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. Bouten; Luuk C. Otterspoor

doi:10.1089/ther.2021.0025

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.

Originele taal-2	Engels
Pagina's (van-tot)	129-137
Aantal pagina's	9
Tijdschrift	Therapeutic Hypothermia and Temperature Management
Volume	12
Nummer van het tijdschrift	2
Vroegere onlinedatum	29 nov. 2021
DOI's	https://doi.org/10.1089/ther.2021.0025
Status	Gepubliceerd - 7 jun. 2022

Financiering

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

Financiers	Financiernummer
Technische Universiteit Eindhoven
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

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El Farissi, M., Buscone, S., Bax, N. A. M., van Rijswijk, J. W., Veenendaal, T., Keulards, D. C. J., Zelis, J. M., van Tuijl, S., Eerdekens, R., Demandt, J., Vervaat, F., Zimmermann, F. M., Bouwmeester, S., Rave, Y., Zhu, K. S., Conrad, C., van 't Veer, M., Pijls, N. H. J., Klumperman, J., ... Otterspoor, L. C. (2022). Ultrastructural Characteristics of Myocardial Reperfusion Injury and Effect of Selective Intracoronary Hypothermia: An Observational Study in Isolated Beating Porcine Hearts. Therapeutic Hypothermia and Temperature Management, 12(2), 129-137. https://doi.org/10.1089/ther.2021.0025

@article{eec66690fc304582b502db62b1307f06,

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

abstract = "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.",

keywords = "STEMI, myocardial reperfusion injury, selective intracoronary hypothermia",

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

year = "2022",

month = jun,

day = "7",

doi = "10.1089/ther.2021.0025",

language = "English",

volume = "12",

pages = "129--137",

journal = "Therapeutic Hypothermia and Temperature Management",

issn = "2153-7658",

publisher = "Mary Ann Liebert Inc.",

number = "2",

}

El Farissi, M, Buscone, S, Bax, NAM, van Rijswijk, JW, Veenendaal, T, Keulards, DCJ, Zelis, JM, van Tuijl, S , Eerdekens, R , Demandt, J , Vervaat, F , Zimmermann, FM, Bouwmeester, S, Rave, Y, Zhu, KS, Conrad, C, van 't Veer, M, Pijls, NHJ, Klumperman, J, Bouten, CVC & Otterspoor, LC 2022, 'Ultrastructural Characteristics of Myocardial Reperfusion Injury and Effect of Selective Intracoronary Hypothermia: An Observational Study in Isolated Beating Porcine Hearts', Therapeutic Hypothermia and Temperature Management, vol. 12, nr. 2, blz. 129-137. https://doi.org/10.1089/ther.2021.0025

Ultrastructural Characteristics of Myocardial Reperfusion Injury and Effect of Selective Intracoronary Hypothermia: An Observational Study in Isolated Beating Porcine Hearts. / El Farissi, Mohamed; Buscone, Serena; Bax, Noortje A.M. et al.
In: Therapeutic Hypothermia and Temperature Management, Vol. 12, Nr. 2, 07.06.2022, blz. 129-137.

Onderzoeksoutput: Bijdrage aan tijdschrift › Tijdschriftartikel › Academic › peer review

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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.

PY - 2022/6/7

Y1 - 2022/6/7

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

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U2 - 10.1089/ther.2021.0025

DO - 10.1089/ther.2021.0025

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SN - 2153-7658

VL - 12

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JO - Therapeutic Hypothermia and Temperature Management

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El Farissi M, Buscone S, Bax NAM, van Rijswijk JW, Veenendaal T, Keulards DCJ et al. Ultrastructural Characteristics of Myocardial Reperfusion Injury and Effect of Selective Intracoronary Hypothermia: An Observational Study in Isolated Beating Porcine Hearts. Therapeutic Hypothermia and Temperature Management. 2022 jun. 7;12(2):129-137. Epub 2021 nov. 29. doi: 10.1089/ther.2021.0025

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

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