P4158Marked impairment of endothelium-dependent digital vasodilatations in patients with microvascular angina compared with those with vasospastic angina

Abstract

Abstract Background/Introduction Nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) factor are the major endothelium-derived relaxing factors. NO plays an important role in conduit arteries, while the importance of EDH factor increases as the vessel size decrease in patients with microvascular angina (MVA) compared with those with vasospastic angina (VSA) remains to be fully elucidated. Purpose We evaluated the roles of NO and EDH factor in conduit (brachial) arteries and resistance (digital) arteries of the patients with MVA, VSA and comorbid MVA+VSA patients. Methods We enrolled 39 patients who underwent diagnostic cardiac catheterization and divided them into 3 groups based on acetylcholine (ACh) provocation test, index of microcirculation resistance (IMR), and coronary flow reserve (CFR); MVA (N=9, mean age 59.9±3.5 years), VSA (N=12, mean age 61.3±1.8 years), and comorbid MVA+VSA (N=18, mean age 64.0±2.2 years). Endothelium-dependent brachial and digital vasodilatations in response to intra-arterial infusion of bradykinin (BK, 25, 50, and 100 ng/min for 2 min) were simultaneously measured by ultrasonography and peripheral arterial tonometry, respectively. Measurements were repeated after oral administration of aspirin (486 mg) and intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA, 8μmol/min for 5 min) in order to inhibit the effects of vasodilator prostaglandins and NO, respectively. Finally, endothelium-independent brachial and digital vasodilatations in response to sublingual nitroglycerin (NTG, 0.3 mg) were measured in the same manner. Results In the brachial artery, dose-dependent vasodilatations to BK were comparable among the 3 groups, and L-NMMA equally attenuated the responses to BK (Figure 1). Endothelium-independent brachial vasodilatation in response to NTG was also comparable among the 3 groups. Surprisingly, dose-dependent digital vasodilatations to BK were almost absent in MVA patients compared with VSA or comorbid MVA+VSA group (Figure 2). Furthermore, the digital vasodilatations were unaffected by L-NMMA in VSA group, but were significantly reduced in comorbid MVA+VSA group (VSA, 16.8±15.1% vs. MVA+VSA, −0.23±6.2%, P<0.05), suggesting reduced EDH and compensatory role of NO in the latter group. In contrast, endothelium-independent digital vasodilatation in response to NTG was comparable among the 3 groups. The main results of this study Conclusions These results provide the first evidence that endothelium-dependent digital vasodilatations (both NO and EDH factor) are markedly impaired in MVA patients compared with VSA or comorbid MVA+VSA patients, whereas the responses are comparable in the brachial artery among the 3 groups, suggesting the involvement of severe endothelial dysfunction in the pathogenesis of MVA.