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

11 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Surgery

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