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).


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.


CONCLUSIONS
Administration of the pharmacologic inhibitors chelerythrine and genistein blunts the cardioprotection caused by STC treatment.
Hedayati
Nasim
N
Division of Cardiothoracic Surgery, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, Ohio 44106-5011, USA.
Schomisch
Steve J
SJ
Carino
Joseph L
JL
Timothy Sherwood
J
J
Lesnefsky
Edward J
EJ
Cmolik
Brian L
BL
D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy; D009206:Myocardium / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000628:therapy; D015398:Signal Transduction / Q000502:physiology
D002314:Cardioplegic Solutions; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C