusion at rates greater than 5.0 micrograms/kg/minute may confer minimal additional haemodynamic benefit, while resulting in significant accumulation of enoximone and enoximone sulphoxide. Ventricular ectopy did not increase significantly in most patients.

Cardiotonic Agents↗
PubMed1990

Effect of duration of ventricular fibrillation on defibrillation efficacy in humans.

The currently available automatic implantable cardioverter-defibrillator has proven highly successful for termination of ventricular tachycardia and fibrillation. Newer devices, however, permit lower energy shocks to be delivered initially and longer episodes of arrhythmia to occur before shocks are delivered. These changes may result in longer durations of arrhythmia before successful termination. Little is known about the effects of the duration of ventricular fibrillation on the efficacy of defibrillating shocks. In this study, we examined the efficacy of defibrillating shocks in 22 patients undergoing automatic implantable cardioverter-defibrillator implantation or generator change. Defibrillating shocks ranging from 300 to 600 V (5.9-24.2 J) were delivered in matched pairs after 5 and 15 seconds of ventricular fibrillation. For the 300-V shocks (5.9 J), defibrillation was accomplished in 82% of patients when the shocks were given after 5 seconds of ventricular fibrillation and in only 45% of patients when the shocks were delivered after 15 seconds (p less than 0.01). At higher energies, there was no difference in the efficacy of defibrillation shocks delivered after 5 compared with 15 seconds of ventricular fibrillation. The postshock aortic, systolic, and diastolic blood pressures were significantly lower when the shocks were given after 15 seconds of ventricular fibrillation than after only 5 seconds. We conclude that the duration of ventricular fibrillation affects defibrillation efficacy especially at energies that are relatively low compared with maximal device outputs and that longer episodes of ventricular fibrillation cause more postshock hemodynamic depression. These observations have implications for defibrillation threshold testing at the time of device implantation and for the design and programming of future automatic implantable antitachycardia devices.

Adult↗
PubMed1986

Procainamide-induced incessant supraventricular tachycardia in the Wolff-Parkinson-White syndrome.

A patient with the Wolff-Parkinson-White syndrome presented with incessant orthodromic atrioventricular tachycardia following initiation of procainamide therapy. This finding was repeatedly documented both clinically as well as during electrophysiologic testing. Escape atrial complexes, which occurred following junctional premature complexes, failed to initiate tachycardia in the control state but tachycardia was always reinitiated by an identical escape sequence after procainamide. In addition, the tachycardia persisted and was repeatedly spontaneously reinitiated for prolonged periods after procainamide. The pro-arrhythmic effects of procainamide may be explained on the basis of both its vagolytic action on the atrioventricular node as well as by prolongation of refractoriness in the accessory pathway. These observations add to the literature on pro-arrhythmic effects of commonly used antiarrhythmic drugs.

Electrophysiology↗
PubMed1986

Catheter atrioventricular junctional ablation in patients with accessory pathways.

Seven patients with accessory pathway and symptomatic atrioventricular reciprocating tachycardia underwent catheter ablation of the atrioventricular junction (AVJ). Four patients had the Wolff-Parkinson-White syndrome, two had concealed left free-wall accessory pathways, and one patient had a nodoventricular connection. All patients failed multiple antiarrhythmic drugs and one failed attempted surgical ablation of a posteroseptal accessory pathway. Chronic interruption of atrioventricular node-His conduction was achieved in all patients. Over a mean follow-up period of 21 +/- 14 months, four patients remained asymptomatic without antiarrhythmic therapy. One patient developed atrial fibrillation after magnet application to her VVI pacemaker, another developed atrial flutter, and a third had nonparoxysmal sinus or atrial tachycardia. Two patients required chronic quinidine therapy. Two patients with concealed accessory pathways had pacemaker-mediated tachycardia which was controlled by pacemaker reprogramming. Atrioventricular junctional ablation in patients with accessory pathways proved effective in that all are currently controlled without need for surgical intervention. On follow-up, a relatively high incidence of atrial arrhythmias requiring antiarrhythmic therapy was found.

Adult↗
PubMed1979

Effect of hysterectomy on genital infections.

In a study of women with anogenital gonorrhoea who had undergone hysterectomy, the sensitivities of urethral, vaginal, and anal canal cultures were 88.9, 55.7, and 40.7% respectively in specimens from 27 woemn. To obtain the greatest sensitivity, however, we recommend that specimens from all three sites should be cultured routinely. After the raising effects of trichomoniasis and menstrual blood on the pH values have been allowed for, the vaginal pH of 74 women in the study group and of 137 healthy controls was similar.

Adult↗
PubMed1978

Effects of prostaglandin E2, analogs, fatty acids, and indomethacin on fibrinogen level.

Dose-response relations in rabbits for 3-h intravenous infusion of prostaglandin E2 (PGE2) and (15S)-15-methyl-1-prostaglandin E2 methyl ester (MePGE2) on plasma fibrinogen and systolic blood pressure were determined and described by regression equations. MePGE2 was 20 times more active than PGE2. Fibrinogen synthetic rate responses to PGE2 and MePGE2 were estimated. Infusion of the PGE2 precursor, arachidonic acid, elevated plasma fibrinogen, but fibrinogen response to 0.5-9 mg/kg arachidonic acid was unrelated to dose and half that given by 3 mg/kg PGE2. Slow infusion of several other fatty acids raised plasma fibrinogen as effectively as arachidonic acid, but prostaglandins D2 and F2alpha had only a slight effect. Infusion of 30 times the indomethacin dose that blocks platelet prostaglandin synthetase did not alter the plasma fibrinogen response to arachidonic acid. Indomethacin did not inhibit plasma fibrinogen elevations following ACTH or endotoxin infusion, or subcutaneous turpentine injection. Intravenous infusion of two cyclic ether prostaglandin endoperoxide analogs, (15S)-hydroxy-9alpha, 11alpha-(epoxymethano) prosta-5Z, 13E-dienoic acid, and (15S)-hydroxy-11alpha, 9alpha(epoxymethano) prosta-5Z, 13E-dienoic acid, failed to increase plasma fibrinogen.

Adrenocorticotropic Hormone↗