Cardioprotection by St. Thomas' solution is mediated by protein kinase C and tyrosine kinase

Nasim Hedayati, Steve J. Schomisch, Joseph L. Carino, J. Timothy Sherwood, Edward J. Lesnefsky, Brian L. Cmolik

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background. Intracellular signaling pathways, specifically the activation of protein kinase C and tyrosine kinase, are essential to the cardioprotection of ischemic preconditioning. We proposed that activation of PKC and TK contribute to the myocardial protection of St. Thomas' No. 2 cardioplegia solution (STC). Materials and methods. Isolated rat hearts were exposed to 40 min of global ischemia followed by 120 min of reperfusion. Before ischemia, hearts received no treatment (control; n = 7), STC (n = 7), phorbol 12-myristate 13-acetate (PMA; n = 6), PMA + chelerythrine (n = 6), anisomycin (n = 6), anisomycin + genistein (n = 7), STC + chelerythrine (n = 7), STC + genistein (n = 7), PMA + genistein (n = 7) or anisomycin + chelerythrine (n = 7). Left ventricular developed pressure (LVDP) recovery, myocardial infarct size, and lactate dehydrogenase release were measured. Results. STC as well as PMA (protein kinase C activator) and anisomycin (tyrosine kinase activator) significantly reduced infarct size (6.9 ± 2.9%, 9.6 ± 2.1%, 14.0 ± 4.4%) compared with controls (42.4 ± 2.9%, P < 0.05). The infarct reduction of PMA and anisomycin were blocked by their inhibitors chelerythrine and genistein, respectively. Both chelerythrine (29.2 ± 4.1%, P < 0.05) and genistein (40.4 ± 4.3%, P < 0.05) attenuated the reduction of infarct size provided by STC. The recovery of LVDP improved with STC, PMA and anisomycin (72.6 ± 1.4%, 60.4 ± 4.7%, 57.2 ± 4.6%) compared with control (33.8 ± 3.6%, P < 0.05). Addition of chelerythrine or genistein to STC impaired recovery of LVDP (52.3 ± 4.4%, 35.1 ± 2.5%, P < 0.05) compared with STC treatment. Conclusion. Administration of the pharmacologic inhibitors chelerythrine and genistein blunts the cardioprotection caused by STC treatment.

Original languageEnglish (US)
Pages (from-to)121-127
Number of pages7
JournalJournal of Surgical Research
Volume113
Issue number1
DOIs
StatePublished - Jul 2003
Externally publishedYes

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Anisomycin
Genistein
Protein-Tyrosine Kinases
Ventricular Pressure
Ischemia
Ischemic Preconditioning
Induced Heart Arrest
chelerythrine
Thomas' solution
protein kinase C kinase
L-Lactate Dehydrogenase
Protein Kinase C
Reperfusion
Acetates
Myocardial Infarction

Keywords

  • Cardioplegia
  • Ischemia-reperfusion
  • Langendorff
  • Protein kinase C
  • Tyrosine kinase

ASJC Scopus subject areas

  • Surgery

Cite this

Cardioprotection by St. Thomas' solution is mediated by protein kinase C and tyrosine kinase. / Hedayati, Nasim; Schomisch, Steve J.; Carino, Joseph L.; Sherwood, J. Timothy; Lesnefsky, Edward J.; Cmolik, Brian L.

In: Journal of Surgical Research, Vol. 113, No. 1, 07.2003, p. 121-127.

Research output: Contribution to journalArticle

Hedayati, Nasim ; Schomisch, Steve J. ; Carino, Joseph L. ; Sherwood, J. Timothy ; Lesnefsky, Edward J. ; Cmolik, Brian L. / Cardioprotection by St. Thomas' solution is mediated by protein kinase C and tyrosine kinase. In: Journal of Surgical Research. 2003 ; Vol. 113, No. 1. pp. 121-127.
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title = "Cardioprotection by St. Thomas' solution is mediated by protein kinase C and tyrosine kinase",
abstract = "Background. Intracellular signaling pathways, specifically the activation of protein kinase C and tyrosine kinase, are essential to the cardioprotection of ischemic preconditioning. We proposed that activation of PKC and TK contribute to the myocardial protection of St. Thomas' No. 2 cardioplegia solution (STC). Materials and methods. Isolated rat hearts were exposed to 40 min of global ischemia followed by 120 min of reperfusion. Before ischemia, hearts received no treatment (control; n = 7), STC (n = 7), phorbol 12-myristate 13-acetate (PMA; n = 6), PMA + chelerythrine (n = 6), anisomycin (n = 6), anisomycin + genistein (n = 7), STC + chelerythrine (n = 7), STC + genistein (n = 7), PMA + genistein (n = 7) or anisomycin + chelerythrine (n = 7). Left ventricular developed pressure (LVDP) recovery, myocardial infarct size, and lactate dehydrogenase release were measured. Results. STC as well as PMA (protein kinase C activator) and anisomycin (tyrosine kinase activator) significantly reduced infarct size (6.9 ± 2.9{\%}, 9.6 ± 2.1{\%}, 14.0 ± 4.4{\%}) compared with controls (42.4 ± 2.9{\%}, P < 0.05). The infarct reduction of PMA and anisomycin were blocked by their inhibitors chelerythrine and genistein, respectively. Both chelerythrine (29.2 ± 4.1{\%}, P < 0.05) and genistein (40.4 ± 4.3{\%}, P < 0.05) attenuated the reduction of infarct size provided by STC. The recovery of LVDP improved with STC, PMA and anisomycin (72.6 ± 1.4{\%}, 60.4 ± 4.7{\%}, 57.2 ± 4.6{\%}) compared with control (33.8 ± 3.6{\%}, P < 0.05). Addition of chelerythrine or genistein to STC impaired recovery of LVDP (52.3 ± 4.4{\%}, 35.1 ± 2.5{\%}, P < 0.05) compared with STC treatment. Conclusion. Administration of the pharmacologic inhibitors chelerythrine and genistein blunts the cardioprotection caused by STC treatment.",
keywords = "Cardioplegia, Ischemia-reperfusion, Langendorff, Protein kinase C, Tyrosine kinase",
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T1 - Cardioprotection by St. Thomas' solution is mediated by protein kinase C and tyrosine kinase

AU - Hedayati, Nasim

AU - Schomisch, Steve J.

AU - Carino, Joseph L.

AU - Sherwood, J. Timothy

AU - Lesnefsky, Edward J.

AU - Cmolik, Brian L.

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N2 - Background. Intracellular signaling pathways, specifically the activation of protein kinase C and tyrosine kinase, are essential to the cardioprotection of ischemic preconditioning. We proposed that activation of PKC and TK contribute to the myocardial protection of St. Thomas' No. 2 cardioplegia solution (STC). Materials and methods. Isolated rat hearts were exposed to 40 min of global ischemia followed by 120 min of reperfusion. Before ischemia, hearts received no treatment (control; n = 7), STC (n = 7), phorbol 12-myristate 13-acetate (PMA; n = 6), PMA + chelerythrine (n = 6), anisomycin (n = 6), anisomycin + genistein (n = 7), STC + chelerythrine (n = 7), STC + genistein (n = 7), PMA + genistein (n = 7) or anisomycin + chelerythrine (n = 7). Left ventricular developed pressure (LVDP) recovery, myocardial infarct size, and lactate dehydrogenase release were measured. Results. STC as well as PMA (protein kinase C activator) and anisomycin (tyrosine kinase activator) significantly reduced infarct size (6.9 ± 2.9%, 9.6 ± 2.1%, 14.0 ± 4.4%) compared with controls (42.4 ± 2.9%, P < 0.05). The infarct reduction of PMA and anisomycin were blocked by their inhibitors chelerythrine and genistein, respectively. Both chelerythrine (29.2 ± 4.1%, P < 0.05) and genistein (40.4 ± 4.3%, P < 0.05) attenuated the reduction of infarct size provided by STC. The recovery of LVDP improved with STC, PMA and anisomycin (72.6 ± 1.4%, 60.4 ± 4.7%, 57.2 ± 4.6%) compared with control (33.8 ± 3.6%, P < 0.05). Addition of chelerythrine or genistein to STC impaired recovery of LVDP (52.3 ± 4.4%, 35.1 ± 2.5%, P < 0.05) compared with STC treatment. Conclusion. Administration of the pharmacologic inhibitors chelerythrine and genistein blunts the cardioprotection caused by STC treatment.

AB - Background. Intracellular signaling pathways, specifically the activation of protein kinase C and tyrosine kinase, are essential to the cardioprotection of ischemic preconditioning. We proposed that activation of PKC and TK contribute to the myocardial protection of St. Thomas' No. 2 cardioplegia solution (STC). Materials and methods. Isolated rat hearts were exposed to 40 min of global ischemia followed by 120 min of reperfusion. Before ischemia, hearts received no treatment (control; n = 7), STC (n = 7), phorbol 12-myristate 13-acetate (PMA; n = 6), PMA + chelerythrine (n = 6), anisomycin (n = 6), anisomycin + genistein (n = 7), STC + chelerythrine (n = 7), STC + genistein (n = 7), PMA + genistein (n = 7) or anisomycin + chelerythrine (n = 7). Left ventricular developed pressure (LVDP) recovery, myocardial infarct size, and lactate dehydrogenase release were measured. Results. STC as well as PMA (protein kinase C activator) and anisomycin (tyrosine kinase activator) significantly reduced infarct size (6.9 ± 2.9%, 9.6 ± 2.1%, 14.0 ± 4.4%) compared with controls (42.4 ± 2.9%, P < 0.05). The infarct reduction of PMA and anisomycin were blocked by their inhibitors chelerythrine and genistein, respectively. Both chelerythrine (29.2 ± 4.1%, P < 0.05) and genistein (40.4 ± 4.3%, P < 0.05) attenuated the reduction of infarct size provided by STC. The recovery of LVDP improved with STC, PMA and anisomycin (72.6 ± 1.4%, 60.4 ± 4.7%, 57.2 ± 4.6%) compared with control (33.8 ± 3.6%, P < 0.05). Addition of chelerythrine or genistein to STC impaired recovery of LVDP (52.3 ± 4.4%, 35.1 ± 2.5%, P < 0.05) compared with STC treatment. Conclusion. Administration of the pharmacologic inhibitors chelerythrine and genistein blunts the cardioprotection caused by STC treatment.

KW - Cardioplegia

KW - Ischemia-reperfusion

KW - Langendorff

KW - Protein kinase C

KW - Tyrosine kinase

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