Cardioprotection by St Thomas' solution is mediated by protein kinase C and tyrosine kinase.
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.[1]References
- Cardioprotection by St Thomas' solution is mediated by protein kinase C and tyrosine kinase. Hedayati, N., Schomisch, S.J., Carino, J.L., Timothy Sherwood, J., Lesnefsky, E.J., Cmolik, B.L. J. Surg. Res. (2003) [Pubmed]
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