Increased myocardial vulnerability to ischemia-reperfusion injury in the presence of left ventricular hypertrophy

Søren Mølgaard; Barbara Faricelli; Max Salomonsson; Thomas Engstrøm; Marek Treiman

doi:10.1097/HJH.0000000000000826

Increased myocardial vulnerability to ischemia-reperfusion injury in the presence of left ventricular hypertrophy

Søren Mølgaard, Barbara Faricelli, Max Salomonsson, Thomas Engstrøm, Marek Treiman^*

^*Corresponding author af dette arbejde

10 Citationer (Scopus)

Abstract

Objective: Despite its high prevalence among patients suffering myocardial infarction, the significance of left ventricle hypertrophy for infarct size is not known. We asked whether infarct size might be increased by this condition, and whether any such increase might be associated with an increased mitochondrial damage following coronary occlusion.

Methods: Occlusion of the left descending artery in isolated, perfused hearts of SHR-SP (spontaneously hypertensive rat stroke-prone) (left ventricular hypertrophy) or Wistar-Kyoto (WKY) (control) rats was used, followed by reperfusion with or without exendin-4 (Exe-4), a glucagon-like peptide-1 receptor agonist. Infarct size relative to area-at-risk was determined. Separately, mitochondria were isolated after global ischemia. Activities of complexes III and IV and amounts of selected complex subunits and cytochromes a, b, c, and c1 were determined.

Results: Infarct size (ischemia 35min and 120min reperfusion) was 65.8% (±3.3%) and 37.1% (±3.4%) in the SHR-SP and WKY hearts, respectively (P<0.05). Exe-4 significantly decreased infarct size and hypercontracture in WKY, but not in SHR-SP, hearts. After ischemia 15min in SHR-SP hearts, Exe-4 reduced the infarct (26.6%, ±3.8% to 9.3% ± 1.5%; P<0.05). Mitochondria from postischemic SHR-SP hearts showed a reduction of complex III (368.1 ± 37.5 to 175.8± 23.0nmoles/min×mg; P<0.05) and complex IV (14.4± 0.22 to 5.8± 0.81/s×mg; P<0.05) activities and decreased amounts of cytochromes a, b, and c.

Conclusion: Hearts from hypertensive (SHR-SP) rats with left ventricle hypertrophy appeared more vulnerable to ischemia-reperfusion injury, as supported by a more profound infarct development and an earlier loss of postconditioning by Exe-4. Mitochondrial complexes III and IV were identified among possible loci of this increased, hypertrophy-associated vulnerability.

Originalsprog	Engelsk
Tidsskrift	Journal of Hypertension
Vol/bind	34
Udgave nummer	3
Sider (fra-til)	513-523
Antal sider	11
ISSN	0263-6352
DOI	https://doi.org/10.1097/HJH.0000000000000826
Status	Udgivet - 2016

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10.1097/HJH.0000000000000826

Citationsformater

@article{2527a6364a5e45bfbf97fc3abe458eb2,

title = "Increased myocardial vulnerability to ischemia-reperfusion injury in the presence of left ventricular hypertrophy",

abstract = "Objective: Despite its high prevalence among patients suffering myocardial infarction, the significance of left ventricle hypertrophy for infarct size is not known. We asked whether infarct size might be increased by this condition, and whether any such increase might be associated with an increased mitochondrial damage following coronary occlusion. Methods: Occlusion of the left descending artery in isolated, perfused hearts of SHR-SP (spontaneously hypertensive rat stroke-prone) (left ventricular hypertrophy) or Wistar-Kyoto (WKY) (control) rats was used, followed by reperfusion with or without exendin-4 (Exe-4), a glucagon-like peptide-1 receptor agonist. Infarct size relative to area-at-risk was determined. Separately, mitochondria were isolated after global ischemia. Activities of complexes III and IV and amounts of selected complex subunits and cytochromes a, b, c, and c1 were determined. Results: Infarct size (ischemia 35min and 120min reperfusion) was 65.8% (±3.3%) and 37.1% (±3.4%) in the SHR-SP and WKY hearts, respectively (P<0.05). Exe-4 significantly decreased infarct size and hypercontracture in WKY, but not in SHR-SP, hearts. After ischemia 15min in SHR-SP hearts, Exe-4 reduced the infarct (26.6%, ±3.8% to 9.3% ± 1.5%; P<0.05). Mitochondria from postischemic SHR-SP hearts showed a reduction of complex III (368.1 ± 37.5 to 175.8± 23.0nmoles/min×mg; P<0.05) and complex IV (14.4± 0.22 to 5.8± 0.81/s×mg; P<0.05) activities and decreased amounts of cytochromes a, b, and c. Conclusion: Hearts from hypertensive (SHR-SP) rats with left ventricle hypertrophy appeared more vulnerable to ischemia-reperfusion injury, as supported by a more profound infarct development and an earlier loss of postconditioning by Exe-4. Mitochondrial complexes III and IV were identified among possible loci of this increased, hypertrophy-associated vulnerability.",

keywords = "exendin-4, left ventricular hypertrophy, mitochondria, myocardial infarction, postconditioning, reperfusion injury",

author = "S{\o}ren M{\o}lgaard and Barbara Faricelli and Max Salomonsson and Thomas Engstr{\o}m and Marek Treiman",

year = "2016",

doi = "10.1097/HJH.0000000000000826",

language = "English",

volume = "34",

pages = "513--523",

journal = "Journal of Hypertension",

issn = "0263-6352",

publisher = "Lippincott Williams & Wilkins, Ltd.",

number = "3",

}

TY - JOUR

T1 - Increased myocardial vulnerability to ischemia-reperfusion injury in the presence of left ventricular hypertrophy

AU - Mølgaard, Søren

AU - Faricelli, Barbara

AU - Salomonsson, Max

AU - Engstrøm, Thomas

AU - Treiman, Marek

PY - 2016

Y1 - 2016

N2 - Objective: Despite its high prevalence among patients suffering myocardial infarction, the significance of left ventricle hypertrophy for infarct size is not known. We asked whether infarct size might be increased by this condition, and whether any such increase might be associated with an increased mitochondrial damage following coronary occlusion. Methods: Occlusion of the left descending artery in isolated, perfused hearts of SHR-SP (spontaneously hypertensive rat stroke-prone) (left ventricular hypertrophy) or Wistar-Kyoto (WKY) (control) rats was used, followed by reperfusion with or without exendin-4 (Exe-4), a glucagon-like peptide-1 receptor agonist. Infarct size relative to area-at-risk was determined. Separately, mitochondria were isolated after global ischemia. Activities of complexes III and IV and amounts of selected complex subunits and cytochromes a, b, c, and c1 were determined. Results: Infarct size (ischemia 35min and 120min reperfusion) was 65.8% (±3.3%) and 37.1% (±3.4%) in the SHR-SP and WKY hearts, respectively (P<0.05). Exe-4 significantly decreased infarct size and hypercontracture in WKY, but not in SHR-SP, hearts. After ischemia 15min in SHR-SP hearts, Exe-4 reduced the infarct (26.6%, ±3.8% to 9.3% ± 1.5%; P<0.05). Mitochondria from postischemic SHR-SP hearts showed a reduction of complex III (368.1 ± 37.5 to 175.8± 23.0nmoles/min×mg; P<0.05) and complex IV (14.4± 0.22 to 5.8± 0.81/s×mg; P<0.05) activities and decreased amounts of cytochromes a, b, and c. Conclusion: Hearts from hypertensive (SHR-SP) rats with left ventricle hypertrophy appeared more vulnerable to ischemia-reperfusion injury, as supported by a more profound infarct development and an earlier loss of postconditioning by Exe-4. Mitochondrial complexes III and IV were identified among possible loci of this increased, hypertrophy-associated vulnerability.

AB - Objective: Despite its high prevalence among patients suffering myocardial infarction, the significance of left ventricle hypertrophy for infarct size is not known. We asked whether infarct size might be increased by this condition, and whether any such increase might be associated with an increased mitochondrial damage following coronary occlusion. Methods: Occlusion of the left descending artery in isolated, perfused hearts of SHR-SP (spontaneously hypertensive rat stroke-prone) (left ventricular hypertrophy) or Wistar-Kyoto (WKY) (control) rats was used, followed by reperfusion with or without exendin-4 (Exe-4), a glucagon-like peptide-1 receptor agonist. Infarct size relative to area-at-risk was determined. Separately, mitochondria were isolated after global ischemia. Activities of complexes III and IV and amounts of selected complex subunits and cytochromes a, b, c, and c1 were determined. Results: Infarct size (ischemia 35min and 120min reperfusion) was 65.8% (±3.3%) and 37.1% (±3.4%) in the SHR-SP and WKY hearts, respectively (P<0.05). Exe-4 significantly decreased infarct size and hypercontracture in WKY, but not in SHR-SP, hearts. After ischemia 15min in SHR-SP hearts, Exe-4 reduced the infarct (26.6%, ±3.8% to 9.3% ± 1.5%; P<0.05). Mitochondria from postischemic SHR-SP hearts showed a reduction of complex III (368.1 ± 37.5 to 175.8± 23.0nmoles/min×mg; P<0.05) and complex IV (14.4± 0.22 to 5.8± 0.81/s×mg; P<0.05) activities and decreased amounts of cytochromes a, b, and c. Conclusion: Hearts from hypertensive (SHR-SP) rats with left ventricle hypertrophy appeared more vulnerable to ischemia-reperfusion injury, as supported by a more profound infarct development and an earlier loss of postconditioning by Exe-4. Mitochondrial complexes III and IV were identified among possible loci of this increased, hypertrophy-associated vulnerability.

KW - exendin-4

KW - left ventricular hypertrophy

KW - mitochondria

KW - myocardial infarction

KW - postconditioning

KW - reperfusion injury

U2 - 10.1097/HJH.0000000000000826

DO - 10.1097/HJH.0000000000000826

M3 - Journal article

C2 - 26820478

AN - SCOPUS:84957570903

SN - 0263-6352

VL - 34

SP - 513

EP - 523

JO - Journal of Hypertension

JF - Journal of Hypertension

IS - 3

ER -

Increased myocardial vulnerability to ischemia-reperfusion injury in the presence of left ventricular hypertrophy

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