Uri Rosenschein

Experimental ultrasonic angioplasty: Disruption of atherosclerotic plaques and thrombi in vitro and arterial recanalization in vivo

To investigate the use of high energy ultrasound as an alternative energy for angioplasty, an experimental ultrasonic angioplasty device was developed. The device was studied in two bioassay systems: an in vitro system for the disruption of atherosclerotic plaques and thrombi and an in vivo system for the recanalization of occluded canine femoral arteries. In vitro, sonication efficiently reduced the size of the plaques. Atheromatous plaques (n = 11) disrupted at a rate of 21 +/- 8 s/cm2; complicated plaques (n = 14) disrupted at a rate of 132 +/- 45 s/cm2 (p less than 0.001). Histologic examination revealed that the disruption of the plaques took place without concurrent damage to the media or adventitia. Ninety percent of the disrupted plaque debris had a diameter of less than 20 microns and was composed primarily of cholesterol monohydrate crystals. Solid thrombus (n = 5) weight was reduced from 1.6 +/- 0.2 to 0.4 +/- 0.1 g (p less than 0.0001) after 20 s of sonication. In vivo, sonication resulted in recanalization in all seven arteries tested in seven dogs. The obstruction was reduced from 93 +/- 11% to 18 +/- 7% (p less than 0.001). On histologic examination, the arterial wall injury index was found to be 1.56 +/- 0.42 in the test arteries compared with 1.37 +/- 0.47 in the control arteries (p = NS). The disruption of atherosclerotic plaques and thrombi, together with the efficient recanalization of the occluded arteries, demonstrates the potential of ultrasound angioplasty as a catheter-based technique for angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasound inhibits the adhesion and migration of smooth muscle cells in vitro

This study investigated in vitro the effect of therapeutic ultrasound (ULS) on smooth muscle cell (SMC) function as adhesion, migration and proliferation. Experiments were conducted on aortic SMC in culture. The LD50 was established (1.5 W for 15 s at a frequency of 20 kHz) and used as standard dose in all experiments. Control SMC and viable sonicated SMC were compared in each experiment. Migratory capacity decreased 2.4-fold after sonication and stayed reduced for up to 24 h. Adhesion capacity decreased 5.5-fold after ULS. The proliferative capacity was similar to that of nonsonicated SMC. Sonication was accompanied by the disorganization of alpha-SM actin fibers and diminished distribution of vinculin; tyrosinated alpha tubulin and vimentin appeared unaffected. These changes might be responsible for the observed inhibition of SMC adhesion and migration. Sonicated cells exhibited less lamellipodia, membrane collapse and bleb formation. The signal transduction cascade, which involves activation of the phospholipase-C pathway, was unaffected by ULS.

Percutaneous Transluminal Coronary Angioplasty in Elderly Patients

Fifty-six patients aged 75 years and older underwent percutaneous transluminal coronary angioplasty (PTCA) at our institution from 1984 to 1991. The average age was 76.7 +/- 1.5 years, and 84% of the patients were males. Single-vessel disease occurred in 21 patients, double-vessel disease in 16, and three-vessel disease in 19 patients. The mean left ventricular ejection fraction was 57 +/- 5%, and 8 patients had an ejection fraction of < 40%. The anginal functional class was I in 1 patient, II in 3, III in 6, and IV in 46 patients. Single-vessel PTCA was attempted in 43 patients, two-vessel PTCA in 8, and three-vessel PTCA in 5 patients. Revascularization was complete in 35% of the patients, incomplete in 57, and no revascularization was obtained in 8% of the patients. Ninety-one percent of the patients had a successful procedure. In 5 patients there was severe dissection, 1 patient died, 1 patient had an acute myocardial infarction, and 1 patient had emergency bypass surgery. Long-term follow-up (6-96 months, mean 21 +/- 4) in the 51 successfully treated patients revealed late cardiac death in 1 patient, repeated PTCA for restenosis in 9, and coronary bypass surgery in 2 patients. Twenty-two patients were asymptomatic, 12 had improved symptoms, and 5 remained symptomatic. PTCA appears to be a safe and effective treatment in elderly patients with one- and two-vessel disease, with excellent long-term results. Age is not a contraindication to PTCA. The results in elderly patients with three-vessel disease are less encouraging.

Prevention of Cardiac Arrest: Risk Assessment After Myocardial Infarction

Last time on CEPR [1] we categorized the (then) most recent developments in cardiac arrest prevention after myocardial infarction (MI) into three different categories: (1) risk stratification, (2) prevention of cardiac arrest with drugs and (3) prevention with the implantable cardioverter defibrillator (ICD). In the first category, the ATRAMI trial had established “heart rate variability” (HRV) and “baroreflex sensitivity” (BRS)—markers of the tonic and the reflex vagal activity, respectively— as strong predictors of death (not necessarily sudden) [2]. The predictive value of these autonomic markers was independent of that of other wellestablished predictors such as the left ventricular ejection fraction (EF). Indeed, the risk of mortality at 2 years in patients with low BRS and low EF was more than 8-fold that observed in patients with normal values. In the prophylactic antiarrhythmic drug category, amiodarone failed to reduce mortality in MI survivors with high-grade ventricular arrhythmias [3] or low EF [4]. With this, amiodarone joined the long list of antiarrhythmic drugs [5–7] that have failed to improve survival after MI. In contrast, good news appeared in the prophylactic ICD category when a dramatic improvement in survival was finally credited to ICD implantation in MADIT (the Multicenter Automatic Defibrillator Implantation Trial) [8]. MADIT was a randomized study comparing ICD implantation to drug therapy (mainly amiodarone) in asymptomatic infarct survivors at very high risk of arrhythmic death. In this “very high risk” group, consisting of post-MI patients with EF 35%, spontaneous nonsustained VT (NSVT) and inducible (drug refractory) sustained VT, the mortality (39% at a mean follow-up period of >2 years) was reduced to 16% with ICD implantation [8]. This represented 23 lives saved per 100 ICD implantations. On the other hand, ICD implantation at the time of coronary artery bypass graft (CABG) surgery provided no survival benefit in the CABG-Patch trial, a randomized comparison of ICD vs. no ICD therapy in patients with EF 35% and a pathological signal averaged electrocardiogram [9]. Taking all this information together, 3 main concepts were already clear two years ago: (1) It is possible to identify patients with a low, high and very high mortality risk after MI. (2) ICDs, rather than antiarrhythmic drugs, will have to be used to prevent arrhythmic death in truly high-risk patients. (3) Because ICDs are expensive and their implantation entails some morbidity, identification of patients who are at very high risk for arrhythmic death, but sufficiently low risk for non-arrhythmic death to allow for survival benefit from ICD implantation, remains the real challenge. It is with these concepts in mind that the more recent developments will be analyzed.

Ultrasound Angioplasty Using the Angiosonics System

The development of transluminal balloon angioplasty has significantly modified the therapeutic approach to obstructive coronary [1,2] and peripheral arterial disease [3], Despite overall favorable results with balloon angioplasty, this technique sustains several limitations. These include a relatively limited success rate in complex vascular lesions (eccentric, thrombus-rich, calcified, long, or ostial lesions), acute complications (thrombosis, dissection, and vascular spasm), and the long-term complication of vascular restenosis. Alternative angioplasty techniques have been developed in the past few years in an attempt to resolve these issues (e.g., directional and rotational atherectomy, laser angioplasty, and vascular stents). Still, their role in transluminal angioplasty has yet to be fully defined.

The Mechanism of the Obstruction in, Calcific Aortic Stenosis with Bicuspid Valve: A Reason for, Failure of Balloon Aortic Valvuloplasty in the Elderly

Percutaneous aortic balloon valvuloplasty failed to relieve the obstruction in 2 elderly patients with calcific aortic stenosis. Intraoperative and pathologic examination showed bicuspid aortic valve with symmetric cusps, straight and fibrotic cusp edges and fractured calcific nodules of the aortic valve. Failure of balloon valvuloplasty in these patients, in spite of successful fractures of calcific nodules, was due to inability to influence the spring-like action of the thickened edges of the valve which represents a specific additional cause of obstruction in calcific bicuspid aortic valve of the elderly.