Biomedical subjects

M J Avitable

Publications and source records attributed to M J Avitable.

7 recordsLinked to original sources

PubMed1996

Effects of azimilide dihydrochloride on circus movement atrial flutter in the canine sterile pericarditis model.

INTRODUCTION: The effects of a Class III agent, azimilide dihydrochloride, on atrial flutter circuits were studies in a functional model of single loop reentrant atrial flutter using dogs, 3 to 5 days after production of sterile pericarditis. METHODS AND RESULTS: A computerized mapping system was used to construct activation maps from 138 to 222 epicardial sites in the right atrium. Doses of 3, 10, and 30 mg/kg i.v. azimilide dihydrochloride were analyzed in 8 dogs in which sustained atrial flutter lasting more than 30 minutes was induced by burst pacing. Atrial flutter was always due to single loop circus movement reentry in the lower right atrium. At 3 mg/kg, azimilide dihydrochloride terminated atrial flutter in 2 dogs; however, atrial flutter was reinduced. At 10 mg/kg, atrial flutter was terminated in all 8 dogs but was reinduced in 4 dogs with slower rate. At 30 mg/kg, atrial flutter was terminated in the remaining 4 dogs and could not be reinduced. Atrial flutter cycle length always increased prior to termination. Isochronal activation maps showed that the increase in cycle length was due to additional conduction delays in the slow zone of the reentrant circuit. The site of termination was always located within the slow conduction zone situated in the lower right atrium between the line of functional conduction block and the AV ring. Effective refractory periods (ERPs) were measured at selected sites in the slow zone and normal zone at twice diastolic threshold for the 10 mg/kg dose. Azimilide preferentially prolonged ERP in the slow zone (42.4 +/- 20.1 msec, mean +/- SD) compared with the normal zone (23.3 +/- 15.4 msec, P < 0.0001). The increase in cycle length corresponded with the increase in ERP in the slow zone. CONCLUSIONS: In a functional model of circus movement atrial flutter, azimilide dihydrochloride terminates and prevents reinduction of atrial flutter by a preferential increase in refractoriness leading to further conduction delay and conduction block in the slow zone of the functional reentrant circuit.

Animals↗

PubMed1995

Reentrant arrhythmias in the subacute infarction period. The proarrhythmic effect of flecainide acetate on functional reentrant circuits.

BACKGROUND: The Cardiac Arrhythmia Suppression Trial has shown that flecainide was associated with an increased incidence of sudden cardiac death in postinfarction patients. The exact mechanism(s) of the proarrhythmic effects of flecainide remain unclear. We performed a detailed analysis of the electrophysiological and proarrhythmic effects of flecainide in a well-characterized model of reentrant arrhythmias in the subacute phase of myocardial infarction. METHODS AND RESULTS: Sixteen dogs were studied 4 days after ligation of the left anterior descending coronary artery. Isochronal mapping of ventricular activation showed that flecainide facilitated both the induction and sustenance of ventricular tachycardia, especially at shorter basic cycle lengths. Flecainide had negligible effect on the length of the arc of functional conduction block but markedly depressed conduction of the common reentrant wave front that was usually oriented parallel to fiber axis. Whole heart mapping was analyzed in combination with basic measurements of the effects of flecainide on conduction and refractory properties of both normal and ischemic myocardia using a high-resolution cross electrode consisting of four orthogonal arms, each comprised of 16 poles with an interelectrode spacing of 500 microns. The electrode was especially designed to study the effects of the drug on anisotropic conduction as determined by a linear regression of activation time and distance in each direction. Flecainide resulted preferentially in more marked rate-dependent depression of conduction in ischemic compared with normal myocardium. On the other hand, the effect of flecainide on refractoriness in both normal and ischemic myocardia was negligible. CONCLUSIONS: Because flecainide caused no significant change in refractoriness in both normal and ischemic myocardia, there was no difference in the dimension of the potential reentrant pathway, that is, the continuous line of functional conduction block, around which the reentrant wave fronts circulate. Yet, flecainide resulted in significant rate-dependent slowing of conduction preferentially in ischemic myocardium. The additional slowing of conduction of the common reentrant wave front coupled with minimal changes in the length of the reentrant pathway allowed additional time for the wave front to reexcite normal myocardium on the proximal side of the arc of block. After flecainide, reentry could be induced in hearts in which reentry could not be induced during control. The same proarrhythmic mechanism explains the propensity of nonsustained figure-8 reentrant tachycardias to become sustained after flecainide.

Animals↗

PubMed1985

Matrix vesicle enzymes in human osteoarthritis.

The enzymatic activities and in vitro calcification properties of matrix vesicle fractions isolated from normal and osteoarthritic (OA) human articular cartilage were compared to determine the essential conditions for calcification in these tissues. Four groups of human cartilage were examined, I, normal articular cartilage from aged, nonOA joints; II, discolored or fibrillated cartilage from OA joints; III, osteophytic cartilage from OA joints; IV, loose body cartilage from OA joints. Fetal bovine growth plate cartilage was also studied. Both ATP- and 5'-AMP-dependent in vitro matrix vesicle calcification occurs in all cartilage groups examined and, for human articular cartilage, these activities increase progressively from Groups I to II to III. Calcification does not occur in the absence of either phosphate or pyrophosphate. Alkaline phosphatase, 5'-AMPase, and ATP:pyrophosphohydrolase activities are increased in Groups III and IV cartilage compared with Group I and are detected at high levels in fetal bovine growth plate cartilage. Pyrophosphatase activity occurs in only those cartilage groups juxtaposed to areas of new bone formation (osteophytic, loose body, and bovine growth plate). These results suggest that OA, growth plate, and even normal articular cartilage all have the potential to undergo calcification as long as both phosphate and pyrophosphate ions can be generated at sufficiently high levels. However, the capacity for cartilage to deposit hydroxyapatite, as it does during bone formation, may depend on the presence of pyrophosphatase activity.

Adenosine Triphosphatases↗

PubMed1981

Modification of bovine pancreatic ribonuclease A with the site-specific reagent 4-arsono-2-nitrofluorobenzene. Spectrophotometric titration of arsononitrophenyl ribonuclease A derivatives.

The 4-arsono-2-nitrophenyl chromophore can serve as a versatile spectrophotometric probe of the surface structure of proteins. Values of pK1' and pK2' for the arsonic acid ionizations are near 3 and 8, respectively, and the presence of nearby positive and negative charges produces substantial alterations in the spectral response of the probe. Changes in the extinction at the wavelength of maximum difference are 30-50% of the extinction coefficients, epsilonmax, for each ionization of the arsonic acid moiety. The titration of 41-(4-arsono-2-nitrophenyl)ribonuclease A indicates that the arsonate dianion binds near the active-site histidine residues. With protonation of a carboxylate side chain in the acidic region, presumably aspartic acid-121, the active site is disrupted. The 41-(4-arsono-2-nitrophenyl) group interacts to a greater degree with the histidine-119 side chain than it does with the histidine-12 residue. Interactions of uridine or 3'-cytidylic acid with the ligand-binding region of 41-(4-arsono-2-nitrophenyl) ribonuclease A modify the spectrophotometric response extensively. 3'-Cytidylic acid binds 41-(4-arsono-2-nitrophenyl) ribonuclease A with an affinity 300 times less than that for native ribonuclease A and 17 times lower than that for 41-(2,4-dinitrophenyl) ribonuclease A. The arsononitrophenyl chromophore is responsive to changes in the active site of ribonuclease A induced by such perturbants as ligand binding, chemical modification, and both acid and thermal denaturation.

Animals↗

PubMed1978

A self-powered, preprogrammable, constant current, electronic stimulator for implantation in conscious and unrestrained, small animals.

A completely implantable electronic brain stimulator was designed and constructed using commercially available Complementary Metal Oxide Semiconductor digital, integrated circuits. All stimulation parameters were preprogrammed prior to implantation. They included bipolar pulse width (0.5 msec), constant current intensity (120 muA) and frequency (125 pulses/sec) as well as pulse train length (33 sec) and the interval between pulse trains (70 min). After complete encapsulation, the unit weighed 6.2 g and measured 30 mm X 15 mm X 8 mm. The units were easily implanted under the skin in the flank areas of 300 g rats. The 5 muW power consumption allowed implanted lifetimes of over 6 months. A miniature magnetic switch was included inside the package to allow testing of the unit after implantation. Stimulators were implanted in 17 rats for periods of 4--62 days in a study exploring the relationship between long term electrical stimulation of the lateral hypothalamus and the development of arterial pathology.

Animals↗

PubMedDate not supplied

The effects of stimulation of trigeminal sensory afferents upon caudate units in cats.

This investigation assessed the influences of trigeminal primary sensory afferents upon caudate neuronal activity in locally anesthetized and chloralose anesthetized cats. Afferents from jaw elevator stretch receptors were stimulated via electrodes in the trigeminal mesencephalic nucleus (Mes 5). Afferents from dental and periodontal receptors were stimulated via electrodes in the inferior dental nerve (IDN). Low intensity electrical stimulation of either locus evoked caudate neuronal responses with Mes 5 being more effective. Higher intensity stimulation of IDN in chloralose anesthetized cats was used to determine if thresholds of trigeminal evoked caudate responses corresponded to thresholds of particular fiber groups in the sensory afferent. In all tested units, neuronal responses were only evoked when stimulation was suprathreshold for both A beta and A delta fibers. These data were discussed in relation to processing of oropharyngeal sensory information within the basal ganglia. Possible implications for bucco-lingual dyskinesias were noted.

Afferent Pathways↗

PubMedDate not supplied

A minimum component AM transmitter to monitor electronic brain stimulation.

Construction of a light weight AM transmitter which can be used to monitor implanted electronic brain stimulators is described. The unit can operate continuously for 40 hours on a single battery and can easily be carried by a small laboratory animal. The range of the unit is limited to approximately 1 meter and the transmitted signal can be detected by a standard AM broadcast band receiver. The unit is simple to construct, inexpensive, and reliable in performance.

Animals↗