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Biomedical subjects

M Akhtar

Publications and source records attributed to M Akhtar.

At least 343 records · Page 19Linked to original sources

Unidirectional retrograde atrioventricular nodal block in man: determinants of reversibility by vagal antagonism.

The mechanism of unidirectional retrograde atrioventricular (AV) nodal block remains largely unknown. In this study, factors determining the reversal of the unidirectional block by atropine were evaluated in 12 patients who had no demonstrable ventriculoatrial (VA) conduction during ventricular pacing. Six patients demonstrated 1:1 VA conduction after atropine (group I), while the remaining six patients continued to show VA block (group II). During the control study there was no significant difference in the sinus cycle length and AH interval between the two groups. The percent decrease in sinus cycle length after atropine was also similar in groups I and II (i.e., 23 +/- 12 and 26 +/- 6, respectively). The effect on antegrade AV nodal conduction (i.e., the percent decrease in AH interval), however, was significantly greater in group I (24 +/- 9) as compared to group II (9 +/- 5) (p less than 0.004). The onset of VA conduction appeared to correlate with the improvement of antegrade conduction. The ratio of these two effects of atropine (i.e., percent decrease in AH interval to percent decrease in sinus cycle length) was higher when VA conduction was first demonstrated in group I (2.3 +/- 1.1) than at the maximal effect of atropine (1.2 +/- 0.3), reflecting a relatively greater decrease in sinus cycle length. Three of six group I patients redeveloped VA block at maximal effect of atropine. The results suggest a functional and dynamic nature of the unidirectional AV nodal block, possibly caused by vagal influence exaggerating the well-known directional asymmetry of AV nodal conduction in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Meobentine sulfate: antiarrhythmic and electrophysiologic effects assessed by programmed electrical stimulation and ambulatory monitoring in patients with complex ventricular tachyarrhythmia. Report of a multicenter evaluation.

Five cardiology centers conducted open-label prospective trials of meobentine sulfate, an intravenously and orally available analog of bethanidine, to assess its potential for treatment of recurrent, drug refractory ventricular tachycardia (VT) or fibrillation (VF), and complex ventricular arrhythmias. The study population comprised 26 patients (mean age, 61 years); 18 were men. Coronary artery disease was present in 15, cardiomyopathy in six, and valvular heart disease in three. Patients presented with both VT and VF (seven), sustained VT alone (12), or frequent ventricular ectopy (PVCs) and nonsustained VT (seven). Of the 26 patients, 5 were enrolled in antiarrhythmic studies (chronic PVC suppression) and 21 were enrolled in programmed electrical stimulation (PES) studies. Two of five in the chronic PVC study showed greater than 75% arrhythmia suppression. Among 21 patients in PES studies, there were eight intravenous (16 mg/kg) and 19 oral trials (400 to 1000 mg every 6 hours, 3 days/dose interval). Five of 22 patients showed efficacy at repeat PES study (neither VT nor VF), one showed partial efficacy, and four were not restudied because of clinical arrhythmia (three) and/or adverse effects (two). Overall, three patients (12%) were continued on the drug for an extended period of time. Adverse experience included hypotension in 50% and gastrointestinal effects (nausea, vomiting, or diarrhea) in 56% (oral trials only). Adverse reactions led to drug discontinuation in six and dosage reduction in eight patients. Thus, meobentine may prevent induction of VT or VF or reduce frequency of complex PVCs in selected patients refractory to other antiarrhythmic agents, but the response rate is relatively low. Symptomatic hypotension or gastrointestinal adverse effects are common and may limit utility of meobentine as a chronic oral antiarrhythmic agent.

Administration, Oral↗

Electrophysiology studies: precordial thumping patients paced into ventricular tachycardia.

The American Heart Association currently recommends the precordial thump as the initial maneuver in the treatment of ventricular tachycardia and monitored ventricular fibrillation. Advocates of the precordial thump maintain that it affords the advantage of immediate availability and might prove lifesaving in cases of ventricular tachycardia. A canine study and a prehospital study have argued that in the cardiac arrest model, thumping ventricular tachycardia causes ventricular fibrillation as often as reversion to a sinus rhythm. We therefore studied the effects of the precordial thump on patients undergoing electrophysiology studies who had been paced into ventricular tachycardia. A total of nine patients received precordial thumps for 11 separate episodes of electrically induced sustained ventricular tachycardia. Our thumps failed on all 11 attempts to convert any of our patients. All 11 were subsequently successfully restored to a supraventricular rhythm with overdrive pacing or countershock. There was no detrimental effect from thumping ventricular tachycardia as has been previously reported. Our results would indicate that countershock is more effective than precordial thumping for converting ventricular tachycardia to a supraventricular rhythm, but previously reported "detrimental effects" of thumping are not confirmed by this study.

Electric Countershock↗

Linking: a dynamic electrophysiologic phenomenon in macroreentry circuits.

The term "linking" has been used specifically to describe the mechanism for perpetuation of functional anterograde bundle branch block: namely, repetitive transseptal retrograde concealed penetration by impulses propagating along the contralateral bundle. We present selected examples that demonstrate tht linking-type phenomena actually have a wide spectrum of expression in human macroreentry circuits, particularly those incorporating either the bundle branches and His bundle or the normal pathway and Kent bundle. The examples presented are as follows: (1) persistent retrograde functional conduction delays in the His-Purkinje system during right ventricular pacing, (2) anterograde Kent bundle condution at rapid rates, dependent on prior block in the normal pathway, (3) persistent anterograde functional infra-His block of atrial impulses during rapid ventricular pacing in the presence of a retrogradely conducting accessory pathway, and (4) transient advancement of His activation with ventricular fusion complexes during overdrive ventricular pacing of bundle branch reentrant tachycardia. Based on these examples, we characterize linking as a generalized electrophysiologic phenomenon in which each successive impulse entering a macroreentry circuit propagates preferentially along one limb because of functional block in the contralateral limb resulting from the effects of the prior impulse. It is proposed that such functional block may be dynamically maintained either by repetitive impulse interference, which perpetuates local refractoriness (examples No. 1 to 3), or by repetitive impulse collision (example No. 4). The general conceptual scheme outlined can be applied to specific electrophysiologic phenomena associated with a wide variety of reentry circuits in man.

Adult↗

Electrophysiologic mechanisms of functional bundle branch block at onset of induced orthodromic tachycardia in the Wolff-Parkinson-White syndrome. Role of stimulation method.

The mechanisms of aberrant conduction at the onset of induced orthodromic tachycardia in the Wolff-Parkinson-White syndrome were analyzed in 20 consecutive patients in whom this tachycardia was initiated by the atrial (A2) and/or right ventricular (V2) extrastimulus techniques. Of 13 patients in whom orthodromic tachycardia was induced by the A2 method, functional right bundle branch block occurred at tachycardia onset in four (31%) and left bundle aberrancy in two (15%), one of whom also manifested right bundle aberrancy. The occurrence of bundle branch block at the onset of tachycardia was linked to aberrant conduction of the initiating A2 impulse which, in turn, was associated with attainment of relatively short His1His2 intervals within the tachycardia initiation zone. Aberrant conduction of A2 was also more common in patients without manifest preexcitation. In contrast, of 14 patients in whom orthodromic tachycardia was induced by the V2 method, left bundle aberrancy occurred at the onset of tachycardia in 11 (79%), one of whom manifested right bundle branch block as well. Left bundle aberrancy was more likely to occur when the interval from the initiating V2 (or macro-reentrant V3) impulse to the first anterograde His deflection was less than 300 ms. This suggests that left bundle aberrancy at the onset of orthodromic tachycardia induced by the V2 method results from concealed retrograde penetration of the His-Purkinje system, with the left bundle being last to recover. Our findings provide the conceptual basis for a physiologic approach to the deliberate induction of specific types of aberrant conduction at onset of orthodromic tachycardia in patients with Wolff-Parkinson-White syndrome.

Adolescent↗

Gastrointestinal malacoplakia in children.

Four children, whose ages ranged from 1 to 13 years, with malacoplakia of the gastrointestinal tract were treated at King Faisal Specialist Hospital between 1979 and 1983. All patients had either a preceding or a coexisting chronic illness. In one patient, malacoplakia was an incidental finding, while the remaining three patients presented with bloody diarrhea, abdominal pain, recurrent fever, and severe malnutrition. Colonoscopy in two patients revealed markedly inflamed and friable mucosa with focal ulceration alternating with patches of normal mucosa and pseudopolyposis. They were treated with antibiotics and cholinergic agonists. Three patients responded favorably, while one patient continued to have extensive active disease. Although the response to therapy is unpredictable, patients may respond if the treatment is continued on a long-term basis.

Adolescent↗

The mechanism of the attachment of esterifying alcohol in bacteriochlorophyll a biosynthesis.

The mechanism through which the C-17(3) carboxy group of bacteriochlorophyllide a is esterified to produce bacteriochlorophyll aphytyl of Rhodopseudomonas spheroides and bacteriochlorophyll ageranylgeranyl of Rhodospirillum rubrum was studied by using 5-aminolaevulinate labelled with 18O at its C-1 carboxy oxygen atoms. The latter species was prepared by an exchange reaction in which 5-aminolaevulinate hydrochloride was heated in H218O in an autoclave. A method for the determination of the 18O content of the C-1 oxygen atoms of 5-aminolaevulinate was developed. As a prelude to the mechanistic work, a systematic study was undertaken to establish the optimal conditions under which a significant proportion of the bacteriochlorophyll a of the two photosynthetic organisms originated from the exogenously added 5-aminolaevulinate. It was found that, when Rps. spheroides and Rsp. rubrum were grown in the presence of about 0.15mM- and 1.2mM-5-aminolaevulinate respectively, 30-40% of their chlorophyll was derived from the added precursor. In these conditions, 5-amino[1,4-18O3]laevulinate was incorporated into bacteriochlorophyll aphytyl and bacteriochlorophyll ageranylgeranyl by the relevant organisms. The samples of chlorophylls were then hydrolysed with alkali to obtain phytol and geranylgeraniol, which were converted into the corresponding trimethylsilyl derivatives and analysed by gas chromatography-mass spectrometry. The data were used to deduce that the alcohols contained 90-95% of the 18O originally present at each of the C-1 oxygen atoms of the precursor 5-aminolaevulinate. In the light of these results it is suggested that the ester bond at C-17(3) is formed, not by a chlorophyllase type of enzymic reaction, but by a process involving the nucleophilic attack by the C-17(3) carboxylate group of the chlorophyllide on the activated form of an isoprenyl alcohol.

Alcohols↗

Facilitation of ventricular tachycardia induction with abrupt changes in ventricular cycle length.

The effect of abrupt short-to-long changes in cycle length (CL) on the postulated reentrant circuit of ventricular tachycardia (VT) was evaluated. This was performed using single and double ventricular extrastimuli in a group of 21 patients clinically suspected of having VT in whom VT could not be induced at comparable or shorter constant CLs. A second group of 10 patients without suspected VT was similarly studied. Compared with constant CLs of equal or shorter duration preceding the single or double ventricular extrastimuli, abrupt short-to-long CL changes resulted in (1) initiation of sustained VT in 13 of 21 patients in whom VT could not be induced at constant CLs despite the use of shorter S1S3 by 66 +/- 17 ms; (2) increased incidence of initiation of sustained VT after the V3 phenomenon resulting from macroreentry within the His-Purkinje system (Re-HPS); (3) a small but higher incidence of sustained VT due to sustained Re-HPS; and (4) no induction of sustained or nonsustained VT with either method in the second group of patients. These results provide additional support for reentry as the basis for sustained ventricular tachyarrhythmias. Abrupt short-to-long CL changes may be effective for initiating sustained VT in patients at risk for these arrhythmias.

Adult↗

Kaposi's sarcoma in renal transplant recipients. Ultrastructural and immunoperoxidase study of four cases.

Tissues from four cases of Kaposi's sarcoma developing in renal transplant recipients were studied by light and electron microscopic examination and by immunoperoxidase staining for Factor-VIII-related antigen. Ultrastructurally, the tumors in all four cases contained a variable mixture of cells, including endothelial cells, pericytes, fibroblasts, and myofibroblasts. These findings support the origin of Kaposi's sarcoma from primitive vasoformative mesenchyme. Immunoperoxidase staining for Factor-VIII-related antigen was limited to endothelial cells. In one case intracytoplasmic virus-like tubular complexes were seen. The significance of this finding is briefly discussed.

Adult↗

Patterns of human atrioventricular nodal accommodation to a sudden acceleration of atrial rate.

Atrioventricular nodal (AVN) accommodation to an abrupt increase in atrial rate was systematically studied in 10 patients using a pacing protocol incorporating a programmable pause (S1S2) between the last beat of basic atrial drive (S1S1) and the onset of an 18-beat paced atrial train (S2S2) of shorter constant cycle length (CL) than that of S1S1. Pacing was repeated, varying S1S2 while keeping S1S1 and S2S2 CLs fixed. In all patients there existed a zone of 1 or more critical S1S2 intervals for which the new steady-state AVN conduction time (S2H2) was attained "instantaneously," that is, with the first beat, and maintained for subsequent beats of the S2S2 train. At S1S2 intervals that exceeded or were less than critical values, S2H2 progressively increased (crescendo pattern) or decreased (decrescendo pattern), respectively, until the steady-state value was achieved. The zone of S1S2 intervals that resulted in decrescendo or instantaneous AVN accommodation contracted when either the S1S1 CL was increased or the S2S2 CL was shortened. These findings have relevance to the interpretation of electrophysiologic studies and explain the spectrum of AVN accommodation patterns observed at the onset of supraventricular tachycardia.

Adaptation, Physiological↗

Practical considerations in the treatment of ventricular arrhythmias with mexiletine.

Mexiletine can be administered by intravenous, intramuscular, or oral route. However, the intramuscular route is seldom used because it offers no advantage over the other routes. Loading doses of about 400 mg may result in unacceptable side effects and are unnecessary for management of chronic ventricular arrhythmias. Therapeutic efficacy as well as side effects increase in proportion to increasing blood levels. At plasma levels of 2.0 mg/L, side effects are encountered in a significant number of patients. Because of its lack of serious toxicity even in patients with various systemic illnesses and its long elimination half-life, mexiletine should be considered as a first-line drug for treatment of ventricular arrhythmias.

Adult↗

Abnormal abdominal computerized tomography with amiodarone therapy and clinical significance.

Although the antiarrhythmic agent, amiodarone, is known to cause elevation of liver function tests, the effect of this drug on abdominal computerized tomography (CT) scans in patients on amiodarone therapy is unknown. Since iodine is in its molecular structure, the presence of amiodarone or its metabolites might be expected to produce higher CT numbers similar to the effect of contrast agents. To test this hypothesis, CT scans were performed in a series of 25 patients receiving amiodarone, 14 receiving short-term (mean 2.5 +/- 1.3 days) and 19 receiving long-term therapy (mean 130 +/- 75 days), as well as in a control group not receiving amiodarone. Gastrointestinal symptoms (if any) and liver function tests (LFT) prior to instituting amiodarone therapy and at the time of CT scan were also documented. CT scans showed a modestly increased density in multiple organs in the short-term group, but a markedly increased hepatic density in all but one patient in the long-term group. Presence of gastrointestinal symptoms or abnormal LFT did not appear to correlate with the CT number. Such findings would suggest that increased hepatic density on CT scan is to be expected in patients receiving long-term amiodarone therapy, and although the exact biologic pathways of amiodarone metabolism are uncertain, the liver appears to be a major site of drug storage and/or metabolism.

Adult↗

Atrioventricular nodal reentrant tachycardia.

This entity represents the most common type of recurrent, regular, narrow QRS tachycardia in the absence of preexcitation syndrome. Electrophysiologic basis for the arrhythmia is reentry within the AV node resulting from dissociation between intranodal pathways. A better understanding of these intranodal pathways helps in the selection of a rational approach to management of these cases.

Anti-Arrhythmia Agents↗

Effect of atrioventricular sequential pacing in patients with no ventriculoatrial conduction.

Candidates for the dual chamber "universal" (DDD) pacemaker are frequently tested for the presence of intact ventriculoatrial (VA) conduction to identify those at risk for developing endless loop tachycardia. However, recent reports have cited instances where clinical endless loop tachycardia has occurred even when no VA conduction could be demonstrated during ventricular pacing. A pacing protocol was designed to assess the effect of atrioventricular (AV) sequential pacing on VA conduction in 13 patients who showed no evidence of VA conduction during routine electrophysiologic testing. The absence of VA conduction was inferred by pacing the ventricle at several cycle lengths without obtaining a retrograde atrial capture. With the AV sequential method, which consisted of an AV sequential drive with a programmed AV interval of 100 to 160 ms, the presence or absence of VA conduction was tested utilizing a premature ventricular stimulus (V2) over a wide range of coupling intervals. During the AV sequential method, the V2 effectively propagated to the atria in 5 of 13 patients with V2A2 intervals ranging from 200 to 460 ms (mean 304 +/- 97). It is concluded that in patients showing absent VA conduction during routine testing, the ability of a paced ventricular impulse to propagate retrogradely can be demonstrated in a significant number of cases with AV sequential pacing. Although the exact mechanism could not be determined, it is postulated that as compared with ventricular pacing alone, a longer input into the AV node (first anterogradely during the AV sequential drive and then retrogradely with V2) may be partly responsible for the facilitative effect of the AV sequential method.

Adult↗