Arterial smooth muscle cells express nitric oxide synthase in response to endothelial injury.

Endothelial cells regulate vascular tone by secreting paracrine mediators that control the contractility of arterial smooth muscle cells. Nitric oxide (NO) is an important vasodilating agent that is generated from L-arginine by the enzyme nitric oxide synthase (NOS), which is expressed constitutively by the endothelium. NO also inhibits platelet aggregation, contributing to the antithrombotic properties of the endothelial surface. It would therefore be expected that loss of the endothelium during arterial injury would lead to vasospasm and thrombosis but instead, the neointima formed after injury has a nonthrombogenic surface and a maintained vascular patency. We report here that arterial smooth muscle cells in the neointima formed after a deendothelializing balloon injury to the rat carotid artery express the cytokine-inducible isoform of NOS. Expression was detectable by reverse transcription-polymerase chain reaction from day 1-14 after injury and in situ hybridization showed expression of NOS mRNA by neointimal smooth muscle cells, particularly at the surface of the lesion. This was associated with systemically detectable NO production as revealed by electron paramagnetic resonance spectroscopic analysis of nitrosylated red cell hemoglobin. Local NO production by intimal smooth muscle cells after endothelial injury could represent an important mechanism for the maintenance of arterial patency and nonthrombogenicity in the injured artery.

Spinal cord stimulation in angina pectoris with normal coronary arteriograms.

BACKGROUND: Patients with angina pectoris with normal coronary arteriograms, also known as Syndrome X (typical exercise-induced angina pectoris, positive exercise testing, and normal coronary arteriograms), are often difficult to treat with conventional forms of medical therapy. Spinal cord stimulation has been used in recent years for the treatment of severe angina pectoris refractory to conventional medical and surgical therapy in coronary artery disease. The aim of this study was to investigate the effects of spinal cord stimulation on angina pectoris with normal coronary arteriograms. METHODS: Twelve patients underwent five bicycle exercise tests, three tests without (control), and two tests with spinal cord stimulation treatment. RESULTS: The exercise tolerance of the patients increased (108 +/- 22 W versus 96 +/- 21 W; P < 0.001), the magnitude of ST-segment depression at comparable work load decreased (1.0 +/- 0.6 mm versus 1.5 +/- 0.9 mm; P < 0.01), time to angina increased (5.4 +/- 2.2 min versus 2.7 +/- 1.9 min; P < 0.01), and time to the appearance of ST-segment depression increased (3.5 +/- 1.9 min versus 2.4 +/- 1.6 min; P < 0.01). The rate-pressure product at maximum work load during treatment increased, compared with the maximum work load during the control session (28,038 +/- 6124 mmHg x bpm versus 25,222 +/- 4519 mmHg x bpm; P < 0.05) and the comparable work load during treatment (28,038 +/- th 6124 mmHg x bpm versus 24,795 +/- 5022 mmHg x bpm; P < 0.01). CONCLUSIONS: Spinal cord stimulation has beneficial effects in angina pectoris with normal coronary arteriograms in terms of relief of symptoms of angina pectoris and improvement of exercise tolerance. These effects may be associated with a reduction in myocardial ischemia.

Reduction in thrombotic events with heparin-coated Palmaz-Schatz stents in normal porcine coronary arteries.

BACKGROUND: The use of stents improves the result after balloon coronary angioplasty. Thrombogenicity of stents is, however, a concern. In the present study, we compared stents with an antithrombotic coating with regular stents. METHODS AND RESULTS: Regular stents were placed in coronary arteries of pigs receiving no aspirin (group 1; n = 8) or aspirin over 4 weeks (group 2, n = 10) or 12 weeks (group 3, n = 9). Stents coated with heparin (antithrombin III uptake, 5 pmol/stent) were placed in 7 pigs that did not receive aspirin (group 4). The other animals received aspirin and coated stents with a heparin activity of 12 pmol antithrombin III/stent (group 5, n = 10) or 20 pmol/stent (group 6, n = 10; group 7, n = 10). Quantitative arteriography was performed at implantation and after 4 (groups 1, 2, and 4 through 6) or 12 weeks (groups 3 and 7). In an additional 5 animals, five regular and five coated stents (20 pmol/stent) were placed and explanted after 5 days for examination of the early responses to the implants. Thrombotic occlusion of the regular stent occurred in 9 of 27 in groups 1 through 3. However, in 0 of 30 of the animals receiving high-activity heparin-coated stents (groups 5 through 7), thrombotic stent occlusion was observed (P < .001). Histological analysis at 4 weeks showed that the neointima in group 6 was thicker compared with its control group 2 (259 +/- 104 and 117 +/- 36 microns, P < .01), but at 12 weeks the thickness was similar (152 +/- 61 and 198 +/- 49 microns, respectively). Comparison at 5 days suggested delayed endothelialization of the coating. CONCLUSIONS: High-activity heparin coating of stents eliminates subacute thrombosis in porcine coronary arteries.