Long-term thyroxine administration protects the heart in a pattern similar to ischemic preconditioning.
We have previously shown that long-term thyroxine administration can protect the heart against ischemia. In the present study, we investigated whether thyroxine-induced cardioprotection can mimic the pattern of protection that is afforded by a well-established cardioprotective means such as ischemic preconditioning. In a Langendorff-perfused rat heart preparation, after an initial stabilization, normal and thyroxine-treated hearts were subjected to 20 minutes of zero-flow global ischemia followed by 45 minutes of reperfusion. In thyroxine-treated hearts, phospho-p38 mitogen-activated protein kinase (MAPK) was found to be less at the end of the ischemic period, whereas ischemic contracture was accelerated and postischemic recovery was increased in comparison to normal hearts. In addition, normal hearts were subjected to a four-cycle preconditioning protocol before ischemia. Phospho-p38 MAPK was found to be less at the end of the ischemic period in preconditioned hearts, whereas ischemic contracture was accelerated and postischemic functional recovery was increased in those hearts in comparison to nonpreconditioned hearts. An increase in basal expression and phosphorylation of PKCdelta was also found to occur after long-term thyroxine administration. We conclude that long-term thyroxine administration can protect the heart from ischemic injury through a pattern of protection that closely resembles that of ischemic preconditioning.
Pantos
Constantinos I
CI
Department of Pharmacology, University of Athens, Goudi, Athens, Greece. cpantos@cc.uoa.gr
Malliopoulou
Vassiliki A
VA
Mourouzis
Iordanis S
IS
Karamanoli
Evangelia P
EP
Paizis
Ioannis A
IA
Steimberg
Natalie
N
Varonos
Dennis D
DD
Cokkinos
Dennis V
DV
D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004334:Drug Administration Schedule; D004789:Enzyme Activation; D006321:Heart / Q000187:drug effects / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000008:administration & dosage* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D002316:Cardiotonic Agents; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013974:Thyroxine