Long-Term Thyroxine Administration Protects the Heart in a Pattern Similar to Ischemic Preconditioning

Abstract

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.

CD36 overexpression predisposes to arrhythmias but reduces infarct size in spontaneously hypertensive rats: gene expression profile analysis

“…Ischemic preconditioning attenuated ischemia-induced reciprocal changes in COX I and COX III levels (59). Moreover, chronic administration of thyroid hormone affected COX I and III expression (46) and protected the heart against lethal ischemic injury (38). In line with these reports, the present study demonstrates increased COX I and decreased COX III gene expression and the improved cardiac ischemic tolerance in SHRCd36.…”

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

“…Buser et al (1990) showed that isolated hyperthyroid rat hearts displayed postischemic functional recovery comparable with euthyroid hearts, whereas hypertrophied hearts from rats with pressure overload due to aortic banding recovered poorly. Pantos et al (1999Pantos et al ( , 2000Pantos et al ( , 2002 showed enhanced postischemic functional recovery in hyperthyroid rat hearts, associ-CARDIOPROTECTION AND RISK FACTORS ated with earlier and greater peak contracture than normal hearts, a consistent feature of global ischemia models of ischemic preconditioning. Interestingly, the effect on contracture seen in hyperthyroid hearts was additive to that of ischemic preconditioning (Pantos et al, 2001).…”

Recent advances in liver preconditioning: Thyroid hormone, n-3 long-chain polyunsaturated fatty acids and iron

“…Organ preconditioning by these hormetic agents is not restricted to the liver [26][27][28] , considering that (1) thyroid 1) thyroid ) thyroid hormone-induced preconditioning against IR injury is also observed in the heart [95,96] , with a pattern of protection comparable to that of ischemic preconditioning [97] ; (�) beneficial effects of n-3 LCPUFA have been dem-�) beneficial effects of n-3 LCPUFA have been dem-) beneficial effects of n-3 LCPUFA have been demonstrated in rheumatoid arthritis, inflammatory bowel disease, coronary artery disease, asthma and sepsis, conditions with inflammation as a key component of their pathology [48] , in addition to neuroinflammation in all major central nervous system diseases [98] ; and (�) protec-�) protec-) protective effects of iron are reported in cardiomyocytes and heart [99][100][101] , oligodendroglia cells [102] and neurones [10�] . T�, n-3 LCPUFA or iron liver preconditioning are suitable to be introduced in the clinical setting, considering that these hormetins are known to be well tolerated in the treatment of hypothyroidism [104] , non-alcoholic fatty liver disease [72][73][74][75][76] and other diseases [48] , or anemia [105,106] , respectively.…”