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Biomedical subjects

R Yee

Publications and source records attributed to R Yee.

At least 217 records · Page 12Linked to original sources

Synthesis and processing of cathepsin L, an elastase, by human alveolar macrophages.

Cathepsin L was partially purified from lysates of freshly isolated macrophages lavaged from lungs of apparently healthy adults and found to be chromatographically and catalytically identical with liver cathepsin L. Western-blotting analysis showed that lung macrophages contain significant levels of a precursor of cathepsin L (43 kDa) in addition to mature enzyme (25 kDa). After culturing for a further 24 h, the precursor disappeared and a new band, corresponding to 34 kDa, appeared, suggesting that the precursor had been processed to an intermediate form of cathepsin L. Biosynthetic labelling of macrophages in vitro with [35S]methionine followed by immunoprecipitation with the cathepsin L antibody confirmed that the cells synthesize cathepsin L as a 43 kDa precursor that is then processed to the mature form (25 kDa) via a 34 kDa intermediate. The precursor, but not the processed forms, was released into the culture medium. During culture in vitro the 34 kDa intermediate accumulated, and little enzyme was processed to the 24 kDa form, consistent with the immunoblot data. Human lung macrophages contain a 1.5 kb transcript of cathepsin L mRNA, whereas none is detectable in human monocytes. These results establish that differentiation of human macrophages within the lung is accompanied by synthesis and expression of an elastinolytic enzyme, cathepsin L. The altered processing of cathepsin L observed during cultivation in vitro suggests caution in the assessment of the elastinolytic potential of human macrophages based on assay in vitro.

Adult↗

Acute effect of disopyramide on atrial fibrillation in the Wolff-Parkinson-White syndrome.

Disopyramide was administered intravenously to 54 patients during atrial fibrillation and predominantly pre-excited QRS configuration at the time of electrophysiologic study. All patients had Wolff-Parkinson-White syndrome and no patient had coexistent heart disease. The drug was given during sustained atrial fibrillation (n = 45) or during sinus rhythm before induction of atrial fibrillation for patients whose atrial fibrillation was self-terminating in the control state (n = 9). Atrial fibrillation converted to sinus rhythm within 15 min after disopyramide in 37 (82%) of the 45 patients. The shortest RR intervals between two pre-excited cycles increased from 208 +/- 42 to 293 +/- 117 ms (p less than 0.0001). The average RR interval of all cycles prolonged from 332 +/- 60 to 396 +/- 117 ms(n = 45, p less than 0.0001). The 9 patients in whom pre-excitation was abolished after the drug had a significantly longer initial shortest RR interval than that of the 36 patients in whom pre-excitation persisted (246 +/- 47 versus 199 +/- 36 ms, p = 0.0022). No patients developed significant hemodynamic or other adverse effects after disopyramide. These data support the intravenous use of disopyramide in patients with normal ventricular function who have atrial fibrillation and a predominant ventricular response over an accessory atrioventricular pathway.

Adolescent↗

Surgical therapy for arrhythmogenic right ventricular adiposis.

Arrhythmogenic right ventricular adiposis, formerly dysplasia, was identified when the first patients underwent map-guided surgery for treatment of their ventricular tachycardia. We report our experience with 12 patients operated on using a conservative approach between 1973 and 1981 (Paris). Subsequently, we used a more comprehensive approach in five patients (London, Canada); the right ventricular free wall disconnection was used to confine all potential right ventricular tachycardias within the excluded right ventricular wall.

Adipose Tissue↗

Localization of accessory pathways in the Wolff-Parkinson-White syndrome.

Operative and ablative therapy in the Wolff-Parkinson-White syndrome requires accurate localization of accessory atrioventricular pathways. A reasonable first approximation to pathway location can be obtained by noninvasive techniques, the 12-lead electrocardiogram being the most readily available of these. Accurate characterization of the number and anatomic localization of accessory pathways still requires invasive electrophysiological assessment. The most useful technique for accessory pathway localization remains endocardial atrial mapping of the tricuspid and mitral (via the coronary sinus) ring during atrioventricular reciprocating tachycardia and ventricular pacing. Other techniques provide important confirmatory evidence and may be the only guides to accessory pathway location in selected individuals.

Algorithms↗

Sequential pulse countershock between two transvenous catheters: feasibility, safety, and efficacy.

We evaluated the feasibility, safety, and efficacy of sequential pulse countershock (SqCS) delivered solely through two endocardial catheters for the termination of ventricular tachycardia (VT) and fibrillation (VF) in patients undergoing electrophysiology studies (EPS). Thirty-four patients (31 men, 3 women) with a mean age of 56.8 +/- 10.1 years were studied. Etiology of VT/VF was ischemic heart disease (n = 26), cardiomyopathy (4) repaired tetralogy of Fallot (n = 1), heart transplant (n = 1), and no identifiable heart disease (n = 2). Catheters were positioned successfully in 29 patients. These were positioned in the right ventricular apex (RVA) and the coronary sinus (CS), respectively. The RVA electrode served as the common cathode for both pulses. The two electrodes located near the right atrium/superior vena cava junction served as anode for pulse 1 while the distal CS electrodes served as anode for pulse 2. Twenty-nine induced VT episodes with cycle length (CL) 220-370 msec were treated. SqCS successfully terminated 15 VT (100-500V) while 14 were accelerated or degenerated to VF. VTCL was longer in successful SqCS episodes than in those that were accelerated (285 +/- 17.3 vs 245 +/- 30.8 msec, P less than .003). Of 26 VF episodes, 21 were terminated with SqCS (500-900V) and 5 were terminated by transthoracic rescue shocks. On 2 occasions, failure to defibrillate was attributable to poor catheter position at the time of shock. No complications occurred. We conclude that SqCS delivered solely between endocardial catheter electrodes is feasible and effective using energy doses within the range of existing implantable cardioverter defibrillators.

Adult↗

Atrioventricular nodal tachycardia in the absence of retrograde conduction.

A patient with atrioventricular (AV) nodal reentrant tachycardia assessed by electrocardiographic and electrophysiological criteria is described. During ventricular pacing, retrograde conduction was absent at the longest cycle length tested with the site of block determined to be the AV node by concealed conduction criteria. These findings localize the tachycardia circuit above the His bundle and exclude a His-atrial bypass tract as the retrograde limb of the tachycardia circuit in this patient.

Adult↗

The coronary sinus diverticulum: a pathologic entity associated with the Wolff-Parkinson-White syndrome.

Of 65 patients with posterior septal accessory pathways, 6 were found intraoperatively to have a previously unrecognized pathologic entity: a coronary sinus (CS) diverticulum in the posterior septal region. The CS diverticulum is a venous pouch within the left ventricular wall, with a neck opening into the CS. The pouch, 2 to 5 cm in diameter, has a deep wall corresponding to the left ventricular wall, with venous channel openings and a thin superficial wall made of myocardium. The CS diverticulum neck is 5 to 10-mm wide, opens into the CS and is proximal to the midcardiac vein. Using an epicardial approach during normothermic bypass, the neck of the CS diverticulum was identified, separated from the left ventricle and then closed. Accessory pathway conduction disappeared only after separation of the CS diverticulum neck. The accessory pathway is intimately related to the diverticulum. The latter is a bridge between the left ventricle and the right or left atrium. The accessory pathways associated with CS diverticula had short anterograde refractory periods and were associated with potentially malignant arrhythmias. An epicardial operative approach with division of the neck of the diverticulum is recommended when surgery is indicated.

Adult↗

An approach to therapy for paroxysmal supraventricular tachycardia.

A variety of options are available for managing recurrent paroxysmal supraventricular tachycardia. These options include empirical drug therapy on a trial and error basis, drug therapy based on the results of electrophysiologic testing and nonpharmacologic treatment including operative therapy, catheter ablation and antitachycardia devices. Empirical drug therapy is appropriate when the tachycardia is relatively well tolerated and the patient has access to a medical facility. Therapy guided by electrophysiologic testing is more appropriate for patients with severe symptoms during tachycardia, patients with a potential for more serious arrhythmias such as atrial fibrillation in the Wolff-Parkinson-White syndrome and in patients who have failed to respond to empirical trials of drug therapy. Electrophysiologic testing usually provides information about the precise mechanism responsible for the tachycardia and allows verification of drug efficacy. It is a strict prerequisite for operative, ablative or antitachycardia device therapy. The choice of therapy depends a great deal on local expertise, patient preference and individual considerations. Operative therapy is very successful in patients with supraventricular tachycardia associated with the Wolff-Parkinson-White syndrome and should be given high priority as an option in younger patients facing a lifelong commitment to antiarrhythmic drugs.

Cardiac Pacing, Artificial↗

Comparative effects of adenosine triphosphate on accessory pathway and atrioventricular nodal conduction.

Adenosine triphosphate (ATP) has potent negative dromotropic effects on the atrioventricular (AV) node, but variable effects on accessory pathway conduction have been described. The effects of an intravenous bolus injection of 8 mg ATP on accessory pathway and AV nodal conduction were determined during electrophysiologic testing with controlled atrial and ventricular rates. AV conduction was monitored during atrial or ventricular pacing at a constant cycle length, 30 msec longer than the cycle length at which block occurred. During atrial pacing antegrade block after administration of ATP occurred in 1 of 30 (3.2%) patients with accessory pathway conduction and 12 of 13 (92%) patients with AV nodal conduction (p less than 0.001). During ventricular pacing only 5 of 26 (16%) patients had accessory pathways blocked, whereas 25 of 35 (71%) patients with AV nodal conduction had block (p less than 0.001). Thus, failure of ATP to produce ventriculoatrial block identified the presence of an accessory pathway with a sensitivity of 84%, specificity of 71%, and predictive value of 72%. There was no correlation between accessory pathway properties and the effects of ATP. The effects of ATP on the AV node were concordant with the effects of a combination of verapamil and propranolol in 21 of 23 patients, suggesting that this dose ATP is an equipotent AV nodal blocker with a short duration of action. Thus, although the effects of ATP on accessory pathways and the AV node differ, block in ventriculoatrial conduction after administration of ATP cannot be used as the sole criterion to distinguish the mechanism of conduction.

Adenosine Triphosphate↗

Surgical approach to anterior septal accessory pathways in 20 patients with the Wolff-Parkinson-White syndrome.

Right anterior septal accessory pathways in the Wolff-Parkinson-White syndrome are generally defined by electrophysiological criteria, the most important being that earliest retrograde atrial activation during AV reciprocating tachycardia occurs at the anterior medial segment of the tricuspid annulus (His bundle catheter). The purpose of our study is to describe intraoperative mapping in 20 patients with anterior septal accessory pathways, and to assess if intraoperative mapping contributes to the operative approach. At surgery, all patients had identical early ventricular activation during pre-excitation at the infundibulum. However, two groups could be identified on the basis of retrograde atrial epicardial activation during AV reciprocating tachycardia or right ventricular pacing. Group 1 comprised 16 patients with earliest activation at the interatrial septum adjacent to the His bundle. Epicardial dissection failed to affect accessory pathway conduction. The accessory pathway was only ablated when a discrete endocardial approach to the atrial septum was used. Group 2 comprised 4 patients with early atrial activation "paraseptally" in the right coronary fossa. These accessory pathways were ablated by an epicardial approach without using cardiopulmonary bypass. We conclude that right anterior septal accessory pathways as defined by electrophysiological criteria can be divided into two groups on the basis of the atrial activation sequence: (1) right septal accessory pathways in the septal para-Hissian region and (2) right anterior 'paraseptal' accessory pathways. This classification is of practical importance because the latter can be ablated using an epicardial approach without the need for cardiopulmonary bypass or atriotomy.

Adolescent↗

"Atypical" posteroseptal accessory pathway in Wolff-Parkinson-White syndrome.

The posteroseptal accessory pathway in the Wolff-Parkinson-White syndrome is associated with a delta wave that is negative in the inferior electrocardiographic (ECG) leads and the occurrence of the earliest retrograde atrial activation near the orifice of the coronary sinus during atrioventricular (AV) reentrant tachycardia. Seventy-two patients with a posteroseptal accessory pathway underwent epicardial mapping before operative ablation. The earliest epicardial activation occurred at the posterosuperior process of the left ventricle in all patients. Dissection of the posteroseptal region (right atrial-left ventricular sulcus) resulted in permanent loss of preexcitation in 69 patients and failure to abolish preexcitation permanently in 3. At reoperation in two patients, preexcitation was abolished by discrete cryoablation of the left side of the interatrial septum near the AV node approached through the atrial septum in the normothermic beating heart. At reoperation, one patient had extensive AV node dissection. All patients have had permanent loss of preexcitation. The vast majority of posteroseptal accessory pathways ("typical") are epicardial and ablated by dissection of the posteroseptal region. Rarely, posteroseptal accessory pathways are "atypical" in that they are intraseptally located near the AV node on the left atrial endocardial surface.

Adult↗

"Nodoventricular" accessory pathway: evidence for a distinct accessory atrioventricular pathway with atrioventricular node-like properties.

Two patients are described with recurrent pre-excited tachycardia and electrophysiologic characteristics typically ascribed to a nodoventricular accessory connection. The accessory pathway in each case demonstrated rate-dependent prolongation of conduction time and a low right ventricular insertion site; it was associated with a left bundle branch block configuration during pre-excitation. Intraoperatively, the pathway was demonstrated to originate at the anterior right atrioventricular (AV) anulus and not at the AV node. These data suggest that a "typical" nodoventricular pathway, by electrophysiologic criteria, may in fact be an AV pathway with AV node-like conduction properties and a distal right ventricular insertion site.

Adult↗

Prediction of defibrillation success from a single defibrillation threshold measurement with sequential pulses and two current pathways in humans.

The ultimate aim of defibrillation testing is to predict consistent defibrillation. This study tested the hypothesis that defibrillation success could be predicted from a single measurement of defibrillation threshold. We measured defibrillation threshold by using three patch electrodes and a standard protocol intraoperatively in 49 patients undergoing arrhythmia surgery. Each patient was then assigned to one of five energy subgroups (0.5, 1.0, 1.5, 2.0, or 2.5 times defibrillation threshold) for a single shock (followed by a rescue shock if necessary) for a subsequent ventricular fibrillation episode. A curve relating percent success to energy was then constructed for the group. Defibrillation threshold averaged 4.7 +/- 2.98 J for the group (mean +/- SD). There was a curvilinear relation between the energy of the defibrillation threshold ratio test shock and percent success: 33.3%, 58.3%, 81.8%, 91.7%, and 100% at mean defibrillation threshold ratios of 0.56 +/- 0.14, 1.02 +/- 0.07, 1.53 +/- 0.14, 1.88 +/- 0.09, and 2.60 +/- 0.14, respectively. We conclude that consistent defibrillation is predictable from a single measurement of defibrillation threshold. Furthermore, for an individual patient, a safety margin of 2.6 times defibrillation threshold should approximate 100% successful defibrillation for a single test shock.

Adult↗

Regulation of the procoagulant activity within the bronchoalveolar compartment of normal human lung.

The nature of the procoagulant activity of normal bronchoalveolar fluid was examined both qualitatively and quantitatively. Unconcentrated, cell-free lavage freshly obtained from normal volunteers clotted normal plasma in a mean of 84 +/- 20 s. The procoagulant activity was initiated by Factor VII-tissue factor complexes as judged by differential activity in various plasmas genetically deficient in single clotting factors, by neutralization of the procoagulant activity with antibodies to either Factor VII or tissue factor, and by a Factor X activation assay. Preincubation of the lavage with calcium was required to demonstrate Factor VII activity in unconcentrated samples. The cell-free fluid contained about 8,500 thromboplastin units/mg protein, equivalent to a third of the thromboplastin standard and indicating high amounts of cofactor. Quantitation of Factor VII was estimated by functional analysis in coagulation and amidolytic assays with reference to dilutions of normal plasma of known Factor VII concentration. When lavage and diluted plasma were adjusted to yield equivalent amidolytic activities, the average ratio of the Factor VII-clotting activity of the alveolar fluid relative to plasma Factor VII was 19 +/- 7, suggesting the presence of Factor VIIa in lavage. In contrast to previous reports with serum or activated plasma, immunoblots of concentrated lavage revealed only single-chain Factor VII, and 125I-Factor VII added to the fluid was not converted to 125I-Factor VIIa, suggesting a unique control mechanism in the lung compartment which differs from plasma. When equivalent Factor VII amidolytic activities in diluted plasma and cell-free lavage were compared, the rates of Factor Xa formation were very similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Factors↗

Relationship between ionic perturbations and electrophysiologic changes in a canine Purkinje fiber model of ischemia and reperfusion.

Standard and ion-sensitive microelectrodes were used to identify the basis of electrophysiologic changes that occur in canine cardiac Purkinje fibers superfused with "ischemic" solution (40 min) and then returned to standard Tyrode's solution. Maximum diastolic potential (EMDP) decreased (-92.6 +/- 2.4 to -86.0 +/- 4.0 mV; n = 19; P less than 0.001) during exposure to "ischemia," and after reperfusion, rapidly hyperpolarized to -90.0 +/- 4.7 (2 min) and then depolarized to -47.0 +/- 7.5 mV (10 min; P less than 0.001). No significant change in intracellular K activity (alpha ik) was noted throughout. Extracellular K activity (alpha ek) changed only during reperfusion, reaching a nadir at 5 min (3.5 +/- 0.4 to 2.6 +/- 0.5 mM, P less than 0.03), and thus can not account for the decrease in EMDP during reperfusion. Mean alpha iNa increased (8.7 +/- 1.3 to 10.9 +/- 1.9 mM; n = 10; P less than 0.01) during ischemia, but rapidly declined during reperfusion to 5.1 +/- 2.2 mM (10 min; P less than 0.01). Exposure to acetylstrophanthidin (4-5 x 10(-7) M) during the final 10 min of ischemia increased alpha iNa to 19.9 +/- 3.8 mM (n = 5), which was unchanged at 5 min of reperfusion. This suggests that Na-K pump inhibition during ischemia was minimal and that the pump was stimulated early during reperfusion, accounting for the initial transient hyperpolarization. Resting tension did not change significantly during exposure to ischemia; however, return to control Tyrode's solution caused a marked rise to 11.3 +/- 9.9 mg/mm2 (n = 13, P less than 0.001). This is consistent with a calcium overload state during reperfusion. The depolarization seen during reperfusion may result from activation of a Ca-activated, nonselective cation channel or enhanced electrogenic Na/Ca exchange.

Animals↗

A Canadian hospital's experience with the automatic implantable cardioverter/defibrillator.

The automatic implantable cardioverter/defibrillator is a device that can be implanted in patients for treatment of recurrent ventricular tachycardia and ventricular fibrillation. It was recently approved for clinical use in Canada. The authors describe their experience with 12 patients (mean age 51.3 years) who underwent implantation of a defibrillator. All 12 patients had a history of documented ventricular fibrillation, which was idiopathic in 3 and due to ischemic heart disease in 9. Electrophysiologic testing revealed inducible ventricular tachycardia or ventricular fibrillation in 8 of the 10 patients tested. An important criterion for selection for implantation was failure of pharmacologic therapy to suppress ventricular arrhythmias induced during electrophysiologic testing. Of the 12 patients, 1 died within 24 hours after implantation. During a mean follow-up period of 15.5 months there were no further deaths. All the surviving patients expressed satisfaction with the device; five of the seven under the age of 60 years have returned to work, and one has returned to school. This initial favourable experience with the automatic implantable cardioverter/defibrillator suggests that future increases in the availability of the device and improvements in its function will lead to much more widespread use, as the population of patients at risk of sudden cardiac death is large.

Adolescent↗