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Biomedical subjects

J M Power

Publications and source records attributed to J M Power.

At least 19 recordsLinked to original sources
PubMed1995

Effects of sensory (teasing) exposure to food on oral propranolol bioavailability.

In order to further examine the mechanism of the increase in the plasma propranolol concentration versus time curve (AUC) caused by ingestion of propranolol with food, we administered R, S-propranolol tablets (0.5 mg kg-1) orally to healthy human volunteers and dogs in the presence and absence of sensory exposure to food without ingestion (teasing). Six healthy human volunteers were fasted on one occasion and on the other they were presented with an appetising meal, without eating it (teasing protocol). There was a strong trend to a greater propranolol AUC in the teasing protocol (139 +/- 54 mg mL-1 h-1 fasting, 178 +/- 105 mg mL-1 h-1 teasing; p = 0.1), and time of peak concentration (tmax) was significantly prolonged (80 +/- 22 min and 120 +/- 32 min, respectively; p < 0.03). Further studies were carried out in dogs who received R-propranolol (2 mg kg-1) as an oral solution by gavage tube on four different occasions: fasting, following intragastric administration of a high-value liquid meal, following teasing with food in the animal house at normal feeding time (high-intensity teasing). There were no significant differences in pharmacokinetic parameters between the fasting and intragastric food protocols. Low-intensity teasing resulted in significantly lower AUC and peak concentrations (Cmax) compared with fasting (p < 0.05), confirming food effect patterns known to occur in dogs. High-intensity teasing resulted in significantly greater AUC and Cmax compared with fasting (p < 0.05), reproducing in dogs the increase in propranolol AUC known to occur with food ingestion in humans. These findings suggest that the mechanism of the 'food effect' may involve physiological responses to the sight and smell of food additional to mechanisms activated by ingestion.

Administration, Oral↗
PubMed1995

Low energy endocardial cardioversion of atrial arrhythmias in humans.

We assessed the feasibility of low energy endocardial defibrillation in patients with atrial fibrillation or atrial flutter who had failed a trial of pharmacological reversion with amiodarone. Low energy endocardial defibrillation under general anesthesia was attempted in 9 patients, 5 with atrial flutter and 4 with atrial fibrillation (median duration of arrhythmia 3.75 months). Two large surface area endocardial leads were introduced percutaneously and sited in the right atrial appendage and at the right ventricular apex. A cutaneous patch electrode was placed on the left thorax. Biphasic shocks synchronized to the ventricular electrogram were used to terminate atrial arrhythmias. Three electrode configurations were evaluated in the following sequence at each energy level: atrial cathode to ventricular anode; ventricular cathode to atrial anode; atrial cathode to a combined ventricular and cutaneous anode. If endocardial defibrillation failed (0.5-10 J), transthoracic defibrillation using 200 joules followed by 360 joules, if required, was performed. Endocardial defibrillation was successful in all five patients with atrial flutter (0.5 J, 1.0 J, 1.0 J, 4.0 J, and 10.0 J) but in only one patient with atrial fibrillation (10 J). On no occasion did successful defibrillation occur with one configuration when it had failed with an alternate configuration at that particular energy level. Ventricular fibrillation did not occur, and there were no other significant complications. Low energy endocardial defibrillation is feasible in patients with atrial flutter using large surface area electrodes. Although the success rate of atrial defibrillation was low, further work is required, particularly in patients with more recent onset of the arrhythmia and using a right to left electrode configuration.

Adult↗
PubMed1995

The effects of period mutations and light on the activity rhythms of Drosophila melanogaster.

Strains of Drosophila melanogaster homozygous for alleles of the period gene (perO, perL, perS, and per+) were reared for multiple generations either in light:dark cycles (LD), continuous illumination (LL), or chronic darkness (DD). The locomotor activity of adult flies from these cultures was monitored in either LL or DD. Flies that were reared and tested in DD had a lower proportion of individuals with normal circadian rhythms than flies reared in LD or LL and tested in DD. The activity rhythms of DD-reared DD-tested animals, when present, showed phase coherence within two out of seven populations, while 8 out of 10 LL-reared DD-tested showed phase coherence. Flies tested in LL were largely devoid of circadian rhythms regardless of their rearing environment. Ultradian rhythms were more evident under conditions disruptive to circadian rhythmicity, but were observed in the presence and absence of circadian rhythms. The periods of the ultradian rhythms of LL-reared DD-tested and LD-reared DD-tested flies varied significantly among genotypes, while in other rearing and testing regimes, no relationship was found.

Activity Cycles↗
PubMed1995

Specific effects of zatebradine on sinus node function: suppression of automaticity, prolongation of sinoatrial conduction and pacemaker shift in the denervated canine heart.

We evaluated the cardiac electrophysiological effects of zatebradine in eight anesthetized and autonomically denervated canines, with particular emphasis on the effects on sinus node automaticity and sinoatrial conduction (SACT), both at rest and after atrial overdrive pacing. Sinus node function was assessed by using the recorded sinus node electrogram and also by applying a previously validated mathematical model of sinus node function which allows separate evaluation of effects of pacing on SACT and suppression of automaticity. Other standard electrophysiological parameters also were measured. Tests were performed before and after incremental doses of zatebradine (0.0625, 0.125 and 0.25 mg/kg). Zatebradine caused a significant, dose-related increase in cardiac cycle length. There also was a significant, dose-related increase in both suppression of automaticity and SACT (independent of changes in cycle length) after zatebradine. The only other significant electrophysiological effect was a relatively minor increase in the ventricular effective refractory period (13%). Higher doses of zatebradine were associated with spontaneous pacemaker shift characterized by loss of the sinus node electrogram and variation in P-wave morphology. Our results confirm that the effects of zatebradine are relatively specific for the sinus node. These included: 1) prolongation of resting sinus cycle length; 2) enhanced suppression of automaticity after overdrive pacing; 3) prolongation of SACT; and 4) induction of sinus node pacemaker shifts. This agent should be used cautiously in patients with possible sinus node dysfunction.

Animals↗
PubMed1993

Importance of electrode design, lead configuration and impedance for successful low energy transcatheter atrial defibrillation in dogs.

OBJECTIVES: We assessed the feasibility of low energy endocardial defibrillation in a canine model of atrial fibrillation, comparing catheters with large surface area electrodes and standard electrode catheters, and evaluated the effects of lead configuration and circuit impedance on defibrillation energy requirements. BACKGROUND: Although recent animal studies have demonstrated the feasibility of low energy endocardial atrial defibrillation, their results have been conflicting with regard to important methodologic aspects. METHODS: In 14 anesthetized greyhounds, atrial fibrillation was induced by rapid atrial pacing and maintained by vagal stimulation. Two large surface area braided electrode catheters and two standard electrode catheters were introduced percutaneously, one of each, in the right atrial appendage and right ventricular apex. A cutaneous patch electrode was placed on the left thorax. Biphasic shocks synchronized to the ventricular electrogram were used to terminate atrial fibrillation. Seven configurations were evaluated. Three used standard electrodes: proximal atrial cathode to distal atrial, ventricular or cutaneous anode. Four used braided electrodes: three with atrial cathode to ventricular, cutaneous or combined anode; one with ventricular cathode to atrial anode. RESULTS: Defibrillation with standard electrode catheters was associated with high impedance (576 +/- 112 omega) and low success rates for all configurations (28% success at < or = 40 J, no successes at 10 J). Low energy defibrillation was readily achieved with the braided electrodes with significantly lower impedance (75 +/- 13 omega, p < 0.0001). Ventricular fibrillation did not occur. The success rate of cardioversion increased in a dose-response manner, allowing fitting of a sigmoid curve and calculation of energy associated with 50% (ED50) and 90% (ED90) success. The most successful configuration was ventricular cathode/atrial anode (ED50 1.5 +/- 0.4 J), and the least successful was atrial anode/cutaneous patch (ED50 6.5 +/- 3.2 J, p = 0.0001). CONCLUSIONS: Low energy atrial defibrillation is feasible using large surface area electrodes but not with standard electrode catheters owing to high impedance. An intracardiac anode provides lower impedance and higher success rates than are provided by a cutaneous anode.

Analysis of Variance↗
PubMed1993

Vetch toxicosis in cattle grazing Vicia villosa ssp dasycarpa and V benghalensis.

The epidemiological, clinical and pathological features of a disease syndrome in adult cattle grazing woolly-pod vetch (Vicia villosa ssp dasycarpa) or popany vetch (V benghalensis) are reported. Outbreaks of toxicosis occurred between midwinter and midsummer in 3 dairy and 6 beef herds on the north coast of New South Wales, between 1982 and 1992. Friesian, Angus, Murray Grey, Guernsey and Hereford breeds were affected. Mean morbidity and case fatality rates in affected herds were 7% (65 of 889) and 69%, respectively. Signs of pruritic dermatitis, illthrift and death were associated with an eosinophilic granulomatous inflammation of many organs, particularly involving the renal cortex, dermis, myocardium, adrenal glands, lymph nodes and hepatic portal triads.

Alopecia↗
PubMed1993

A simplified approach to the anesthesia of porcine laparoscopic surgical subjects.

At a series of laparoscopic surgical workshops, 155 pigs were successfully anesthetised for up to 4 hours by using Profolol (Diprivan) as the anesthetic agent and without provision of positive pressure ventilation. On the basis of our findings, we believe this methodology presents a useful alternative to gaseous anesthesia and provides definite logistical and technical advantages.

Anesthesia↗
PubMedDate not supplied

Pharmacokinetic interaction between verapamil and metoprolol in the dog. Stereochemical aspects.

The effect of verapamil co-administration on the hepatic first-pass clearance of metoprolol was investigated in dogs. Plasma concentration-time course of metoprolol enantiomers and urinary recovery of oxidative metabolites were determined after a single iv (0.51 mg/kg) and an oral (1.37 mg/kg) dose of deuterium-labeled pseudoracemic metoprolol, with or without concomitant administration of racemic verapamil (3 mg/kg). Verapamil inhibited both the systemic and oral clearance of metoprolol by about 50-70%. The first-pass effect of metoprolol was completely abolished after co-administration of verapamil, reflecting a marked alteration in the degree of hepatic extraction of metoprolol from intermediate to low. The hepatic clearance of metoprolol was slightly (S)-enantioselective (R/S ratio = 0.89 +/- 0.04) in control dogs. Inhibition of hepatic clearance of metoprolol by verapamil was selective towards (S)-metoprolol, such that the enantioselectivity in hepatic clearance toward (S)-metoprolol disappeared following verapamil co-administration (R/S ratio = 1.01 +/- 0.05). Urinary metabolite profiles indicated that O-demethylation and N-dealkylation were the major pathways of oxidative metabolism in the dog. alpha-Hydroxymetoprolol was a minor metabolite in urine. N-Dealkylation showed a strong preference for (S)-metoprolol, whereas O-demethylation and alpha-hydroxylation exhibited a modest selectivity toward (R)-metoprolol; hence, the slight (S)-enantioselectivity in the overall hepatic clearance. Comparison of metoprolol metabolite formation clearances in the absence or presence of verapamil co-administration showed that all three oxidative pathways were inhibited by 60-80%. The greater inhibition of hepatic clearance observed with (S)-metoprolol as compared to (R)-metoprolol was attributed to a significant (S)-enantioselective inhibition in the O-demethylation of metoprolol by verapamil.

Administration, Oral↗
PubMedDate not supplied

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Dental Care↗