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 (ACS/SA, 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 edema and microvascular obstruction on cardiac MRI, 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 microM). Immunohistochemistry of the human coronary microvasculature demonstrated the presence of vascular smooth muscle Y1 receptors.
Conclusions:
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.
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 (ACS/SA, 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 edema and microvascular obstruction on cardiac MRI, 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 microM). Immunohistochemistry of the human coronary microvasculature demonstrated the presence of vascular smooth muscle Y1 receptors.
Conclusions:
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.
Original language | English |
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Article number | ehz115 |
Pages (from-to) | 1920-1929 |
Number of pages | 10 |
Journal | European Heart Journal |
Volume | 40 |
Issue number | 24 |
Early online date | 11 Mar 2019 |
DOIs | |
Publication status | Published - 21 Jun 2019 |
Keywords
- Neuropeptide-Y
- myocardial infarction
- percutaneous coronary intervention
- cardiac magnetic resonance imaging
- microvascular function
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Professor Raimondo Ascione
- Elizabeth Blackwell Institute for Health Research
- Bristol Medical School (THS) - Professor of Cardiac Surgery and Translational Research and Director of TBRC
Person: Academic , Member