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Selective endothelin A-receptor blockade attenuates coronary microvascular dysfunction after coronary stenting in
Nikolaos Ostlund Papadogeorgos1, Mattias Bengtsson, Majid Kalani
1Karolinska 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.
Insights
Endothelin-1 blockade improved myocardial microcirculation in type 2 diabetes patients undergoing coronary stenting. Selective endothelin A-receptor blockade reversed coronary microvascular dysfunction, suggesting a protective role against ischemic events.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Endothelin-1 is implicated in diabetic microangiopathy.
- Myocardial microcirculation during coronary stenting in diabetics requires investigation.
Purpose of the Study:
- To assess the impact of endothelin-1 blockade on myocardial microcirculation.
- To evaluate the efficacy of bosentan and BQ123 in diabetic patients undergoing percutaneous coronary intervention (PCI).
Main Methods:
- Randomized trial involving type 2 diabetes patients undergoing elective PCI.
- Interventions included bosentan (dual endothelin receptor blocker), BQ123 (selective endothelin A-receptor blocker), or placebo.
- Coronary flow reserve (CFR) measured post-PCI, compared with nondiabetic controls.
Main Results:
- Placebo group showed significantly lower CFR compared to endothelin blockade groups and controls.
- BQ123 treatment resulted in significantly higher CFR than placebo.
- Nondiabetic patients exhibited higher CFR than diabetic patients post-stenting.
Conclusions:
- Coronary microvascular dysfunction occurs during stenting in type 2 diabetes patients.
- Selective endothelin A-receptor blockade can reverse this dysfunction.
- Targeting the endothelin system may protect the myocardium during PCI in diabetic patients.
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