Low-dose, beta-particle emission from 'stent' wire results in complete, localized inhibition of smooth muscle cell proliferation.

BACKGROUND: Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by medial and/or intimal smooth muscle cell (SMC) proliferation. The objective of this study was investigate the ability of local emission of beta-particles from a 32P-impregnated titanium "stent" wire source to inhibit vascular SMC and endothelial cell proliferation in cell culture and to determine the dose-response characteristics of this inhibition. METHODS AND RESULTS: A series of experiments were performed using 0.20-mm-diameter titanium wires that were impregnated with varying low concentrations of 32P (activity range, 0.002 to 0.06 microCi/cm wire, n = 47) or 31P (nonradioactive control, n = 28) in cultures of rat and human aortic SMCs and in cultured bovine aortic endothelial cells. The zone of complete cell growth inhibition (in millimeters from stent wire) was measured using light microscopy in the cultures exposed to the radioactive (32P) or control (31P) wires at 6 and 12 days after plating. In both rat and human SMC cultures there was a distinct 5.5- to 10.6-mm zone of complete SMC inhibition at wire activity levels > or = 0.006 microCi/cm. In contrast, there was no zone of inhibition surrounding the control (31P impregnated) wires (P < .001 versus 32P wires at all wire activities > or = 0.006 microCi/cm for human and rat SMCs). Proliferating bovine endothelial cells were more radioresistant than SMCs, with no zone of inhibition observed at wire activity levels up to 0.019 microCi/cm (P < .001 versus SMCs at 0.006 microCi/cm and 0.019 microCi/cm). CONCLUSIONS: We conclude that very low doses of beta-particle emission from a 32P-impregnated stent wire (activity levels as low as 0.006 microCi/cm of wire) completely inhibit the growth and migration of both rat and human SMCs within a range of 5.5 to 10.6 mm from the wire. Endothelial cells appear to be much more radioresistant than SMCs. These data suggest that an intra-arterial stent impregnated with a low concentration of 32P may have a salutary effect on the restenosis process. Whether this approach can be used successfully and safely to inhibit restenosis in vivo and in the clinical setting is under investigation.

Cyclosporine effect on anti-CD3 monoclonal antibody-stimulated mitogenesis, phorbol ester comitogenesis, and PGE2 production.

Human peripheral blood mononuclear cells (H-PBMC) from 10 healthy donors were stimulated to proliferate with phytohemagglutinin lectin (PHA), anti-CD3 monoclonal antibody (mAb), and anti-CD3 mAb plus phorbol 12, myristate 13 acetate (TPA), a protein kinase C (PKC) agonist. Anti-CD3 mAb-mediated mitogenesis was 35-75% of that observed with PHA. When TPA was added to a dose of mAb that by itself did not cause mitogenesis, proliferation equal to 50-90% of the maximally mitogenic dose occurred. TPA did not enhance proliferation with maximally mitogenic doses of antibody. Dimethyl-prostaglandin E2, dibutyryl cyclic AMP, and forskolin (an adenyl cyclase agonist) inhibited PHA, anti-CD3, and anti-CD3/PMA-mediated mitogenesis. Cyclosporine (CSA) inhibited anti-CD3 and anti-CD3/TPA mitogenesis in a dose-dependent fashion. While CSA inhibited anti-CD3 and anti-CD3/TPA mitogenic signals, it did not affect PGE2 production by anti-CD3 mAb-stimulated H-PBMC. In the presence of CSA, PGE2 production in PHA-stimulated H-PBMC was increased. PGE2 inhibits lymphocyte proliferation via a cyclic AMP-mediated mechanism and may enhance maturation of suppressor cells. CSA inhibits anti-CD3 mAb and anti-CD3/TPA proliferative signals in H-PBMC yet has no effect or may even enhance production of suppressive PGE2. The maturation of antigen-specific suppressor cells elicited by CSA may involve active down-regulation of CD3 receptor and PKC-dependent events while PGE2 production continues.

The temporal relationship in arterial and venous prostacyclin and thromboxane activity during 24 hours of intraaortic balloon counterpulsation in dogs.

We studied the effects of intraaortic balloon counterpulsation (IABCP) on prostacyclin (PGI2) and thromboxane (TXB2) levels in dogs during 24 hours of 1:1 IABCP or a sham procedure in which the balloon was positioned but left deflated. The arterial PGI2 levels in the IABCP group increased from control values of 95 +/- 20 pg/ml to 268 +/- 95 pg/ml at 1 hour, 429 +/- 95 pg/ml at 4 hours, and 1,884 +/- 532 pg/ml at 24 hours. The arterial PGI2 levels were consistently higher in the IABCP group. Although the TXB2 measurements revealed no significant differences between groups, the IABCP group consistently had a higher level than the sham group. The platelet count in the control group decreased to 45% of baseline levels versus 55% for the IABCP group. We conclude that prolonged IABCP results in either net production of PGI2 or decreased degradation. The correlation between TXB2 and platelet counts is unclear and remains to be defined.

Neuroblastoma: a rare primary intrathoracic neurogenic tumor in adults.

Mediastinal neuroblastomas, which are common malignancies of childhood, are extremely rare in adults. This article presents a case of mediastinal neuroblastoma in a 57-year-old man. To the authors' knowledge, this is only the second recorded case of such a tumor in an adult. The patient's clinical course is described and is compared with other cases (in children, except for one instance) cited in the literature. The authors discuss the early diagnosis and surgical management of these uncommon lesions, which tend to be quite extensive and rapidly fatal, and which should be suspected in adults who present with a mediastinal mass.

Left-to-right shunts in control of bleeding following surgery for aneurysms of the ascending aorta.

Surgical repair of complex thoracic aneurysms requiring aortic valve replacement and coronary revascularization is occasionally complicated by significant bleeding despite the experience of the surgeon. While bleeding from the mediastinal tissues and the anterior suture line is usually easily controlled, posterior bleeding may require dismantling the repair and a second bypass run. The synergism of a second bypass run and continued bleeding may result in increased mortality and/or morbidity. We recently encountered bleeding in a patient who developed ventricular dysfunction after bypass and opted to interpose a Gore-tex graft between the aneurysm wall and the right atrium with immediate hemostasis and a benign course. Subsequently we used four different shunts successfully in 9 of 33 patients. The average bleeding rate 30 minutes after protamine was 221 +/- 60 ml/minute with a range of 190 to 350 ml/minute. The initial two hour chest tube drainage averaged 880 +/- 285 ml with a range of 490 to 1300 ml. There were no re-explorations for bleeding. The shunt in the first patient has remained open without cardiac decompensation. The last patient developed heart failure and required elective repair of a leak at the descending end of an arch replacement. Our experience suggests that these shunts can be effective, particularly if posterior suture line bleeding is encountered.