Dissecting the Effects of Ischemia and Reperfusion on the Coronary Microcirculation in a Rat Model of Acute Myocardial Infarction

• Published in: PloS one Vol. 11; no. 7; p. e0157233
• Main Authors: Hollander, Maurits R, de Waard, Guus A, Konijnenberg, Lara S F, Meijer-van Putten, Rosalie M E, van den Brom, Charissa E, Paauw, Nanne, de Vries, Helga E, van de Ven, Peter M, Aman, Jurjan, Van Nieuw-Amerongen, Geerten P, Hordijk, Peter L, Niessen, Hans W M, Horrevoets, Anton J G, Van Royen, Niels
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.07.2016; Public Library of Science (PLoS)
• Subjects: Animals; Apoptosis; Biology; Biology and Life Sciences; Blood clots; Capillaries; Cardiology; Cardiovascular disease; Cell Communication; Cell Nucleus - metabolism; Chromatin; Chromatin - chemistry; Complications and side effects; Coronary Circulation; Density; Diagnosis; Disease Models, Animal; Electron microscopy; Etiology; Extravasation; Fluorescence; Heart - physiopathology; Heart attack; Heart attacks; Immunology; Infarction; Ischemia; Ischemia - physiopathology; Male; Medicine and Health Sciences; Membrane permeability; Microcirculation; Microspheres; Microvasculature; Morbidity; Myocardial infarction; Myocardial Infarction - physiopathology; Myocardial Reperfusion; Myocardial Reperfusion Injury - physiopathology; NMR; Nuclear magnetic resonance; Nuclei; Perfusion; Permeability; Physical Sciences; Physiology; Rats; Rats, Wistar; Reperfusion; Reperfusion injury; Research and Analysis Methods; Risk factors; Rodents; Ultrastructure; Wall thickness; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0157233

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. 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. 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.