Format

Send to

Choose Destination
Eur Heart J. 2019 Mar 11. pii: ehz115. doi: 10.1093/eurheartj/ehz115. [Epub ahead of print]

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

Author information

1
Department of Physiology, Anatomy and Genetics, Burdon Sandersn Cardiac Science Centre, University of Oxford, Parks Road, Oxford, UK.
2
Department of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, UK.
3
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, UK.
4
Oxford Acute Vascular Imaging Centre, Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, UK.
5
Bristol Heart Institute, Bristol Royal Infirmary, and Faculty of Health Sciences, University of Bristol, Horfield Road, Bristol, UK.
6
National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way Oxford, UK.

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 μM). 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.

KEYWORDS:

Cardiac magnetic resonance imaging; Microvascular function; Myocardial infarction; Neuropeptide-Y; Percutaneous coronary intervention

PMID:
30859228
DOI:
10.1093/eurheartj/ehz115
Free full text

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for White Rose Research Online
Loading ...
Support Center