Selective endothelin A-receptor blockade attenuates coronary microvascular dysfunction after coronary stenting in patients with type 2 diabetes

Nikolaos Östlund Papadogeorgos, Mattias Bengtsson, Majid Kalani

Karolinska Institute, Department of Clinical Sciences, Department of Cardiology, Danderyd Hospital, Stockholm, Sweden

Background: Endothelin-1 may be involved in the development of diabetic microangiopathy. We studied the effect of endothelin-1 blockade on myocardial microcirculation during coronary stenting.

Patients and methods: Patients with type 2 diabetes and stable coronary artery disease undergoing elective percutaneous coronary intervention (PCI) were randomized to bolus dose of 500 mg bosentan (n = 4), a dual endothelin receptor blocker, or intracoronary administration of 0.03 mmol BQ123 (n = 6), a selective endothelin A-receptor blocker, or placebo (n = 5), respectively. Coronary flow reserve (CFR) was measured immediately post-PCI. CFR was also measured in five nondiabetic controls post-coronary stenting.

Results: Patients in the placebo group had (P < 0.05) lower values of CFR (2.3 ± 1.2) as compared to those who received endothelin blockade (n = 10; 3.1 ± 0.7) and nondiabetic controls (4.9 ± 2.3). Patients who received BQ123 showed significantly higher CFR (3.3 ± 0.5; P < 0.05) as compared to those on placebo. Nondiabetic patients had significantly higher CFR as compared to patients with diabetes (4.9 ± 2.3 and 2.8 ± 1.0, respectively; P < 0.05).

Conclusion: Coronary microvascular dysfunction is present during coronary stenting in patients with type 2 diabetes and may be reversed by selective endothelin A-receptor blockade. Targeting endothelin system may be of importance in protecting the myocardium against ischemic events during elective PCI in type 2 diabetic patients.

Keywords: coronary flow reserve, diabetes, endothelin-1, coronary artery disease, coronary angioplasty