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Biomedical subjects

S Denker

Publications and source records attributed to S Denker.

32 records · Page 2Linked to original sources

Facilitation of macroreentry within the His-Purkinje system with abrupt changes in cycle length.

We have recently described the ability of abrupt short-to-long changes in atrial cycle length (CL) to prolong refractoriness of the His-Purkinje system (HPS) and increase the likelihood of aberrant ventricular conduction. We have also shown similar functional behavior in retrograde refractoriness of the HPS during changes in ventricular CL. To further assess these characteristics we evaluated the effect of abrupt short-to-long change in ventricular CL on the phenomenon of macroreentry within the HPS (Re-HPS) in 20 patients in whom Re-HPS occurred during application of a ventricular extrastimulus (V2) at a constant ventricular CL (method I) and/or with abrupt short-to-long change in CL (method II). For both methods V2 was coupled to a CL of identical duration, designated the reference CL (CLR). In method I the CLs preceding (CLP) the CLR equaled CLR, whereas in method II CLP was less than CLR. The results showed a dramatic increase in occurrence of Re-HPS with abrupt short-to-long change in CL with Re-HPS occurring in 19 patients with this method compared with in 11 patients during constant CL. In 10 patients manifesting Re-HPS with both methods the associated retrograde conduction (V2H2) delays were equal or less during abrupt short-to-long changes in CL and, remarkably, there were concomitantly shorter antegrade conduction (H2V3) delays compared with at a constant CL. Moreover, despite the resulting shorter V2V3, additional Re-HPS beats were also more likely to occur with abrupt short-to-long change in CL compared with at a constant CL.(ABSTRACT TRUNCATED AT 250 WORDS)

Bundle of His↗

Postextrasystolic alterations in refractoriness of the His-Purkinje system and ventricular myocardium in man.

The changes in refractoriness of the His-Purkinje system (HPS) and ventricular myocardium (VM) that are associated with the occurrence of postextrasystolic beats in man are unknown. Accordingly, using a pacing model of the cycle length changes created by a ventricular extrasystole-postextrasystole sequence, we measured retrograde HPS and VM relative and effective refractory periods (RRP and ERP) in 15 patients with the use of ventricular test extrastimuli during preextrasystolic basic control drive (method I) and after programmed extrasystolic (method II) and postextrasystolic (method III) beats. The basic cycle length (same for all three methods) ranged from 500 to 700 msec (mean 613 +/- 74 msec) and the extrasystolic coupling interval (identical for methods II and III) comprised 68 +/- 4% of the basic cycle length. In method III the postextrasystolic pause was programmed to equal the basic cycle length (i.e., noncompensatory) so that method I could serve as control for method III. RRP-HPS decreased from 331 +/- 37 msec in method I to 245 +/- 37 msec or less during the extrasystolic beat (p less than .001). A less dramatic corresponding shortening of ERP-VM and RRP-VM was observed, i.e., from 245 +/- 21 and 264 +/- 23 msec (method I) to 233 +/- 23 and 251 +/- 22 msec (method II), respectively (p less than .001). With the postextrasystolic beat, however, RRP-HPS increased to exceed the control value of method I by 23 +/- 11 msec (p less than .001). This greater-than-expected RP prolongation was also associated with significantly increased retrograde HPS conduction times (in method III vs method I) at both long and short test stimulus coupling intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Bundle of His↗

Retrograde concealed conduction in the atrioventricular node: differential manifestations related to level of intranodal penetration.

Although concealed conduction in the atrioventricular node (AVN) has been the focus of numerous experimental and clinical studies, little is known about the differential effects on AVN functional behavior of prior concealed retrograde impulse penetration alone vs prior anterograde or dual AVN activation. This study was undertaken specifically to investigate this aspect of human AVN physiology in patients without intact ventriculoatrial conduction to provide a model with which to analyze concealed retrograde AVN conduction. In 13 such patients AVN behavior during a subsequent anterograde input was characterized for each of three different manners of prior AVN activation: anterograde alone (method I), simultaneous anterograde and retrograde excitation (method II), or equivalently timed retrograde concealed AVN penetration alone (method III). In all patients evidence for retrograde AVN concealment was documented by longer anterograde conduction in the AVN during method III than that observed when the retrograde impulse was omitted (method IV). Furthermore, in these patients lacking intact ventriculoatrial conduction, anterograde conduction in the AVN was facilitated and refractoriness was decreased during dual excitation vs anterograde activation alone (method II vs method I). However, when each of methods I and II were compared with concealed retrograde AVN penetration alone (method III), two patterns of AVN responses were observed: In 11 of 13 patients (group A) conduction in the AVN was "worse" and refractoriness was greater both in methods I and II compared with method III; in the remaining two patients (group B) the opposite relationships were observed. The results suggest that among patients with no ventriculoatrial AVN conduction there exist at least two subpopulations whose AVN functional characteristics differ markedly when the effects of anterograde and dual excitation are compared with equivalently timed concealed retrograde activation alone. These findings may be related to differences in level of retrograde AVN concealment in groups A and B, which can be unmasked by the outlined pacing techniques.

Adult↗

Effects of alternating cycle lengths on refractoriness of the His-Purkinje system.

The effects of alternating cycle lengths (bigeminal rhythm) on His-Purkinje system refractoriness were studied in 14 patients using His bundle and right bundle recordings. Programmed atrial stimulation at constant cycle length (method I) was scanned using the atrial extrastimulus technique (A2) and compared with an atrial cycle length of identical duration coupled to A2 on alternate beats (method II). The results showed that (a) despite shorter cycle length of the His-Purkinje system with method II due to effect of A2 on atrioventricular nodal conduction (699 +/- 90 vs. 743 +/- 87 ms, P less than 0.001), the relative refractory period of the His-Purkinje system was always longer with method II (463 +/- 52 vs. 440 +/- 43 ms, P less than 0.001). A similar increase also occurred in effective refractory period of the His-Purkinje system; (b) while functional right bundle branch block occurred in eight patients and functional left bundle branch block in two patients with method I, functional right bundle branch block occurred in all 14 patients and left bundle branch block in seven patients with method II; (c) in two patients where both functional right and left bundle branch block occurred with method I this never was manifest at identical degree of abbreviation of His-Purkinje system cycle length but was manifest at identical abbreviation in each of seven patients with method II; (d) site of conduction delay and/or block during functional right bundle branch block was always proximal, i.e., between the His bundle and right bundle recordings with both methods. During method II this resulted in shortening of the subsequent right bundle cycle length relative to the subsequent His bundle (and of necessity left bundle) cycle length. The finding of increased His-Purkinje system refractoriness despite shorter preceding cycle length of the His-Purkinje system during atrial bigeminy has never been previously described and suggests that classical concepts of His-Purkinje system behavior may require revision in this setting. Secondly, during atrial bigeminy the occurrence of alternating functional bundle branch block cannot be accounted for solely by the degree of abbreviation of His-Purkinje system cycle length, but may be explained by a relative shortening of the next ipsilateral bundle branch cycle length in the bundle manifesting block.

Atrial Function↗

Role of cardiac electrophysiologic studies in patients with unexplained recurrent syncope.

Cardiac electrophysiologic studies (EPS) with programmed electrical stimulation (PES) were performed in 30 patients with recurrent syncope to uncover possible arrhythmic etiology. All patients had undergone thorough medical and neurologic evaluation prior to EPS without finding a definitive cause for syncope. In the majority of patients an arrhythmic etiology for syncope was suspected but could not be documented utilizing the 12-lead surface ECG, extended in-hospital and/or ambulatory monitoring (for greater than or equal to 48 hours) and exercise testing prior to the EPS. The studies provided a clue to the possible underlying rhythm disturbance which could have caused syncope in 16/30 patients. Sustained or nonsustained ventricular tachycardia and/or ventricular fibrillation was induced in 11/30, sinus node dysfunction in 4/30 and intra-His block in the remaining one. Fourteen of the 16 have remained free of symptoms following therapy based on results of EPS during a follow-up period ranging from 6-30 months (mean 16.5 +/- 7.8). In 2/16 syncope recurred (one arrhythmic and one non-arrhythmic) despite pacemaker therapy for sinus node dysfunction detected during EPS. In the remaining 14/30 patients, EPS and PES did not induce arrhythmia which could account for patient symptomatology and therefore no specific therapy could be recommended. Eleven of these 14 patients experienced a recurrence of symptoms within a 6-25 month period (mean 16.2 +/- 6.8). Of the 16 patients with inducible arrhythmias considered clinically significant, 15 had associated structural heart disease. On the other hand, of the 14 patients without clinically significant arrhythmias, structural heart disease could be detected in only three. It is concluded that cardiac arrhythmias constitute a common cause of unexplained syncope, particularly in patients with structural heart disease, and that EPS with PES can uncover the type of arrhythmic disturbance in a significant number of cases.

Adult↗

Effects of abrupt changes in cycle length on refractoriness of the His-Purkinje system in man.

Abrupt changes in cycle length (CL) occur frequently in the clinical setting of atrial fibrillation. However, the effects of such changes on the His-Purkinje system (HPS) have not previously been considered during aberrant ventricular conduction (VAb). In 12 patients who manifested VAb with atrial premature stimulation (A2) during sinus rhythm, the relative refractory period (RRP) of the HPS was evaluated during a constant atrial CL (method I) and during abrupt changes in the CL (method II), wherein the A2 was coupled to an atrial CL (last A1A1) comparable to method I. This last A1A1 during method II was preceded by a series of constant atrial CLs 100-200 msec longer (method IIA) in 11 of 12 patients, or 109-300 msec shorter (method IIB) in all 12 patients. Although abrupt changes in the atrial CL using method IIA resulted in a longer HH interval (by 0-30 msec; mean 13.2 +/- 9.2 msec) preceding the A2, the RRP-HPS was 5-20 msec shorter (mean 9.3 +/- 5.3 msec) compared with method I in eight patients. The effect of abrupt changes was further evaluated in nine patients using method III, with a constant atrial CL, with a duration equal to the last H1H1 interval of method IIA. The VAb that occurred with method III was not manifested with method IIA in seven of nine patients, and in two patients the RRP-HPS was the same or less. Conversely, method IIB resulted in a shorter HH interval (by 0.110 msec; mean 28.9 +/- 21.1 msec) preceding A2, but in 10 patients, RRP-HPS was 5-40 msec longer (mean 20.7 +/- 10.5 msec) than that of method I and in two, VAb was only manifested using method IIB. Further scanning with method III, derived from the HH interval immediately preceding A2 of method IIB, was performed in seven patients and compared with method IIB. Prolongation in the RRP-HPS was shown using the latter method. The results indicate that abrupt changes in CL influence the functional behavior of the HPS in a manner not anticipated. Such changes may have important implications in determining the occurrence of VAb during atrial fibrillation.

Adult↗

Atrioventricular sequential pacing: differential effect on retrograde conduction related to level of impulse collision.

Patients with DDD pacemakers who have intact retrograde conduction are known to be at risk of developing ventricular and "endless loop" tachycardia. To address this problem, a pacing protocol was designed in which V2A2 conduction was assessed in 16 patients during ventricular pacing alone (standard method) and during paced atrioventricular (AV) sequential drive (AV sequential method); the results were then compared. In eight of 16 patients who had intact retrograde conduction with both methods (group 1), the V2A2 intervals were significantly shorter (by 60 to 340 msec) with the AV sequential method. In the remaining eight patients, who demonstrated V2A2 block with the standard method, no V2A2 block occurred with the AV sequential method. In this study, two sets of AV intervals were programmed to produce collision of the two impulses (atrial and ventricular), either in the AV node or the His-Purkinje system (HPS). The site of V2A2 facilitation was related to the site of impulse collision. These results can be explained by earlier excitation by the atrial impulse (of AV node and/or HPS) during AV sequential pacing. However, in some cases it was evident that antegrade propagation of the atrial impulse was responsible for subsequent facilitation. The data suggest that assessment of retrograde conduction in candidates for DDD pacemakers can be made most accurately by the AV sequential method.

Adult↗

Divergence between refractoriness of His-Purkinje system and ventricular muscle with abrupt changes in cycle length.

The concept that refractoriness of the His-Purkinje system (HPS) and ventricular muscle both vary directly with cycle length is based on observations during the use of constant cycle length. During abrupt changes in ventricular cycle length, refractoriness of the ventricular muscle is known to reflect the cumulative durations of preceding cycle lengths. The effect of such changes on retrograde refractoriness of the HPS is not known. In this study refractoriness of ventricular muscle and of the HPS was evaluated in 30 patients with normal intraventricular conduction by the ventricular extrastimulus (V2) technique during constant cycle length (method I) and during abrupt cycle length changes (method II). During method II the cycle length immediately before V2 was identical to the constant cycle length of method I and therefore was designated as the reference cycle length (CLR); however, the cycle length preceding (CLP) CLR was either longer than CLR (method IIA) by 100 to 300 msec in 11 patients or shorter than CLR (method IIB) by 100 to 300 msec in 30 patients. Results showed that compared with method I, method IIA shortened the relative refractory period (RRP) of the HPS from 350 +/- 29 to 344 +/- 29 msec (p less than .04), whereas the effective refractory period (ERP) of the ventricular muscle increased from 225 +/- 21 to 233 +/- 20 msec (p less than .0001). In contrast, compared with method I, method IIB lengthened the RRP of the HPS from 335 +/- 30 to 351 +/- 35 msec (p less than .0001), whereas ERP of the ventricular muscle decreased from 223 +/- 23 to 213 +/- 22 msec (p less than .0001). Similar to the inverse relationship between CLP and RRP of the HPS, ERP of the HPS was prolonged with short CLP (method IIB) compared with long CLP (method IIA). The results indicate a marked divergence between refractoriness of the HPS and of ventricular muscle during abrupt cycle length changes; these results were not previously anticipated. Whereas ventricular muscle responded to cumulative effects of preceding cycle lengths and varied directly with CLP, the HPS appeared to respond to directional and/or dynamic changes in cycle length and varied inversely with CLP. Moreover, in contrast to ventricular muscle, the HPS appeared to be responsive to rate of change in cycle length whereby short-to-long change in cycle length had a greater effect than long-to-short change in cycle length.

Adult↗

Biotransformation enzymes in two renal epithelial cell lines (LLC-PK1 and RK-L).

The activities of smooth endoplasmic reticulum (SER) and cytosolic xenobiotic-metabolizing enzymes were studied in two established renal tubular cell lines, LLC-PK1 and RK-L (rat kidney, Lübeck). The glutathione content in both cell lines was about 20-fold higher than in rat kidney homogenates; this is explained by a 20- to 50-fold lower activity of gamma-glutamyl transpeptidase in the cell lines. Among SER enzymes, the cytochrome P-450-dependent dimethylhydrazine demethylase was in the same range in both cell lines as compared with rat kidney S9 fraction. Pretreatment with phenobarbital (0.1 mM in the culture medium for 3 d) did not induce SER or cytosolic enzyme activities. The glutathione content in both epithelial cell lines can be modified by an inhibitor of GSH synthesis (buthionine sulfoximine, BSO), whereas inhibition of gamma-glutamyl transpeptidase (acivicin) did not significantly increase the GSH-concentration. Despite these biochemical characteristics, the utility of the new RK-L-line needs to be evaluated in experimental studies on renal transport processes and metabolism as well as cytotoxicity and genotoxicity of xenobiotics.

Animals↗