Open AccessIschemic preconditioning fails to confer additional protection against ischemia-reperfusion injury in the hypothyroid rat heart
Author(s) -
Iordanis Mourouzis,
Antonios Dimopoulos,
Theodosios Saranteas,
N. Tsinarakis,
E. Livadarou,
Danai Spanou,
Kokkinos Ad,
Christodoulos Xinaris,
Constantinos Pantos,
DV Cokkinos
Publication year - 2009
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.931387
Subject(s) - ischemia , medicine , cardiology , myocardial infarction , ischemic preconditioning , cardioprotection , lactate dehydrogenase , cardiac function curve , reperfusion injury , infarction , heart failure , endocrinology , anesthesia , chemistry , enzyme , biochemistry
There is accumulating evidence showing that ischemicpreconditioning (PC) may lose its cardioprotective effect in thediseased states. The present study investigated whether PC canbe effective in hypothyroidism, a clinical condition which iscommon and often accompanies cardiac diseases such as heartfailure and myocardial infarction. Hypothyroidism was induced inrats by 3-week administration of 6n-propyl-2-thiouracil in water(0.05 %). Normal and hypothyroid hearts (HYPO) were perfusedin Langendorff mode and subjected to 20 min of zero-flow globalischemia and 45 min of reperfusion. A preconditioning protocol(PC) was also applied prior to ischemia. HYPO hearts hadsignificantly improved post-ischemic recovery of left ventriculardeveloped pressure, end-diastolic pressure and reduced lactatedehydrogenase release. Furthermore, phospho-JNK and p38MAPK levels after ischemia and reperfusion were 4.0 and 3.0 foldlower in HYPO as compared to normal hearts (P<0.05). Adifferent response to PC was observed in normal than in HYPOhearts. PC improved the post-ischemic recovery of function andreduced the extent of injury in normal hearts but had noadditional effect on the hypothyroid hearts. This response, in thepreconditioned normal hearts, resulted in 2.5 and 1.8 fold smallerexpression of the phospho-JNK and phospho-p38 MAPK levels atthe end of reperfusion, as compared to non-PC hearts (P<0.05),while in HYPO hearts, no additional reduction in thephosphorylation of these kinases was observed after PC.Hypothyroid hearts appear to be tolerant to ischemia-reperfusioninjury. This response may be, at least in part, due to the downregulation of ischemia-reperfusion induced activation of JNKs andp38 MAPK kinases. PC is not associated with further reduction inthe activation of these kinases in the hypothyroid hearts and failsto confer added protection in those hearts.