Biomedical subjects
Publications and source records attributed to G Keren.
Three children are reported who each had two documented febrile episodes, compatible with the diagnostic criteria of mucocutaneous lymph node syndrome (Kawasaki disease). The recurrence of this syndrome in these three children, sporadically, may indicate that Kawasaki disease is related to host immunologic factors.
A 24-year-old woman with a history of syncope and recurrent hemopericardium was urgently hospitalized with signs of severe right-sided heart failure. Two-dimensional echocardiography demonstrated a largedechogenic mass that compressed the right ventricle. The patient was referred for emergency surgery. A large angiosarcoma originating in the right atrium was excised, and the patient was treated with chemotherapy. The role of echocardiography in the detection of cardiac tumors is discussed.
Thirty-three patients with ventricular tachyarrhythmias were referred for evaluation of their arrhythmias using programmed electrical stimulation to guide antiarrhythmic therapy. Cibenzoline succinate, a new antiarrhythmic agent, was compared to procainamide in patients with ventricular tachycardia. Cibenzoline was given intravenously, initially 1.0 mg/kg, then in 1 mg/kg increments to a maximum of 3.0 mg/kg, during electrophysiologic testing. The results were compared to procainamide, which was also administered intravenously to 1000 and then to 1500 mg. Cibenzoline provided protection against ventricular tachycardia induction in 16 of 33 patients. The PR interval increased 13%, QRS duration widened 26%, and QTc interval was prolonged by 7%. There was a 9% fall in mean arterial blood pressure. Procainamide prevented ventricular tachycardia induction in 21 out of 31 patients tested. The PR interval increased 11%, QRS duration widened 27%, and QTc interval prolonged by 8%. Cibenzoline was given orally to 13 patients for chronic treatment. Chronic oral cibenzoline therapy after a mean follow-up of 8.8 months caused a reduction of ventricular ectopy from 666 to 190 beats/hr. Ventricular tachycardia events decreased per Holter monitor recording from 6 to 0.6. Cibenzoline therapy was discontinued in 5 of 13 patients due to break-through arrhythmias (nonsustained ventricular tachycardia on Holter monitor and recurrence of symptoms). Cibenzoline may be an effective antiarrhythmic agent in selected patients.
The changes in plasma fibronectin and IgG, and monocyte- and lymphocyte-associated fibronectin were studied in patients undergoing elective cardiopulmonary bypass surgery. A significant fall (P = less than 0.0005) in plasma fibronectin occurred during bypass, resulting largely from hemodilution as assessed by IgG concentrations, but also related to consumption of fibronectin. Plasma levels were still reduced 48 hours following the operative procedure, despite variable amounts of blood components infused in the immediate post-bypass period. Monocyte-associated fibronectin increased significantly (P = less than 0.05) during bypass, and lymphocyte-associated fibronectin levels decreased. Our studies confirm a reduction in circulating fibronectin in cardiac surgery, with accompanying fall in lymphocyte-associated levels presumed to reflect nonspecific adsorption. In contrast, the increased binding to monocytes may be an important functional aspect requiring further investigation, together with assessment of monocyte-macrophage function, before empiric use of cryoprecipitate therapy in these patients is recommended.
The clinical significance of sustained nonclinical ventricular tachycardia (VT) induced during electrophysiologic studies was studied in 10 amiodarone-treated patients. Nine patients had previous myocardial infarction while 1 patient had right ventricular dysplasia. All patients had only a single morphologic type of VT recorded during the multiple spontaneous episodes of tachycardia. After serial pharmacological electrophysiologic testing, the patients were placed on antiarrhythmic regimens which included amiodarone in all cases. These drugs did not prevent the induction of nonclinical VT in any of the 10 patients and of sustained clinical VT in 7 patients. Nonclinical VT was sustained, requiring cardioversion (7 patients) or rapid ventricular pacing (3 patients) for termination. After a mean follow-up period of 27 +/- 10 months (range 12 to 36 months), 4 patients did not exhibit recurrent VT, 3 patients with inducible clinical VT experienced a recurrent episode of clinical VT after 16, 27 and 49 months, respectively, 2 patients had nonarrhythmia related deaths after 11 and 12 months, and 1 patient died suddenly after 17 months. These results suggest that laboratory induction of sustained nonclinical VT in amiodarone-treated patients does not imply the likelihood of their future spontaneous occurrence and, therefore, their prevention may not be required.
Over a 3 year period we evaluated 23 patients (16 men, seven women) with apical hypertrophic cardiomyopathy by noninvasive and invasive methods. Sixteen patients had chest pain. In 17, results of cardiovascular examination were normal. The electrocardiogram showed precordial inverted T waves in all patients and these were of mild-to-moderate amplitude (less than 10 mm) in 18 and giant (greater than 10 mm) in five. M mode echocardiography revealed a typical pattern of contraction and relaxation in the apical region of the left ventricle that was associated with significant hypertrophy. These findings were confirmed by two-dimensional echocardiography. Systolic anterior motion of the mitral valve was not observed nor was there any evidence of obstruction of the left ventricular outflow tract. Results of Doppler echocardiographic study of the mitral and aortic flow were normal in all patients but one who had mild mitral insufficiency. Radionuclide studies of 14 patients revealed a mean left ventricular ejection fraction of 66 +/- 6% (range 55% to 79%), with normal left ventricular contraction in all patients but two with apical hypokinesis. In all six patients who underwent catheterization a characteristic appearance of the left ventricle at end-systole as well as abnormal end-diastolic contour were noted on the left ventricular angiogram, but the "ace of spades" configuration was seen in only one. We conclude that the 23 patients studied form a homogeneous group of individuals with nonobstructive apical hypertrophic cardiomyopathy, which differs in many respects from cardiomyopathies reported by other investigators.
We studied the physiology of pulmonary venous flow in 13 normal subjects and five patients with atrial rhythm disorders and atrioventricular conduction disturbances with pulsed Doppler and two-dimensional echocardiography. The left atrium, mitral valve, and pulmonary venous ostia were visualized through the apical four-chamber view. Mitral and pulmonary venous flows were obtained by placing the Doppler sample volume at the appropriate orifice. Pulmonary venous flow was biphasic: a rapid filling wave was observed during systole when the mitral valve was closed; a second wave was observed in diastole during the rapid ventricular filling phase of mitral flow, but was significantly delayed. In patients without atrial contraction (atrial fibrillation and sinoatrial standstill), the initial rapid filling was greatly diminished and only the second diastolic wave appeared to contribute to left atrial filling. In patients with high-grade atrioventricular block, each atrial contraction was followed by a surge in flow from the pulmonary veins. These results are consistent with data obtained from invasive measurements in both dogs and man, and confirm the validity of the use of pulsed Doppler echocardiography in the study of pulmonary venous flow. We suggest that pulmonary venous flow is influenced by dynamic changes in left atrial pressure created by contraction and relaxation of the atrium and ventricle. The initial peak in pulmonary venous flow occurs with atrial relaxation simultaneously with the reduction of left atrial pressure, and the second peak occurs with left ventricular relaxation and rapid transmitral filling of the ventricle.
Non-sustained ventricular tachycardia (VT) in the late post myocardial infarction (MI) period (7-21 days) has been reported to be a predictor of sudden death. We suspected that patients with 3 beat VT on Holter monitoring in the late infarction period would demonstrate electrical instability at electrophysiologic studies. Forty-seven patients were identified as having at least 3 beat VT on Holter monitoring. Eighteen patients refused electrophysiologic studies or were not referred by their attending physician. The mean ejection fraction of this group was 43 +/- 16%. Eight patients have died, 3 sudden deaths in 13 +/- 5 months, a 17% incidence of sudden death. Twenty-nine patients underwent invasive electrophysiologic studies. Their mean ejection fraction was 37 +/- 7%, and 28 had inducible, 18 sustained ventricular tachycardia and 10 non-sustained VT. No complications were noted with electrophysiological testing in the post infarction patients. Using programmed electrical stimulation studies an effective antiarrhythmic agent preventing VT induction (usually experimental) could be found for each patient. After a mean follow-up of 12.5 +/- 4 months, the patient without inducible VT is alive and 26 of the 28 "inducible" patients are alive and well. Two patients died, one of stroke and one due to pump failure following a second MI. No sudden deaths were observed in this group. Two patients had breakthrough arrhythmias and were treated by alternative antiarrhythmic therapy that was also effective at the initial electrophysiologic studies. Thus, PES studies post MI are safe and may be an effective way to assess therapy for patients in the early post MI period, identified at high risk for sudden death.
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Human monocytes were infected in vitro with Leishmania tropica major (L. major) promastigotes which transformed to intracellular amastigotes. A spontaneous increase in lymphocyte proliferation occurred in mononuclear cell cultures where the monocytes had been infected with L. major organisms. In addition, an apparent additive effect of lymphocyte proliferation was seen in cultures infected with L. major following phytohaemagglutinin stimulation. This effect was apparent after 3 days in culture and the amount of increase in response was dependent on the number of monocytes in the culture. The effect was also dependent on the number of parasites ingested by the monocytes. The presence of monocytes was essential for this effect, as no enhancement was observed with supernatants from infected cells. This enhanced effect of lymphocyte proliferation was observed predominantly in the B lymphocyte subpopulation. These findings may be of relevance in the immunopathogenesis of Leishmania infections.
Twenty-six patients (19 men and 7 women) with symptomatic ventricular tachycardia (VT) were studied using invasive and noninvasive techniques to induce VT. Of the study population, 12% had syncope and VT on Holter monitoring, 30% had cardiac arrest and 58% had symptomatic VT. All patients had antiarrhythmic agents stopped 5 half-lives before evaluation and then had autonomic profile (upright tilt, cold pressor test, exercise testing and hand grip) as well as programmed electrical stimulation studies performed. Autonomic profile testing induced VT in 5 of 26 patients (19%) and in only 1 patient was the arrhythmia reproducibly induced. All 26 patients had VT induced on electrophysiologic testing; 9 patients had nonsustained and 17 had sustained VT. Lorcainide administered intravenously prevented VT induction in 20 of 26 patients tested, whereas procainamide was effective in 11 of 24 patients. Ten of the 13 not protected by procainamide were protected by lorcainide. Twenty patients were started on long-term lorcainide therapy and followed up for 29 +/- 3.4 months. Five patients have discontinued therapy, 2 because of breakthrough arrhythmias, 2 because of severe sleep-wake disturbances and 1 because of private physician preference. An additional 3 patients died during therapy because of myocardial infarction in 1, progressive myopathy in 1 and sudden death in 1. Sixty percent of patients started on lorcainide therapy have continued. In this patient population, noninvasive induction of VT is not a sensitive or reproducible technique in assessing antiarrhythmic therapy. Furthermore, when selected on the basis of electrophysiologic testing, lorcainide is a well-tolerated and effective antiarrhythmic agent.
Studies were performed in 20 patients with symptomatic ventricular tachycardia (VT) to determine the efficacy of bethanidine compared with procainamide in preventing VT induced by programmed electrical stimulation. Before administering bethanidine, 5 to 10 mg/kg, the patients received 15 mg of protriptyline orally 24 and 2 hours before electrophysiologic studies to prevent the orthostatic hypotensive effects of bethanidine. Sustained VT (VT not spontaneously stopping) was induced in 8 and nonsustained VT (10 beats or more, terminating spontaneously) was induced in 4 patients. Bethanidine, 5 mg/kg, protected in 7 patients, and 10 mg/kg protected 1 additional patient. Procainamide, 1,000 and 1,500 mg intravenously, protected 8 of 16 patients. Bethanidine prevented VT induction in 50% of the patients not protected by procainamide. Bethanidine facilitated VT induction in 3 patients, while procainamide facilitated VT induction in 1 patient. Four patients with symptomatic VT have received bethanidine therapy for an average of 11 +/- 1.3 months, without clinical recurrence of their VT. Concomitant administration of protriptyline attenuated the acute hemodynamic changes caused by bethanidine and chronic combined therapy of protriptyline and bethanidine abolished the severe orthostatic changes in blood pressure caused by bethanidine. These studies show that bethanidine is effective in preventing VT induction and, thus, its use may not be restricted only to cases of primary ventricular fibrillation.
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The electrophysiologic effects of cibenzoline were studied using programmed electrical stimulation (PES) techniques and were compared to those of quinidine. Cibenzoline, like the conventional class 1 agent quinidine, was effective in preventing arrhythmia induction. Twelve dogs were given 0.02 mg/kg digoxin intravenously for seven days to achieve a steady-state digoxin level. On the eighth day, cibenzoline was administered in incremental doses (0.5 to 10.5 mg/kg) and PES was performed at 30-minute intervals. A mean dose of 2.6 +/- 0.8 mg/kg cibenzoline prevented ventricular tachycardia induction. At this dose, cibenzoline had no significant effect on mean arterial blood pressure, but PR interval increased by 17 +/- 9 per cent, QRS duration by 27 +/- 14 per cent, and the ventricular refractory period (ERP) for the first extra stimulus increased by 35 +/- 9 per cent. A gradual decrease in heart rate and an increase in PR interval and QRS duration was caused by incremental doses of cibenzoline. In six additional animals, quinidine was administered in incremental doses (1 to 30 mg/kg) and PES performed at 30-minute intervals. A mean of 15 +/- 5 mg/kg prevented induction of ventricular tachycardia in five animals. No significant change in heart rate, PR, QRS, and ERP was found at the effective dose.
The success of pacing stimuli interruption of ventricular tachycardia (VT) was examined in 77 episodes of sustained VT induced in 31 patients undergoing programmed electrical stimulation studies. Once VT was induced, a trial to terminate the arrhythmia by means of the technique of entrainment was attempted. If this failed, rapid burst pacing faster than the VT was begun to try and terminate the tachycardia. In 30 patients off antiarrhythmic agents, entrainment was effective in terminating VT in 27%, while burst pacing was also effective in 27%. In 37% of patients, VT was accelerated or ventricular fibrillation was produced by pacing techniques, and these patients required defibrillation. Following antiarrhythmic therapy that failed to prevent VT induction but did result in slowing of VT rate, entrainment was only successful in 23% of trials, while burst pacing was successful in 34% of trials. The incidence of acceleration of VT on therapy was 32%. There was no appreciable difference in acceleration noted with or without antiarrhythmic therapy. Regardless of therapy, the slower the VT rate, the greater success of pacing termination of VT and the lower the incidence of VT acceleration. Antiarrhythmic agents that significantly slow the VT rate increase the success rate of pacing stimuli interruption of VT and decrease the incidence of VT acceleration and thus the need for defibrillation. The results suggest that antiarrhythmic agents that slow the VT rate may increase the effectiveness of antiarrhythmic pacemakers in terminating VT.
Bepridil, a new antianginal agent, has calcium channel-blocking activity and antiarrhythmic properties. To test the efficacy of bepridil as an antidysrhythmic agent, we looked at its effect on the induction of ventricular tachycardia (VT) in dogs, utilizing programmed electrical stimulation (PES). Incremental doses of bepridil up to 20 mg/kg were given to five nondigitalized dogs and verapamil up to 20 mg, and PES was performed at each dose. Both drugs were not found to facilitate arrhythmia induction. Seventeen dogs were chronically digitalized and following digitalization, VT could be induced in all animals by PES. Six dogs were given bepridil and PES was reperformed at each dose. An average of 1.8 mg/kg was found to protect against induction of VT. Five dogs received verapamil and none was protected (all had VT induced), while five of six dogs given quinidine were protected at an average dose of 15.4 mg/kg. Bepridil produced a significant decrease in heart rate. A significant correlation was found at the effective antiarrhythmic dose of bepridil between percentage change in the effective refractory period for the first extrastimulus (ERP S2) and QTc (r = 0.96), suggesting that a parallel and homogeneous prolongation in repolarization and refractoriness is essential for the antiarrhythmic effect of bepridil. Bepridil is thus an effective antiarrhythmic agent that affords protection against induction of VT, and this action is similar to the conventional class I antiarrhythmic agent, quinidine, while lacking in another calcium channel blocker, verapamil.
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