Elucidation of a tripartite mechanism underlying the improvement in cardiac tolerance to ischemia by coenzyme Q10 pretreatment

J. A. Crestanello, J. Kamelgard, D. M. Lingle, S. A. Mortensen, M. Rhode, Glenn Whitman, P. J. Del Nido, M. A. Rowland

Research output: Contribution to journalArticle

Abstract

Coenzyme Q10, which is involved in mitochondrial adenosine triphosphate production, is also a powerful antioxidant. We hypothesize that coenzyme Q10 pretreatment protects myocardium from ischemia reperfusion injury both by its ability to increase aerobic energy production and by protecting creatine kinase from oxidative inactivation during reperfusion. Isolated hearts (six per group) from rats pretreated with either coenzyme Q10, 20 mg/kg intramuscularly and 10 mg/kg intraperitoneally (treatment) or vehicle only (control) 24 and 2 hours before the experiment were subjected to 15 minutes of equilibration, 25 minutes of ischemia, and 40 minutes of reperfusion. Developed pressure, contractility, compliance, myocardial oxygen consumption, and myocardial aerobic efficiency were measured. Phosphorus 31 nuclear magnetic resonance (31P-NMR) spectroscopy was used to determine adenosine triphosphate and phosphocreatine concentrations as a percentage of a methylene diphosphonic acid standard. Hearts were assayed for myocardial coenzyme Q10 and myocardial creatine kinase activity at end equilibration and at reperfusion. Treated hearts showed higher myocardial coenzyme Q10 levels (133 ± 5 μg/gm ventricle versus 117 ± 4 μg/gm ventricle, p <0.05). Developed pressure at end reperfusion was 62% ± 2% of equilibration in treatment group versus 37% ± 2% in control group, p <0.005. Preischemic myocardial aerobic efficiency was preserved during reperfusion in treatment group (0.84 ± 0.08 mm Hg/(μl O2/min/gm ventricle) vs 1.00 ± 0.08 mm Hg/(μl O2/min/gm ventricle) at equilibration, p = not significant), whereas in the control group it fell to 0.62 ± 0.07 mm Hg/(μl O2/min/gm ventricle, p <0.05 vs equilibration and vs the treatment group at reperfusion. Treated hearts showed higher adenosine triphosphate and phosphocreatine levels during both equilibration (adenosine triphosphate 49% ± 2% for the treatment group vs 33% ± 3% in the control group, p <0.005; phosphocreatine 49% ± 3% in the treatment group vs 35% ± 3% in the control group, p <0.005) and reperfusion (adenosine triphosphate 18% ± 3% in the treatment group vs 11% ± 2% in the control group, CTRL p <0.05; phosphocreatine 45% ± 2% in the treatment group vs 23% ± 3% in the control group, p <0.005). Creatine kinase activity in treated hearts at end reperfusion was 74% ± 3% of equilibration activity vs 65% ± 2% in the control group, p <0.05). Coenzyme Q10 pretreatment improves myocardial function after ischemia and reperfusion. This results from a tripartite effect: (1) higher concentration of adenosine triphosphate and phosphocreatine, initially and during reperfusion, (2) improved myocardial aerobic efficiency during reperfusion, and (3) protection of creatine kinase from oxidative inactivation during reperfusion.

Original languageEnglish (US)
Pages (from-to)443-450
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume111
Issue number2
DOIs
StatePublished - 1996
Externally publishedYes

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coenzyme Q10
Reperfusion
Ischemia
Phosphocreatine
Adenosine Triphosphate
Control Groups
Creatine Kinase
Magnetic Resonance Spectroscopy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Elucidation of a tripartite mechanism underlying the improvement in cardiac tolerance to ischemia by coenzyme Q10 pretreatment. / Crestanello, J. A.; Kamelgard, J.; Lingle, D. M.; Mortensen, S. A.; Rhode, M.; Whitman, Glenn; Del Nido, P. J.; Rowland, M. A.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 111, No. 2, 1996, p. 443-450.

Research output: Contribution to journalArticle

Crestanello, J. A. ; Kamelgard, J. ; Lingle, D. M. ; Mortensen, S. A. ; Rhode, M. ; Whitman, Glenn ; Del Nido, P. J. ; Rowland, M. A. / Elucidation of a tripartite mechanism underlying the improvement in cardiac tolerance to ischemia by coenzyme Q10 pretreatment. In: Journal of Thoracic and Cardiovascular Surgery. 1996 ; Vol. 111, No. 2. pp. 443-450.
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abstract = "Coenzyme Q10, which is involved in mitochondrial adenosine triphosphate production, is also a powerful antioxidant. We hypothesize that coenzyme Q10 pretreatment protects myocardium from ischemia reperfusion injury both by its ability to increase aerobic energy production and by protecting creatine kinase from oxidative inactivation during reperfusion. Isolated hearts (six per group) from rats pretreated with either coenzyme Q10, 20 mg/kg intramuscularly and 10 mg/kg intraperitoneally (treatment) or vehicle only (control) 24 and 2 hours before the experiment were subjected to 15 minutes of equilibration, 25 minutes of ischemia, and 40 minutes of reperfusion. Developed pressure, contractility, compliance, myocardial oxygen consumption, and myocardial aerobic efficiency were measured. Phosphorus 31 nuclear magnetic resonance (31P-NMR) spectroscopy was used to determine adenosine triphosphate and phosphocreatine concentrations as a percentage of a methylene diphosphonic acid standard. Hearts were assayed for myocardial coenzyme Q10 and myocardial creatine kinase activity at end equilibration and at reperfusion. Treated hearts showed higher myocardial coenzyme Q10 levels (133 ± 5 μg/gm ventricle versus 117 ± 4 μg/gm ventricle, p <0.05). Developed pressure at end reperfusion was 62{\%} ± 2{\%} of equilibration in treatment group versus 37{\%} ± 2{\%} in control group, p <0.005. Preischemic myocardial aerobic efficiency was preserved during reperfusion in treatment group (0.84 ± 0.08 mm Hg/(μl O2/min/gm ventricle) vs 1.00 ± 0.08 mm Hg/(μl O2/min/gm ventricle) at equilibration, p = not significant), whereas in the control group it fell to 0.62 ± 0.07 mm Hg/(μl O2/min/gm ventricle, p <0.05 vs equilibration and vs the treatment group at reperfusion. Treated hearts showed higher adenosine triphosphate and phosphocreatine levels during both equilibration (adenosine triphosphate 49{\%} ± 2{\%} for the treatment group vs 33{\%} ± 3{\%} in the control group, p <0.005; phosphocreatine 49{\%} ± 3{\%} in the treatment group vs 35{\%} ± 3{\%} in the control group, p <0.005) and reperfusion (adenosine triphosphate 18{\%} ± 3{\%} in the treatment group vs 11{\%} ± 2{\%} in the control group, CTRL p <0.05; phosphocreatine 45{\%} ± 2{\%} in the treatment group vs 23{\%} ± 3{\%} in the control group, p <0.005). Creatine kinase activity in treated hearts at end reperfusion was 74{\%} ± 3{\%} of equilibration activity vs 65{\%} ± 2{\%} in the control group, p <0.05). Coenzyme Q10 pretreatment improves myocardial function after ischemia and reperfusion. This results from a tripartite effect: (1) higher concentration of adenosine triphosphate and phosphocreatine, initially and during reperfusion, (2) improved myocardial aerobic efficiency during reperfusion, and (3) protection of creatine kinase from oxidative inactivation during reperfusion.",
author = "Crestanello, {J. A.} and J. Kamelgard and Lingle, {D. M.} and Mortensen, {S. A.} and M. Rhode and Glenn Whitman and {Del Nido}, {P. J.} and Rowland, {M. A.}",
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T1 - Elucidation of a tripartite mechanism underlying the improvement in cardiac tolerance to ischemia by coenzyme Q10 pretreatment

AU - Crestanello, J. A.

AU - Kamelgard, J.

AU - Lingle, D. M.

AU - Mortensen, S. A.

AU - Rhode, M.

AU - Whitman, Glenn

AU - Del Nido, P. J.

AU - Rowland, M. A.

PY - 1996

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N2 - Coenzyme Q10, which is involved in mitochondrial adenosine triphosphate production, is also a powerful antioxidant. We hypothesize that coenzyme Q10 pretreatment protects myocardium from ischemia reperfusion injury both by its ability to increase aerobic energy production and by protecting creatine kinase from oxidative inactivation during reperfusion. Isolated hearts (six per group) from rats pretreated with either coenzyme Q10, 20 mg/kg intramuscularly and 10 mg/kg intraperitoneally (treatment) or vehicle only (control) 24 and 2 hours before the experiment were subjected to 15 minutes of equilibration, 25 minutes of ischemia, and 40 minutes of reperfusion. Developed pressure, contractility, compliance, myocardial oxygen consumption, and myocardial aerobic efficiency were measured. Phosphorus 31 nuclear magnetic resonance (31P-NMR) spectroscopy was used to determine adenosine triphosphate and phosphocreatine concentrations as a percentage of a methylene diphosphonic acid standard. Hearts were assayed for myocardial coenzyme Q10 and myocardial creatine kinase activity at end equilibration and at reperfusion. Treated hearts showed higher myocardial coenzyme Q10 levels (133 ± 5 μg/gm ventricle versus 117 ± 4 μg/gm ventricle, p <0.05). Developed pressure at end reperfusion was 62% ± 2% of equilibration in treatment group versus 37% ± 2% in control group, p <0.005. Preischemic myocardial aerobic efficiency was preserved during reperfusion in treatment group (0.84 ± 0.08 mm Hg/(μl O2/min/gm ventricle) vs 1.00 ± 0.08 mm Hg/(μl O2/min/gm ventricle) at equilibration, p = not significant), whereas in the control group it fell to 0.62 ± 0.07 mm Hg/(μl O2/min/gm ventricle, p <0.05 vs equilibration and vs the treatment group at reperfusion. Treated hearts showed higher adenosine triphosphate and phosphocreatine levels during both equilibration (adenosine triphosphate 49% ± 2% for the treatment group vs 33% ± 3% in the control group, p <0.005; phosphocreatine 49% ± 3% in the treatment group vs 35% ± 3% in the control group, p <0.005) and reperfusion (adenosine triphosphate 18% ± 3% in the treatment group vs 11% ± 2% in the control group, CTRL p <0.05; phosphocreatine 45% ± 2% in the treatment group vs 23% ± 3% in the control group, p <0.005). Creatine kinase activity in treated hearts at end reperfusion was 74% ± 3% of equilibration activity vs 65% ± 2% in the control group, p <0.05). Coenzyme Q10 pretreatment improves myocardial function after ischemia and reperfusion. This results from a tripartite effect: (1) higher concentration of adenosine triphosphate and phosphocreatine, initially and during reperfusion, (2) improved myocardial aerobic efficiency during reperfusion, and (3) protection of creatine kinase from oxidative inactivation during reperfusion.

AB - Coenzyme Q10, which is involved in mitochondrial adenosine triphosphate production, is also a powerful antioxidant. We hypothesize that coenzyme Q10 pretreatment protects myocardium from ischemia reperfusion injury both by its ability to increase aerobic energy production and by protecting creatine kinase from oxidative inactivation during reperfusion. Isolated hearts (six per group) from rats pretreated with either coenzyme Q10, 20 mg/kg intramuscularly and 10 mg/kg intraperitoneally (treatment) or vehicle only (control) 24 and 2 hours before the experiment were subjected to 15 minutes of equilibration, 25 minutes of ischemia, and 40 minutes of reperfusion. Developed pressure, contractility, compliance, myocardial oxygen consumption, and myocardial aerobic efficiency were measured. Phosphorus 31 nuclear magnetic resonance (31P-NMR) spectroscopy was used to determine adenosine triphosphate and phosphocreatine concentrations as a percentage of a methylene diphosphonic acid standard. Hearts were assayed for myocardial coenzyme Q10 and myocardial creatine kinase activity at end equilibration and at reperfusion. Treated hearts showed higher myocardial coenzyme Q10 levels (133 ± 5 μg/gm ventricle versus 117 ± 4 μg/gm ventricle, p <0.05). Developed pressure at end reperfusion was 62% ± 2% of equilibration in treatment group versus 37% ± 2% in control group, p <0.005. Preischemic myocardial aerobic efficiency was preserved during reperfusion in treatment group (0.84 ± 0.08 mm Hg/(μl O2/min/gm ventricle) vs 1.00 ± 0.08 mm Hg/(μl O2/min/gm ventricle) at equilibration, p = not significant), whereas in the control group it fell to 0.62 ± 0.07 mm Hg/(μl O2/min/gm ventricle, p <0.05 vs equilibration and vs the treatment group at reperfusion. Treated hearts showed higher adenosine triphosphate and phosphocreatine levels during both equilibration (adenosine triphosphate 49% ± 2% for the treatment group vs 33% ± 3% in the control group, p <0.005; phosphocreatine 49% ± 3% in the treatment group vs 35% ± 3% in the control group, p <0.005) and reperfusion (adenosine triphosphate 18% ± 3% in the treatment group vs 11% ± 2% in the control group, CTRL p <0.05; phosphocreatine 45% ± 2% in the treatment group vs 23% ± 3% in the control group, p <0.005). Creatine kinase activity in treated hearts at end reperfusion was 74% ± 3% of equilibration activity vs 65% ± 2% in the control group, p <0.05). Coenzyme Q10 pretreatment improves myocardial function after ischemia and reperfusion. This results from a tripartite effect: (1) higher concentration of adenosine triphosphate and phosphocreatine, initially and during reperfusion, (2) improved myocardial aerobic efficiency during reperfusion, and (3) protection of creatine kinase from oxidative inactivation during reperfusion.

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