Dataset Information

Neuropeptide-Y causes coronary microvascular constriction and is associated with reduced ejection fraction following ST-elevation myocardial infarction.

ABSTRACT:

Aims

The co-transmitter neuropeptide-Y (NPY) is released during high sympathetic drive, including ST-elevation myocardial infarction (STEMI), and can be a potent vasoconstrictor. We hypothesized that myocardial NPY levels correlate with reperfusion and subsequent recovery following primary percutaneous coronary intervention (PPCI), and sought to determine if and how NPY constricts the coronary microvasculature.

Methods and results

Peripheral venous NPY levels were significantly higher in patients with STEMI (n?=?45) compared to acute coronary syndromes/stable angina ( n?=?48) or with normal coronary arteries (NC, n?=?16). Overall coronary sinus (CS) and peripheral venous NPY levels were significantly positively correlated (r?=?0.79). STEMI patients with the highest CS NPY levels had significantly lower coronary flow reserve, and higher index of microvascular resistance measured with a coronary flow wire. After 2?days they also had significantly higher levels of myocardial oedema and microvascular obstruction on cardiac magnetic resonance imaging, and significantly lower ejection fractions and ventricular dilatation 6?months later. NPY (100-250?nM) caused significant vasoconstriction of rat microvascular coronary arteries via increasing vascular smooth muscle calcium waves, and also significantly increased coronary vascular resistance and infarct size in Langendorff hearts. These effects were blocked by the Y1 receptor antagonist BIBO3304 (1??M). Immunohistochemistry of the human coronary microvasculature demonstrated the presence of vascular smooth muscle Y1 receptors.

Conclusion

High CS NPY levels immediately after reperfusion correlate with microvascular dysfunction, greater myocardial injury, and reduced ejection fraction 6?months after STEMI. NPY constricts the coronary microcirculation via the Y1 receptor, and antagonists may be a useful PPCI adjunct therapy.

SUBMITTER: Herring N

PROVIDER: S-EPMC6588241 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Neuropeptide-Y causes coronary microvascular constriction and is associated with reduced ejection fraction following ST-elevation myocardial infarction.

Herring Neil N Tapoulal Nidi N Kalla Manish M Ye Xi X Borysova Lyudmyla L Lee Regent R Dall'Armellina Erica E Stanley Christopher C Ascione Raimondo R Lu Chieh-Ju CJ Banning Adrian P AP Choudhury Robin P RP Neubauer Stefan S Dora Kim K Kharbanda Rajesh K RK Channon Keith M KM

European heart journal 20190601 24

<h4>Aims</h4>The co-transmitter neuropeptide-Y (NPY) is released during high sympathetic drive, including ST-elevation myocardial infarction (STEMI), and can be a potent vasoconstrictor. We hypothesized that myocardial NPY levels correlate with reperfusion and subsequent recovery following primary percutaneous coronary intervention (PPCI), and sought to determine if and how NPY constricts the coronary microvasculature.<h4>Methods and results</h4>Peripheral venous NPY levels were significantly hi ...[more]

PMID: 30859228

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Project description:BACKGROUND:Failed myocardial reperfusion is common and prognostically important after acute ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate coronary flow reserve (CFR), a measure of vasodilator capacity, and the index of microvascular resistance (IMR; mmHg × s) in the culprit artery of STEMI survivors. METHODS:IMR (n = 288) and CFR (n = 283; mean age [SD], 60 [12] years) were measured acutely using guide wire-based thermodilution. Cardiac MRI disclosed left ventricular pathology, function, and volumes at 2 days (n = 281) and 6 months after STEMI (n = 264). All-cause death or first heart failure hospitalization was independently adjudicated (median follow-up 845 days). RESULTS:Myocardial hemorrhage and microvascular obstruction occurred in 89 (42%) and 114 (54%) patients with evaluable T2*-MRI maps. IMR and CFR were associated with microvascular pathology (none vs. microvascular obstruction only vs. microvascular obstruction and myocardial hemorrhage) (median [interquartile range], IMR: 17 [12.0-33.0] vs. 17 [13.0-39.0] vs. 37 [21.0-63.0], P < 0.001; CFR: 1.7 [1.4-2.5] vs. 1.5 [1.1-1.8] vs. 1.4 [1.0-1.8], P < 0.001), whereas thrombolysis in myocardial infarction blush grade was not. IMR was a multivariable associate of changes in left ventricular end-diastolic volume (regression coefficient [95% CI] 0.13 [0.01, 0.24]; P = 0.036), whereas CFR was not (P = 0.160). IMR (5 units) was a multivariable associate of all-cause death or heart failure hospitalization (n = 30 events; hazard ratio [95% CI], 1.09 [1.04, 1.14]; P < 0.001), whereas CFR (P = 0.124) and thrombolysis in myocardial infarction blush grade (P = 0.613) were not. IMR had similar prognostic value for these outcomes as <50% ST-segment resolution on the ECG. CONCLUSIONS:IMR is more closely associated with microvascular pathology, left ventricular remodeling, and health outcomes than the angiogram or CFR. TRIAL REGISTRATION:NCT02072850. FUNDING:A British Heart Foundation Project Grant (PG/11/2/28474), the National Health Service, the Chief Scientist Office, a Scottish Funding Council Senior Fellowship, a British Heart Foundation Intermediate Fellowship (FS/12/62/29889), and a nonfinancial research agreement with Siemens Healthcare.

Dataset Information

Neuropeptide-Y causes coronary microvascular constriction and is associated with reduced ejection fraction following ST-elevation myocardial infarction.

Aims

Methods and results

Conclusion

Publications

Neuropeptide-Y causes coronary microvascular constriction and is associated with reduced ejection fraction following ST-elevation myocardial infarction.

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