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Capillary pericytes mediate coronary no-reflow after myocardial ischaemia.

ABSTRACT: After cardiac ischaemia, a prolonged decrease of coronary microvascular perfusion often occurs even after flow is restored in an upstream artery. This 'no-reflow' phenomenon worsens patient prognosis. In the brain, after stroke, a similar post-ischaemic 'no-reflow' has been attributed to capillary constriction by contractile pericytes. We now show that occlusion of a rat coronary artery, followed by reperfusion, blocks 40% of cardiac capillaries and halves perfused blood volume within the affected region. Capillary blockages colocalised strongly with pericytes, where capillary diameter was reduced by 37%. The pericyte relaxant adenosine increased capillary diameter by 21% at pericyte somata, decreased capillary block by 25% and increased perfusion volume by 57%. Thus, cardiac pericytes constrict coronary capillaries and reduce microvascular blood flow after ischaemia, despite re-opening of the culprit artery. Cardiac pericytes are therefore a novel therapeutic target in ischaemic heart disease.

SUBMITTER: O'Farrell FM

PROVIDER: S-EPMC5705208 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Capillary pericytes mediate coronary no-reflow after myocardial ischaemia.

O'Farrell Fergus M FM Mastitskaya Svetlana S Hammond-Haley Matthew M Freitas Felipe F Wah Wen Rui WR Attwell David D

eLife 20171109

After cardiac ischaemia, a prolonged decrease of coronary microvascular perfusion often occurs even after flow is restored in an upstream artery. This 'no-reflow' phenomenon worsens patient prognosis. In the brain, after stroke, a similar post-ischaemic 'no-reflow' has been attributed to capillary constriction by contractile pericytes. We now show that occlusion of a rat coronary artery, followed by reperfusion, blocks 40% of cardiac capillaries and halves perfused blood volume within the affect ...[more]

PMID: 29120327

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Project description:BackgroundMyocardial ischaemia with non-obstructive coronary arteries (INOCA) represents a challenging and frequent, but largely underdiagnosed, condition.AimsWe aimed to investigate the feasibility and diagnostic value of angiography-derived coronary microcirculatory resistance in patients with INOCA syndrome.MethodsThis is an investigator-driven, prospective and blinded study. The diagnostic yield of angiography-derived index of coronary microcirculatory resistance (angio-IMR) was investigated against thermodilution-derived IMR (thermo-IMR) in patients with clinically indicated coronary angiography due to suspected myocardial ischaemia and angiographically normal or non-obstructive coronary arteries. The angio-IMR was derived from resting angiograms (contrast-flow angio-IMR [cAngio-IMR]) by an expert analyst blinded to the thermo-IMR. An independent, blinded, physiology core laboratory analysed the raw intracoronary physiology data and provided the final thermo-IMR values.ResultsA total of 104 patients (108 coronary vessels) were analysed after fulfilling predefined inclusion criteria. Most patients were female (67%). Obstructive epicardial disease was angiographically (percent diameter stenosis <50%) and physiologically (fractional flow reserve>0.80) ruled out in all cases. Median thermo-IMR and cAngio-IMR were 16.6 (12.7, 23.0) and 16.8 (12.8, 23.1) units, respectively (median difference -0.31, 95% confidence interval: -1.53 to 1.00; p=0.654). cAngio-IMR showed good correlation (Pearson coefficient 0.76; p<0.001), agreement (mean bias 0.4), discriminatory power (area under the curve from the receiver operator characteristics 0.865; p<0.001) and accuracy (85%), compared to thermo-IMR (≥25 U).ConclusionsEvaluating coronary microcirculatory resistance in patients with INOCA syndrome using cAngio-IMR is feasible and accurate. By circumventing the need of coronary instrumentation and hyperaemic drugs, this method may facilitate the assessment of coronary microcirculatory resistance in patients with suspected INOCA.Clinicaltrialsgov: NCT04827498.

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Capillary pericytes mediate coronary no-reflow after myocardial ischaemia.

Publications

Capillary pericytes mediate coronary no-reflow after myocardial ischaemia.

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