In this study we used transmural multipolar electrodes, sonomicrometers implanted within the left ventricular wall, and cardiac electrical stimulation techniques to examine the effect of transient mechanical posterior papillary muscle traction on local myocardial electrophysiologic characteristics. Nine open-chest dogs were atrially paced (cycle length 400 msec) followed by insertion of timed premature extrastimuli at left ventricular epicardial pacing sites either in the vicinity of (traction zone) or remote from (nontraction zone) the site of papillary muscle traction. Electrophysiologic recordings were made before and during periods of intermittent papillary muscle traction of predetermined timing, application rate (25 cm/sec), and duration (170 msec). Papillary muscle traction was applied in late diastole just before the last beat of each atrial drive train. In seven of nine dogs application of transient papillary muscle traction resulted in significantly earlier local ventricular activation (mean activation advancement 30 ± 13 msec), altered QRS morphology of the last conducted atrial drive-train beat, and relative prolongation of ventricular functional refractory period in the traction zone. Conversely, in nontraction zones in these seven dogs, early activation did not occur and refractoriness remained unchanged as tested by a locally placed extrastimulus. In two of nine dogs traction failed to induce early activation and changes in refractoriness did not occur. Alterations in regional myocardial blood flow (assessed by radioactive microsphere technique) did not appear responsible for the observed changes, since there was no demonstrable traction-induced difference in regional blood flow between the traction and nontraction zones. Thus, in normal myocardium in situ, regional abnormal wall motion may be associated with alterations of local ventricular activation and refractoriness, factors that in the diseased heart may lead to increased susceptibility to arrhythmias.

We have tompared the activities of fluconazole, and ketoconazole against ketoconazole-susceptible and -resistant strains of Candida albicans in a neutropenic-site rabbit model. Oral treatment with fluconazole resulted in much higher serum and extravascular concentrations of this antifungal agent than did comparable doses of ketoconazole. Fluconazole had no additional in vivo activity against the ketoconazole-susceptible strains; no fungicidal activity was observed with peak drug levels as high as -75 ,ug/ml in the infection sites. Significant fungistatic activity against the ketoconazole-resistant strains was observed with fluconazole treatment (80 mg/kg), but not with less fluconazole (20 mg/kg) or with ketoconazole (-67 mg/kg). In vitro susceptibility tests separated the ketoconazole-susceptible strains from the ketoconazole-resistant strains, but the results were variable when the resistant strains were tested with fluconazole.Fluconazole (UK 49,858) is a bis-triazole antifungal agent that is active when administered both orally and parenterally. Pharmacologically, the drug is characterized by excellent oral absorption, high serum and extravascular levels, and a long half-life that allows once-daily administration (8). These properties may explain why fluconazole has appeared to be more active than ketoconazole in some studies of experimental infections with Candida albicans despite its apparently lower in vitro activity (16; K. Richardson, R. J. Andrews, T. T. Howarth, M. S. Marriott, M. H. Tarbit, and P. F. Troke, Program Abstr. 25th Intersci. Conf. Antimicrob. Agents Chemother., abstr. no. 813, 1985). However, previous animal studies (10,12,15) have not shown any activity of fluconazole against strains of C. albicans which have become resistant to ketoconazole, i.e., strains obtained from patients with chronic mucocutaneous candidiasis who relapsed during prolonged oral therapy with ketoconazole (4, 13).In the present study we investigated the activities of fluconazole and ketoconazole against ketoconazole-susceptible and -resistant C. albicans strains, using semipermeable Visking chambers (molecular weight cutoff, 15,000) implanted subcutaneously in rabbits as the infection sites. The study was designed to use doses of fluconazole that yield much higher fluconazole levels than those attainable with ketoconazole to determine whether fluconazole is fungicidal or active against the ketoconazole-resistant strains. In vitro susceptibility tests were also performed to further assess the correlation with the in vivo studies. with shaking at 150 rpm, the cultures were then diluted in broth media to concentrations of _105 CFU/ml as determined by plate counts, and 1-ml aliquots were added to the drug dilutions. For each yeast strain, the dilutions were set up in triplicate; in addition, the tests were repeated one or more times on different dates. After 24 and 48 h of incubation at 37°C, the tubes were read turbidimetrically with a Coleman 295 spectrophotometer at 540 nm, using drug-free medium as a blank. The 24-a...

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In a 70-year-old man who had angina, exercise-induced ventricular tachycardia, and presyncopal symptoms, transthoracic and transesophageal echocardiography disclosed a large atrial mass that resembled a myxoma. Subsequent evaluation by magnetic resonance imaging identified the mass as an intracardiac lipoma attached to the posterior wall of the right atrium, a diagnosis that was confirmed by surgical intervention. Thus, the diagnostic utility of magnetic resonance imaging as an adjunct to echocardiographic evaluation of intracardiac masses was demonstrated.