Free-radical-mediated damage during myocardial ischemia and reperfusion and protection by carnitine esters

R. Subramanian, S. Plehn, J. Noonan, M. Schmidt, A. L. Shug

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Ischemic injury may be exacerbated by readmission of oxygen into the myocardium, probably due to the formation of free radicals and their interaction with membrane lipids. We tested the hypothesis that ischemic myocardial damage is potentiated during reperfusion with excess free fatty acids in the globally ischemic rat heart, and in parallel studies, we investigated the protective effects of carnitine derivatives. Intermittent ischemia, i.e. three 20 min periods of ischemia followed by 10 min reperfusion each, was induced in isolated working rat hearts perfused with either glucose (11 mM) alone or glucose with palmitate (11 mM and 1.2 mM). The ischemic coronary flow was reduced to 1.1 ml/min in a low-flow group are equalled 0 ml/min in a no-flow group. Loss of functional recovery in the low-flow and no-flow group was more pronounced when palmitate was present in the perfusate. This was associated with increased levels of long-chain acyl-CoA esters in the palmitate perfused hearts. Malondialdehyde, an indicator of free radical formation, was elevated in both low-flow and no-flow groups when either substrate was used. We therefore suggest that free radical formation contributes to myocardial injury in intermittent ischemia. The mechanism of free radical formation and their sites of action have not yet been completely elucidated - the peroxidation of membrane lipids is probably involved, particularly in the presence of high palmitate. The protective effect of the carnitine derivatives D-propionylcarnitine, L-propionylcarnitine and propionylcarnitine taurine amide was studied in the no-flow hearts. No protective effect was found with D-propionylcarnitine whereas L-Propionylcarnitine-treated hearts showed a significantly improved recovery when compared to controls. The most complete recovery was found with propionylcarnitine taurine amide. In agreement with other investigators, we suggest that the protective action of propionylcarnitine and propionylcarnitine taurine amide includes decreased myocardial extraction of free fatty acids, improved translocation of long-chain acyl-CoA esters across membranes and/or repletion of cellular carnitine stores as well as, possibly, reduced free radical formation.

Original languageEnglish (US)
Pages (from-to)41-45
Number of pages5
JournalZeitschrift fur Kardiologie
Volume76
Issue numberSUPPL. 5
StatePublished - Dec 1 1987

Fingerprint

propionylcarnitine
Myocardial Reperfusion
Carnitine
Palmitates
Free Radicals
Myocardial Ischemia
Esters
Acyl Coenzyme A
Ischemia
Membrane Lipids
Nonesterified Fatty Acids
Reperfusion
Glucose
Wounds and Injuries
Malondialdehyde
Myocardium
Research Personnel
Oxygen

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Subramanian, R., Plehn, S., Noonan, J., Schmidt, M., & Shug, A. L. (1987). Free-radical-mediated damage during myocardial ischemia and reperfusion and protection by carnitine esters. Zeitschrift fur Kardiologie, 76(SUPPL. 5), 41-45.

Free-radical-mediated damage during myocardial ischemia and reperfusion and protection by carnitine esters. / Subramanian, R.; Plehn, S.; Noonan, J.; Schmidt, M.; Shug, A. L.

In: Zeitschrift fur Kardiologie, Vol. 76, No. SUPPL. 5, 01.12.1987, p. 41-45.

Research output: Contribution to journalArticle

Subramanian, R, Plehn, S, Noonan, J, Schmidt, M & Shug, AL 1987, 'Free-radical-mediated damage during myocardial ischemia and reperfusion and protection by carnitine esters', Zeitschrift fur Kardiologie, vol. 76, no. SUPPL. 5, pp. 41-45.
Subramanian, R. ; Plehn, S. ; Noonan, J. ; Schmidt, M. ; Shug, A. L. / Free-radical-mediated damage during myocardial ischemia and reperfusion and protection by carnitine esters. In: Zeitschrift fur Kardiologie. 1987 ; Vol. 76, No. SUPPL. 5. pp. 41-45.
@article{58c0b03d3f96471590c05a7d4eeada55,
title = "Free-radical-mediated damage during myocardial ischemia and reperfusion and protection by carnitine esters",
abstract = "Ischemic injury may be exacerbated by readmission of oxygen into the myocardium, probably due to the formation of free radicals and their interaction with membrane lipids. We tested the hypothesis that ischemic myocardial damage is potentiated during reperfusion with excess free fatty acids in the globally ischemic rat heart, and in parallel studies, we investigated the protective effects of carnitine derivatives. Intermittent ischemia, i.e. three 20 min periods of ischemia followed by 10 min reperfusion each, was induced in isolated working rat hearts perfused with either glucose (11 mM) alone or glucose with palmitate (11 mM and 1.2 mM). The ischemic coronary flow was reduced to 1.1 ml/min in a low-flow group are equalled 0 ml/min in a no-flow group. Loss of functional recovery in the low-flow and no-flow group was more pronounced when palmitate was present in the perfusate. This was associated with increased levels of long-chain acyl-CoA esters in the palmitate perfused hearts. Malondialdehyde, an indicator of free radical formation, was elevated in both low-flow and no-flow groups when either substrate was used. We therefore suggest that free radical formation contributes to myocardial injury in intermittent ischemia. The mechanism of free radical formation and their sites of action have not yet been completely elucidated - the peroxidation of membrane lipids is probably involved, particularly in the presence of high palmitate. The protective effect of the carnitine derivatives D-propionylcarnitine, L-propionylcarnitine and propionylcarnitine taurine amide was studied in the no-flow hearts. No protective effect was found with D-propionylcarnitine whereas L-Propionylcarnitine-treated hearts showed a significantly improved recovery when compared to controls. The most complete recovery was found with propionylcarnitine taurine amide. In agreement with other investigators, we suggest that the protective action of propionylcarnitine and propionylcarnitine taurine amide includes decreased myocardial extraction of free fatty acids, improved translocation of long-chain acyl-CoA esters across membranes and/or repletion of cellular carnitine stores as well as, possibly, reduced free radical formation.",
author = "R. Subramanian and S. Plehn and J. Noonan and M. Schmidt and Shug, {A. L.}",
year = "1987",
month = "12",
day = "1",
language = "English (US)",
volume = "76",
pages = "41--45",
journal = "Clinical Research in Cardiology",
issn = "1861-0684",
publisher = "D. Steinkopff-Verlag",
number = "SUPPL. 5",

}

TY - JOUR

T1 - Free-radical-mediated damage during myocardial ischemia and reperfusion and protection by carnitine esters

AU - Subramanian, R.

AU - Plehn, S.

AU - Noonan, J.

AU - Schmidt, M.

AU - Shug, A. L.

PY - 1987/12/1

Y1 - 1987/12/1

N2 - Ischemic injury may be exacerbated by readmission of oxygen into the myocardium, probably due to the formation of free radicals and their interaction with membrane lipids. We tested the hypothesis that ischemic myocardial damage is potentiated during reperfusion with excess free fatty acids in the globally ischemic rat heart, and in parallel studies, we investigated the protective effects of carnitine derivatives. Intermittent ischemia, i.e. three 20 min periods of ischemia followed by 10 min reperfusion each, was induced in isolated working rat hearts perfused with either glucose (11 mM) alone or glucose with palmitate (11 mM and 1.2 mM). The ischemic coronary flow was reduced to 1.1 ml/min in a low-flow group are equalled 0 ml/min in a no-flow group. Loss of functional recovery in the low-flow and no-flow group was more pronounced when palmitate was present in the perfusate. This was associated with increased levels of long-chain acyl-CoA esters in the palmitate perfused hearts. Malondialdehyde, an indicator of free radical formation, was elevated in both low-flow and no-flow groups when either substrate was used. We therefore suggest that free radical formation contributes to myocardial injury in intermittent ischemia. The mechanism of free radical formation and their sites of action have not yet been completely elucidated - the peroxidation of membrane lipids is probably involved, particularly in the presence of high palmitate. The protective effect of the carnitine derivatives D-propionylcarnitine, L-propionylcarnitine and propionylcarnitine taurine amide was studied in the no-flow hearts. No protective effect was found with D-propionylcarnitine whereas L-Propionylcarnitine-treated hearts showed a significantly improved recovery when compared to controls. The most complete recovery was found with propionylcarnitine taurine amide. In agreement with other investigators, we suggest that the protective action of propionylcarnitine and propionylcarnitine taurine amide includes decreased myocardial extraction of free fatty acids, improved translocation of long-chain acyl-CoA esters across membranes and/or repletion of cellular carnitine stores as well as, possibly, reduced free radical formation.

AB - Ischemic injury may be exacerbated by readmission of oxygen into the myocardium, probably due to the formation of free radicals and their interaction with membrane lipids. We tested the hypothesis that ischemic myocardial damage is potentiated during reperfusion with excess free fatty acids in the globally ischemic rat heart, and in parallel studies, we investigated the protective effects of carnitine derivatives. Intermittent ischemia, i.e. three 20 min periods of ischemia followed by 10 min reperfusion each, was induced in isolated working rat hearts perfused with either glucose (11 mM) alone or glucose with palmitate (11 mM and 1.2 mM). The ischemic coronary flow was reduced to 1.1 ml/min in a low-flow group are equalled 0 ml/min in a no-flow group. Loss of functional recovery in the low-flow and no-flow group was more pronounced when palmitate was present in the perfusate. This was associated with increased levels of long-chain acyl-CoA esters in the palmitate perfused hearts. Malondialdehyde, an indicator of free radical formation, was elevated in both low-flow and no-flow groups when either substrate was used. We therefore suggest that free radical formation contributes to myocardial injury in intermittent ischemia. The mechanism of free radical formation and their sites of action have not yet been completely elucidated - the peroxidation of membrane lipids is probably involved, particularly in the presence of high palmitate. The protective effect of the carnitine derivatives D-propionylcarnitine, L-propionylcarnitine and propionylcarnitine taurine amide was studied in the no-flow hearts. No protective effect was found with D-propionylcarnitine whereas L-Propionylcarnitine-treated hearts showed a significantly improved recovery when compared to controls. The most complete recovery was found with propionylcarnitine taurine amide. In agreement with other investigators, we suggest that the protective action of propionylcarnitine and propionylcarnitine taurine amide includes decreased myocardial extraction of free fatty acids, improved translocation of long-chain acyl-CoA esters across membranes and/or repletion of cellular carnitine stores as well as, possibly, reduced free radical formation.

UR - http://www.scopus.com/inward/record.url?scp=0023502539&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023502539&partnerID=8YFLogxK

M3 - Article

VL - 76

SP - 41

EP - 45

JO - Clinical Research in Cardiology

JF - Clinical Research in Cardiology

SN - 1861-0684

IS - SUPPL. 5

ER -