title: Assessment of coronary microvascular resistance in the chronic infarcted pig heart.
abstract: Pre-clinical studies aimed at treating ischemic heart disease (i.e. stem cell- and growth factor therapy) often consider restoration of the impaired microvascular circulation as an important treatment goal. However, serial in vivo measurement hereof is often lacking. The purpose of this study was to evaluate the applicability of intracoronary pressure and flow velocity as a measure of microvascular resistance in a large animal model of chronic myocardial infarction (MI). Myocardial infarction was induced in Dalland Landrace pigs (n = 13; 68.9 ± 4.1 kg) by a 75-min. balloon occlusion of the left circumflex artery (LCX). Intracoronary pressure and flow velocity parameters were measured simultaneously at rest and during adenosine-induced hyperemia, using the Combowire (Volcano) before and 4 weeks after MI. Various pressure- and/or flow-derived indices were evaluated. Hyperemic microvascular resistance (HMR) was significantly increased by 28% in the infarct-related artery, based on a significantly decreased peak average peak flow velocity (pAPV) by 20% at 4 weeks post-MI (P = 0.03). Capillary density in the infarct zone was decreased compared to the remote area (658 ± 207/mm(2) versus 1650 ± 304/mm(2) , P = 0.017). In addition, arterioles in the infarct zone showed excessive thickening of the alpha smooth muscle actin (αSMA) positive cell layer compared to the remote area (33.55 ± 4.25 μm versus 14.64 ± 1.39 μm, P = 0.002). Intracoronary measurement of HMR successfully detected increased microvascular resistance that might be caused by the loss of capillaries and arteriolar remodelling in the chronic infarcted pig heart. Thus, HMR may serve as a novel outcome measure in pre-clinical studies for serial assessment of microvascular circulation.
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Koudstaal
authors.forename: Sanne J
authors.initials: SJ
authors.lastname: Jansen Of Lorkeers
authors.forename: Frebus J
authors.initials: FJ
authors.lastname: van Slochteren
authors.forename: Tycho I G
authors.initials: TI
authors.lastname: van der Spoel
authors.forename: Tim P
authors.initials: TP
authors.lastname: van de Hoef
authors.forename: Joost P
authors.initials: JP
authors.lastname: Sluijter
authors.forename: Maria
authors.initials: M
authors.lastname: Siebes
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
authors.forename: Steven A J
authors.initials: SA
authors.lastname: Chamuleau
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001160:Arterioles / Q000378:metabolism / Q000473:pathology; D001783:Blood Flow Velocity / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002908:Chronic Disease; D002921:Cicatrix / Q000473:pathology / Q000503:physiopathology; D003326:Coronary Circulation / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D008833:Microcirculation / Q000502:physiology*; D055806:Microvessels / Q000473:pathology / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D014655:Vascular Resistance / Q000502:physiology*
chemical_list: D000199:Actins
keywords: Angiogenesis; Capillary density; Chronic MI; Coronary microvascular resistance
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