In vivo MRI and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning, postconditioning and remote conditioning in a closed-chest porcine model of reperfused acute myocardial infarction: Importance of microvasculature

Tamás Baranyai, Z. Giricz, Zoltán V. Varga, Gábor Koncsos, Dominika Lukovic, András Makkos, Márta Sárközy, Noémi Pávó, András Jakab, Csilla Czimbalmos, Hajnalka Vágó, Zoltán Ruzsa, Levente Tóth, Rita Garamvölgyi, B. Merkely, Rainer Schulz, Mariann Gyöngyösi, Péter Ferdinandy

Research output: Contribution to journalArticle

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Abstract

Background: Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI, may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI. Methods and results: Acute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 × 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 × 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 × 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO. Conclusion: We conclude that IPostC and RIC interventions may protect the coronary microvasculature even without reducing myocardial necrosis.

Original languageEnglish
Article number67
JournalJournal of Translational Medicine
Volume15
Issue number1
DOIs
Publication statusPublished - Apr 1 2017

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Ischemic Postconditioning
Ischemic Preconditioning
Magnetic resonance
Microvessels
Reperfusion
Swine
Thorax
Myocardial Infarction
Magnetic Resonance Imaging
Imaging techniques
Edema
Necrosis
Ischemia
Evans Blue
Balloons
Gadolinium
Clinical Trials
Staining and Labeling
Balloon Occlusion
Animals

Keywords

  • Area at risk
  • Ischemia/reperfusion injury
  • Ischemic postconditioning
  • Ischemic preconditioning
  • Myocardial edema
  • Remote conditioning

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

In vivo MRI and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning, postconditioning and remote conditioning in a closed-chest porcine model of reperfused acute myocardial infarction : Importance of microvasculature. / Baranyai, Tamás; Giricz, Z.; Varga, Zoltán V.; Koncsos, Gábor; Lukovic, Dominika; Makkos, András; Sárközy, Márta; Pávó, Noémi; Jakab, András; Czimbalmos, Csilla; Vágó, Hajnalka; Ruzsa, Zoltán; Tóth, Levente; Garamvölgyi, Rita; Merkely, B.; Schulz, Rainer; Gyöngyösi, Mariann; Ferdinandy, Péter.

In: Journal of Translational Medicine, Vol. 15, No. 1, 67, 01.04.2017.

Research output: Contribution to journalArticle

Baranyai, Tamás ; Giricz, Z. ; Varga, Zoltán V. ; Koncsos, Gábor ; Lukovic, Dominika ; Makkos, András ; Sárközy, Márta ; Pávó, Noémi ; Jakab, András ; Czimbalmos, Csilla ; Vágó, Hajnalka ; Ruzsa, Zoltán ; Tóth, Levente ; Garamvölgyi, Rita ; Merkely, B. ; Schulz, Rainer ; Gyöngyösi, Mariann ; Ferdinandy, Péter. / In vivo MRI and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning, postconditioning and remote conditioning in a closed-chest porcine model of reperfused acute myocardial infarction : Importance of microvasculature. In: Journal of Translational Medicine. 2017 ; Vol. 15, No. 1.
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T1 - In vivo MRI and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning, postconditioning and remote conditioning in a closed-chest porcine model of reperfused acute myocardial infarction

T2 - Importance of microvasculature

AU - Baranyai, Tamás

AU - Giricz, Z.

AU - Varga, Zoltán V.

AU - Koncsos, Gábor

AU - Lukovic, Dominika

AU - Makkos, András

AU - Sárközy, Márta

AU - Pávó, Noémi

AU - Jakab, András

AU - Czimbalmos, Csilla

AU - Vágó, Hajnalka

AU - Ruzsa, Zoltán

AU - Tóth, Levente

AU - Garamvölgyi, Rita

AU - Merkely, B.

AU - Schulz, Rainer

AU - Gyöngyösi, Mariann

AU - Ferdinandy, Péter

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Background: Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI, may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI. Methods and results: Acute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 × 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 × 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 × 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO. Conclusion: We conclude that IPostC and RIC interventions may protect the coronary microvasculature even without reducing myocardial necrosis.

AB - Background: Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI, may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI. Methods and results: Acute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 × 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 × 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 × 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO. Conclusion: We conclude that IPostC and RIC interventions may protect the coronary microvasculature even without reducing myocardial necrosis.

KW - Area at risk

KW - Ischemia/reperfusion injury

KW - Ischemic postconditioning

KW - Ischemic preconditioning

KW - Myocardial edema

KW - Remote conditioning

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