Ultrastructural Characteristics of Myocardial Reperfusion Injury and Effect of Selective Intracoronary Hypothermia: An Observational Study in Isolated Beating Porcine Hearts

Mohamed El Farissi, Serena Buscone, Noortje A.M. Bax, Jan Willem van Rijswijk, Tineke Veenendaal, Danielle C.J. Keulards, Jo M. Zelis, Sjoerd van Tuijl, Rob Eerdekens, Jesse Demandt, Fabienne Vervaat, Frederik M. Zimmermann, Sjoerd Bouwmeester, Yahav Rave, Kwankwan S. Zhu, Cecile Conrad, Marcel van 't Veer, Nico H.J. Pijls, Judith Klumperman, Carlijn V.C. BoutenLuuk C. Otterspoor (Corresponding author)

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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.

Original languageEnglish
Pages (from-to)129-137
Number of pages9
JournalTherapeutic Hypothermia and Temperature Management
Issue number2
Early online date29 Nov 2021
Publication statusPublished - 7 Jun 2022


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). 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

FundersFunder number
Eindhoven University of Technology
Nederlandse Organisatie voor Wetenschappelijk Onderzoek


    • STEMI
    • myocardial reperfusion injury
    • selective intracoronary hypothermia


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