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E Downar

Publications and source records attributed to E Downar.

At least 37 records · Page 2Linked to original sources
PubMed1991

A three-dimensional display for cardiac activation mapping.

A three-dimensional display is described that allows activation sequences from the epicardium and endocardium to be shown simultaneously on the same image. Three electrode arrays (epicardial sock, left ventricular balloon, right ventricular balloon) are represented in a three-dimensional perspective by an array of dots that are intensified when activated. This arrangement requires fewer calculations and is easier to interpret than sliced-isochronal maps but cannot represent a complete heart cycle in one image. The three-dimensional display eliminates the distortion caused by two-dimensional diagrams and facilitates activation correlation between electrode arrays. A standard, low cost microcomputer has been used to implement the activation display.

Arrhythmias, Cardiac↗
PubMed1991

The construction of endocardial balloon arrays for cardiac mapping.

The advent of multichannel recording systems has enabled clinical mapping to be performed on a beat-by-beat basis using multi-electrode arrays. Surgical ablation of ventricular arrhythmias generally requires endocardial mapping. Clinical usage has indicated that an inflatable balloon array is the most practical design and can obviate the need for ventriculotomy by a transatrial introduction in the deflated state. Successful experience with the left ventricular balloon led to the development of a right ventricular balloon array suitably configured to extend into the outflow tract. Custom moulds are used to create an appropriate balloon from liquid latex. Nylon cloth is cut from a cardboard pattern to fashion a stretchable sock to envelope the balloon. Electrodes are formed by stitching 2-mm silver beads to the balloon sock in a preconfigured pattern. Teflon-coated 31 G multi-strand stainless-steel wires 130 mm in length connect the electrode beads by solder to the multipin connectors for easy hookup to the amplifier inputs. Tygon tubing 0.53 cm in diameter fitted to the balloon allows inflation and pressure monitoring. This basic design has been successfully implemented for the last 6 years.

Arrhythmias, Cardiac↗
PubMed1990

Transatrial balloon technique for activation mapping during operations for recurrent ventricular tachycardia.

Results of operations for recurrent ventricular tachycardia have improved since methods of mapping that allow a directed approach to the problem have been developed. With standard operative techniques (ventriculotomy and introduction of a hand-held probe or multiple electrode array), it has not always been possible to obtain satisfactory endocardial activation maps during the tachycardia. We have recently developed a new transatrial balloon approach that has greatly facilitated intraoperative mapping. This paper describes our total experience with the new approach and draws attention to details of the cardiopulmonary bypass technique and the surgical approach needed for safe balloon insertion across the mitral valve. We describe how correlation between position of target electrodes on the balloon and the internal geometry of the heart is achieved and discuss the choice and application of appropriate ablation techniques. In our series of 37 consecutive patients, 35% had a grade IV ventricle (ejection fraction less than 20%), 32% had a previous posterior infarct, 51% did not have a resectable aneurysm, and 54% had been receiving amiodarone within 1 month of the operation. These factors have been associated with poor operative results in other series. With the transatrial balloon technique, we were able to induce and map ventricular tachycardia in 100% of patients (average 2.6 +/- 1.3 morphologies per patient). Using a variety of ablation techniques (endocardial excision, cryoablation, or balloon electric shock ablation), we have achieved surgical control of the arrhythmias in 84% of patients with an operative mortality rate of 14%. We recommend transatrial balloon mapping as the procedure of choice for intraoperative identification of arrhythmogenic foci in patients with recurrent ventricular tachycardia.

Catheterization↗
PubMed1988

Endocardial mapping of ventricular tachycardia in the intact human ventricle: evidence for reentrant mechanisms.

A balloon array of 112 electrodes was used to obtain simultaneous recordings of endocardial electrograms during intraoperative mapping studies of ventricular tachycardia. Introduction of the balloon through a left atriotomy and across the mitral valve allowed endocardial activation maps to be obtained in the intact left ventricle. Of 20 patients with coronary artery disease studied in this way, suggestive evidence of endocardial reentry was found in 6. Three separate reentrant mechanisms were observed. In two patients, a single broad wave front of continuous recirculating activation reminiscent of a vortex was initiated by the formation of a functional arc of block in response to premature stimuli. In five patients, premature stimuli again produced a functional arc of block, which was circumvented by two opposing wave fronts that united on the distal side. Retrograde penetration by a narrow isthmus of slow conduction through the block initiated the tachycardia, whose activation sequence was consistent with figure eight reentry. In one patient, premature stimuli produced a region of delayed potentials. Critical timing of these resulted in microreentry in an adjacent circumscribed site, which formed the site of origin of the ensuing tachycardia. The microreentrant signals were not detected by standard unipolar recordings, but were seen on simultaneously recorded high gain electrograms. In 14 patients, although mapping identified a site of origin, the activation patterns showed either radial spread or incomplete circles. Detection of reentrant mechanisms during intraoperative mapping required high density electrode arrays and refined high gain recordings. An intact ventricle may facilitate intraoperative initiation of tachycardia.

Electrocardiography↗
PubMed1988

Electrical ablation with a balloon electrode array: chronic electrophysiologic response.

An intraoperative endocardial array of electrodes which permits simultaneous recordings from multiple sites in the intact ventricle is currently in clinical use and has provided the opportunity for exploring electrical ablation as an alternative to standard surgical ablative techniques requiring a ventriculotomy. A variation of the electrical ablative procedure adapted for this intraoperative purpose was studied in seven dogs to determine its long-term electrophysiologic and structural effects on ventricular myocardium. With the dogs on cardiopulmonary bypass, a mesh-covered latex balloon was introduced into the left ventricle via an atriotomy. Five damped sinusoidal discharges (4 of 200 J per 2 electrodes, one of 100 J to the remaining electrode) were delivered to nine silver bead electrodes sutured at 1 cm intervals onto the mesh and arranged in a 2 x 2 cm2 array. At 5-8 weeks following the ablation, no ventricular arrhythmias could be induced in any of the dogs using standard stimulation techniques. The scar produced by the ablation consisted of dense fibrous tissue, and was well demarcated from surrounding normal myocardium. Cellular electrophysiology confirmed that no action potentials could be recorded within the scarred area while at distances of 1 mm from the scar border, normal responses could be elicited from both muscle cells and Purkinje fibers. The adaptation of the described electrical ablative procedure produces an electrophysiologically inert scar.

Action Potentials↗
PubMed1988

Direct endocardial recording and catheter ablation of an accessory pathway in a patient with incessant supraventricular tachycardia.

A patient presented with incessant supraventricular tachycardia due to a concealed accessory pathway. The His bundle electrocardiogram showed a large discrete accessory pathway potential following ventricular activation and resulting in retrograde atrial activation. Percutaneous catheter ablation in the region of the accessory pathway potential left nodal conduction intact but prevented retrograde activation of the atria. Symptomatic tachycardia has not recurred. Direct endocardial recording of accessory pathway potentials is rare but may offer the opportunity for catheter ablation.

Adult↗
PubMed1988

Antiarrhythmic potential of chloroquine: new use for an old drug.

Amiodarone and chlorpromazine are phospholipase inhibitors which produce cytoplasmic inclusion bodies and have important electrophysiologic properties. Chloroquine also inhibits phospholipase activity, resulting in similar inclusion bodies, but electrophysiologic information about this drug is lacking. In this study, the cellular electrophysiologic effects of two doses of chloroquine were examined in sheep Purkinje fibres and ventricular muscle cells. Both concentrations produced a significant reduction in maximum velocity of upstroke of the action potential and prolongation of the action potential duration and refractory period in Purkinje fibres. These effects were observed in the absence of significant changes in threshold of stimulation or action potential amplitude and were partially reversible following washout of the lower drug concentration. In addition to these experimental data, clinical evidence of antiarrhythmic action was determined by administering 500 mg chloroquine daily over nine weeks to six subjects with frequent asymptomatic ventricular premature complexes. In four patients there was a reduction in ventricular ectopy, which recurred when the drug was discontinued, while a fifth patient reverted to sinus rhythm from atrial fibrillation previously resistant to other antiarrhythmic medication. Thus, chloroquine has important electrophysiologic properties. The underlying mechanism of this action remains unproven at the present time.

Action Potentials↗
PubMed1988

A new intraoperative approach for endocardial mapping of ventricular tachycardia.

Results of operation for control of ventricular tachycardia have improved since endocardial mapping techniques have been developed that allow a directed approach to the problem. In some patients, a limitation of established techniques has been difficulty in initiating the arrhythmia after a ventriculotomy has been made to allow introduction of endocardial recording electrodes. This paper describes a transatrial approach for endocardial mapping with a balloon array of 112 electrodes, which has been used intraoperatively in 15 patients. Surgical success in this group has been compared to that obtained in a similar group of patients in whom standard techniques of intraoperative mapping were used. With our new balloon technique we have been able to easily induce and map multiple episodes of ventricular tachycardia in all cases. On the basis of detailed endocardial maps, the locations of earliest activation and possible reentry loops have been identified and ablated with either endocardial excision or application of the cryoprobe. When indicated, concomitant procedures including aneurysm resection (9/15) and bypass grafting (14/15) have been performed. Hospital mortality in this group was 20%. None of the deaths have been related to recurrent ventricular tachycardia or complications of the mapping technique. Postoperative electrophysiologic studies performed at 2 weeks have been normal in 11 of 12 or 92% of patients. To date (mean follow-up 12 +/- 6 months) there has been no clinical recurrence or evidence of ventricular tachycardia by Holter monitoring in these patients. We conclude that the transatrial balloon approach to endocardial mapping facilitates intraoperative induction of ventricular tachycardia, allows complete mapping during multiple runs of the arrhythmia without prolonging cardiopulmonary bypass time, and improves results of operation using standard ablation techniques.

Cardiac Pacing, Artificial↗
PubMed1987

Amiodarone--an inhibitor of phospholipase activity: a comparative study of the inhibitory effects of amiodarone, chloroquine and chlorpromazine.

Amiodarone, an antiarrhythmic drug, like chloroquine and chlorpromazine, is a tertiary amine with amphiphilic properties. Chloroquine and chlorpromazine are known inhibitors of phospholipases. All three drugs produce characteristic microcorneal deposits consistent with lysosomal accumulations of phospholipid. Similar lysosomal bodies were found in leukocytes of 15 patients on chronic amiodarone treatment as well as 3 patients each on chloroquine and chlorpromazine, suggestive of widespread systemic inhibition of lysosomal phospholipases. These lysosomal inclusions were similar in morphology, irrespective of the drug given, and were of four types: multilamellar, amorphous dense, amorphous light, or a combination of 2 or more of the preceding types. There was no simple relationship between the number of inclusion bodies per cell and the cumulative dose of amiodarone (r = 0.02) or amiodarone serum levels (r = 0.11). An in vitro assay was used to compare the effects of the three drugs on Ca2+-dependent phospholipase A2 and C activities. Phospholipase A2 activity was inhibited in a dose-dependent fashion (1-8 mg/assay) by all three drugs in the order: chlorpromazine greater than amiodarone greater than chloroquine. The inhibitory effect on phospholipase C was more pronounced with all three drugs, producing almost total inhibition at 8 mg/assay. In a Ca2+-independent lysosomal phospholipase A system, amiodarone had a greater effect, producing 85% inhibition at 1.2 mg/assay. These observations suggest that amiodarone, like other cationic amphiphiles, induces a generalized phospholipidosis by inhibiting phospholipid catabolism. Its therapeutic and toxic effects may be due to its ability to modulate both Ca2+-dependent membrane phospholipases and Ca2+-independent acid phospholipases.

Amiodarone↗
PubMed1987

Effects of chronic amiodarone treatment on cat myocardial phospholipid content and on in vitro phospholipid catabolism.

Amiodarone is used extensively for the chronic treatment of life-threatening arrhythmias caused by ischemic heart disease. However, chronic therapy with this agent results in phospholipidosis in various tissues and it has been suggested that the inhibition of lysosomal phospholipase A by this drug contributes to this abnormality. Exogenous amiodarone has been shown to inhibit purified rat liver lysosomal phospholipase A1, as well as acid phospholipase activities of alveolar macrophage homogenates and those of snake venom phospholipase A2 and bacterial phospholipase C. The effects of drug treatment on heart have not been explored. The results described here demonstrate that amiodarone also significantly increases (37%, p less than 0.001) phospholipid content in cat hearts. This increase is proportionately distributed to all major phospholipid classes, with the exception of sphingomyelin which appears to increase more than the others. In addition, the data also show that following amiodarone treatment, the endogenous drug levels in the heart were sufficient to reduce in vitro losses of membrane phospholipid at 37 degrees C by inhibiting a variety of endogenous phospholipases at physiological (7.4), ischemic (6.2) and acidic (5.0) pH values. This protection is more pronounced at acidic pH values than at physiological pH. Endogenous amiodarone also affects myocardial phospholipase activities towards exogenous phosphatidylcholine and again the extent of inhibition is more at acidic pH. These results suggest that amiodarone induces phospholipidosis in the heart by inhibiting phospholipid catabolism and that its antiarrhythmic properties may reside in its ability to modulate alkaline, neutral and acid phospholipase activities in ischemia. To what extent amiodarone metabolites (desethylamiodarone and bis-desethylamiodarone) are involved in these actions remains to be determined.

Administration, Oral↗
PubMed1987

Cutaneous ultrastructural changes and photosensitivity associated with amiodarone therapy.

Amiodarone, an antiarrhythmic agent, is known to cause photosensitivity and cutaneous hyperpigmentation. Five patients taking this drug for periods of 1 to 48 months were studied. Skin biopsy specimens taken from a sun-exposed site were assessed by light microscopy, electron microscopy, and direct immunofluorescence. Three patients allowed comparative studies to be done on a biopsy specimen from non-sun-exposed skin. Light microscopy findings, including special stains, were not diagnostic of amiodarone-associated cutaneous changes. Electron microscopy, however, displayed distinctive intracytoplasmic inclusions in many cell types, some of which have not been reported previously. These inclusions represent phospholipid membranes associated with amiodarone or its metabolites as the result of a drug-induced lipidosis. Previous reports had postulated the inclusions were lipofuscin. Sun exposure may accelerate the formation of these intracellular deposits because they are more prominent in sun-exposed skin. Four of the above five cases, plus two additional patients, had symptoms compatible with a photosensitivity. Porphyrin assays were normal. Of the six patients phototested, three showed acute reactions to ultraviolet A (UVA) and ultraviolet B (UVB) and significant delayed reactions to UVA and/or UVB. The patients who had normal phototesting were on the drug for shorter periods than those with positive tests.

Adult↗
PubMed1987

Activation sequence of ventricular tachycardia: endocardial and epicardial mapping studies in the human ventricle.

Thirty-five patients with ischemic heart disease and ventricular arrhythmias underwent intraoperative activation mapping at the time of coronary artery bypass surgery. During ventricular tachycardia, the sequence of activation in the intact ventricle was recorded simultaneously from 110 endocardial or 110 epicardial sites, or both. A balloon array of electrodes, inserted across the mitral valve, was used to obtain endocardial recordings in the left ventricle, and this appeared to facilitate the induction of ventricular tachycardia. Of 61 episodes of tachycardia, 16 (15 patients) were recorded with the epicardial sock and 45 (20 patients) with the additional use of the endocardial balloon. The sequence of activation during tachycardia was observed to conform to one of four configurations: monoregional spread was the most common activation sequence recorded on both the endocardium and epicardium, while biregional activation and figure eight sequences were recorded exclusively on the epicardium and endocardium, respectively. The fourth sequence was a circular spread of activation observed on both surfaces. Continuous activation throughout the tachycardia cycle length was an infrequent finding. Simultaneous recordings of endocardial and epicardial activation were obtained in 45% of episodes. The sequence of activation recorded on one surface was matched by a similar sequence on the remaining surface in less than half of these. The onset of endocardial activation preceded that of the epicardium in greater than 90% of tachycardia episodes, and the duration of left ventricular endocardial excitation often exceeded that recorded epicardially over both ventricles. The epicardium, however, did appear to be an important determinant of surface electrocardiographic configuration.

Cardiac Catheterization↗
PubMed1987

Intraoperative electrical ablation of ventricular arrhythmias: a "closed heart" procedure.

Both intraoperative endocardial mapping and surgical ablation for ventricular arrhythmias have until now required a ventriculotomy. Such an incision may be associated with an increase in morbidity and mortality, especially when performed through friable myocardium. A "closed heart" technique of intraoperative endocardial mapping and ablation of ventricular arrhythmias was developed in which a balloon array of 112 electrodes was introduced into the left ventricular cavity by a transmitral approach. The array permitted safe delivery of repeated electrical discharges of up to 150 J at each electrode. In four patients with coronary artery disease and no ventricular aneurysm, this "closed heart" technique was used to map and treat seven distinct ventricular tachycardias. The time taken to map each tachycardia varied from 3 to 13 minutes. Between 100 and 150 J was then delivered at each of 10 to 42 electrode sites, and the ablation procedure took 7 to 16 minutes per patient to complete. One patient died 24 hours postoperatively from preexisting thrombocytopenic purpura. There was no significant deterioration in left ventricular function in the three survivors and all have remained arrhythmia free, without antiarrhythmic agents, for 4 to 11 months. This technique offers a new method of surgical treatment of ventricular tachycardia without ventriculotomy, and is particularly suited to patients without a discernible left ventricular aneurysm.

Arrhythmias, Cardiac↗
PubMed1986

Endocardial photoablation by excimer laser.

A xenon-chlorine excimer laser was used to irradiate normal endocardium of fresh sheep and pig hearts as well as unfixed human endocardial scar. Forty pulses of 370 J and 35 ns each resulted in penetration of up to 12 mm in normal tissue and only 3.5 mm in scarred endocardium. Dosimetry indicated that the volume of vaporized scarred tissue was 1/10th that of normal endocardium (0.19 to 0.40 versus 1.35 to 3.22 mm3/J). Ultrastructurally, there was a sharp demarcation of only 10 mu between the region of injury and normal myocardium, with little evidence of heat injury. The high power and short duration of these lasers coupled with the lack of a boundary zone of injury suggest that excimers may be an ideal tool for arrhythmia ablation.

Animals↗
PubMed1986

Amiodarone pulmonary toxicity: functional and ultrastructural evaluation.

Pulmonary function, chest radiographic appearances, and the cellular composition of bronchoalveolar lavage fluid were assessed in 13 patients who were receiving amiodarone treatment. Eight of the patients had developed clinical and radiological evidence of lung disease and five were symptom free. The proportions of lymphocytes (mean 8.6 (SD 6.9)) and neutrophils (mean 3.4 (3.3)) obtained by bronchoalveolar lavage were similar in patients with and without lung complications. Electron microscopic examination of alveolar macrophages showed intralysosomal inclusion bodies in all subjects, regardless of clinical state. There was no significant difference in the mean number of inclusion bodies per macrophage transection between those with and those without lung disease. The differential cell count in bronchoalveolar lavage fluid and the presence of macrophage inclusion bodies were therefore not useful as markers of disease activity. Among those who developed clinical and radiological evidence of lung disease, the cumulative drug dose per kilogram of body weight and the duration of treatment (mean 16.5 (SD 9.0) months) were significantly correlated with the degree of lung restriction as measured by total lung capacity and forced vital capacity. It is concluded that, while the severity of the restrictive pulmonary defect that is induced by amiodarone is largely dose related, the development of lung toxicity is to some extent idiosyncratic.

Adult↗
PubMed1984

Ultrastructural changes of ischemic injury due to coronary artery occlusion in the porcine heart.

Using the ultrastructural criteria established by Schaper et al. 1979 [27] for distinguishing between different degrees of ischemic change in dog myocardium, slight ischemic changes are observed in the pig suboendocardium as early as 1 min after occlusion of the LAD artery. Moderate change throughout the thickness of the myocardium is seen after 6 to 12 min of ischemia and continues to be found up until 20 min after commencement of the ischemic period. 20 to 30 min ischemia produces severe ischemic damage and more than 30 min leads to irreversible damage. The changes are uniform at all stages of ischemia and there is no evidence of a transmural gradient of ultrastructural damage. Of particular interest in the early part of the ischemic period is the observation of ultrastructural changes in the subendocardial specialized conducting tissue. In these specialized cells, although morphological features consistent with slight and moderate ischemia are found as early as 1 to 2 min after occlusion, spontaneous recovery occurs and is complete by 15 min. This biphasic time course parallels the electro-physiological changes known to occur in ischemic Purkinje fibres.

Animals↗