Hydrocortisone reduces restenosis after stenting of small coronary arteries.

Stenting of small coronary arteries has been limited by high rates of restenosis, and restenosis after stenting has chiefly been attributed to inflammatory reactions resulting in cell proliferation and intimal hyperplasia. In order to suppress this inflammatory process, we examined the effects of hydrocortisone, an antiinflammatory agent, on restenosis after stenting in a nonrandomized retrospective registry. The study population consisted of 193 patients treated at two hospitals, who underwent stent implantations in coronary arteries of reference diameter <3 mm between February 1999 and September 2001. Target lesions included complex, restenotic, diabetic, or chronic total lesions and types of implanted stents were Multi-Link, S-series, and gfx stents. Effect of intravenous administration of hydrocortisone (200 mg) before stenting was compared to control patients who did not receive this treatment. There was no significant difference of early outcomes between the hydrocortisone group and the control group. On angiographic follow-up at 6 months after stenting, the rate of restenosis was significantly lower in patients treated with hydrocortisone as compared with control group (22.8% vs 37%, respectively; P < 0.05). The revascularization rate of target lesion at 6 months was also significantly lower in the treated group (16.5% vs 29%, respectively; P < 0.05). These results suggest that preprocedural intravenous administration of hydrocortisone reduces restenosis after stenting of small coronary arteries. Prospectively controlled trials will be necessary to confirm this preventive effect of hydrocortisone on coronary in-stent restenosis.

The effect of hydrocortisone on reducing rates of restenosis and target lesion revascularization after coronary stenting less than 3 mm in stent diameter.

OBJECTIVE: Stenting of small coronary arteries has always been limited by high rates of restenosis, and restenosis has mainly been attributed to inflammatory reactions resulting in cell proliferation and intimal hyperplasia. Based on our experience for several years, we retrospectively investigated the effect of hydrocortisone on reducing in-stent restenosis. PATIENTS AND METHODS: Study population consisted of consecutive 166 patients, 221 lesions, who electively underwent stent implantations stent diameter less than 3 mm into coronary arteries between February 1999 and October 2002. We intravenously administered hydrocortisone before the procedure to 40 patients for preventing allergic reactions due to contrast material, and the effect of hydrocortisone on reducing restenosis was retrospectively compared with 126 patients who did not receive this treatment. RESULTS: There was no significant difference in the prevalence of diabetes mellitus, hyperlipidemia, or hypertension between the two groups. There was no significant difference in the type of lesion, length of stent, balloon/artery ratio, or initial success rate between the two groups, but stent diameter was significantly smaller in the hydrocortisone group compared with the control group. On six-month angiographic follow-up, the restenosis rate was significantly lower in the hydrocortisone group compared with the control group (16.2% vs 34.0%, respectively), and the target lesion revascularization rate was also significantly lower in the hydrocortisone group compared with the control group (13.2% vs 27.5%, respectively). CONCLUSION: These results suggest that intravenous administration of hydrocortisone reduces in-stent restenosis of small coronary arteries. Prospectively controlled trials will be necessary to confirm this preventive effect of hydrocortisone.

Thrombosis increases circulatory hepatocyte growth factor by degranulation of mast cells.

BACKGROUND: Plasma concentrations of hepatocyte growth factor (HGF), a powerful angiogenic growth factor inducible by heparin, increase in thrombus-associated disorders such as myocardial infarction and unstable angina. The mechanism of this thrombus-associated HGF release, however, is unknown. METHODS AND RESULTS: Wistar rats received through the tail vein (1) normal saline (NS), (2) 50 micro g of the mast cell-degranulating agent CP48/80, or (3) 1000 U/kg heparin. Blood samples were collected at 10 minutes or 30 minutes after the injections, or from untreated rats, for measurements of HGF. The same experiments were performed in mast cell-deficient white spotting (Ws) rats. Ws rats have a small deletion of the c-kit gene and are deficient in mast cells. Intravenous heparin immediately increased plasma HGF in both Wistar (38.02+/-2.08 ng/mL versus 1.11+/-0.70 ng/mL in untreated rats, P<0.0001) and Ws rats (36.39+/-4.15 ng/mL versus 0.66+/-0.18 ng/mL in NS-treated rats, P<0.0001). Injection of CP48/80 also increased plasma HGF in Wistar rats (9.12+/-1.11 ng/mL versus 0.65+/-0.24 ng/mL in NS group, P=0.004) but not in Ws rats (0.67+/-0.27 ng/mL versus 0.66+/-0.18 ng/mL in NS group, P=0.997). In a rat carotid artery microthrombus model, intra-arterial thrombus formation increased circulating HGF in Wistar rats (2.12+/-0.70 ng/mL versus sham 0.61+/-0.15 ng/mL in sham-operated Wistar rats, P=0.0064) but not in Ws rats (0.76+/-0.33 ng/mL versus 0.21+/-0.04 ng/mL in sham-operated Ws rats, P=0.29). In addition, in vitro stimulation of rat peritoneal mast cells with thrombin rapidly induced degranulation in a dose-dependent manner. CONCLUSIONS: These observations indicate that mast cell degranulation stimulated by thrombin is necessary for the rapid induction of plasma HGF in intravascular thrombus-associated disorders.