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Biomedical subjects

R Waksman

Publications and source records attributed to R Waksman.

9 recordsLinked to original sources
PubMed1995

Intracoronary low-dose beta-irradiation inhibits neointima formation after coronary artery balloon injury in the swine restenosis model.

BACKGROUND: Neointima formation contributing to recurrent stenosis remains a major limitation of percutaneous transluminal angioplasty. Endovascular low-dose gamma-irradiation has been shown to reduce intimal thickening (hyperplasia) after balloon overstretch injury in pig coronary arteries, a model of restenosis. The objective of this study was to determine whether the use of a beta-emitting radioisotope for this application would have similar effects and to examine the dose-response relations with this approach. METHODS AND RESULTS: Normal domestic pigs underwent balloon overstretch injury in the left anterior descending and left circumflex and coronary arteries. A flexible catheter was introduced by random assignment into one of these arteries and was afterloaded with a 2.5-cm ribbon of encapsulated 90Strontium/90Yttrium sources (90Sr/Y, a pure beta-emitter). It was left in place for a period of time sufficient to deliver one of four doses: 7, 14, 28, or 56 Gy, to a depth of 2 mm. Animals were killed 14 days after balloon injury, the coronary vasculature was pressure-perfusion fixed, and histomorphometric analysis of arterial cross sections was performed. All arteries treated with radiation demonstrated significantly decreased neointima formation compared with control arteries. The ratio of intimal area to medial fracture length was inversely correlated with increasing radiation dose: control (no radiation), 0.47; 7 Gy, 0.34; 14 Gy, 0.20; 28 Gy, 0.08; and 56 Gy, 0.02 (r = -.78, P < .000001). Scanning electron microscopy demonstrated a confluent layer of endothelium-like cells both in control and in 14 Gy-irradiated arteries. There was neither evidence of significant necrosis nor excess fibrosis in the media, adventitia, or perivascular space of the coronary arteries or adjacent myocardium in the irradiated groups. Furthermore, the exposure to the staff and the total body exposure to the pig with the beta source was a small fraction of the dose previously measured and calculated with 192Ir, a gamma-emitting radioisotope. CONCLUSIONS: Administration of endovascular beta-radiation to the site of coronary arterial overstretch balloon injury in pigs with 90Sr/Y is technically feasible and safe. Radiation doses between 7 and 56 Gy showed evidence of inhibition of neointima formation. A dose-response relation was demonstrated, but no further inhibitory effect was seen beyond 28 Gy. These data suggest that intracoronary beta-irradiation is practical and feasible and may aid in preventing clinical restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1995

Intracoronary radiation before stent implantation inhibits neointima formation in stented porcine coronary arteries.

BACKGROUND: Stent implantation has been shown to reduce restenosis by establishing a larger lumen but not by reducing neointima formation. We have previously shown that ionizing radiation reduced neointima formation after balloon injury in a swine model of restenosis. The purpose of this study was to determine whether endovascular irradiation of the coronary artery before stent implantation would affect neointima formation. METHODS AND RESULTS: Nine normolipemic pigs underwent coronary angiography, and segments of the left anterior descending and left circumflex arteries were chosen as targets for stenting. A high-activity 192Ir source was used to deliver 14 Gy by random assignment to one of the vessels. After this, 3.5-mm tantalum stents were implanted in both arteries. Three additional pigs were treated with a 90Sr/Y source (a pure beta-emitter) delivering 14 Gy to five segments of coronary vessels that were stented immediately after irradiation. Stent-to-artery ratio was similar in the radiated and the control arteries. Animals received aspirin 325 mg daily and were killed at 28 days. The intimal area was significantly reduced in the irradiated stented arteries compared with control arteries treated with stent only (1.98 mm2 with 192Ir and 2.53 mm2 with 90Sr/Y versus 3.82 mm2 in the control stented arteries, P < .005). CONCLUSIONS: Endovascular radiation before coronary stenting reduces neointima formation and may further reduce the restenosis rate after stent implantation.

Animals↗
PubMed1995

Predictors of groin complications after balloon and new-device coronary intervention.

We reviewed the clinical course of 5,042 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) using balloons or new devices: (stent, laser, directional and rotational atherectomy). A vascular complication was defined as the formation of a groin hematoma, bleeding, pseudoaneurysm, fistula, or the need for surgical repair. Vascular complications occurred in 309 (6.1%) patients, and 117 (2.3%) required vascular repair; among these patients, surgery was performed for correction of an an arteriovenous fistula in 12%, repair of pseudoaneurysm in 72%, repair for expanding hematoma and femoral artery lacerations in 10%, and retroperitoneal bleeding in 6%. The correlates of vascular complications were older age (66.8 vs 62.1 years; p < 0.0001), female gender (43% vs 26%; p < 0.0001), increased weight (82.1 +/- 16.46 vs 78.0 +/- 16.6 kg; p < 0.001), higher systolic blood pressure (140 +/- 25 vs 134 +/- 20 mm Hg; p < 0.001), increased heparin dose during the procedure (14,352 +/- 3,879 vs 13,599 +/- 3,508 IU; p = 0.001), administration of heparin after the procedure (232 vs 2,985 patients; p < 0.0001) and intracoronary stenting (14.9% vs 3.5%; p < 0.0001). Fifteen patients of 214 (7.0%) who underwent stent implantation had surgical repair. Vascular complications were not related to the size of the arterial sheath (8.11 +/- 0.8 vs 8.8 +/- 0.7Fr; p = 0.11) and the use of devices other than stents (laser, atherectomy) did not increase the rate of vascular complications.

Aged↗
PubMed1992

Autodecremental pacing for the interruption of ventricular tachycardia and atrial flutter.

The efficacy and safety of autodecremental pacing (ADP) to interrupt ventricular tachycardia (VT) and atrial flutter was examined. Once tachycardia was recognized, ADP was initiated using a short train of stimuli with gradual shortening (3%) of the interstimulus interval. ADP was applied to 13 consecutive patients during 75 episodes of VT (mostly following induction by ventricular stimulation). Successful interruption of VT occurred in 88% of the episodes. In 6 episodes (8%), ADP resulted in ventricular fibrillation and in 3 episodes VT was unaffected by ADP. The only significant discriminator between the failure or success of ADP was the rate of VT. ADP was also applied to 17 consecutive patients with an atrial flutter that was resistant to conventional antiarrhythmic agents. Successful conversion of atrial flutter to sinus was seen in only 8 patients (47%). A temporary acceleration to atrial fibrillation appeared in 3 patients (18%), and in 6 patients atrial flutter was unaffected by ADP. ADP was successful in 70% (7/10) of patients with type 1 (< 300 beats/min) atrial flutter. The authors conclude that ADP is beneficial in the interruption of VT and atrial flutter in a selected group of patients, especially with a slower rate of tachyarrhythmia (atrial rate during atrial flutter < 300 beats/min and ventricular tachycardia < 180 beats/min).

Adult↗
PubMed1990

Systemic embolization following thrombolytic therapy for acute myocardial infarction.

We describe a patient with acute inferior myocardial infarction who developed a "saddle" aortic embolus during streptokinase infusion. Three months previously, this patient had sustained an anterior infarction, and an apical aneurysm was found. This patient's embolus had most probably originated from a left ventricular mural thrombus that had been dislodged by streptokinase. As fibrinolytic treatment is gaining wide acceptance, physicians should be aware of this rare, but possible, complication.

Aged↗
PubMed1988

Nitrendipine prevents the development of cardiac hypertrophy in DOCA-salt-treated hypertension-prone (SBH) and -resistant (SBN) rats through nonhemodynamic mechanisms.

Recent studies indicate that cardiac and renal hypertrophy develop during desoxycorticosterone acetate (DOCA)-salt (DOC) treatment in hypertension-prone (SBH) and -resistant (SBN) rats, irrespective of systemic hemodynamic changes. The effect of nitrendipine on the development of left and right ventricular hypertrophy (LVH and RVH, respectively) was evaluated in 16-week-old rats. Members of each strain were divided into six groups (n = 10): 1--control; 2--nitrendipine treated for 3 weeks; 3, 4, and 5--DOC for 10 days, 3 weeks, and 6 weeks, respectively; 6--DOC for 6 weeks and nitrendipine for the last 3 weeks. Cannulae were inserted into the left ventricle and abdominal aorta. The radioactive reference sample microsphere technique was used to measure cardiac index. Mean arterial pressure (MAP) and total peripheral resistance index (TPRI) were unchanged in all six groups of SBN rats, whereas MAP and TPRI increased progressively in the DOC-treated SBH groups. Concomitant administration of nitrendipine in Group 6 was associated with a reduction of MAP and TPRI to control levels. Cardiac index and heart rate did not change in any group. Despite the different hemodynamic changes, both SBH and SBN rats developed LVH and RVH. The concomitant administration of nitrendipine prevented the progression of LVH and allowed regression of RVH in both strains. It is concluded that nitrendipine can affect the pathogenesis of LVH through nonhemodynamic mechanisms.

Animals↗
PubMed1984

Early right atrial pacing after myocardial infarction. I. Comparison with early treadmill testing.

Right atrial (RA) pacing and modified treadmill testing (TT) were performed in 111 patients recovering from acute myocardial infarction (MI) before hospital discharge to determine whether ischemic responses are more common with RA pacing than with TT and whether the prognosis could be better determined by the results of 1 test compared with the other. Patients with predischarge congestive heart failure, chest pain, physical disability or age older than 70 years were excluded. Ischemic responses were significantly more frequent during RA pacing than during TT (41% vs 34%, p = 0.02). The results of the 2 tests were concordant in 102 patients (92%): Both were positive in 37 and both negative in 65. In 8 patients, results of RA pacing were positive and results of TT were negative; only 1 patient had positive TT and negative RA pacing responses. The higher percentage of positive responses during RA pacing than during TT can be attributed to the significantly higher pressure-rate product achieved during pacing (18,773 vs 16,831 mm Hg/min, p less than 0.001). The ischemic threshold, defined as the pressure-rate product at which an ischemic change was first noted in a particular patient, was almost identical in both tests. During a mean follow-up period of 16 months, 10 patients had recurrent MI; 8 had positive predischarge RA pacing but only 5 had positive TT responses (p = 0.008). Six patients died; in 3 RA pacing responses were positive and in 2 TT responses were positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗