Protective effects of an indenoindole antioxidant on coronary endothelial function after long-term storage

L. Wiklund, Virginia M Miller, C. G A McGregor, P. O. Sjoquist, H. Berggren, F. Nilsson

Research output: Contribution to journalArticle

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Abstract

Experiments were designed to evaluate function of the endothelium and smooth muscle of coronary arteries following storage of hearts in cardioplegia containing an inhibitor of lipid peroxidation (H 290/51, cis-7- metyl-9-methoxy-5,5a, 6,10b tetrahydroindeno [2,1-b] indole). Canine hearts were perfused with crystalloid cardioplegia (Plegisol, 15 ml/kg, 4°C) and left circumflex arteries were isolated and studied either immediately (group I, n=6), or after storage of the hearts at 4°C for 10 (group II, n=6) or 24 hr with (group III, n=6) or without (group IV, n=6) addition of H 290/51. The final concentration of H 290/51 was 1 μmol/L. Arteries were removed, cut into rings, and suspended in organ chambers for measurements of isometric force. In selected rings, the endothelium was removed in order to study the function of the smooth muscle. In order to discriminate effects of ischemia/reperfusion and protective properties on coronary endothelium or smooth muscle, drugs with different mechanisms were used. The function of the endothelium were studied with the α2-adrenergic agonist UK 14,304, bradykinin and A 23187. The smooth muscle function were studied with isoproterenol and nitric oxide. Endothelium-dependent relaxations to the α2-adrenergic agonist UK 14,304 and bradykinin, but not to A 23187, were reduced significantly in arteries from hearts stored for 24 hr in cardioplegic solution alone. Relaxations of arteries from hearts stored for 24 hr with H 290/51 were comparable to those arteries from hearts that were not stored. Endothelium-independent relaxations to isoproterenol and nitric oxide among the different groups were comparable. These results suggest that storage of canine hearts with crystalloid cardioplegia selectively inhibits endothelium-dependent relaxations mediated by receptor activation. Inhibition of lipid peroxidation with H 290/51 preserves these relaxations and may therefore represent a therapeutic alternative to preserve hearts used for transplantation.

Original languageEnglish (US)
Pages (from-to)774-778
Number of pages5
JournalTransplantation
Volume60
Issue number8
StatePublished - 1995

Fingerprint

Endothelium
Antioxidants
Arteries
Induced Heart Arrest
Smooth Muscle
Adrenergic Agonists
Calcimycin
Bradykinin
Isoproterenol
Canidae
Nitric Oxide
Cardioplegic Solutions
Heart Transplantation
indenoindole
Lipid Peroxidation
Reperfusion
Coronary Vessels
Ischemia
H290-51
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology
  • Transplantation

Cite this

Wiklund, L., Miller, V. M., McGregor, C. G. A., Sjoquist, P. O., Berggren, H., & Nilsson, F. (1995). Protective effects of an indenoindole antioxidant on coronary endothelial function after long-term storage. Transplantation, 60(8), 774-778.

Protective effects of an indenoindole antioxidant on coronary endothelial function after long-term storage. / Wiklund, L.; Miller, Virginia M; McGregor, C. G A; Sjoquist, P. O.; Berggren, H.; Nilsson, F.

In: Transplantation, Vol. 60, No. 8, 1995, p. 774-778.

Research output: Contribution to journalArticle

Wiklund, L, Miller, VM, McGregor, CGA, Sjoquist, PO, Berggren, H & Nilsson, F 1995, 'Protective effects of an indenoindole antioxidant on coronary endothelial function after long-term storage', Transplantation, vol. 60, no. 8, pp. 774-778.
Wiklund, L. ; Miller, Virginia M ; McGregor, C. G A ; Sjoquist, P. O. ; Berggren, H. ; Nilsson, F. / Protective effects of an indenoindole antioxidant on coronary endothelial function after long-term storage. In: Transplantation. 1995 ; Vol. 60, No. 8. pp. 774-778.
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abstract = "Experiments were designed to evaluate function of the endothelium and smooth muscle of coronary arteries following storage of hearts in cardioplegia containing an inhibitor of lipid peroxidation (H 290/51, cis-7- metyl-9-methoxy-5,5a, 6,10b tetrahydroindeno [2,1-b] indole). Canine hearts were perfused with crystalloid cardioplegia (Plegisol, 15 ml/kg, 4°C) and left circumflex arteries were isolated and studied either immediately (group I, n=6), or after storage of the hearts at 4°C for 10 (group II, n=6) or 24 hr with (group III, n=6) or without (group IV, n=6) addition of H 290/51. The final concentration of H 290/51 was 1 μmol/L. Arteries were removed, cut into rings, and suspended in organ chambers for measurements of isometric force. In selected rings, the endothelium was removed in order to study the function of the smooth muscle. In order to discriminate effects of ischemia/reperfusion and protective properties on coronary endothelium or smooth muscle, drugs with different mechanisms were used. The function of the endothelium were studied with the α2-adrenergic agonist UK 14,304, bradykinin and A 23187. The smooth muscle function were studied with isoproterenol and nitric oxide. Endothelium-dependent relaxations to the α2-adrenergic agonist UK 14,304 and bradykinin, but not to A 23187, were reduced significantly in arteries from hearts stored for 24 hr in cardioplegic solution alone. Relaxations of arteries from hearts stored for 24 hr with H 290/51 were comparable to those arteries from hearts that were not stored. Endothelium-independent relaxations to isoproterenol and nitric oxide among the different groups were comparable. These results suggest that storage of canine hearts with crystalloid cardioplegia selectively inhibits endothelium-dependent relaxations mediated by receptor activation. Inhibition of lipid peroxidation with H 290/51 preserves these relaxations and may therefore represent a therapeutic alternative to preserve hearts used for transplantation.",
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