TY - JOUR
T1 - Ultrastructural Characteristics of Myocardial Reperfusion Injury and Effect of Selective Intracoronary Hypothermia
T2 - An Observational Study in Isolated Beating Porcine Hearts
AU - el Farissi, Mohamed
AU - Buscone, Serena
AU - Bax, Noortje A. M.
AU - van Rijswijk, Jan Willem
AU - Veenendaal, Tineke
AU - Keulards, Danielle C. J.
AU - Zelis, Jo M.
AU - van Tuijl, Sjoerd
AU - Eerdekens, Rob
AU - Demandt, Jesse
AU - Vervaat, Fabienne
AU - Zimmermann, Frederik M.
AU - Bouwmeester, Sjoerd
AU - Rave, Yahav
AU - Zhu, Kwankwan S.
AU - Conrad, Cecile
AU - van 't Veer, Marcel
AU - Pijls, Nico H. J.
AU - Klumperman, Judith
AU - Bouten, Carlijn V. C.
AU - Otterspoor, Luuk C.
N1 - Funding Information: The electron microscopy infrastructure used for this work is partially financed by the research program National Roadmap for Large-Scale Research Infrastructure (NEMI; project number 184.034.014 to J.K.), which is financed by the Dutch Research Council (NWO). Funding Information: The Eindhoven Center for Multiscale Electron Microscopy (CMEM of Eindhoven University of Technology) is acknowledged for their support in tissue preservation for electron microscopy analysis Publisher Copyright: © Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - In acute myocardial infarction (AMI), myocardial reperfusion injury may undo part of the recovery after revascularization of the occluded coronary artery. Selective intracoronary hypothermia is a novel method aimed at reducing myocardial reperfusion injury, but its presumed protective effects in AMI still await further elucidation. This proof-of-concept study assesses the potential protective effects of selective intracoronary hypothermia in an ex-vivo, isolated beating heart model of AMI. In four isolated Langendorff perfused beating pig hearts, an anterior wall myocardial infarction was created by inflating a balloon in the mid segment of the left anterior descending (LAD) artery. After one hour, two hearts were treated with selective intracoronary hypothermia followed by normal reperfusion (cooled hearts). In the other two hearts, the balloon was deflated after one hour, allowing normal reperfusion (control hearts). Biopsies for histologic and electron microscopic evaluation were taken from the myocardium at risk at different time points: before occlusion (t = BO); 5 minutes before reperfusion (t = BR); and 10 minutes after reperfusion (t = AR). Electron microscopic analysis was performed to evaluate the condition of the mitochondria. Histological analyses included evaluation of sarcomeric collapse and intramyocardial hematoma. Electron microscopic analysis revealed intact mitochondria in the hypothermia treated hearts compared to the control hearts where mitochondria were more frequently damaged. No differences in the prespecified histological parameters were observed between cooled and control hearts at t = AR. In the isolated beating porcine heart model of AMI, reperfusion was associated with additional myocardial injury beyond ischemic injury. Selective intracoronary hypothermia preserved mitochondrial integrity compared to nontreated controls.
AB - In acute myocardial infarction (AMI), myocardial reperfusion injury may undo part of the recovery after revascularization of the occluded coronary artery. Selective intracoronary hypothermia is a novel method aimed at reducing myocardial reperfusion injury, but its presumed protective effects in AMI still await further elucidation. This proof-of-concept study assesses the potential protective effects of selective intracoronary hypothermia in an ex-vivo, isolated beating heart model of AMI. In four isolated Langendorff perfused beating pig hearts, an anterior wall myocardial infarction was created by inflating a balloon in the mid segment of the left anterior descending (LAD) artery. After one hour, two hearts were treated with selective intracoronary hypothermia followed by normal reperfusion (cooled hearts). In the other two hearts, the balloon was deflated after one hour, allowing normal reperfusion (control hearts). Biopsies for histologic and electron microscopic evaluation were taken from the myocardium at risk at different time points: before occlusion (t = BO); 5 minutes before reperfusion (t = BR); and 10 minutes after reperfusion (t = AR). Electron microscopic analysis was performed to evaluate the condition of the mitochondria. Histological analyses included evaluation of sarcomeric collapse and intramyocardial hematoma. Electron microscopic analysis revealed intact mitochondria in the hypothermia treated hearts compared to the control hearts where mitochondria were more frequently damaged. No differences in the prespecified histological parameters were observed between cooled and control hearts at t = AR. In the isolated beating porcine heart model of AMI, reperfusion was associated with additional myocardial injury beyond ischemic injury. Selective intracoronary hypothermia preserved mitochondrial integrity compared to nontreated controls.
KW - STEMI
KW - myocardial reperfusion injury
KW - selective intracoronary hypothermia
UR - http://www.scopus.com/inward/record.url?scp=85124967160&partnerID=8YFLogxK
U2 - https://doi.org/10.1089/ther.2021.0025
DO - https://doi.org/10.1089/ther.2021.0025
M3 - Article
C2 - 34847796
SN - 2153-7658
VL - 12
SP - 129
EP - 137
JO - Therapeutic hypothermia and temperature management
JF - Therapeutic hypothermia and temperature management
IS - 2
ER -