Comparison of self-expanding and balloon-expandable stents for the reduction of restenosis.

To compare the efficacy of self-expanding (SE) and balloon-expandable (BE) stents in native coronary arteries, we randomly assigned 1,096 patients with new and restenotic lesions to receive either device. Baseline demographics and coronary angiographic characteristics were similar in the 2 groups. The incidence of major adverse cardiac events including death, myocardial infarction, bypass surgery, and repeat intervention was similar for both groups at 1 month (2.9% vs 3.1% for SE vs BE, respectively) and at 9 months (19.3% vs 20.1%, SE vs BE respectively). In a subgroup of patients who underwent follow-up angiography (n = 250), the binary restenosis rates (24.2% vs 18.7%, p = 0.30), late loss (0.98 vs 94 mm, p = 0.60), and loss index (0.55 vs 55, p = 0.95) were not significantly different for both groups. In 62 patients who underwent intravascular ultrasound examination (IVUS), there was a trend toward a lower incidence of edge tears in the SE group (6% vs 23%, p = 0.06). Follow-up IVUS analysis showed that the minimum stent area of the SE stent increased by 33% at 6 months, whereas no change occurred in the BE stents; this was accompanied by a greater degree of intimal proliferation in the SE stents compared with BE stents (3.1 +/- 2.0 vs 1.7 +/- 1.7 mm(2)). Thus, the SE stents had similar clinical and angiographic outcomes in patients with lesions in native coronary arteries.

Cessation of platelet-mediated cyclic canine coronary occlusion after thrombolysis by combining nitric oxide inhalation with phosphodiesterase-5 inhibition.

OBJECTIVES: We sought to evaluate the ability of type 5 phosphodiesterase (PDE5) inhibitors to augment the antithrombotic effects of inhaled nitric oxide (NO) in a canine model of platelet-mediated coronary thrombosis after thrombolysis. BACKGROUND: Type 5 phosphodiesterase inhibitors potentiate the ability of NO to inhibit platelet aggregation in vitro by preventing platelet cyclic guanosine monophosphate catabolism. We previously reported that breathing low concentrations of NO gas attenuated, but did not prevent, cyclic flow reductions (CFRs) in a canine model of coronary thrombosis after thrombolysis. METHODS: Cyclic flow reductions were induced after creation of a left anterior descending coronary artery stenosis, endothelial injury, thrombus formation and thrombolysis. Dogs were either untreated or treated with inhaled NO (20 ppm by volume), intravenous zaprinast, intravenous dipyridamole or the combination of inhaled NO with either PDE5 inhibitor (n = 4 per group). RESULTS: Cyclic flow reductions ceased, and complete coronary patency was achieved in all dogs after they breathed NO combined with zaprinast (by 12.0+/-4.7 min [mean +/- SEM]) or dipyridamole (by 9.8+/-4.7 min). The frequency of CFRs was unaffected by NO, dipyridamole or zaprinast alone. Systemic arterial blood pressure and bleeding time were unchanged with any treatment. Ex vivo thrombin-induced platelet aggregation in dogs breathing NO and receiving dipyridamole was reduced by 75+/-7% (p < 0.05). CONCLUSIONS: The PDE5 inhibitors potentiated the antithrombotic properties of inhaled NO in a canine model of platelet-mediated coronary artery thrombosis after thrombolysis, without prolonging the bleeding time or causing systemic hypotension.

Heparin/heparan sulfate chelation inhibits control of vascular repair by tissue-engineered endothelial cells.

The relative importance of heparin-like compounds in mediating vascular repair is unclear. We investigated how protamine, a chelator of heparin, affected endothelial cell inhibition of vascular smooth muscle cell growth and intimal hyperplasia. The 52% (P < 0.001) reduction in smooth muscle cell proliferation produced by postconfluent endothelial cell-conditioned medium was entirely reversed by pretreatment of medium with heparinase and heparitinase and was inhibited in a dose-dependent fashion by the coadministration of protamine. Pretreatment of conditioned medium with heparinase and heparitinase largely prevented protamine's mitogenic activity, suggesting that protamine affects growth by interacting with heparin-like compounds. Perivascular implantation of polymerengrafted endothelial cells reduced neointima formation in denuded rat carotid arteries by 92% (P < 0.001) and cell proliferation by 81% (P < 0.001). Coadministration of protamine abolished the inhibitory potential of the cell implants, resulting in a nearly twofold exacerbation of intimal hyperplasia compared with controls (P < 0.001). Thus heparin-like molecules are essential to the biochemical regulation of vascular repair provided by endothelial cells, and the continued routine clinical use of heparin chelators, like protamine, may be questionable.

Detection of interleukin and interleukin-receptor mRNA in human heart by polymerase chain reaction.

Diminished cardiac contractility associated with inflammatory infiltration may be mediated by the release of interleukins. To test this hypothesis, we assessed the presence of interleukin and interleukin-receptor mRNAs in non-failing human heart and in endomyocardial biopsies from patients with dilated cardiomyopathy or inflammatory myocarditis. Only those interleukins expressed by non-circulating cells (interleukin-1 beta, -4, and -8) were detected in samples of human heart while interleukins specific for activated leukocytes (interleukins-1 alpha and -2) were not detected in any samples. While interleukin-1-receptor mRNA was present in samples from non-failing hearts and those with idiopathic myopathy, it was absent from patients with inflammatory myocarditis, suggesting receptor mRNA down-regulation.