title: Dissecting the Effects of Ischemia and Reperfusion on the Coronary Microcirculation in a Rat Model of Acute Myocardial Infarction.
abstract: BACKGROUND
  Microvascular injury (MVI) after coronary ischemia-reperfusion is associated with high morbidity and mortality. Both ischemia and reperfusion are involved in MVI, but to what degree these phases contribute is unknown. Understanding the etiology is essential for the development of new potential therapies.
  
  
  RESULTS
  Rats were divided into 3 groups receiving either 30 minutes ischemia, 90 minutes ischemia or 30 minutes ischemia followed by 60 minutes reperfusion. Subsequently hearts were ex-vivo perfused in a Langendorff-model. Fluorescence and electron microscopy was used for analysis of capillary density, vascular permeability and ultrastructure. Most MVI was observed after 30 minutes ischemia followed by 60 minutes reperfusion. In comparison to the 30' and 90' ischemia group, wall thickness decreased (207.0±74 vs 407.8±75 and 407.5±71, p = 0.02). Endothelial nuclei in the 30'-60' group showed irreversible damage and decreased chromatin density variation (50.5±9.4, 35.4±7.1 and 23.7±3.8, p = 0.03). Cell junction density was lowest in the 30'-60' group (0.15±0.02 vs 2.5±0.6 and 1.8±0.7, p<0.01). Microsphere extravasation was increased in both the 90' ischemia and 30'-60' group.
  
  
  CONCLUSIONS
  Ischemia alone for 90 minutes induces mild morphological changes to the coronary microcirculation, with increased vascular permeability. Ischemia for 30 minutes, followed by 60 minutes of reperfusion, induces massive MVI. This shows the direct consequences of reperfusion on the coronary microcirculation. These data imply that a therapeutic window exists to protect the microcirculation directly upon coronary revascularization.
authors.affiliation: Department of Cardiology, VU Medical Center, Amsterdam, The Netherlands.|Institute for Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Maurits R
authors.initials: MR
authors.lastname: Hollander
authors.affiliation: Department of Cardiology, VU Medical Center, Amsterdam, The Netherlands.|Institute for Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Guus A
authors.initials: GA
authors.lastname: de Waard
authors.affiliation: Department of Cardiology, VU Medical Center, Amsterdam, The Netherlands.|Institute for Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Lara S F
authors.initials: LS
authors.lastname: Konijnenberg
authors.affiliation: Department of Cardiology, VU Medical Center, Amsterdam, The Netherlands.|Institute for Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Rosalie M E
authors.initials: RM
authors.lastname: Meijer-van Putten
authors.affiliation: Institute for Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.|Department of Anesthesiology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Charissa E
authors.initials: CE
authors.lastname: van den Brom
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Nanne
authors.initials: N
authors.lastname: Paauw
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Helga E
authors.initials: HE
authors.lastname: de Vries
authors.affiliation: Department of Epidemiology and Biostatistics, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter M
authors.initials: PM
authors.lastname: van de Ven
authors.affiliation: Institute for Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.|Department of Physiology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Jurjan
authors.initials: J
authors.lastname: Aman
authors.affiliation: Institute for Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.|Department of Physiology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Geerten P
authors.initials: GP
authors.lastname: Van Nieuw-Amerongen
authors.affiliation: Institute for Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.|Department of Physiology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Hordijk
authors.affiliation: Institute for Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.|Department of Pathology and Cardiac Surgery, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.affiliation: Institute for Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.|Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Anton J G
authors.initials: AJ
authors.lastname: Horrevoets
authors.affiliation: Department of Cardiology, VU Medical Center, Amsterdam, The Netherlands.|Institute for Cardiovascular Research, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Niels
authors.initials: N
authors.lastname: Van Royen
mesh_terms: D000818:Animals; D002196:Capillaries; D002450:Cell Communication; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry; D003326:Coronary Circulation; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D008863:Microspheres; D009203:Myocardial Infarction / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D010477:Perfusion; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002843:Chromatin